Hepatology

TOPLINE:

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.

METHODOLOGY:

• Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
• Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.

TAKEAWAY:

• Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
• The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
• In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
• The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).

IN PRACTICE:

“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.

SOURCE:

The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.

LIMITATIONS:

The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.

DISCLOSURES:

The authors have disclosed no conflicts of interest.
 

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

TOPLINE:

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.

METHODOLOGY:

• Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
• Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.

TAKEAWAY:

• Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
• The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
• In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
• The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).

IN PRACTICE:

“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.

SOURCE:

The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.

LIMITATIONS:

The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.

DISCLOSURES:

The authors have disclosed no conflicts of interest.
 

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

TOPLINE:

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.

METHODOLOGY:

• Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
• Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.

TAKEAWAY:

• Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
• The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
• In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
• The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).

IN PRACTICE:

“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.

SOURCE:

The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.

LIMITATIONS:

The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.

DISCLOSURES:

The authors have disclosed no conflicts of interest.
 

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

TOPLINE:

An expert panel has updated recommendations for emergency department assessment, management, and treatment of acetaminophen poisoning.

METHODOLOGY:

The United States and Canada have no formal guidelines for managing acetaminophen poisoning, which is characterized by hepatocellular damage and potential liver failure, which can be life-threatening.

The past 25 years has seen the introduction of products that contain greater amounts of acetaminophen, extended-release preparations, and new drugs that combine acetaminophen with opioids or other ingredients.

From the medical literature and current poison control guidelines, the panel used a modified Delphi method to create a decision framework and determine appropriate management, including triage and laboratory evaluation, for acetaminophen poisoning, addressing scenarios such as extended-release and high-risk ingestion, co-ingestion of anticholinergics or opioids, pregnancy, weight greater than 100 kg, and criteria for consultation with a toxicologist.

TAKEAWAY:

The panel emphasized the role of the patient’s history; an inaccurate estimate of the time of ingestion, for example, can lead to the erroneous conclusion that acetylcysteine, a medication used to treat overdose, is not needed or can be discontinued prematurely – a potentially fatal mistake.

The initial dose of acetylcysteine should be administered as soon as the need becomes evident, with the panel recommending at least 300 mg/kg orally or intravenously during the first 20 or 24 hours of treatment.

Management of ingestion of extended-release preparations is the same, with the exception of obtaining a second acetaminophen blood concentration in some cases.

When acetaminophen is co-ingested with anticholinergic or opioid agonist medications, management is the same, except if the first acetaminophen concentration measured at 4-24 hours after ingestion is 10 mcg/mL or less, another measurement and acetylcysteine treatment are not needed.

IN PRACTICE:

“A guideline that provides management guidance could optimize patient outcomes, reduce disruption for patients and caregivers, and reduce costs by shortening the length of hospitalization,” write the authors.

SOURCE:

The study was conducted by Richard C. Dart, MD, PhD, Rocky Mountain Poison and Drug Safety, University of Colorado, Denver, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

The work lacked high-quality data that address clinical decisions needed for managing acetaminophen poisoning. There were only a few well-controlled comparative studies, which focused on specific issues and not on patient management.

DISCLOSURES:

The work was supported by a grant from Johnson & Johnson Consumer Inc. Dr. Dart has reported receiving grants from Johnson & Johnson outside the submitted work. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

An expert panel has updated recommendations for emergency department assessment, management, and treatment of acetaminophen poisoning.

METHODOLOGY:

The United States and Canada have no formal guidelines for managing acetaminophen poisoning, which is characterized by hepatocellular damage and potential liver failure, which can be life-threatening.

The past 25 years has seen the introduction of products that contain greater amounts of acetaminophen, extended-release preparations, and new drugs that combine acetaminophen with opioids or other ingredients.

From the medical literature and current poison control guidelines, the panel used a modified Delphi method to create a decision framework and determine appropriate management, including triage and laboratory evaluation, for acetaminophen poisoning, addressing scenarios such as extended-release and high-risk ingestion, co-ingestion of anticholinergics or opioids, pregnancy, weight greater than 100 kg, and criteria for consultation with a toxicologist.

TAKEAWAY:

The panel emphasized the role of the patient’s history; an inaccurate estimate of the time of ingestion, for example, can lead to the erroneous conclusion that acetylcysteine, a medication used to treat overdose, is not needed or can be discontinued prematurely – a potentially fatal mistake.

The initial dose of acetylcysteine should be administered as soon as the need becomes evident, with the panel recommending at least 300 mg/kg orally or intravenously during the first 20 or 24 hours of treatment.

Management of ingestion of extended-release preparations is the same, with the exception of obtaining a second acetaminophen blood concentration in some cases.

When acetaminophen is co-ingested with anticholinergic or opioid agonist medications, management is the same, except if the first acetaminophen concentration measured at 4-24 hours after ingestion is 10 mcg/mL or less, another measurement and acetylcysteine treatment are not needed.

IN PRACTICE:

“A guideline that provides management guidance could optimize patient outcomes, reduce disruption for patients and caregivers, and reduce costs by shortening the length of hospitalization,” write the authors.

SOURCE:

The study was conducted by Richard C. Dart, MD, PhD, Rocky Mountain Poison and Drug Safety, University of Colorado, Denver, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

The work lacked high-quality data that address clinical decisions needed for managing acetaminophen poisoning. There were only a few well-controlled comparative studies, which focused on specific issues and not on patient management.

DISCLOSURES:

The work was supported by a grant from Johnson & Johnson Consumer Inc. Dr. Dart has reported receiving grants from Johnson & Johnson outside the submitted work. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

An expert panel has updated recommendations for emergency department assessment, management, and treatment of acetaminophen poisoning.

METHODOLOGY:

The United States and Canada have no formal guidelines for managing acetaminophen poisoning, which is characterized by hepatocellular damage and potential liver failure, which can be life-threatening.

The past 25 years has seen the introduction of products that contain greater amounts of acetaminophen, extended-release preparations, and new drugs that combine acetaminophen with opioids or other ingredients.

From the medical literature and current poison control guidelines, the panel used a modified Delphi method to create a decision framework and determine appropriate management, including triage and laboratory evaluation, for acetaminophen poisoning, addressing scenarios such as extended-release and high-risk ingestion, co-ingestion of anticholinergics or opioids, pregnancy, weight greater than 100 kg, and criteria for consultation with a toxicologist.

