Hepatology

A test that uses a single drop of dried blood to detect HIV, hepatitis B virus, and HCV has been validated and is now in use in some high-risk settings in Denmark, according to research presented at the annual European Congress of Clinical Microbiology & Infectious Diseases.

Molecular biologist Stephen Nilsson-Møller, MSc, and colleagues at the department of clinical microbiology, Copenhagen University Hospital, developed and validated the test, known as the Dried Blood Spot (DBS), for HIV, HBV, and HCV.

The “test that can detect low viral loads for all three viruses from a single drop of blood, and can be done using existing hospital equipment,” Mr. Nilsson-Møller said in an interview. “Importantly, it does not require venipuncture, but can be done from a drop of dried blood from the finger.”

He highlighted the utility of the new test in more challenging settings. “This method is particularly useful in high-risk settings such as homeless shelters, drug rehabilitation centers, and prisons, where needles might be misused, and it can be difficult to convince people to have the more invasive test.”

“Also, in some places – such as in low- and middle-income settings – there is a distinct risk of ruining blood samples before analysis due to limited refrigeration for transit and storage,” he added. “[Standard] blood samples need to be analyzed within 6 hours when kept at room temperature, while dried blood spots can last for 9 months at room temperature and can be mailed to a laboratory with the right equipment to analyze it.” 
 

Tiny amounts of virus detected

Mr. Nilsson-Møller was tasked with developing a test for use by the university’s department of infectious diseases to screen people in high-risk settings in the capital region of Copenhagen. The work forms part of a PhD project by Jonas Demant at the University of Copenhagen, for which he is screening for HIV, HBV, and HCV in drug rehabilitation centers, prisons, and homeless shelters. 

The study is the first to use the Hologic Panther system (a nucleic acid amplification test) combining all three viruses, Mr. Nilsson-Møller pointed out. “A tiny amount of virus can be detected because it is a very sensitive platform using transcription-mediated amplification.”

“If it detects low amounts of virus, it will create many copies very quickly, creating a signal that tells us that the sample is positive,” he explained.

The researchers collected whole blood from a finger prick, dried it out on a protein saver card (filter paper), and cut out a 1.2-cm diameter dry blood spot which was then prepared for analysis.

Twenty blood samples with known amounts of HIV, HBV, and HCV were analyzed via the DBS method (60 in total) and the viruses were detected in all of the samples.

To validate the method, the researchers used plasma with a known viral load, and a series of dilutions were performed to determine the lower limit for positive detection of all three viruses.

“Untreated patients typically have above 1 million IU/mL of viral loads in their plasma, and we found that we can detect much lower levels,” said Mr. Nilsson-Møller. “Ideally, 40 mcL of blood is good, but less should be sufficient if the test is on untreated patients.”
 

Early testing and treatment reduces morbidity and mortality

Elimination of HBV, HCV, and HIV by 2030 is a global health strategy set by the World Health Organization, but to meet this goal, new approaches for diagnostic testing are required. The DBS test for HIV, HBV, and HCV promises to make a significant contribution toward this goal.

“One in two people currently living with HIV is diagnosed late in the course of their infection, and an even larger proportion of the estimated 6 million Europeans living with chronic hepatitis B or C are not aware that they are infected,” said Anastasia Pharris, PhD, from the European Center for Disease Prevention and Control Principal Expert Infectious Diseases.

“Increasing testing coverage and uptake, especially for those most at risk, is an essential element of any strategy to eliminate HBV, HCV, and HIV in the European Union and European Economic Area,” she pointed out.

Dr. Pharris also highlighted that, while HIV, and often HBV infection, require lifelong treatment, HCV infection is now curable within a few weeks. “To maximize the benefits of individual treatment for all three infections, it is critical to test and diagnose people as soon as possible – in itself a challenge given that these infections can typically be asymptomatic for years.

“Early diagnosis of HBV, HCV, or HIV is vital as it allows people to access treatment, which significantly reduces associated long-term morbidity and mortality.

“In many cases, those most at risk of one of these infections are also more vulnerable to infection with one or both of the other viruses, making the argument for integrated testing even stronger,” she said in an interview.

Mr. Nilsson-Møller and Dr. Pharris reported no relevant financial relationships. Aptima kits for validation were provided by Hologic.

A version of this article first appeared on Medscape.com.

A test that uses a single drop of dried blood to detect HIV, hepatitis B virus, and HCV has been validated and is now in use in some high-risk settings in Denmark, according to research presented at the annual European Congress of Clinical Microbiology & Infectious Diseases.

Molecular biologist Stephen Nilsson-Møller, MSc, and colleagues at the department of clinical microbiology, Copenhagen University Hospital, developed and validated the test, known as the Dried Blood Spot (DBS), for HIV, HBV, and HCV.

The “test that can detect low viral loads for all three viruses from a single drop of blood, and can be done using existing hospital equipment,” Mr. Nilsson-Møller said in an interview. “Importantly, it does not require venipuncture, but can be done from a drop of dried blood from the finger.”

He highlighted the utility of the new test in more challenging settings. “This method is particularly useful in high-risk settings such as homeless shelters, drug rehabilitation centers, and prisons, where needles might be misused, and it can be difficult to convince people to have the more invasive test.”

“Also, in some places – such as in low- and middle-income settings – there is a distinct risk of ruining blood samples before analysis due to limited refrigeration for transit and storage,” he added. “[Standard] blood samples need to be analyzed within 6 hours when kept at room temperature, while dried blood spots can last for 9 months at room temperature and can be mailed to a laboratory with the right equipment to analyze it.” 
 

Tiny amounts of virus detected

Mr. Nilsson-Møller was tasked with developing a test for use by the university’s department of infectious diseases to screen people in high-risk settings in the capital region of Copenhagen. The work forms part of a PhD project by Jonas Demant at the University of Copenhagen, for which he is screening for HIV, HBV, and HCV in drug rehabilitation centers, prisons, and homeless shelters. 

The study is the first to use the Hologic Panther system (a nucleic acid amplification test) combining all three viruses, Mr. Nilsson-Møller pointed out. “A tiny amount of virus can be detected because it is a very sensitive platform using transcription-mediated amplification.”

“If it detects low amounts of virus, it will create many copies very quickly, creating a signal that tells us that the sample is positive,” he explained.

The researchers collected whole blood from a finger prick, dried it out on a protein saver card (filter paper), and cut out a 1.2-cm diameter dry blood spot which was then prepared for analysis.

Twenty blood samples with known amounts of HIV, HBV, and HCV were analyzed via the DBS method (60 in total) and the viruses were detected in all of the samples.

To validate the method, the researchers used plasma with a known viral load, and a series of dilutions were performed to determine the lower limit for positive detection of all three viruses.

“Untreated patients typically have above 1 million IU/mL of viral loads in their plasma, and we found that we can detect much lower levels,” said Mr. Nilsson-Møller. “Ideally, 40 mcL of blood is good, but less should be sufficient if the test is on untreated patients.”
 

Early testing and treatment reduces morbidity and mortality

Elimination of HBV, HCV, and HIV by 2030 is a global health strategy set by the World Health Organization, but to meet this goal, new approaches for diagnostic testing are required. The DBS test for HIV, HBV, and HCV promises to make a significant contribution toward this goal.

“One in two people currently living with HIV is diagnosed late in the course of their infection, and an even larger proportion of the estimated 6 million Europeans living with chronic hepatitis B or C are not aware that they are infected,” said Anastasia Pharris, PhD, from the European Center for Disease Prevention and Control Principal Expert Infectious Diseases.

“Increasing testing coverage and uptake, especially for those most at risk, is an essential element of any strategy to eliminate HBV, HCV, and HIV in the European Union and European Economic Area,” she pointed out.

Dr. Pharris also highlighted that, while HIV, and often HBV infection, require lifelong treatment, HCV infection is now curable within a few weeks. “To maximize the benefits of individual treatment for all three infections, it is critical to test and diagnose people as soon as possible – in itself a challenge given that these infections can typically be asymptomatic for years.

“Early diagnosis of HBV, HCV, or HIV is vital as it allows people to access treatment, which significantly reduces associated long-term morbidity and mortality.

“In many cases, those most at risk of one of these infections are also more vulnerable to infection with one or both of the other viruses, making the argument for integrated testing even stronger,” she said in an interview.

Mr. Nilsson-Møller and Dr. Pharris reported no relevant financial relationships. Aptima kits for validation were provided by Hologic.

A version of this article first appeared on Medscape.com.

A test that uses a single drop of dried blood to detect HIV, hepatitis B virus, and HCV has been validated and is now in use in some high-risk settings in Denmark, according to research presented at the annual European Congress of Clinical Microbiology & Infectious Diseases.

Molecular biologist Stephen Nilsson-Møller, MSc, and colleagues at the department of clinical microbiology, Copenhagen University Hospital, developed and validated the test, known as the Dried Blood Spot (DBS), for HIV, HBV, and HCV.

The “test that can detect low viral loads for all three viruses from a single drop of blood, and can be done using existing hospital equipment,” Mr. Nilsson-Møller said in an interview. “Importantly, it does not require venipuncture, but can be done from a drop of dried blood from the finger.”

He highlighted the utility of the new test in more challenging settings. “This method is particularly useful in high-risk settings such as homeless shelters, drug rehabilitation centers, and prisons, where needles might be misused, and it can be difficult to convince people to have the more invasive test.”

“Also, in some places – such as in low- and middle-income settings – there is a distinct risk of ruining blood samples before analysis due to limited refrigeration for transit and storage,” he added. “[Standard] blood samples need to be analyzed within 6 hours when kept at room temperature, while dried blood spots can last for 9 months at room temperature and can be mailed to a laboratory with the right equipment to analyze it.” 
 

Tiny amounts of virus detected

Mr. Nilsson-Møller was tasked with developing a test for use by the university’s department of infectious diseases to screen people in high-risk settings in the capital region of Copenhagen. The work forms part of a PhD project by Jonas Demant at the University of Copenhagen, for which he is screening for HIV, HBV, and HCV in drug rehabilitation centers, prisons, and homeless shelters. 

The study is the first to use the Hologic Panther system (a nucleic acid amplification test) combining all three viruses, Mr. Nilsson-Møller pointed out. “A tiny amount of virus can be detected because it is a very sensitive platform using transcription-mediated amplification.”