TAKEAWAY:

The panel emphasized the role of the patient’s history; an inaccurate estimate of the time of ingestion, for example, can lead to the erroneous conclusion that acetylcysteine, a medication used to treat overdose, is not needed or can be discontinued prematurely – a potentially fatal mistake.

The initial dose of acetylcysteine should be administered as soon as the need becomes evident, with the panel recommending at least 300 mg/kg orally or intravenously during the first 20 or 24 hours of treatment.

Management of ingestion of extended-release preparations is the same, with the exception of obtaining a second acetaminophen blood concentration in some cases.

When acetaminophen is co-ingested with anticholinergic or opioid agonist medications, management is the same, except if the first acetaminophen concentration measured at 4-24 hours after ingestion is 10 mcg/mL or less, another measurement and acetylcysteine treatment are not needed.

IN PRACTICE:

“A guideline that provides management guidance could optimize patient outcomes, reduce disruption for patients and caregivers, and reduce costs by shortening the length of hospitalization,” write the authors.

SOURCE:

The study was conducted by Richard C. Dart, MD, PhD, Rocky Mountain Poison and Drug Safety, University of Colorado, Denver, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

The work lacked high-quality data that address clinical decisions needed for managing acetaminophen poisoning. There were only a few well-controlled comparative studies, which focused on specific issues and not on patient management.

DISCLOSURES:

The work was supported by a grant from Johnson & Johnson Consumer Inc. Dr. Dart has reported receiving grants from Johnson & Johnson outside the submitted work. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

In the decade since safe, curative oral treatments were approved for treating hepatitis C virus (HCV) infections, only one in three U.S. patients diagnosed with the disease have been cleared of it, according to new data from the Centers for Disease Control and Prevention.

The findings indicate that current progress falls far short of the goal of the Viral Hepatitis National Strategic Plan for the United States, which calls for eliminating HCV for at least 80% of patients with the virus by 2030.

Lead author Carolyn Wester, MD, with the CDC’s Division of Viral Hepatitis, called the low numbers “stunning” and said that the researchers found that patients face barriers to being cured at every step of the way, from being diagnosed to accessing breakthrough direct-acting antiviral (DAA) agents.

The article was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Outcomes vary by age and insurance

Using longitudinal data from Quest Diagnostics laboratories, the researchers identified 1.7 million people who had a history of HCV infection from Jan. 1, 2013, to Dec. 31, 2022.

Of those patients, 1.5 million (88%) were categorized as having undergone viral testing.

Among those who underwent such testing, 1 million (69%) were categorized as having an initial infection. Just 356,807 patients with initial infection (34%) were cured or cleared of HCV. Of those found to be cured or cleared, 23,518 (7%) were found to have persistent infection or reinfection.

Viral clearance varied greatly by insurance. While 45% of the people covered under Medicare experienced viral clearance, only 23% of the uninsured and 31% of those on Medicaid did so.

Age also played a role in viral clearance. It was highest (42%) among those aged 60 and older. Clearance was lowest (24%) among patients in the 20-39 age group, the group most likely to be newly infected in light of the surge in HCV cases because of the opioid epidemic, Dr. Wester said. Persistent infection or reinfection was also highest in the 20-39 age group.

With respect to age and insurance type combined, the highest HCV clearance rate (49%) was for patients aged 60 and older who had commercial insurance; the lowest (16%) was for uninsured patients in the 20-39 age group.

The investigators evaluated people who had been diagnosed with HCV, Dr. Wester said. “It’s estimated about 40% of people in the U.S. are unaware of their infection.” Because of this, the numbers reported in the study may vastly underestimate the true picture, she told this news organization.
 

Barriers to treatment ‘insurmountable’ without major transformation

Increased access to diagnosis, treatment, and prevention services for persons with or at risk for acquiring hepatitis C needs to be addressed to prevent progression of disease and ongoing transmission and to achieve national hepatitis C elimination goals, the authors wrote.

The biggest barriers to improving HCV clearance are the high cost of treatment, widely varying insurance coverage, insurer restrictions, and challenges in diagnosing the disease, Dr. Wester added.

Overcoming these barriers requires implementation of universal HCV screening recommendations, including HCV RNA testing for all persons with reactive HCV antibody results, provision of treatment for all persons regardless of payer, and prevention services for persons at risk for acquiring new HCV infection, the authors concluded.

“The current barriers are insurmountable without a major transformation in our nation’s response,” Dr. Wester noted.

She expressed her support of the National Hepatitis C Elimination Program, offered as part of the Biden Administration’s 2024 budget proposal. She said that the initiative “is what we need to prevent the needless suffering from hepatitis C and to potentially save not only tens of thousands of lives but tens of billions of health care dollars.”

The three-part proposal includes a national subscription model to purchase DAA agents for those most underserved: Medicaid beneficiaries, incarcerated people, the uninsured, and American Indian and Alaska Native individuals treated through the Indian Health Service.

Under this model, the federal government would negotiate with manufacturers to buy as much treatment as needed for all individuals in the underserved groups.
 

What can physicians do?

Physicians can help improve HCV treatment and outcomes by being aware of the current testing guidelines, Dr. Wester said.

Guidelines now call for hepatitis C screening at least once in a lifetime for all adults, except in settings where the prevalence of HCV infection is less than 0.1%. They also call for screening during each pregnancy, with the same regional-prevalence exception.

Recommendations include curative treatment “for nearly everybody who is living with hepatitis C,” Dr. Wester added.

These CDC guidelines came out in April 2020, a time when the medical focus shifted to COVID-19, and that may have hurt awareness, she noted.

Physicians can also help by fighting back against non–evidence-based reasons insurance companies give for restricting coverage, Dr. Wester said.

Those restrictions include requiring specialists to prescribe DAA agents instead of allowing primary care physicians to do so, as well as requiring patients to have advanced liver disease or requiring patients to demonstrate sobriety or prove they are receiving counseling prior to their being eligible for treatment, Dr. Wester said.
 

Prior authorization a problem

Stacey B. Trooskin MD, PhD, MPH, assistant professor of medicine at the University of Pennsylvania in Philadelphia, told this news organization that prior authorization has been a major barrier for obtaining medications. Prior authorization requirements differ by state.

The paperwork must be submitted by already-stretched physician offices, and appeals are common. In that time, the window for keeping patients with HCV in the health care system may be lost, said Dr. Trooskin, chief medical adviser to the National Viral Hepatitis Roundtable.

“We know that about half of all Medicaid programs have removed prior authorization for most patients entirely,” she said, “but there are still half that require prior authorization.”

Action at the federal level is also needed, Dr. Trooskin said.

The countries that are successfully eliminating HCV and have successfully deployed the lifesaving medications provide governmental support for meeting patients where they are, she added.

Support can include inpatient and outpatient substance use disorder treatment programs or support in mental health settings, she noted.

“It’s not enough to want patients to come into their primary care provider and for that primary care provider to screen them,” Dr. Trooskin said. “This is about creating health care infrastructure so that we are finding patients at greatest risk for hepatitis C and integrating hepatitis C treatment into the services they are already accessing.”

Coauthor Harvey W. Kaufman, MD, is an employee of and owns stock in Quest Diagnostics. Coauthor William A. Meyer III, PhD, is a consultant to Quest Diagnostics. No other potential conflicts of interest were disclosed. Dr. Trooskin oversees C-Change, a hepatitis C elimination program, which receives funding from Gilead Sciences.

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

In the decade since safe, curative oral treatments were approved for treating hepatitis C virus (HCV) infections, only one in three U.S. patients diagnosed with the disease have been cleared of it, according to new data from the Centers for Disease Control and Prevention.

The findings indicate that current progress falls far short of the goal of the Viral Hepatitis National Strategic Plan for the United States, which calls for eliminating HCV for at least 80% of patients with the virus by 2030.

Lead author Carolyn Wester, MD, with the CDC’s Division of Viral Hepatitis, called the low numbers “stunning” and said that the researchers found that patients face barriers to being cured at every step of the way, from being diagnosed to accessing breakthrough direct-acting antiviral (DAA) agents.

The article was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Outcomes vary by age and insurance

Using longitudinal data from Quest Diagnostics laboratories, the researchers identified 1.7 million people who had a history of HCV infection from Jan. 1, 2013, to Dec. 31, 2022.

Of those patients, 1.5 million (88%) were categorized as having undergone viral testing.

Among those who underwent such testing, 1 million (69%) were categorized as having an initial infection. Just 356,807 patients with initial infection (34%) were cured or cleared of HCV. Of those found to be cured or cleared, 23,518 (7%) were found to have persistent infection or reinfection.

Viral clearance varied greatly by insurance. While 45% of the people covered under Medicare experienced viral clearance, only 23% of the uninsured and 31% of those on Medicaid did so.

Age also played a role in viral clearance. It was highest (42%) among those aged 60 and older. Clearance was lowest (24%) among patients in the 20-39 age group, the group most likely to be newly infected in light of the surge in HCV cases because of the opioid epidemic, Dr. Wester said. Persistent infection or reinfection was also highest in the 20-39 age group.

With respect to age and insurance type combined, the highest HCV clearance rate (49%) was for patients aged 60 and older who had commercial insurance; the lowest (16%) was for uninsured patients in the 20-39 age group.

The investigators evaluated people who had been diagnosed with HCV, Dr. Wester said. “It’s estimated about 40% of people in the U.S. are unaware of their infection.” Because of this, the numbers reported in the study may vastly underestimate the true picture, she told this news organization.
 

Barriers to treatment ‘insurmountable’ without major transformation

Increased access to diagnosis, treatment, and prevention services for persons with or at risk for acquiring hepatitis C needs to be addressed to prevent progression of disease and ongoing transmission and to achieve national hepatitis C elimination goals, the authors wrote.

The biggest barriers to improving HCV clearance are the high cost of treatment, widely varying insurance coverage, insurer restrictions, and challenges in diagnosing the disease, Dr. Wester added.

Overcoming these barriers requires implementation of universal HCV screening recommendations, including HCV RNA testing for all persons with reactive HCV antibody results, provision of treatment for all persons regardless of payer, and prevention services for persons at risk for acquiring new HCV infection, the authors concluded.

“The current barriers are insurmountable without a major transformation in our nation’s response,” Dr. Wester noted.

She expressed her support of the National Hepatitis C Elimination Program, offered as part of the Biden Administration’s 2024 budget proposal. She said that the initiative “is what we need to prevent the needless suffering from hepatitis C and to potentially save not only tens of thousands of lives but tens of billions of health care dollars.”

The three-part proposal includes a national subscription model to purchase DAA agents for those most underserved: Medicaid beneficiaries, incarcerated people, the uninsured, and American Indian and Alaska Native individuals treated through the Indian Health Service.

Under this model, the federal government would negotiate with manufacturers to buy as much treatment as needed for all individuals in the underserved groups.
 

What can physicians do?

Physicians can help improve HCV treatment and outcomes by being aware of the current testing guidelines, Dr. Wester said.

Guidelines now call for hepatitis C screening at least once in a lifetime for all adults, except in settings where the prevalence of HCV infection is less than 0.1%. They also call for screening during each pregnancy, with the same regional-prevalence exception.

Recommendations include curative treatment “for nearly everybody who is living with hepatitis C,” Dr. Wester added.

These CDC guidelines came out in April 2020, a time when the medical focus shifted to COVID-19, and that may have hurt awareness, she noted.

Physicians can also help by fighting back against non–evidence-based reasons insurance companies give for restricting coverage, Dr. Wester said.

Those restrictions include requiring specialists to prescribe DAA agents instead of allowing primary care physicians to do so, as well as requiring patients to have advanced liver disease or requiring patients to demonstrate sobriety or prove they are receiving counseling prior to their being eligible for treatment, Dr. Wester said.
 

Prior authorization a problem

Stacey B. Trooskin MD, PhD, MPH, assistant professor of medicine at the University of Pennsylvania in Philadelphia, told this news organization that prior authorization has been a major barrier for obtaining medications. Prior authorization requirements differ by state.

The paperwork must be submitted by already-stretched physician offices, and appeals are common. In that time, the window for keeping patients with HCV in the health care system may be lost, said Dr. Trooskin, chief medical adviser to the National Viral Hepatitis Roundtable.

“We know that about half of all Medicaid programs have removed prior authorization for most patients entirely,” she said, “but there are still half that require prior authorization.”

Action at the federal level is also needed, Dr. Trooskin said.

The countries that are successfully eliminating HCV and have successfully deployed the lifesaving medications provide governmental support for meeting patients where they are, she added.

Support can include inpatient and outpatient substance use disorder treatment programs or support in mental health settings, she noted.