“If it detects low amounts of virus, it will create many copies very quickly, creating a signal that tells us that the sample is positive,” he explained.

The researchers collected whole blood from a finger prick, dried it out on a protein saver card (filter paper), and cut out a 1.2-cm diameter dry blood spot which was then prepared for analysis.

Twenty blood samples with known amounts of HIV, HBV, and HCV were analyzed via the DBS method (60 in total) and the viruses were detected in all of the samples.

To validate the method, the researchers used plasma with a known viral load, and a series of dilutions were performed to determine the lower limit for positive detection of all three viruses.

“Untreated patients typically have above 1 million IU/mL of viral loads in their plasma, and we found that we can detect much lower levels,” said Mr. Nilsson-Møller. “Ideally, 40 mcL of blood is good, but less should be sufficient if the test is on untreated patients.”
 

Early testing and treatment reduces morbidity and mortality

Elimination of HBV, HCV, and HIV by 2030 is a global health strategy set by the World Health Organization, but to meet this goal, new approaches for diagnostic testing are required. The DBS test for HIV, HBV, and HCV promises to make a significant contribution toward this goal.

“One in two people currently living with HIV is diagnosed late in the course of their infection, and an even larger proportion of the estimated 6 million Europeans living with chronic hepatitis B or C are not aware that they are infected,” said Anastasia Pharris, PhD, from the European Center for Disease Prevention and Control Principal Expert Infectious Diseases.

“Increasing testing coverage and uptake, especially for those most at risk, is an essential element of any strategy to eliminate HBV, HCV, and HIV in the European Union and European Economic Area,” she pointed out.

Dr. Pharris also highlighted that, while HIV, and often HBV infection, require lifelong treatment, HCV infection is now curable within a few weeks. “To maximize the benefits of individual treatment for all three infections, it is critical to test and diagnose people as soon as possible – in itself a challenge given that these infections can typically be asymptomatic for years.

“Early diagnosis of HBV, HCV, or HIV is vital as it allows people to access treatment, which significantly reduces associated long-term morbidity and mortality.

“In many cases, those most at risk of one of these infections are also more vulnerable to infection with one or both of the other viruses, making the argument for integrated testing even stronger,” she said in an interview.

Mr. Nilsson-Møller and Dr. Pharris reported no relevant financial relationships. Aptima kits for validation were provided by Hologic.

A version of this article first appeared on Medscape.com.

Researchers studying differences in treatment initiation for chronic hepatitis B (CHB) among a large, multiracial cohort in North America did not find evidence of disparities by race or socioeconomic status.

Instead, they observed a similar gap across races between the number of people eligible for treatment and those receiving it.

That gap suggests that treatment guidelines need to be simplified and that efforts to increase hepatitis B virus (HBV) awareness and train more clinicians are needed to achieve the World Health Organization’s goal of eliminating HBV by 2030, the researchers write.

The Hepatitis B Research Network study was published online in JAMA Network Open.

The prevalence of CHB in the United States is estimated at 2.4 million. It disproportionately affects persons of Asian or African descent, the investigators note. Their study examined whether treatment initiation and outcomes differ between African American and Black, Asian, and White participants, as well as between African American and Black participants born in North America and East or West Africa.

The research involved 1,550 adult patients: 1,157 Asian American, 193 African American or Black (39 born in the United States, 90 in East Africa, 53 in West Africa, and 11 elsewhere), 157 White, and 43 who identified as being of “other races.” All had CHB but were not receiving antiviral treatment at enrollment.

Participants came from 20 centers in the United States and one in Canada. They underwent clinical and laboratory assessments and could receive anti-HBV treatment after they enrolled. Enrollment was from Jan. 14, 2011, to Jan. 28, 2018. Participants were followed at 12 and 24 weeks and every 24 weeks thereafter in the longitudinal cohort study by Mandana Khalili, MD, division of gastroenterology and hepatology, University of California, San Francisco, and colleagues.

Information on patients’ country of birth, duration of U.S. or Canadian residency, educational level, employment, insurance, prior antiviral treatment, family history of HBV or hepatocellular carcinoma (HCC), and mode of transmission were collected by research coordinators.
 

Treatment initiation

During the study period, slightly fewer than one-third (32.5%) of the participants initiated treatment. The incidences were 4.8 per 100 person-years in African American or Black participants, 9.9 per 100 person-years in Asian participants, 6.6 per 100 person-years in White participants, and 7.9 per 100 person-years in those of other races (P < .001).

A lower percentage of African American and Black participants (14%) met the American Association for the Study of Liver Diseases treatment criteria, compared with Asian (22%) and White (27%) participants (P = .01).

When the researchers compared cumulative probability of initiating treatment by race for those who met criteria for treatment, they found no significant differences by race.

At 72 weeks, initiation probability was 0.45 for African American and Black patients and 0.51 for Asian and White patients (P = .68). Similarly, among African American and Black participants who met treatment criteria, there were no significant differences in cumulative probability of treatment by region of birth.

The cumulative percentage of treatment initiation for those who met guideline-based criteria was 62%.

“Among participants with a treatment indication, treatment rates did not differ significantly by race, despite marked differences in educational level, income, and type of health care insurance across the racial groups,” the researchers write. “Moreover, race was not an independent estimator of treatment initiation when adjusting for known factors associated with a higher risk of adverse clinical outcomes, namely, HBV DNA, disease severity, sex, and age.”

Adverse liver outcomes (hepatic decompensation, HCC, liver transplant, and death) were rare and did not vary significantly by race, the researchers write.

One study limitation is that participants were linked to specialty liver clinics, so the findings may not be generalizable to patients who receive care in other settings, the authors note.

The results are “reassuring,” said senior author Anna S. Lok, MD, division of gastroenterology and hepatology at University of Michigan in Ann Arbor. However, she noted, study participants had already overcome barriers to receiving care at major academic centers.

“Once you get into the big academic liver centers, then maybe everything is equal, but in the real world, a lot of people don’t ever get to the big liver centers,” she said. The question becomes: “Are we serving only a portion of the patient population?”

Many factors drive the decision to undergo treatment, including the doctor’s opinion as to need and the patient’s desire to receive treatment, she said.

The study participants who were more likely to get treated were those with higher-level disease who had a stronger indication for treatment, Dr. Lok said.
 

Finding the disparities

Centers for Disease Control and Prevention statistics show that Black people are 3.9 times more likely to have CHB and 2.5 times more likely to die from it than White people, notes H. Nina Kim, MD, with the department of medicine, University of Washington, Seattle, in an accompanying invited commentary.

“The fact that we have not observed racial disparities in treatment initiation does not mean none exist; it means we have to look harder to find them,” she writes.

“We need to examine whether our guidelines for HBV treatment are so complex that it becomes the purview of specialists, thereby restricting access and deepening inequities,” Dr. Kim adds. “We should look closely at retention in care, the step that precedes treatment, and stratify this outcome by race and ethnicity.”

Primary care physicians in some regions might find it difficult to manage patients who have hepatitis B because they see so few of them, Dr. Lok noted.

Dr. Khalili has received grants and consulting fees from Gilead Sciences Inc and grants from Intercept Pharmaceuticals outside the submitted work. Dr. Lok has received grants from Target and consultant fees from Abbott, Ambys, Arbutus, Chroma, Clear B, Enanta, Enochian, GNI, GlaxoSmithKline, Eli Lilly, and Virion outside the submitted work. Coauthors have received grants, consulting fees, or personal fees from Bayer, Boston Scientific, Exact Sciences, Fujifilm Medical Sciences, Gilead Sciences, Glycotest, Redhill Biopharma, Target RWE, MedEd Design, Pontifax, Global Life, the Lynx Group, AstraZeneca, Eisai, Novartis Venture Fund, Grail, QED Therapeutics, Genentech, Hepion Pharmaceuticals, Roche, Abbott, AbbVie, and Pfizer. Dr. Kim has received grants from Gilead Sciences (paid to her institution) outside the submitted work.

A version of this article first appeared on Medscape.com.

Researchers studying differences in treatment initiation for chronic hepatitis B (CHB) among a large, multiracial cohort in North America did not find evidence of disparities by race or socioeconomic status.

Instead, they observed a similar gap across races between the number of people eligible for treatment and those receiving it.

That gap suggests that treatment guidelines need to be simplified and that efforts to increase hepatitis B virus (HBV) awareness and train more clinicians are needed to achieve the World Health Organization’s goal of eliminating HBV by 2030, the researchers write.

The Hepatitis B Research Network study was published online in JAMA Network Open.

The prevalence of CHB in the United States is estimated at 2.4 million. It disproportionately affects persons of Asian or African descent, the investigators note. Their study examined whether treatment initiation and outcomes differ between African American and Black, Asian, and White participants, as well as between African American and Black participants born in North America and East or West Africa.

The research involved 1,550 adult patients: 1,157 Asian American, 193 African American or Black (39 born in the United States, 90 in East Africa, 53 in West Africa, and 11 elsewhere), 157 White, and 43 who identified as being of “other races.” All had CHB but were not receiving antiviral treatment at enrollment.

Participants came from 20 centers in the United States and one in Canada. They underwent clinical and laboratory assessments and could receive anti-HBV treatment after they enrolled. Enrollment was from Jan. 14, 2011, to Jan. 28, 2018. Participants were followed at 12 and 24 weeks and every 24 weeks thereafter in the longitudinal cohort study by Mandana Khalili, MD, division of gastroenterology and hepatology, University of California, San Francisco, and colleagues.

Information on patients’ country of birth, duration of U.S. or Canadian residency, educational level, employment, insurance, prior antiviral treatment, family history of HBV or hepatocellular carcinoma (HCC), and mode of transmission were collected by research coordinators.
 

Treatment initiation

During the study period, slightly fewer than one-third (32.5%) of the participants initiated treatment. The incidences were 4.8 per 100 person-years in African American or Black participants, 9.9 per 100 person-years in Asian participants, 6.6 per 100 person-years in White participants, and 7.9 per 100 person-years in those of other races (P < .001).

A lower percentage of African American and Black participants (14%) met the American Association for the Study of Liver Diseases treatment criteria, compared with Asian (22%) and White (27%) participants (P = .01).

When the researchers compared cumulative probability of initiating treatment by race for those who met criteria for treatment, they found no significant differences by race.