“It’s not enough to want patients to come into their primary care provider and for that primary care provider to screen them,” Dr. Trooskin said. “This is about creating health care infrastructure so that we are finding patients at greatest risk for hepatitis C and integrating hepatitis C treatment into the services they are already accessing.”

Coauthor Harvey W. Kaufman, MD, is an employee of and owns stock in Quest Diagnostics. Coauthor William A. Meyer III, PhD, is a consultant to Quest Diagnostics. No other potential conflicts of interest were disclosed. Dr. Trooskin oversees C-Change, a hepatitis C elimination program, which receives funding from Gilead Sciences.

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

In the decade since safe, curative oral treatments were approved for treating hepatitis C virus (HCV) infections, only one in three U.S. patients diagnosed with the disease have been cleared of it, according to new data from the Centers for Disease Control and Prevention.

The findings indicate that current progress falls far short of the goal of the Viral Hepatitis National Strategic Plan for the United States, which calls for eliminating HCV for at least 80% of patients with the virus by 2030.

Lead author Carolyn Wester, MD, with the CDC’s Division of Viral Hepatitis, called the low numbers “stunning” and said that the researchers found that patients face barriers to being cured at every step of the way, from being diagnosed to accessing breakthrough direct-acting antiviral (DAA) agents.

The article was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Outcomes vary by age and insurance

Using longitudinal data from Quest Diagnostics laboratories, the researchers identified 1.7 million people who had a history of HCV infection from Jan. 1, 2013, to Dec. 31, 2022.

Of those patients, 1.5 million (88%) were categorized as having undergone viral testing.

Among those who underwent such testing, 1 million (69%) were categorized as having an initial infection. Just 356,807 patients with initial infection (34%) were cured or cleared of HCV. Of those found to be cured or cleared, 23,518 (7%) were found to have persistent infection or reinfection.

Viral clearance varied greatly by insurance. While 45% of the people covered under Medicare experienced viral clearance, only 23% of the uninsured and 31% of those on Medicaid did so.

Age also played a role in viral clearance. It was highest (42%) among those aged 60 and older. Clearance was lowest (24%) among patients in the 20-39 age group, the group most likely to be newly infected in light of the surge in HCV cases because of the opioid epidemic, Dr. Wester said. Persistent infection or reinfection was also highest in the 20-39 age group.

With respect to age and insurance type combined, the highest HCV clearance rate (49%) was for patients aged 60 and older who had commercial insurance; the lowest (16%) was for uninsured patients in the 20-39 age group.

The investigators evaluated people who had been diagnosed with HCV, Dr. Wester said. “It’s estimated about 40% of people in the U.S. are unaware of their infection.” Because of this, the numbers reported in the study may vastly underestimate the true picture, she told this news organization.
 

Barriers to treatment ‘insurmountable’ without major transformation

Increased access to diagnosis, treatment, and prevention services for persons with or at risk for acquiring hepatitis C needs to be addressed to prevent progression of disease and ongoing transmission and to achieve national hepatitis C elimination goals, the authors wrote.

The biggest barriers to improving HCV clearance are the high cost of treatment, widely varying insurance coverage, insurer restrictions, and challenges in diagnosing the disease, Dr. Wester added.

Overcoming these barriers requires implementation of universal HCV screening recommendations, including HCV RNA testing for all persons with reactive HCV antibody results, provision of treatment for all persons regardless of payer, and prevention services for persons at risk for acquiring new HCV infection, the authors concluded.

“The current barriers are insurmountable without a major transformation in our nation’s response,” Dr. Wester noted.

She expressed her support of the National Hepatitis C Elimination Program, offered as part of the Biden Administration’s 2024 budget proposal. She said that the initiative “is what we need to prevent the needless suffering from hepatitis C and to potentially save not only tens of thousands of lives but tens of billions of health care dollars.”

The three-part proposal includes a national subscription model to purchase DAA agents for those most underserved: Medicaid beneficiaries, incarcerated people, the uninsured, and American Indian and Alaska Native individuals treated through the Indian Health Service.

Under this model, the federal government would negotiate with manufacturers to buy as much treatment as needed for all individuals in the underserved groups.
 

What can physicians do?

Physicians can help improve HCV treatment and outcomes by being aware of the current testing guidelines, Dr. Wester said.

Guidelines now call for hepatitis C screening at least once in a lifetime for all adults, except in settings where the prevalence of HCV infection is less than 0.1%. They also call for screening during each pregnancy, with the same regional-prevalence exception.

Recommendations include curative treatment “for nearly everybody who is living with hepatitis C,” Dr. Wester added.

These CDC guidelines came out in April 2020, a time when the medical focus shifted to COVID-19, and that may have hurt awareness, she noted.

Physicians can also help by fighting back against non–evidence-based reasons insurance companies give for restricting coverage, Dr. Wester said.

Those restrictions include requiring specialists to prescribe DAA agents instead of allowing primary care physicians to do so, as well as requiring patients to have advanced liver disease or requiring patients to demonstrate sobriety or prove they are receiving counseling prior to their being eligible for treatment, Dr. Wester said.
 

Prior authorization a problem

Stacey B. Trooskin MD, PhD, MPH, assistant professor of medicine at the University of Pennsylvania in Philadelphia, told this news organization that prior authorization has been a major barrier for obtaining medications. Prior authorization requirements differ by state.

The paperwork must be submitted by already-stretched physician offices, and appeals are common. In that time, the window for keeping patients with HCV in the health care system may be lost, said Dr. Trooskin, chief medical adviser to the National Viral Hepatitis Roundtable.

“We know that about half of all Medicaid programs have removed prior authorization for most patients entirely,” she said, “but there are still half that require prior authorization.”

Action at the federal level is also needed, Dr. Trooskin said.

The countries that are successfully eliminating HCV and have successfully deployed the lifesaving medications provide governmental support for meeting patients where they are, she added.

Support can include inpatient and outpatient substance use disorder treatment programs or support in mental health settings, she noted.

“It’s not enough to want patients to come into their primary care provider and for that primary care provider to screen them,” Dr. Trooskin said. “This is about creating health care infrastructure so that we are finding patients at greatest risk for hepatitis C and integrating hepatitis C treatment into the services they are already accessing.”

Coauthor Harvey W. Kaufman, MD, is an employee of and owns stock in Quest Diagnostics. Coauthor William A. Meyer III, PhD, is a consultant to Quest Diagnostics. No other potential conflicts of interest were disclosed. Dr. Trooskin oversees C-Change, a hepatitis C elimination program, which receives funding from Gilead Sciences.