At 72 weeks, initiation probability was 0.45 for African American and Black patients and 0.51 for Asian and White patients (P = .68). Similarly, among African American and Black participants who met treatment criteria, there were no significant differences in cumulative probability of treatment by region of birth.

The cumulative percentage of treatment initiation for those who met guideline-based criteria was 62%.

“Among participants with a treatment indication, treatment rates did not differ significantly by race, despite marked differences in educational level, income, and type of health care insurance across the racial groups,” the researchers write. “Moreover, race was not an independent estimator of treatment initiation when adjusting for known factors associated with a higher risk of adverse clinical outcomes, namely, HBV DNA, disease severity, sex, and age.”

Adverse liver outcomes (hepatic decompensation, HCC, liver transplant, and death) were rare and did not vary significantly by race, the researchers write.

One study limitation is that participants were linked to specialty liver clinics, so the findings may not be generalizable to patients who receive care in other settings, the authors note.

The results are “reassuring,” said senior author Anna S. Lok, MD, division of gastroenterology and hepatology at University of Michigan in Ann Arbor. However, she noted, study participants had already overcome barriers to receiving care at major academic centers.

“Once you get into the big academic liver centers, then maybe everything is equal, but in the real world, a lot of people don’t ever get to the big liver centers,” she said. The question becomes: “Are we serving only a portion of the patient population?”

Many factors drive the decision to undergo treatment, including the doctor’s opinion as to need and the patient’s desire to receive treatment, she said.

The study participants who were more likely to get treated were those with higher-level disease who had a stronger indication for treatment, Dr. Lok said.
 

Finding the disparities

Centers for Disease Control and Prevention statistics show that Black people are 3.9 times more likely to have CHB and 2.5 times more likely to die from it than White people, notes H. Nina Kim, MD, with the department of medicine, University of Washington, Seattle, in an accompanying invited commentary.

“The fact that we have not observed racial disparities in treatment initiation does not mean none exist; it means we have to look harder to find them,” she writes.

“We need to examine whether our guidelines for HBV treatment are so complex that it becomes the purview of specialists, thereby restricting access and deepening inequities,” Dr. Kim adds. “We should look closely at retention in care, the step that precedes treatment, and stratify this outcome by race and ethnicity.”

Primary care physicians in some regions might find it difficult to manage patients who have hepatitis B because they see so few of them, Dr. Lok noted.

Dr. Khalili has received grants and consulting fees from Gilead Sciences Inc and grants from Intercept Pharmaceuticals outside the submitted work. Dr. Lok has received grants from Target and consultant fees from Abbott, Ambys, Arbutus, Chroma, Clear B, Enanta, Enochian, GNI, GlaxoSmithKline, Eli Lilly, and Virion outside the submitted work. Coauthors have received grants, consulting fees, or personal fees from Bayer, Boston Scientific, Exact Sciences, Fujifilm Medical Sciences, Gilead Sciences, Glycotest, Redhill Biopharma, Target RWE, MedEd Design, Pontifax, Global Life, the Lynx Group, AstraZeneca, Eisai, Novartis Venture Fund, Grail, QED Therapeutics, Genentech, Hepion Pharmaceuticals, Roche, Abbott, AbbVie, and Pfizer. Dr. Kim has received grants from Gilead Sciences (paid to her institution) outside the submitted work.

A version of this article first appeared on Medscape.com.

Researchers studying differences in treatment initiation for chronic hepatitis B (CHB) among a large, multiracial cohort in North America did not find evidence of disparities by race or socioeconomic status.

Instead, they observed a similar gap across races between the number of people eligible for treatment and those receiving it.

That gap suggests that treatment guidelines need to be simplified and that efforts to increase hepatitis B virus (HBV) awareness and train more clinicians are needed to achieve the World Health Organization’s goal of eliminating HBV by 2030, the researchers write.

The Hepatitis B Research Network study was published online in JAMA Network Open.

The prevalence of CHB in the United States is estimated at 2.4 million. It disproportionately affects persons of Asian or African descent, the investigators note. Their study examined whether treatment initiation and outcomes differ between African American and Black, Asian, and White participants, as well as between African American and Black participants born in North America and East or West Africa.

The research involved 1,550 adult patients: 1,157 Asian American, 193 African American or Black (39 born in the United States, 90 in East Africa, 53 in West Africa, and 11 elsewhere), 157 White, and 43 who identified as being of “other races.” All had CHB but were not receiving antiviral treatment at enrollment.

Participants came from 20 centers in the United States and one in Canada. They underwent clinical and laboratory assessments and could receive anti-HBV treatment after they enrolled. Enrollment was from Jan. 14, 2011, to Jan. 28, 2018. Participants were followed at 12 and 24 weeks and every 24 weeks thereafter in the longitudinal cohort study by Mandana Khalili, MD, division of gastroenterology and hepatology, University of California, San Francisco, and colleagues.

Information on patients’ country of birth, duration of U.S. or Canadian residency, educational level, employment, insurance, prior antiviral treatment, family history of HBV or hepatocellular carcinoma (HCC), and mode of transmission were collected by research coordinators.
 

Treatment initiation

During the study period, slightly fewer than one-third (32.5%) of the participants initiated treatment. The incidences were 4.8 per 100 person-years in African American or Black participants, 9.9 per 100 person-years in Asian participants, 6.6 per 100 person-years in White participants, and 7.9 per 100 person-years in those of other races (P < .001).

A lower percentage of African American and Black participants (14%) met the American Association for the Study of Liver Diseases treatment criteria, compared with Asian (22%) and White (27%) participants (P = .01).

When the researchers compared cumulative probability of initiating treatment by race for those who met criteria for treatment, they found no significant differences by race.

At 72 weeks, initiation probability was 0.45 for African American and Black patients and 0.51 for Asian and White patients (P = .68). Similarly, among African American and Black participants who met treatment criteria, there were no significant differences in cumulative probability of treatment by region of birth.

The cumulative percentage of treatment initiation for those who met guideline-based criteria was 62%.

“Among participants with a treatment indication, treatment rates did not differ significantly by race, despite marked differences in educational level, income, and type of health care insurance across the racial groups,” the researchers write. “Moreover, race was not an independent estimator of treatment initiation when adjusting for known factors associated with a higher risk of adverse clinical outcomes, namely, HBV DNA, disease severity, sex, and age.”

Adverse liver outcomes (hepatic decompensation, HCC, liver transplant, and death) were rare and did not vary significantly by race, the researchers write.

One study limitation is that participants were linked to specialty liver clinics, so the findings may not be generalizable to patients who receive care in other settings, the authors note.

The results are “reassuring,” said senior author Anna S. Lok, MD, division of gastroenterology and hepatology at University of Michigan in Ann Arbor. However, she noted, study participants had already overcome barriers to receiving care at major academic centers.

“Once you get into the big academic liver centers, then maybe everything is equal, but in the real world, a lot of people don’t ever get to the big liver centers,” she said. The question becomes: “Are we serving only a portion of the patient population?”

Many factors drive the decision to undergo treatment, including the doctor’s opinion as to need and the patient’s desire to receive treatment, she said.

The study participants who were more likely to get treated were those with higher-level disease who had a stronger indication for treatment, Dr. Lok said.
 

Finding the disparities

Centers for Disease Control and Prevention statistics show that Black people are 3.9 times more likely to have CHB and 2.5 times more likely to die from it than White people, notes H. Nina Kim, MD, with the department of medicine, University of Washington, Seattle, in an accompanying invited commentary.

“The fact that we have not observed racial disparities in treatment initiation does not mean none exist; it means we have to look harder to find them,” she writes.

“We need to examine whether our guidelines for HBV treatment are so complex that it becomes the purview of specialists, thereby restricting access and deepening inequities,” Dr. Kim adds. “We should look closely at retention in care, the step that precedes treatment, and stratify this outcome by race and ethnicity.”

Primary care physicians in some regions might find it difficult to manage patients who have hepatitis B because they see so few of them, Dr. Lok noted.

Dr. Khalili has received grants and consulting fees from Gilead Sciences Inc and grants from Intercept Pharmaceuticals outside the submitted work. Dr. Lok has received grants from Target and consultant fees from Abbott, Ambys, Arbutus, Chroma, Clear B, Enanta, Enochian, GNI, GlaxoSmithKline, Eli Lilly, and Virion outside the submitted work. Coauthors have received grants, consulting fees, or personal fees from Bayer, Boston Scientific, Exact Sciences, Fujifilm Medical Sciences, Gilead Sciences, Glycotest, Redhill Biopharma, Target RWE, MedEd Design, Pontifax, Global Life, the Lynx Group, AstraZeneca, Eisai, Novartis Venture Fund, Grail, QED Therapeutics, Genentech, Hepion Pharmaceuticals, Roche, Abbott, AbbVie, and Pfizer. Dr. Kim has received grants from Gilead Sciences (paid to her institution) outside the submitted work.

A version of this article first appeared on Medscape.com.

Investigators found that simultaneous infection with adeno-associated virus type 2 (AAV2) and certain other viruses is associated with the outbreak of mysterious pediatric hepatitis cases worldwide.

Coinfection with AAV2 and a human adenovirus (HAdV), in particular, appears to leave some children more vulnerable to this acute hepatitis of unknown origin, researchers reported in three studies published online in Nature. Coinfection with Epstein-Barr virus (EBV), herpes, and enterovirus also were found. Adeno-associated viruses are not considered pathogenic on their own and require a “helper” virus for productive infection.

“I am quite confident that we have identified the key viruses involved because we used a comprehensive metagenomic sequencing approach to look for potential infections from any virus or non-viral pathogen,” Charles Chiu, MD, PhD, senior author and professor of laboratory medicine and medicine/infectious diseases at the University of California, San Francisco, said in an interview.

Dr. Chiu and colleagues propose that lockdowns and social isolation during the COVID-19 pandemic left more children susceptible. A major aspect of immunity in childhood is the adaptive immune response – both cell-mediated and humoral – shaped in part by exposure to viruses and other pathogens early in life, Dr. Chiu said.

“Due to COVID-19, a large population of children did not experience this, so it is possible once restrictions were lifted, they were suddenly exposed over a short period of time to multiple viruses that, in a poorly trained immune system, would have increased their risk of developing severe disease,” he said.