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

Topline

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use lowers the risk for death, cardiovascular disease, decompensated cirrhosis, and liver failure in adults with type 2 diabetes (T2D) and compensated liver cirrhosis, new observational data show.

Methodology

• Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
• Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
• All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.

Takeaway

• During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
• GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
• A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.

In practice

“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.

Study details

The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.

Limitations 

Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.

Disclosures

The authors disclosed no relevant financial relationships.
 

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

Topline

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use lowers the risk for death, cardiovascular disease, decompensated cirrhosis, and liver failure in adults with type 2 diabetes (T2D) and compensated liver cirrhosis, new observational data show.

Methodology

• Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
• Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
• All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.

Takeaway

• During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
• GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
• A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.

In practice

“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.

Study details

The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.

Limitations 

Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.

Disclosures

The authors disclosed no relevant financial relationships.
 

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

Topline

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use lowers the risk for death, cardiovascular disease, decompensated cirrhosis, and liver failure in adults with type 2 diabetes (T2D) and compensated liver cirrhosis, new observational data show.

Methodology

• Population-based cohort study using data from the National Health Insurance Research Database of Taiwan.
• Propensity-score matching was used to construct 467 matched pairs of GLP-1 RA users and nonusers (mean age, 57) with T2D and compensated liver cirrhosis.
• All-cause mortality, cardiovascular events, decompensated cirrhosis, and other key outcomes were compared using multivariable-adjusted Cox proportional hazards models.

Takeaway

• During mean follow-up of about 3 years, rates of death per 1,000 person-years were 27.5 in GLP-1 RA users versus 55.9 in nonusers.
• GLP-1 RA users had a significantly lower risk for mortality (adjusted hazard ratio [aHR], 0.47), cardiovascular events (aHR, 0.6), decompensated cirrhosis (aHR, 0.7), hepatic encephalopathy (aHR, 0.59), and liver failure (aHR, 0.54).
• A longer cumulative duration of GLP-1 RA use was associated with lower risk for these outcomes compared with no use.

In practice

“GLP-1 RAs may be a treatment option for diabetes patients with liver cirrhosis. However, additional studies are needed to confirm our results and to explore the mechanisms of GLP-1 RAs, cirrhotic decompensation and hepatic encephalopathy,” the researchers concluded.

Study details

The study was led by Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan. It was published online June 16, 2023, in Clinical Gastroenterology and Hepatology. Funding was provided in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center, China Medical University Hospital, Taipei Veterans General Hospital, and the Ministry of Science and Technology.

Limitations 

Limitations of the study include a lack of complete information on family history, diet, body weight, and physical activity, as well as biochemical tests, hemoglobin A1c, pathology, and imaging findings that could potentially influence the results.

Disclosures

The authors disclosed no relevant financial relationships.
 

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

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

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

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

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

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

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

VIENNA – An algorithm, the Steatosis-Associated Fibrosis Estimator (SAFE), was developed to detect clinically significant fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). It is effective at detecting chronic liver disease from all causes with or without NAFLD in the general population, according the results of a U.S. population-based study. The algorithm was designed for use in primary care to help slow the steep rise in liver disease burden.

On the basis of the SAFE score, 61.3% of participants were at low risk for clinically significant fibrosis; 11.2% were at high risk; and 27.5% were at intermediate risk. Upon validation, very few of the low-risk participants had liver fibrosis, while nearly a third of those with a high-risk score had clinically significant fibrosis. In addition, a high percentage of the patients with high-risk SAFE scores had viral hepatitis and elevations in ferritin level.

“This is the first time that there has been a test that provides a score to detect low-risk liver disease in primary care,” said Ray Kim, MD, from Stanford (Calif.) University, senior investigator, who was speaking to this news organization at the annual International Liver Congress sponsored by the European Association for the Study of the Liver

“Primary care doctors currently detect liver disease through a serendipitous abnormal finding on ultrasound or blood tests that detect elevated transaminases, and then the patient is referred to a hepatologist, who figures out what is really going on,” said Dr. Kim.

“This approach is limited, so we need to get SAFE into primary care so these doctors can automatically calculate their scores, and if the patient is over 100 [high risk of chronic liver disease], then they need help [referral to a hepatologist].”
 

Liver deaths sharply rising

Public health data show that more people are dying of liver disease today than previously. Deaths in the United States have doubled over the past 20 years, said Dr. Kim. “If our mission is to help these patients and prevent death, [things are] moving in the wrong direction.”

He stressed that in order to change the direction, “primary care doctors need to engage with the issue and have appropriate tools to identify people with liver disease.”

Most often, the reason for this rise in deaths is that cases are being diagnosed at advanced stages of disease in which reversibility is limited, he added. “We want to move upstream where people might have early-stage disease and where we can intervene and make a difference.”

In an effort to help earlier detection of liver disease, the SAFE score was developed and validated by Dr. Kim and his colleagues to detect clinically significant (greater than stage 2) fibrosis in patients with NAFLD in primary care. The score is based upon age, body mass index, diabetes, platelet level, aspartate and alanine aminotransferase levels, and globulin level. A score of less than zero signifies that a patient is at low risk for liver fibrosis, while a score greater than 100 signifies a high risk of fibrosis. A score between 0 and 99 denotes intermediate risk of fibrosis.

“Unlike other noninvasive tests that detect advanced fibrosis, this one detects early-stage fibrosis. We’ve shown that the SAFE estimator is better than all other blood-based markers,” explained Dr. Kim.
 

Applying SAFE to the general population

In the study presented here at EASL, Dr. Kim aimed to expand the horizon for SAFE testing to the U.S. general population and to assess whether SAFE was effective in screening for chronic liver disease regardless of steatosis of the liver.

Together with first author Nakia Chung, MD, also from Stanford University, Dr. Kim applied the SAFE score to data from 7,156 participants of the National Health and Nutrition Examination Survey (NHANES) for 2017-2020. NHANES is representative of the noninstitutionalized, civilian population of the United States. It includes broad demographic, clinical, and laboratory data, including transient elastography data. FibroScans were first used in 2017, so the investigators had 3 years of FibroScan data with which to validate the score.