This theory has been popular, especially because cases of unexplained acute hepatitis peaked during the height of the COVID-19 pandemic when isolation was common, William F. Balistreri, MD, who was not affiliated with the study, told this news organization. Dr. Balistreri is professor of pediatrics and director emeritus of the Pediatric Liver Care Center at Cincinnati Children’s Hospital Medical Center.
 

Identifying the culprits

Determining what factors might be involved was the main aim of the etiology study by Dr. Chiu and colleagues published online  in Nature.

The journal simultaneously published a genomic study confirming the presence of AAV2 and other suspected viruses and a genomic and laboratory study further corroborating the results.

More than 1,000 children worldwide had been diagnosed with unexplained acute pediatric hepatitis as of August 2022. In the United States, there have been 358 cases, including 22 in which the child required a liver transplant and 13 in which the child died.

This new form of hepatitis, first detected in October 2021, does not fit into existing classifications of types A through E, so some researchers refer to the condition as acute non–A-E hepatitis of unknown etiology.

The investigators started with an important clue based on previous research: the role adenovirus might play. Dr. Chiu and colleagues assessed 27 blood, stool, and other samples from 16 affected children who each previously tested positive for adenoviruses. The researchers included cases of the condition identified up until May 22, 2022. The median age was 3 years, and approximately half were boys.

They compared viruses present in these children with those in 113 controls without the mysterious hepatitis. The control group consisted of 15 children who were hospitalized with a nonhepatitis inflammatory condition, 27 with a noninflammatory condition, 30 with acute hepatitis of known origin, 12 with acute gastroenteritis and an HAdV-positive stool sample, and 11 with acute gastroenteritis and an HAdV-negative stool sample, as well as 18 blood donors. The median age was 7 years.

The researchers assessed samples using multiple technologies, including metagenomic sequencing, tiling multiplex polymerase chain reaction (PCR) amplicon sequencing, metagenomic sequencing with probe capture viral enrichment, and virus-specific PCR. Many of these advanced techniques were not even available 5-10 years ago, Dr. Chiu said.
 

Key findings

Blood samples were available for 14 of the 16 children with acute hepatitis of unknown origin. Among this study group, AAV2 was found in 13 (93%). No other adeno-associated viruses were found. HAdV was detected in all 14 children: HAdV-41 in 11 children and HAdV-40, HAdV-2, and an untypeable strain in one child each. This finding was not intuitive because HAdVs are not commonly associated with hepatitis, according to the study.

AAV2 was much less common in the control group. For example, it was found in none of the children with hepatitis of known origin and in only four children (3.5%) with acute gastroenteritis and HAdV-positive stool. Of note, neither AAV2 nor HAdV-41 was detected among the 30 pediatric controls with acute hepatitis of defined etiology nor 42 of the hospitalized children without hepatitis, the researchers wrote.

In the search for other viruses in the study group, metagenomic sequencing detected EBV, also known as human herpesvirus (HHV)–4, in two children, cytomegalovirus (CMV) in one child, and HAdV type C in one child.

Analysis of whole blood revealed enterovirus A71 in one patient. HAdV type C also was detected in one child on the basis of a nasopharyngeal swab, and picobirnavirus was found in a stool sample from another patient.

Researchers conducted virus-specific PCR tests on both patient groups to identify additional viruses that may be associated with the unexplained acute hepatitis. EBV/HHV-4 was detected in 11 children (79%) in the study group vs. in 1 child (0.88%) in the control group. HHV-6 was detected in seven children (50%) in the study group, compared with one case in the control group. CMV was not detected in any of the children in the study group versus vs. two children (1.8%) in the control group.

“Although we found significant differences in the relative proportions of EBV and HHV-6 in cases compared to controls, we do not believe that these viruses are the primary cause of acute severe hepatitis,” the researchers wrote. The viral load of the two herpes viruses were very low, so the positive results could represent integrated proviral DNA rather than bona fide low-level herpesvirus. In addition, herpesvirus can be reactivated by an inflammatory condition.

“Nevertheless, it is striking that among the 16 cases (in the study group), dual, triple, or quadruple infections with AAV2, adenovirus, and one or both herpesviruses were detected in whole blood from at least 12 cases (75%),” the researchers wrote.
 

Management of suspected hepatitis

The study’s key messages for parents and health care providers “are awareness and reassurance,” Dr. Balistreri said in an interview.

Vigilance also is warranted if a child develops prodromal symptoms including respiratory and/or gastrointestinal signs such as nausea, vomiting, diarrhea, and abdomen pain, he said. If jaundice or scleral icterus is noted, then hepatitis should be suspected.

Some patients need hospitalization and quickly recover. In very rare instances, the inflammation may progress to liver failure and transplantation, Dr. Balistreri said.

“Reassurance is based on the good news that most children with acute hepatitis get better. If a case arises, it is good practice to keep the child well hydrated, offer a normal diet, and avoid medications that may be cleared by the liver,” Dr. Balistreri added.

“Of course, COVID-19 vaccination is strongly suggested,” he said.

Some existing treatments could help against unexplained acute hepatitis, Dr. Chiu said. “The findings suggest that antiviral therapy might be effective in these cases.”

Cidofovir can be effective against adenovirus, according to a report in The Lancet . Similarly, ganciclovir or valganciclovir may have activity against EBV/HHV-4 or HHV-6, Dr. Chiu said. “However, antiviral therapy is not available for AAV2.”

The three studies published in Nature “offer compelling evidence, from disparate centers, of a linkage of outbreak cases to infection by AAV2,” Dr. Balistreri said. The studies also suggest that liver injury was related to abnormal immune responses. This is an important clinical distinction, indicating a potential therapeutic approach to future cases – immunosuppression rather than anti-adenoviral agents, he said.

“We await further studies of this important concept,” Dr. Balistreri said.

Many unanswered questions remain about the condition’s etiology, he added. Is there a synergy or shared susceptibility related to SARS-CoV-2? Is the COVID-19 virus helping to trigger these infections, or does it increase the risk once infected? Also, are other epigenetic factors or viruses involved?
 

Moving forward

The next steps in the research could go beyond identifying presence of these different viruses and determining which one(s) are contributing the most to the acute pediatric hepatitis, Dr. Chiu said.

The researchers also would like to test early results from the United Kingdom that identified a potential association of acute severe hepatitis with the presence of human leukocyte antigen genotype DRB1*04:01, he added.

They also might investigate other unintended potential clinical consequences of the COVID-19 pandemic, including long COVID and resurgence of infections from other viruses, such as respiratory syncytial virus, influenza, and enterovirus D68.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, the Department of Homeland Security, and other grants. Dr. Chiu is a founder of Delve Bio and on the scientific advisory board for Delve Bio, Mammoth Biosciences, BiomeSense, and Poppy Health. Dr. Balistreri had no relevant disclosures.
 

A version of this article first appeared on Medscape.com.

Investigators found that simultaneous infection with adeno-associated virus type 2 (AAV2) and certain other viruses is associated with the outbreak of mysterious pediatric hepatitis cases worldwide.

Coinfection with AAV2 and a human adenovirus (HAdV), in particular, appears to leave some children more vulnerable to this acute hepatitis of unknown origin, researchers reported in three studies published online in Nature. Coinfection with Epstein-Barr virus (EBV), herpes, and enterovirus also were found. Adeno-associated viruses are not considered pathogenic on their own and require a “helper” virus for productive infection.

“I am quite confident that we have identified the key viruses involved because we used a comprehensive metagenomic sequencing approach to look for potential infections from any virus or non-viral pathogen,” Charles Chiu, MD, PhD, senior author and professor of laboratory medicine and medicine/infectious diseases at the University of California, San Francisco, said in an interview.

Dr. Chiu and colleagues propose that lockdowns and social isolation during the COVID-19 pandemic left more children susceptible. A major aspect of immunity in childhood is the adaptive immune response – both cell-mediated and humoral – shaped in part by exposure to viruses and other pathogens early in life, Dr. Chiu said.

“Due to COVID-19, a large population of children did not experience this, so it is possible once restrictions were lifted, they were suddenly exposed over a short period of time to multiple viruses that, in a poorly trained immune system, would have increased their risk of developing severe disease,” he said.

This theory has been popular, especially because cases of unexplained acute hepatitis peaked during the height of the COVID-19 pandemic when isolation was common, William F. Balistreri, MD, who was not affiliated with the study, told this news organization. Dr. Balistreri is professor of pediatrics and director emeritus of the Pediatric Liver Care Center at Cincinnati Children’s Hospital Medical Center.
 

Identifying the culprits

Determining what factors might be involved was the main aim of the etiology study by Dr. Chiu and colleagues published online  in Nature.

The journal simultaneously published a genomic study confirming the presence of AAV2 and other suspected viruses and a genomic and laboratory study further corroborating the results.

More than 1,000 children worldwide had been diagnosed with unexplained acute pediatric hepatitis as of August 2022. In the United States, there have been 358 cases, including 22 in which the child required a liver transplant and 13 in which the child died.

This new form of hepatitis, first detected in October 2021, does not fit into existing classifications of types A through E, so some researchers refer to the condition as acute non–A-E hepatitis of unknown etiology.

The investigators started with an important clue based on previous research: the role adenovirus might play. Dr. Chiu and colleagues assessed 27 blood, stool, and other samples from 16 affected children who each previously tested positive for adenoviruses. The researchers included cases of the condition identified up until May 22, 2022. The median age was 3 years, and approximately half were boys.

They compared viruses present in these children with those in 113 controls without the mysterious hepatitis. The control group consisted of 15 children who were hospitalized with a nonhepatitis inflammatory condition, 27 with a noninflammatory condition, 30 with acute hepatitis of known origin, 12 with acute gastroenteritis and an HAdV-positive stool sample, and 11 with acute gastroenteritis and an HAdV-negative stool sample, as well as 18 blood donors. The median age was 7 years.

The researchers assessed samples using multiple technologies, including metagenomic sequencing, tiling multiplex polymerase chain reaction (PCR) amplicon sequencing, metagenomic sequencing with probe capture viral enrichment, and virus-specific PCR. Many of these advanced techniques were not even available 5-10 years ago, Dr. Chiu said.
 

Key findings

Blood samples were available for 14 of the 16 children with acute hepatitis of unknown origin. Among this study group, AAV2 was found in 13 (93%). No other adeno-associated viruses were found. HAdV was detected in all 14 children: HAdV-41 in 11 children and HAdV-40, HAdV-2, and an untypeable strain in one child each. This finding was not intuitive because HAdVs are not commonly associated with hepatitis, according to the study.

AAV2 was much less common in the control group. For example, it was found in none of the children with hepatitis of known origin and in only four children (3.5%) with acute gastroenteritis and HAdV-positive stool. Of note, neither AAV2 nor HAdV-41 was detected among the 30 pediatric controls with acute hepatitis of defined etiology nor 42 of the hospitalized children without hepatitis, the researchers wrote.

In the search for other viruses in the study group, metagenomic sequencing detected EBV, also known as human herpesvirus (HHV)–4, in two children, cytomegalovirus (CMV) in one child, and HAdV type C in one child.

Analysis of whole blood revealed enterovirus A71 in one patient. HAdV type C also was detected in one child on the basis of a nasopharyngeal swab, and picobirnavirus was found in a stool sample from another patient.

Researchers conducted virus-specific PCR tests on both patient groups to identify additional viruses that may be associated with the unexplained acute hepatitis. EBV/HHV-4 was detected in 11 children (79%) in the study group vs. in 1 child (0.88%) in the control group. HHV-6 was detected in seven children (50%) in the study group, compared with one case in the control group. CMV was not detected in any of the children in the study group versus vs. two children (1.8%) in the control group.

“Although we found significant differences in the relative proportions of EBV and HHV-6 in cases compared to controls, we do not believe that these viruses are the primary cause of acute severe hepatitis,” the researchers wrote. The viral load of the two herpes viruses were very low, so the positive results could represent integrated proviral DNA rather than bona fide low-level herpesvirus. In addition, herpesvirus can be reactivated by an inflammatory condition.

“Nevertheless, it is striking that among the 16 cases (in the study group), dual, triple, or quadruple infections with AAV2, adenovirus, and one or both herpesviruses were detected in whole blood from at least 12 cases (75%),” the researchers wrote.
 

Management of suspected hepatitis

The study’s key messages for parents and health care providers “are awareness and reassurance,” Dr. Balistreri said in an interview.

Vigilance also is warranted if a child develops prodromal symptoms including respiratory and/or gastrointestinal signs such as nausea, vomiting, diarrhea, and abdomen pain, he said. If jaundice or scleral icterus is noted, then hepatitis should be suspected.

Some patients need hospitalization and quickly recover. In very rare instances, the inflammation may progress to liver failure and transplantation, Dr. Balistreri said.

“Reassurance is based on the good news that most children with acute hepatitis get better. If a case arises, it is good practice to keep the child well hydrated, offer a normal diet, and avoid medications that may be cleared by the liver,” Dr. Balistreri added.

“Of course, COVID-19 vaccination is strongly suggested,” he said.

Some existing treatments could help against unexplained acute hepatitis, Dr. Chiu said. “The findings suggest that antiviral therapy might be effective in these cases.”

Cidofovir can be effective against adenovirus, according to a report in The Lancet . Similarly, ganciclovir or valganciclovir may have activity against EBV/HHV-4 or HHV-6, Dr. Chiu said. “However, antiviral therapy is not available for AAV2.”

The three studies published in Nature “offer compelling evidence, from disparate centers, of a linkage of outbreak cases to infection by AAV2,” Dr. Balistreri said. The studies also suggest that liver injury was related to abnormal immune responses. This is an important clinical distinction, indicating a potential therapeutic approach to future cases – immunosuppression rather than anti-adenoviral agents, he said.

“We await further studies of this important concept,” Dr. Balistreri said.

Many unanswered questions remain about the condition’s etiology, he added. Is there a synergy or shared susceptibility related to SARS-CoV-2? Is the COVID-19 virus helping to trigger these infections, or does it increase the risk once infected? Also, are other epigenetic factors or viruses involved?
 

Moving forward

The next steps in the research could go beyond identifying presence of these different viruses and determining which one(s) are contributing the most to the acute pediatric hepatitis, Dr. Chiu said.

The researchers also would like to test early results from the United Kingdom that identified a potential association of acute severe hepatitis with the presence of human leukocyte antigen genotype DRB1*04:01, he added.

They also might investigate other unintended potential clinical consequences of the COVID-19 pandemic, including long COVID and resurgence of infections from other viruses, such as respiratory syncytial virus, influenza, and enterovirus D68.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, the Department of Homeland Security, and other grants. Dr. Chiu is a founder of Delve Bio and on the scientific advisory board for Delve Bio, Mammoth Biosciences, BiomeSense, and Poppy Health. Dr. Balistreri had no relevant disclosures.
 

A version of this article first appeared on Medscape.com.

Investigators found that simultaneous infection with adeno-associated virus type 2 (AAV2) and certain other viruses is associated with the outbreak of mysterious pediatric hepatitis cases worldwide.

Coinfection with AAV2 and a human adenovirus (HAdV), in particular, appears to leave some children more vulnerable to this acute hepatitis of unknown origin, researchers reported in three studies published online in Nature. Coinfection with Epstein-Barr virus (EBV), herpes, and enterovirus also were found. Adeno-associated viruses are not considered pathogenic on their own and require a “helper” virus for productive infection.

“I am quite confident that we have identified the key viruses involved because we used a comprehensive metagenomic sequencing approach to look for potential infections from any virus or non-viral pathogen,” Charles Chiu, MD, PhD, senior author and professor of laboratory medicine and medicine/infectious diseases at the University of California, San Francisco, said in an interview.

Dr. Chiu and colleagues propose that lockdowns and social isolation during the COVID-19 pandemic left more children susceptible. A major aspect of immunity in childhood is the adaptive immune response – both cell-mediated and humoral – shaped in part by exposure to viruses and other pathogens early in life, Dr. Chiu said.

“Due to COVID-19, a large population of children did not experience this, so it is possible once restrictions were lifted, they were suddenly exposed over a short period of time to multiple viruses that, in a poorly trained immune system, would have increased their risk of developing severe disease,” he said.

This theory has been popular, especially because cases of unexplained acute hepatitis peaked during the height of the COVID-19 pandemic when isolation was common, William F. Balistreri, MD, who was not affiliated with the study, told this news organization. Dr. Balistreri is professor of pediatrics and director emeritus of the Pediatric Liver Care Center at Cincinnati Children’s Hospital Medical Center.
 

Identifying the culprits

Determining what factors might be involved was the main aim of the etiology study by Dr. Chiu and colleagues published online  in Nature.

The journal simultaneously published a genomic study confirming the presence of AAV2 and other suspected viruses and a genomic and laboratory study further corroborating the results.

More than 1,000 children worldwide had been diagnosed with unexplained acute pediatric hepatitis as of August 2022. In the United States, there have been 358 cases, including 22 in which the child required a liver transplant and 13 in which the child died.

This new form of hepatitis, first detected in October 2021, does not fit into existing classifications of types A through E, so some researchers refer to the condition as acute non–A-E hepatitis of unknown etiology.

The investigators started with an important clue based on previous research: the role adenovirus might play. Dr. Chiu and colleagues assessed 27 blood, stool, and other samples from 16 affected children who each previously tested positive for adenoviruses. The researchers included cases of the condition identified up until May 22, 2022. The median age was 3 years, and approximately half were boys.

They compared viruses present in these children with those in 113 controls without the mysterious hepatitis. The control group consisted of 15 children who were hospitalized with a nonhepatitis inflammatory condition, 27 with a noninflammatory condition, 30 with acute hepatitis of known origin, 12 with acute gastroenteritis and an HAdV-positive stool sample, and 11 with acute gastroenteritis and an HAdV-negative stool sample, as well as 18 blood donors. The median age was 7 years.

The researchers assessed samples using multiple technologies, including metagenomic sequencing, tiling multiplex polymerase chain reaction (PCR) amplicon sequencing, metagenomic sequencing with probe capture viral enrichment, and virus-specific PCR. Many of these advanced techniques were not even available 5-10 years ago, Dr. Chiu said.
 

Key findings

Blood samples were available for 14 of the 16 children with acute hepatitis of unknown origin. Among this study group, AAV2 was found in 13 (93%). No other adeno-associated viruses were found. HAdV was detected in all 14 children: HAdV-41 in 11 children and HAdV-40, HAdV-2, and an untypeable strain in one child each. This finding was not intuitive because HAdVs are not commonly associated with hepatitis, according to the study.

AAV2 was much less common in the control group. For example, it was found in none of the children with hepatitis of known origin and in only four children (3.5%) with acute gastroenteritis and HAdV-positive stool. Of note, neither AAV2 nor HAdV-41 was detected among the 30 pediatric controls with acute hepatitis of defined etiology nor 42 of the hospitalized children without hepatitis, the researchers wrote.

In the search for other viruses in the study group, metagenomic sequencing detected EBV, also known as human herpesvirus (HHV)–4, in two children, cytomegalovirus (CMV) in one child, and HAdV type C in one child.

Analysis of whole blood revealed enterovirus A71 in one patient. HAdV type C also was detected in one child on the basis of a nasopharyngeal swab, and picobirnavirus was found in a stool sample from another patient.

Researchers conducted virus-specific PCR tests on both patient groups to identify additional viruses that may be associated with the unexplained acute hepatitis. EBV/HHV-4 was detected in 11 children (79%) in the study group vs. in 1 child (0.88%) in the control group. HHV-6 was detected in seven children (50%) in the study group, compared with one case in the control group. CMV was not detected in any of the children in the study group versus vs. two children (1.8%) in the control group.

“Although we found significant differences in the relative proportions of EBV and HHV-6 in cases compared to controls, we do not believe that these viruses are the primary cause of acute severe hepatitis,” the researchers wrote. The viral load of the two herpes viruses were very low, so the positive results could represent integrated proviral DNA rather than bona fide low-level herpesvirus. In addition, herpesvirus can be reactivated by an inflammatory condition.

“Nevertheless, it is striking that among the 16 cases (in the study group), dual, triple, or quadruple infections with AAV2, adenovirus, and one or both herpesviruses were detected in whole blood from at least 12 cases (75%),” the researchers wrote.
 

Management of suspected hepatitis

The study’s key messages for parents and health care providers “are awareness and reassurance,” Dr. Balistreri said in an interview.

Vigilance also is warranted if a child develops prodromal symptoms including respiratory and/or gastrointestinal signs such as nausea, vomiting, diarrhea, and abdomen pain, he said. If jaundice or scleral icterus is noted, then hepatitis should be suspected.