The researchers extrapolated the NHANES sample data to the U.S. population. They found that the proportion of adults with steatosis (CAP score > 274 dB/m) and significant fibrosis (LSM > 8.0 kPa) was 42.7% (95% confidence interval, 41.0%- 44.3%) and 8.9% (7.6%-10.2%), respectively. In addition, 11.3% (10.2%-12.5%) of the adult U.S. population demonstrated a significant amount of alcohol use, 2.3% (1.4%-3.3%) showed evidence of hepatitis B or C, and 5.4% (4.6%-6.2%) had elevated serum ferritin levels.

The researchers then stratified the patients according to previously defined SAFE tiers of low, intermediate, and high risk and projected findings to the U.S. general population.

“When we applied our score to the general population, we found multiple abnormalities in the high-risk groups [SAFE >100] having Fibroscan data that are consistent with stage 2 or higher fibrosis regardless of etiology, “Dr. Kim pointed out.

Results also showed that very few patients with SAFE less than 0 had liver fibrosis (4% among those with liver stiffness measure [LSM] > 8kPa, and 0.8% with LSM > 12kPa). Among those with SAFE > 100, nearly a third (31.5%) had LSM of > 8kPa, and 16.5% had LSM > 12kPa.

In addition to fibrosis, liver abnormalities were common among patients with SAFE greater than 100, including steatosis (68.0%), viral hepatitis (7.0%), and abnormal ferritin levels (12.9%); 10.8% of these patients used alcohol.

“Right now, some patients are referred, but on examination and FibroScan, they might actually be okay, so it it’s a waste of time and money for everyone. We can preempt all of this by doing a blood test and focusing on those people who really need a scan,” said Dr. Kim.

The researcher is now working with primary care colleagues to help further develop and integrate SAFE into the primary care setting.
 

Fibrosis score in patients with metabolic dysfunction

Also presenting at the same session on population health was Willem Pieter Brouwer, MD, PhD, from Erasmus University Medical Center, Rotterdam, the Netherlands. He reported results of a validation study of a new risk score – the Metabolic Dysfunction-Associated Fibrosis–5 (MAF-5) score – for use for people with metabolic dysfunction who are recommended for screening for liver fibrosis.

“We believe the MAF-5 score may be a good alternative to the FIB-4 [a liver fibrosis biomarker] for use in the referral pathway for liver health evaluation,” remarked Dr. Brouwer. “The clinical practice guidelines recommend using FIB-4 scores, but these have a poor-moderate performance in the population setting.

“We developed and validated our score in a population of 5,500 from the NHANES 2017-2020 cycle and validated the score in populations from Rotterdam, which is a cohort of elderly participants, and in fibrosis among patients with biopsy-proven NAFLD from Colombia and Belgium,” he explained.

He also validated the score against different existing scoring systems and different methods of measuring liver stiffness and validated it for prognostic use to predict all-cause mortality in the NHANES III cohort.

Dr. Brouwer removed age as a factor of his new MAF-5 score; the score is thus stable for patients of all ages and is suitable for detecting liver disease in younger patients. “This is very important because these patients are currently underserved and have the most years of life to win.”

Referring to the SAFE score discussed by Dr. Kim, as well as other scores, he said, “The FIB-4, SAFE, and NFS [NAFLD fibrosis score] all include age in the scores, which causes problems and limitations in aging populations, as more and more patients will be referred due to an increasing score. Hence, the elderly are mostly all referred for liver checkups.”

Dr. Kim and Dr. Brouwer have disclosed no relevant financial relationships.

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

VIENNA – An algorithm, the Steatosis-Associated Fibrosis Estimator (SAFE), was developed to detect clinically significant fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). It is effective at detecting chronic liver disease from all causes with or without NAFLD in the general population, according the results of a U.S. population-based study. The algorithm was designed for use in primary care to help slow the steep rise in liver disease burden.

On the basis of the SAFE score, 61.3% of participants were at low risk for clinically significant fibrosis; 11.2% were at high risk; and 27.5% were at intermediate risk. Upon validation, very few of the low-risk participants had liver fibrosis, while nearly a third of those with a high-risk score had clinically significant fibrosis. In addition, a high percentage of the patients with high-risk SAFE scores had viral hepatitis and elevations in ferritin level.

“This is the first time that there has been a test that provides a score to detect low-risk liver disease in primary care,” said Ray Kim, MD, from Stanford (Calif.) University, senior investigator, who was speaking to this news organization at the annual International Liver Congress sponsored by the European Association for the Study of the Liver

“Primary care doctors currently detect liver disease through a serendipitous abnormal finding on ultrasound or blood tests that detect elevated transaminases, and then the patient is referred to a hepatologist, who figures out what is really going on,” said Dr. Kim.

“This approach is limited, so we need to get SAFE into primary care so these doctors can automatically calculate their scores, and if the patient is over 100 [high risk of chronic liver disease], then they need help [referral to a hepatologist].”
 

Liver deaths sharply rising

Public health data show that more people are dying of liver disease today than previously. Deaths in the United States have doubled over the past 20 years, said Dr. Kim. “If our mission is to help these patients and prevent death, [things are] moving in the wrong direction.”

He stressed that in order to change the direction, “primary care doctors need to engage with the issue and have appropriate tools to identify people with liver disease.”

Most often, the reason for this rise in deaths is that cases are being diagnosed at advanced stages of disease in which reversibility is limited, he added. “We want to move upstream where people might have early-stage disease and where we can intervene and make a difference.”

In an effort to help earlier detection of liver disease, the SAFE score was developed and validated by Dr. Kim and his colleagues to detect clinically significant (greater than stage 2) fibrosis in patients with NAFLD in primary care. The score is based upon age, body mass index, diabetes, platelet level, aspartate and alanine aminotransferase levels, and globulin level. A score of less than zero signifies that a patient is at low risk for liver fibrosis, while a score greater than 100 signifies a high risk of fibrosis. A score between 0 and 99 denotes intermediate risk of fibrosis.

“Unlike other noninvasive tests that detect advanced fibrosis, this one detects early-stage fibrosis. We’ve shown that the SAFE estimator is better than all other blood-based markers,” explained Dr. Kim.
 

Applying SAFE to the general population

In the study presented here at EASL, Dr. Kim aimed to expand the horizon for SAFE testing to the U.S. general population and to assess whether SAFE was effective in screening for chronic liver disease regardless of steatosis of the liver.

Together with first author Nakia Chung, MD, also from Stanford University, Dr. Kim applied the SAFE score to data from 7,156 participants of the National Health and Nutrition Examination Survey (NHANES) for 2017-2020. NHANES is representative of the noninstitutionalized, civilian population of the United States. It includes broad demographic, clinical, and laboratory data, including transient elastography data. FibroScans were first used in 2017, so the investigators had 3 years of FibroScan data with which to validate the score.

The researchers extrapolated the NHANES sample data to the U.S. population. They found that the proportion of adults with steatosis (CAP score > 274 dB/m) and significant fibrosis (LSM > 8.0 kPa) was 42.7% (95% confidence interval, 41.0%- 44.3%) and 8.9% (7.6%-10.2%), respectively. In addition, 11.3% (10.2%-12.5%) of the adult U.S. population demonstrated a significant amount of alcohol use, 2.3% (1.4%-3.3%) showed evidence of hepatitis B or C, and 5.4% (4.6%-6.2%) had elevated serum ferritin levels.

The researchers then stratified the patients according to previously defined SAFE tiers of low, intermediate, and high risk and projected findings to the U.S. general population.

“When we applied our score to the general population, we found multiple abnormalities in the high-risk groups [SAFE >100] having Fibroscan data that are consistent with stage 2 or higher fibrosis regardless of etiology, “Dr. Kim pointed out.

Results also showed that very few patients with SAFE less than 0 had liver fibrosis (4% among those with liver stiffness measure [LSM] > 8kPa, and 0.8% with LSM > 12kPa). Among those with SAFE > 100, nearly a third (31.5%) had LSM of > 8kPa, and 16.5% had LSM > 12kPa.

In addition to fibrosis, liver abnormalities were common among patients with SAFE greater than 100, including steatosis (68.0%), viral hepatitis (7.0%), and abnormal ferritin levels (12.9%); 10.8% of these patients used alcohol.

“Right now, some patients are referred, but on examination and FibroScan, they might actually be okay, so it it’s a waste of time and money for everyone. We can preempt all of this by doing a blood test and focusing on those people who really need a scan,” said Dr. Kim.

The researcher is now working with primary care colleagues to help further develop and integrate SAFE into the primary care setting.
 

Fibrosis score in patients with metabolic dysfunction

Also presenting at the same session on population health was Willem Pieter Brouwer, MD, PhD, from Erasmus University Medical Center, Rotterdam, the Netherlands. He reported results of a validation study of a new risk score – the Metabolic Dysfunction-Associated Fibrosis–5 (MAF-5) score – for use for people with metabolic dysfunction who are recommended for screening for liver fibrosis.

“We believe the MAF-5 score may be a good alternative to the FIB-4 [a liver fibrosis biomarker] for use in the referral pathway for liver health evaluation,” remarked Dr. Brouwer. “The clinical practice guidelines recommend using FIB-4 scores, but these have a poor-moderate performance in the population setting.

“We developed and validated our score in a population of 5,500 from the NHANES 2017-2020 cycle and validated the score in populations from Rotterdam, which is a cohort of elderly participants, and in fibrosis among patients with biopsy-proven NAFLD from Colombia and Belgium,” he explained.

He also validated the score against different existing scoring systems and different methods of measuring liver stiffness and validated it for prognostic use to predict all-cause mortality in the NHANES III cohort.

Dr. Brouwer removed age as a factor of his new MAF-5 score; the score is thus stable for patients of all ages and is suitable for detecting liver disease in younger patients. “This is very important because these patients are currently underserved and have the most years of life to win.”

Referring to the SAFE score discussed by Dr. Kim, as well as other scores, he said, “The FIB-4, SAFE, and NFS [NAFLD fibrosis score] all include age in the scores, which causes problems and limitations in aging populations, as more and more patients will be referred due to an increasing score. Hence, the elderly are mostly all referred for liver checkups.”

Dr. Kim and Dr. Brouwer have disclosed no relevant financial relationships.

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

VIENNA – An algorithm, the Steatosis-Associated Fibrosis Estimator (SAFE), was developed to detect clinically significant fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). It is effective at detecting chronic liver disease from all causes with or without NAFLD in the general population, according the results of a U.S. population-based study. The algorithm was designed for use in primary care to help slow the steep rise in liver disease burden.

On the basis of the SAFE score, 61.3% of participants were at low risk for clinically significant fibrosis; 11.2% were at high risk; and 27.5% were at intermediate risk. Upon validation, very few of the low-risk participants had liver fibrosis, while nearly a third of those with a high-risk score had clinically significant fibrosis. In addition, a high percentage of the patients with high-risk SAFE scores had viral hepatitis and elevations in ferritin level.

“This is the first time that there has been a test that provides a score to detect low-risk liver disease in primary care,” said Ray Kim, MD, from Stanford (Calif.) University, senior investigator, who was speaking to this news organization at the annual International Liver Congress sponsored by the European Association for the Study of the Liver

“Primary care doctors currently detect liver disease through a serendipitous abnormal finding on ultrasound or blood tests that detect elevated transaminases, and then the patient is referred to a hepatologist, who figures out what is really going on,” said Dr. Kim.

“This approach is limited, so we need to get SAFE into primary care so these doctors can automatically calculate their scores, and if the patient is over 100 [high risk of chronic liver disease], then they need help [referral to a hepatologist].”
 

Liver deaths sharply rising

Public health data show that more people are dying of liver disease today than previously. Deaths in the United States have doubled over the past 20 years, said Dr. Kim. “If our mission is to help these patients and prevent death, [things are] moving in the wrong direction.”

He stressed that in order to change the direction, “primary care doctors need to engage with the issue and have appropriate tools to identify people with liver disease.”

Most often, the reason for this rise in deaths is that cases are being diagnosed at advanced stages of disease in which reversibility is limited, he added. “We want to move upstream where people might have early-stage disease and where we can intervene and make a difference.”

In an effort to help earlier detection of liver disease, the SAFE score was developed and validated by Dr. Kim and his colleagues to detect clinically significant (greater than stage 2) fibrosis in patients with NAFLD in primary care. The score is based upon age, body mass index, diabetes, platelet level, aspartate and alanine aminotransferase levels, and globulin level. A score of less than zero signifies that a patient is at low risk for liver fibrosis, while a score greater than 100 signifies a high risk of fibrosis. A score between 0 and 99 denotes intermediate risk of fibrosis.

“Unlike other noninvasive tests that detect advanced fibrosis, this one detects early-stage fibrosis. We’ve shown that the SAFE estimator is better than all other blood-based markers,” explained Dr. Kim.
 