Some patients need hospitalization and quickly recover. In very rare instances, the inflammation may progress to liver failure and transplantation, Dr. Balistreri said.

“Reassurance is based on the good news that most children with acute hepatitis get better. If a case arises, it is good practice to keep the child well hydrated, offer a normal diet, and avoid medications that may be cleared by the liver,” Dr. Balistreri added.

“Of course, COVID-19 vaccination is strongly suggested,” he said.

Some existing treatments could help against unexplained acute hepatitis, Dr. Chiu said. “The findings suggest that antiviral therapy might be effective in these cases.”

Cidofovir can be effective against adenovirus, according to a report in The Lancet . Similarly, ganciclovir or valganciclovir may have activity against EBV/HHV-4 or HHV-6, Dr. Chiu said. “However, antiviral therapy is not available for AAV2.”

The three studies published in Nature “offer compelling evidence, from disparate centers, of a linkage of outbreak cases to infection by AAV2,” Dr. Balistreri said. The studies also suggest that liver injury was related to abnormal immune responses. This is an important clinical distinction, indicating a potential therapeutic approach to future cases – immunosuppression rather than anti-adenoviral agents, he said.

“We await further studies of this important concept,” Dr. Balistreri said.

Many unanswered questions remain about the condition’s etiology, he added. Is there a synergy or shared susceptibility related to SARS-CoV-2? Is the COVID-19 virus helping to trigger these infections, or does it increase the risk once infected? Also, are other epigenetic factors or viruses involved?
 

Moving forward

The next steps in the research could go beyond identifying presence of these different viruses and determining which one(s) are contributing the most to the acute pediatric hepatitis, Dr. Chiu said.

The researchers also would like to test early results from the United Kingdom that identified a potential association of acute severe hepatitis with the presence of human leukocyte antigen genotype DRB1*04:01, he added.

They also might investigate other unintended potential clinical consequences of the COVID-19 pandemic, including long COVID and resurgence of infections from other viruses, such as respiratory syncytial virus, influenza, and enterovirus D68.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, the Department of Homeland Security, and other grants. Dr. Chiu is a founder of Delve Bio and on the scientific advisory board for Delve Bio, Mammoth Biosciences, BiomeSense, and Poppy Health. Dr. Balistreri had no relevant disclosures.
 

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to open this week with a case.

A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.

In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.

The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.

An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.

This week, we unravel the curious case of Ludwig van Beethoven, thanks to modern DNA extraction techniques, genome-wide association studies, and eight locks of hair.

Beethoven-Haus Bonn

We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.

The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.

The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.

Kevin Brown

Current Biology

Ira F. Brilliant Center for Beethoven Studies, San Jose State University

Current Biology

Current Biology

Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to open this week with a case.

A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.

In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.

The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.

An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.

This week, we unravel the curious case of Ludwig van Beethoven, thanks to modern DNA extraction techniques, genome-wide association studies, and eight locks of hair.

Beethoven-Haus Bonn

We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.

The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.

The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.

Kevin Brown

Current Biology

Ira F. Brilliant Center for Beethoven Studies, San Jose State University

Current Biology

Current Biology

Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to open this week with a case.

A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.

In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.

The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.

An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.

This week, we unravel the curious case of Ludwig van Beethoven, thanks to modern DNA extraction techniques, genome-wide association studies, and eight locks of hair.

Beethoven-Haus Bonn

We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.

The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.

The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.

Kevin Brown

Current Biology

Ira F. Brilliant Center for Beethoven Studies, San Jose State University

Current Biology

Current Biology

Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

All adults should be tested for hepatitis B virus (HBV) at least once in their lifetime, according to updated guidelines from the Centers for Disease Control and Prevention.

This is the first update to HBV screening guidelines since 2008, the agency said.

“Risk-based testing alone has not identified most persons living with chronic HBV infection and is considered inefficient for providers to implement,” the authors wrote in the new guidance, published in the CDC’s Morbidity and Mortality Weekly Report. “Universal screening of adults for HBV infection is cost-effective, compared with risk-based screening and averts liver disease and death. Although a curative treatment is not yet available, early diagnosis and treatment of chronic HBV infections reduces the risk for cirrhosis, liver cancer, and death.”

Howard Lee, MD, an assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine in Houston, agreed that risk-based screening has not been effective. A universal screening approach “is the way to go,” he said. With this new screening approach, patients can get tested without having to admit that they may be at risk for a chronic disease like HIV and HBV, which can be stigmatizing, said Dr. Lee, who was not involved with making these recommendations.

An estimated 580,000 to 2.4 million individuals are living with HBV infection in the United States, and two-thirds may be unaware they are infected, according to the CDC. The virus spreads through contact with blood, semen, and other body fluids of an infected person.

The guidance now recommends using the triple panel (HBsAg, anti-HBs, total anti-HBc) for initial screening.

“It can help identify persons who have an active HBV infection and could be linked to care; have resolved infection and might be susceptible to reactivation (for example, immunosuppressed persons); are susceptible and need vaccination; or are vaccinated,” the authors wrote.

Patients with previous HBV infection can have the infection reactivated with immunosuppressive treatments, Dr. Lee said, which is why detecting prior infection via the triple panel screening is important.

Women who are pregnant should be screened, ideally, in the first trimester of each pregnancy, regardless of vaccination status or testing history. If they have already received timely triple panel screening for hepatitis B and have no new HBV exposures, pregnant women only need HBsAg screening, the guidelines state.

The guidelines also specify that higher risk groups, specifically those incarcerated or formerly incarcerated, adults with current or past hepatitis C virus infection, and those with current or past sexually transmitted infections and multiple sex partners.

People who are susceptible for infection, refuse vaccination and are at higher risk for HBV should be screened periodically, but how often they should be screened should be based on shared decision-making between the provider and patient as well as individual risk and immune status.

Additional research into the optimal frequency of periodic testing is necessary, the authors say.

“Along with vaccination strategies, universal screening of adults and appropriate testing of persons at increased risk for HBV infection will improve health outcomes, reduce the prevalence of HBV infection in the United States, and advance viral hepatitis elimination goals,” the authors wrote.

The new recommendations now contrast with the 2020 screening guidelines issued by the U.S. Preventive Services Task Force (USPSTF) that recommend risk-based screening for hepatitis B.

“When that recommendation was published, the Task Force was aligned with several other organizations, including the CDC, in supporting screening for hepatitis B in high-risk populations — and importantly, we’re all still aligned in making sure that people get the care that they need,” said Michael Barry, MD, chair of the USPSTF, in an emailed statement. “The evidence on clinical preventive services is always changing, and the Task Force aims to keep all recommendations current, updating each recommendation approximately every 5 years.”

“In the meantime, we always encourage clinicians to use their judgment as they provide care for their patients — including those who may benefit from screening for hepatitis B — and to decide together with each patient which preventive services can best help them live a long and healthy life,” Dr. Barry said.

The American Association for the Study of Liver Diseases is currently updating their HBV screening recommendations, Dr. Lee said, and he expects other professional societies to follow the CDC recommendations.

“It’s not uncommon that we see the CDC or societies making recommendations and the USPSTF following along, so hopefully that’s the case for hepatitis B as well,” he said.

The authors reported no potential conflicts of interest.

A version of this article originally appeared on Medscape.com.

All adults should be tested for hepatitis B virus (HBV) at least once in their lifetime, according to updated guidelines from the Centers for Disease Control and Prevention.

This is the first update to HBV screening guidelines since 2008, the agency said.

“Risk-based testing alone has not identified most persons living with chronic HBV infection and is considered inefficient for providers to implement,” the authors wrote in the new guidance, published in the CDC’s Morbidity and Mortality Weekly Report. “Universal screening of adults for HBV infection is cost-effective, compared with risk-based screening and averts liver disease and death. Although a curative treatment is not yet available, early diagnosis and treatment of chronic HBV infections reduces the risk for cirrhosis, liver cancer, and death.”

Howard Lee, MD, an assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine in Houston, agreed that risk-based screening has not been effective. A universal screening approach “is the way to go,” he said. With this new screening approach, patients can get tested without having to admit that they may be at risk for a chronic disease like HIV and HBV, which can be stigmatizing, said Dr. Lee, who was not involved with making these recommendations.

An estimated 580,000 to 2.4 million individuals are living with HBV infection in the United States, and two-thirds may be unaware they are infected, according to the CDC. The virus spreads through contact with blood, semen, and other body fluids of an infected person.

The guidance now recommends using the triple panel (HBsAg, anti-HBs, total anti-HBc) for initial screening.

“It can help identify persons who have an active HBV infection and could be linked to care; have resolved infection and might be susceptible to reactivation (for example, immunosuppressed persons); are susceptible and need vaccination; or are vaccinated,” the authors wrote.

Patients with previous HBV infection can have the infection reactivated with immunosuppressive treatments, Dr. Lee said, which is why detecting prior infection via the triple panel screening is important.

Women who are pregnant should be screened, ideally, in the first trimester of each pregnancy, regardless of vaccination status or testing history. If they have already received timely triple panel screening for hepatitis B and have no new HBV exposures, pregnant women only need HBsAg screening, the guidelines state.

The guidelines also specify that higher risk groups, specifically those incarcerated or formerly incarcerated, adults with current or past hepatitis C virus infection, and those with current or past sexually transmitted infections and multiple sex partners.

People who are susceptible for infection, refuse vaccination and are at higher risk for HBV should be screened periodically, but how often they should be screened should be based on shared decision-making between the provider and patient as well as individual risk and immune status.

Additional research into the optimal frequency of periodic testing is necessary, the authors say.

“Along with vaccination strategies, universal screening of adults and appropriate testing of persons at increased risk for HBV infection will improve health outcomes, reduce the prevalence of HBV infection in the United States, and advance viral hepatitis elimination goals,” the authors wrote.

The new recommendations now contrast with the 2020 screening guidelines issued by the U.S. Preventive Services Task Force (USPSTF) that recommend risk-based screening for hepatitis B.

“When that recommendation was published, the Task Force was aligned with several other organizations, including the CDC, in supporting screening for hepatitis B in high-risk populations — and importantly, we’re all still aligned in making sure that people get the care that they need,” said Michael Barry, MD, chair of the USPSTF, in an emailed statement. “The evidence on clinical preventive services is always changing, and the Task Force aims to keep all recommendations current, updating each recommendation approximately every 5 years.”

“In the meantime, we always encourage clinicians to use their judgment as they provide care for their patients — including those who may benefit from screening for hepatitis B — and to decide together with each patient which preventive services can best help them live a long and healthy life,” Dr. Barry said.

The American Association for the Study of Liver Diseases is currently updating their HBV screening recommendations, Dr. Lee said, and he expects other professional societies to follow the CDC recommendations.

“It’s not uncommon that we see the CDC or societies making recommendations and the USPSTF following along, so hopefully that’s the case for hepatitis B as well,” he said.

The authors reported no potential conflicts of interest.

A version of this article originally appeared on Medscape.com.

All adults should be tested for hepatitis B virus (HBV) at least once in their lifetime, according to updated guidelines from the Centers for Disease Control and Prevention.

This is the first update to HBV screening guidelines since 2008, the agency said.

“Risk-based testing alone has not identified most persons living with chronic HBV infection and is considered inefficient for providers to implement,” the authors wrote in the new guidance, published in the CDC’s Morbidity and Mortality Weekly Report. “Universal screening of adults for HBV infection is cost-effective, compared with risk-based screening and averts liver disease and death. Although a curative treatment is not yet available, early diagnosis and treatment of chronic HBV infections reduces the risk for cirrhosis, liver cancer, and death.”

Howard Lee, MD, an assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine in Houston, agreed that risk-based screening has not been effective. A universal screening approach “is the way to go,” he said. With this new screening approach, patients can get tested without having to admit that they may be at risk for a chronic disease like HIV and HBV, which can be stigmatizing, said Dr. Lee, who was not involved with making these recommendations.

An estimated 580,000 to 2.4 million individuals are living with HBV infection in the United States, and two-thirds may be unaware they are infected, according to the CDC. The virus spreads through contact with blood, semen, and other body fluids of an infected person.

The guidance now recommends using the triple panel (HBsAg, anti-HBs, total anti-HBc) for initial screening.

“It can help identify persons who have an active HBV infection and could be linked to care; have resolved infection and might be susceptible to reactivation (for example, immunosuppressed persons); are susceptible and need vaccination; or are vaccinated,” the authors wrote.

Patients with previous HBV infection can have the infection reactivated with immunosuppressive treatments, Dr. Lee said, which is why detecting prior infection via the triple panel screening is important.

Women who are pregnant should be screened, ideally, in the first trimester of each pregnancy, regardless of vaccination status or testing history. If they have already received timely triple panel screening for hepatitis B and have no new HBV exposures, pregnant women only need HBsAg screening, the guidelines state.

The guidelines also specify that higher risk groups, specifically those incarcerated or formerly incarcerated, adults with current or past hepatitis C virus infection, and those with current or past sexually transmitted infections and multiple sex partners.

People who are susceptible for infection, refuse vaccination and are at higher risk for HBV should be screened periodically, but how often they should be screened should be based on shared decision-making between the provider and patient as well as individual risk and immune status.

Additional research into the optimal frequency of periodic testing is necessary, the authors say.

“Along with vaccination strategies, universal screening of adults and appropriate testing of persons at increased risk for HBV infection will improve health outcomes, reduce the prevalence of HBV infection in the United States, and advance viral hepatitis elimination goals,” the authors wrote.

The new recommendations now contrast with the 2020 screening guidelines issued by the U.S. Preventive Services Task Force (USPSTF) that recommend risk-based screening for hepatitis B.

“When that recommendation was published, the Task Force was aligned with several other organizations, including the CDC, in supporting screening for hepatitis B in high-risk populations — and importantly, we’re all still aligned in making sure that people get the care that they need,” said Michael Barry, MD, chair of the USPSTF, in an emailed statement. “The evidence on clinical preventive services is always changing, and the Task Force aims to keep all recommendations current, updating each recommendation approximately every 5 years.”

“In the meantime, we always encourage clinicians to use their judgment as they provide care for their patients — including those who may benefit from screening for hepatitis B — and to decide together with each patient which preventive services can best help them live a long and healthy life,” Dr. Barry said.

The American Association for the Study of Liver Diseases is currently updating their HBV screening recommendations, Dr. Lee said, and he expects other professional societies to follow the CDC recommendations.

“It’s not uncommon that we see the CDC or societies making recommendations and the USPSTF following along, so hopefully that’s the case for hepatitis B as well,” he said.

The authors reported no potential conflicts of interest.

A version of this article originally appeared on Medscape.com.

Liver transplant recipients with nonalcoholic steatohepatitis (NASH) who received grafts from older donors are at higher risk for posttransplant death, especially from infection, according to a new study.

All-cause mortality was twice as high and death from an infectious cause was more than three times as high for patients with NASH who received liver grafts from octogenarian donors than for those who received a liver from someone younger than 50.

“The findings from this study implicate a critical need to investigate donor age as an important risk factor for poorer host and graft survival,” wrote the authors, led by David Lee, MD, of the University of Maryland, Baltimore.

“Given the possibility of infectious graft complications, post–liver transplant follow-ups may need to be more comprehensive and frequent in these individuals who receive grafts from older donors,” they add.

The study was published online in Digestive and Liver Disease.
 

Donor age trends

Dr. Lee and colleagues pulled data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research database, a national database of deidentified donor and recipient transplant data. The analysis excluded recipients younger than 18, those with a living donor, those who had hepatocellular carcinoma prior to transplant, and those who had been diagnosed with additional liver disorders apart from NASH.

The team identified 8,88 recipients with NASH who received a liver transplant from 2005–2019. They stratified recipients by donor age. The 5,187 patients who received livers from donors who were younger than 50 served as the reference group. The remainder were placed into four cohorts – 1,842 whose donors were in their 50s, 1,290 whose donors were in their 60s, 504 whose donors were in their 70s, and 65 whose donors were in their 80s.

The researchers found that in comparison with the reference group, the average age of recipients in each donor-age cohort was progressively older. Two donor-age cohorts had significantly higher proportions of recipients with diabetes than the 46.5% in the reference group – the sexagenarian cohort (51.7%) and the octogenarian group (66.2%).

The median follow-up time ranged from 2.35–3.61 years across all age groups.

The researchers found that for all donor-age groups excluding donors in their 60s, recipients had higher risk of all-cause mortality after transplant than the reference group. Recipients with donors in their 50s had a 16% greater risk for death (P = .01), and recipients with donors in their 70s had a 20% greater risk (P = .05). For recipients with octogenarian donors, the adjusted hazard ratio for all-cause mortality was 2.01 (P < .001).

Only recipients in the octogenarian donor cohort were at increased risk of graft failure, compared with the reference group (aHR, 3.72; P = .002).

As donor age increased, the recipient’s risk of dying from sepsis and infectious causes rose, compared with the reference group. Recipients’ likelihood of sepsis death increased by 71% (P = .001) with donors in their 50s, 73% (P = .003) with donors in their 60s, and 76% (P = .03) with donors in their 70s. For recipients with octogenarian donors, the risk more than tripled (aHR, 3.58; P = .007). Likewise, recipients with donors in their 70s were 73% more likely to die from infectious causes. That risk nearly quadrupled among those with donors in their 80s.
 

Recipient factors at play?

While the study found a relationship between liver donor age and recipient outcomes, it is not clear whether any other recipient factors may have contributed to the higher risk of all-cause mortality, sad Nancy Reau, MD, chief of the hepatology section at Rush University Medical Center, Chicago. The researchers did not parse out whether younger recipients did better with older organs than older recipients or whether older recipients fared worse with younger organs, she said in an interview.

“I wasn’t convinced that they had demonstrated that the recipient may not have played a role in that,” said Dr. Reau, who wasn’t involved with the study.

The analysis only a found an increased risk of graft failure among recipients who received organs from octogenarian donors, so factors other than liver transplant may have contributed to all-cause mortality, she noted.

The UNOS database has some limitations, noted Timothy Pruett, MD, who directs the liver transplant program at the University of Minnesota, Minneapolis. Because the database pulls information from transplantation centers across the country, it can be difficult to standardize specific patient variables in the data.

While it’s clear that a patient died, it’s less certain whether an infection was the cause of death and whether that infection was somehow associated with the liver, noted Dr. Pruett, who wasn’t involved in the research. For example, a patient could have had broken a hip, gone to the hospital, and contracted pneumonia, which led to their death.

“There’s just not much granularity in the database, and we can’t overextrapolate what we see,” Dr. Pruett said in an interview.
 

Knowledge gaps

Dr. Lee agreed that more research is needed to understand what may be driving higher mortality rates among patients who receive older organs. “There are still a lot of gaps in knowledge with respect to why.”

Dr. Reau said she is curious as to whether certain comorbidities, such as previous infection, diabetes, or obesity, could predict worse outcomes for recipients with older organs.

“We would love to give all of our patients younger organs, but if that leads to even more disparity in need [compared] to availability and the alternative is not surviving, I think you have to place [this work] into context,” she said.

The study findings shouldn’t be used to deter patients with NASH from considering older organs, Dr. Reau said. More insight as to which populations might want to be choosier owing to an elevated risk would be beneficial, she added.

Dr. Lee, Dr. Pruett, and Dr. Reau reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Liver transplant recipients with nonalcoholic steatohepatitis (NASH) who received grafts from older donors are at higher risk for posttransplant death, especially from infection, according to a new study.

All-cause mortality was twice as high and death from an infectious cause was more than three times as high for patients with NASH who received liver grafts from octogenarian donors than for those who received a liver from someone younger than 50.

“The findings from this study implicate a critical need to investigate donor age as an important risk factor for poorer host and graft survival,” wrote the authors, led by David Lee, MD, of the University of Maryland, Baltimore.

“Given the possibility of infectious graft complications, post–liver transplant follow-ups may need to be more comprehensive and frequent in these individuals who receive grafts from older donors,” they add.

The study was published online in Digestive and Liver Disease.
 

Donor age trends

Dr. Lee and colleagues pulled data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research database, a national database of deidentified donor and recipient transplant data. The analysis excluded recipients younger than 18, those with a living donor, those who had hepatocellular carcinoma prior to transplant, and those who had been diagnosed with additional liver disorders apart from NASH.

The team identified 8,88 recipients with NASH who received a liver transplant from 2005–2019. They stratified recipients by donor age. The 5,187 patients who received livers from donors who were younger than 50 served as the reference group. The remainder were placed into four cohorts – 1,842 whose donors were in their 50s, 1,290 whose donors were in their 60s, 504 whose donors were in their 70s, and 65 whose donors were in their 80s.

The researchers found that in comparison with the reference group, the average age of recipients in each donor-age cohort was progressively older. Two donor-age cohorts had significantly higher proportions of recipients with diabetes than the 46.5% in the reference group – the sexagenarian cohort (51.7%) and the octogenarian group (66.2%).

The median follow-up time ranged from 2.35–3.61 years across all age groups.

The researchers found that for all donor-age groups excluding donors in their 60s, recipients had higher risk of all-cause mortality after transplant than the reference group. Recipients with donors in their 50s had a 16% greater risk for death (P = .01), and recipients with donors in their 70s had a 20% greater risk (P = .05). For recipients with octogenarian donors, the adjusted hazard ratio for all-cause mortality was 2.01 (P < .001).

Only recipients in the octogenarian donor cohort were at increased risk of graft failure, compared with the reference group (aHR, 3.72; P = .002).

As donor age increased, the recipient’s risk of dying from sepsis and infectious causes rose, compared with the reference group. Recipients’ likelihood of sepsis death increased by 71% (P = .001) with donors in their 50s, 73% (P = .003) with donors in their 60s, and 76% (P = .03) with donors in their 70s. For recipients with octogenarian donors, the risk more than tripled (aHR, 3.58; P = .007). Likewise, recipients with donors in their 70s were 73% more likely to die from infectious causes. That risk nearly quadrupled among those with donors in their 80s.
 

Recipient factors at play?

While the study found a relationship between liver donor age and recipient outcomes, it is not clear whether any other recipient factors may have contributed to the higher risk of all-cause mortality, sad Nancy Reau, MD, chief of the hepatology section at Rush University Medical Center, Chicago. The researchers did not parse out whether younger recipients did better with older organs than older recipients or whether older recipients fared worse with younger organs, she said in an interview.

“I wasn’t convinced that they had demonstrated that the recipient may not have played a role in that,” said Dr. Reau, who wasn’t involved with the study.

The analysis only a found an increased risk of graft failure among recipients who received organs from octogenarian donors, so factors other than liver transplant may have contributed to all-cause mortality, she noted.

The UNOS database has some limitations, noted Timothy Pruett, MD, who directs the liver transplant program at the University of Minnesota, Minneapolis. Because the database pulls information from transplantation centers across the country, it can be difficult to standardize specific patient variables in the data.

While it’s clear that a patient died, it’s less certain whether an infection was the cause of death and whether that infection was somehow associated with the liver, noted Dr. Pruett, who wasn’t involved in the research. For example, a patient could have had broken a hip, gone to the hospital, and contracted pneumonia, which led to their death.

“There’s just not much granularity in the database, and we can’t overextrapolate what we see,” Dr. Pruett said in an interview.
 

Knowledge gaps

Dr. Lee agreed that more research is needed to understand what may be driving higher mortality rates among patients who receive older organs. “There are still a lot of gaps in knowledge with respect to why.”

Dr. Reau said she is curious as to whether certain comorbidities, such as previous infection, diabetes, or obesity, could predict worse outcomes for recipients with older organs.

“We would love to give all of our patients younger organs, but if that leads to even more disparity in need [compared] to availability and the alternative is not surviving, I think you have to place [this work] into context,” she said.

The study findings shouldn’t be used to deter patients with NASH from considering older organs, Dr. Reau said. More insight as to which populations might want to be choosier owing to an elevated risk would be beneficial, she added.

Dr. Lee, Dr. Pruett, and Dr. Reau reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Liver transplant recipients with nonalcoholic steatohepatitis (NASH) who received grafts from older donors are at higher risk for posttransplant death, especially from infection, according to a new study.

All-cause mortality was twice as high and death from an infectious cause was more than three times as high for patients with NASH who received liver grafts from octogenarian donors than for those who received a liver from someone younger than 50.

“The findings from this study implicate a critical need to investigate donor age as an important risk factor for poorer host and graft survival,” wrote the authors, led by David Lee, MD, of the University of Maryland, Baltimore.

“Given the possibility of infectious graft complications, post–liver transplant follow-ups may need to be more comprehensive and frequent in these individuals who receive grafts from older donors,” they add.

The study was published online in Digestive and Liver Disease.
 

Donor age trends

Dr. Lee and colleagues pulled data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research database, a national database of deidentified donor and recipient transplant data. The analysis excluded recipients younger than 18, those with a living donor, those who had hepatocellular carcinoma prior to transplant, and those who had been diagnosed with additional liver disorders apart from NASH.

The team identified 8,88 recipients with NASH who received a liver transplant from 2005–2019. They stratified recipients by donor age. The 5,187 patients who received livers from donors who were younger than 50 served as the reference group. The remainder were placed into four cohorts – 1,842 whose donors were in their 50s, 1,290 whose donors were in their 60s, 504 whose donors were in their 70s, and 65 whose donors were in their 80s.

The researchers found that in comparison with the reference group, the average age of recipients in each donor-age cohort was progressively older. Two donor-age cohorts had significantly higher proportions of recipients with diabetes than the 46.5% in the reference group – the sexagenarian cohort (51.7%) and the octogenarian group (66.2%).

The median follow-up time ranged from 2.35–3.61 years across all age groups.

The researchers found that for all donor-age groups excluding donors in their 60s, recipients had higher risk of all-cause mortality after transplant than the reference group. Recipients with donors in their 50s had a 16% greater risk for death (P = .01), and recipients with donors in their 70s had a 20% greater risk (P = .05). For recipients with octogenarian donors, the adjusted hazard ratio for all-cause mortality was 2.01 (P < .001).

Only recipients in the octogenarian donor cohort were at increased risk of graft failure, compared with the reference group (aHR, 3.72; P = .002).

As donor age increased, the recipient’s risk of dying from sepsis and infectious causes rose, compared with the reference group. Recipients’ likelihood of sepsis death increased by 71% (P = .001) with donors in their 50s, 73% (P = .003) with donors in their 60s, and 76% (P = .03) with donors in their 70s. For recipients with octogenarian donors, the risk more than tripled (aHR, 3.58; P = .007). Likewise, recipients with donors in their 70s were 73% more likely to die from infectious causes. That risk nearly quadrupled among those with donors in their 80s.
 

Recipient factors at play?

While the study found a relationship between liver donor age and recipient outcomes, it is not clear whether any other recipient factors may have contributed to the higher risk of all-cause mortality, sad Nancy Reau, MD, chief of the hepatology section at Rush University Medical Center, Chicago. The researchers did not parse out whether younger recipients did better with older organs than older recipients or whether older recipients fared worse with younger organs, she said in an interview.

“I wasn’t convinced that they had demonstrated that the recipient may not have played a role in that,” said Dr. Reau, who wasn’t involved with the study.

The analysis only a found an increased risk of graft failure among recipients who received organs from octogenarian donors, so factors other than liver transplant may have contributed to all-cause mortality, she noted.

The UNOS database has some limitations, noted Timothy Pruett, MD, who directs the liver transplant program at the University of Minnesota, Minneapolis. Because the database pulls information from transplantation centers across the country, it can be difficult to standardize specific patient variables in the data.

While it’s clear that a patient died, it’s less certain whether an infection was the cause of death and whether that infection was somehow associated with the liver, noted Dr. Pruett, who wasn’t involved in the research. For example, a patient could have had broken a hip, gone to the hospital, and contracted pneumonia, which led to their death.

“There’s just not much granularity in the database, and we can’t overextrapolate what we see,” Dr. Pruett said in an interview.
 

Knowledge gaps

Dr. Lee agreed that more research is needed to understand what may be driving higher mortality rates among patients who receive older organs. “There are still a lot of gaps in knowledge with respect to why.”

Dr. Reau said she is curious as to whether certain comorbidities, such as previous infection, diabetes, or obesity, could predict worse outcomes for recipients with older organs.

“We would love to give all of our patients younger organs, but if that leads to even more disparity in need [compared] to availability and the alternative is not surviving, I think you have to place [this work] into context,” she said.

The study findings shouldn’t be used to deter patients with NASH from considering older organs, Dr. Reau said. More insight as to which populations might want to be choosier owing to an elevated risk would be beneficial, she added.

Dr. Lee, Dr. Pruett, and Dr. Reau reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

Exercise training is 3.5 times more likely to result in a clinically meaningful response in liver fat, compared with standard clinical care, for patients with nonalcoholic fatty liver disease (NAFLD), according to a new systematic review and meta-analysis.

An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.

“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.

“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.

The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
 

Analyzing studies

Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.

However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.

In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.

The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg². The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.

No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.

Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.

In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.

Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.

For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.

For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.

Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.

An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.

The treatment response was independent of clinically significant body weight loss of more than 5%.

“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
 

Ongoing research

Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.

“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”

Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.

Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.

“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.

Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.

“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exercise training is 3.5 times more likely to result in a clinically meaningful response in liver fat, compared with standard clinical care, for patients with nonalcoholic fatty liver disease (NAFLD), according to a new systematic review and meta-analysis.

An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.

“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.

“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.

The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
 

Analyzing studies

Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.

However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.

In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.

The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg². The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.

No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.

Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.

In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.

Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.

For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.

For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.

Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.

An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.

The treatment response was independent of clinically significant body weight loss of more than 5%.

“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
 

Ongoing research

Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.

“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”

Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.

Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.

“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.

Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.

“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exercise training is 3.5 times more likely to result in a clinically meaningful response in liver fat, compared with standard clinical care, for patients with nonalcoholic fatty liver disease (NAFLD), according to a new systematic review and meta-analysis.

An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.

“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.

“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.

The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
 

Analyzing studies

Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.

However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.

In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.

The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg². The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.

No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.

Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.

In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.

Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.

For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.

For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.

Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.

An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.

The treatment response was independent of clinically significant body weight loss of more than 5%.

“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
 

Ongoing research

Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.

“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”

Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.

Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.

“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.

Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.

“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.

Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”

For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).

The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.

An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.

There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).

No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.

“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.

She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”

Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”

As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”

At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”

The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).

Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.

Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”

For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).

The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.

An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.

There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).

No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.

“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.

She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”

Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”

As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”

At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”

The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).

Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.

Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”

For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).

The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.

An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.

There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).

No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.

“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.

She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”

Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”

As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”

At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”

The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).