Applying SAFE to the general population

In the study presented here at EASL, Dr. Kim aimed to expand the horizon for SAFE testing to the U.S. general population and to assess whether SAFE was effective in screening for chronic liver disease regardless of steatosis of the liver.

Together with first author Nakia Chung, MD, also from Stanford University, Dr. Kim applied the SAFE score to data from 7,156 participants of the National Health and Nutrition Examination Survey (NHANES) for 2017-2020. NHANES is representative of the noninstitutionalized, civilian population of the United States. It includes broad demographic, clinical, and laboratory data, including transient elastography data. FibroScans were first used in 2017, so the investigators had 3 years of FibroScan data with which to validate the score.

The researchers extrapolated the NHANES sample data to the U.S. population. They found that the proportion of adults with steatosis (CAP score > 274 dB/m) and significant fibrosis (LSM > 8.0 kPa) was 42.7% (95% confidence interval, 41.0%- 44.3%) and 8.9% (7.6%-10.2%), respectively. In addition, 11.3% (10.2%-12.5%) of the adult U.S. population demonstrated a significant amount of alcohol use, 2.3% (1.4%-3.3%) showed evidence of hepatitis B or C, and 5.4% (4.6%-6.2%) had elevated serum ferritin levels.

The researchers then stratified the patients according to previously defined SAFE tiers of low, intermediate, and high risk and projected findings to the U.S. general population.

“When we applied our score to the general population, we found multiple abnormalities in the high-risk groups [SAFE >100] having Fibroscan data that are consistent with stage 2 or higher fibrosis regardless of etiology, “Dr. Kim pointed out.

Results also showed that very few patients with SAFE less than 0 had liver fibrosis (4% among those with liver stiffness measure [LSM] > 8kPa, and 0.8% with LSM > 12kPa). Among those with SAFE > 100, nearly a third (31.5%) had LSM of > 8kPa, and 16.5% had LSM > 12kPa.

In addition to fibrosis, liver abnormalities were common among patients with SAFE greater than 100, including steatosis (68.0%), viral hepatitis (7.0%), and abnormal ferritin levels (12.9%); 10.8% of these patients used alcohol.

“Right now, some patients are referred, but on examination and FibroScan, they might actually be okay, so it it’s a waste of time and money for everyone. We can preempt all of this by doing a blood test and focusing on those people who really need a scan,” said Dr. Kim.

The researcher is now working with primary care colleagues to help further develop and integrate SAFE into the primary care setting.
 

Fibrosis score in patients with metabolic dysfunction

Also presenting at the same session on population health was Willem Pieter Brouwer, MD, PhD, from Erasmus University Medical Center, Rotterdam, the Netherlands. He reported results of a validation study of a new risk score – the Metabolic Dysfunction-Associated Fibrosis–5 (MAF-5) score – for use for people with metabolic dysfunction who are recommended for screening for liver fibrosis.

“We believe the MAF-5 score may be a good alternative to the FIB-4 [a liver fibrosis biomarker] for use in the referral pathway for liver health evaluation,” remarked Dr. Brouwer. “The clinical practice guidelines recommend using FIB-4 scores, but these have a poor-moderate performance in the population setting.

“We developed and validated our score in a population of 5,500 from the NHANES 2017-2020 cycle and validated the score in populations from Rotterdam, which is a cohort of elderly participants, and in fibrosis among patients with biopsy-proven NAFLD from Colombia and Belgium,” he explained.

He also validated the score against different existing scoring systems and different methods of measuring liver stiffness and validated it for prognostic use to predict all-cause mortality in the NHANES III cohort.

Dr. Brouwer removed age as a factor of his new MAF-5 score; the score is thus stable for patients of all ages and is suitable for detecting liver disease in younger patients. “This is very important because these patients are currently underserved and have the most years of life to win.”

Referring to the SAFE score discussed by Dr. Kim, as well as other scores, he said, “The FIB-4, SAFE, and NFS [NAFLD fibrosis score] all include age in the scores, which causes problems and limitations in aging populations, as more and more patients will be referred due to an increasing score. Hence, the elderly are mostly all referred for liver checkups.”

Dr. Kim and Dr. Brouwer have disclosed no relevant financial relationships.

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

VIENNA – Resolution of nonalcoholic steatohepatitis (NASH), and reduction of fibrosis on liver biopsy were achieved with the oral, thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in patients with NASH and associated cirrhosis in a pivotal phase 3 clinical trial. The primary results of the MAESTRO-NASH (NCT03900429) trial were reported at the European Association for the Study of the Liver Congress 2023.

Both doses of resmetirom – 80 mg and 100 mg – met the primary endpoints of NASH resolution and no worsening of fibrosis on liver biopsy. The key secondary endpoint of LDL cholesterol lowering was also achieved with statistical significance. Likewise, improvement was seen in liver enzymes, and liver and spleen volumes.

In the intent-to-treat population, NASH resolution was achieved in 26% (P < .0001) in the 80-mg resmetirom group, 30% (P < .0001) in the 100-mg group, and 10% in those taking placebo. And ≥ 1-stage improvement in fibrosis with no worsening of the nonalcoholic fatty liver disease activity score (NAS) was achieved by 24% (P < .0002), 26% (P < .0001), and 14% in these groups respectively.

The investigational, liver-directed agent, designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity, was well tolerated overall with a favorable safety profile.

“This is an exciting time for NASH because we are at the forefront of having a drug to treat these patients, and the benefit to patients promises to be huge,” asserted Stephen Harrison, MD, principal investigator of the MAESTRO studies, gastroenterologist and hepatologist, and founder of Pinnacle Clinical Research, San Antonio, in reporting 52-week results.

“This is the first treatment to achieve meaningful effects on both primary liver biopsy endpoints – disease activity and fibrosis – which is absolutely critical because fibrosis pertains to a worse prognosis. [These results] are reasonably likely to predict clinical benefit in a phase 3 trial in patients with NASH,” he added.
 

FDA-chosen endpoints likely to predict clinical outcomes

The ongoing 54-month, phase 3, registrational, double-blind, placebo-controlled trial involved taking liver biopsies from 966 patients at around 200 global sites. Biopsy readings were taken by two pathologists that were then combined into a single treatment effect. 

Patients had biopsy-proven NASH with fibrosis stages F1B, F2, or F3, the presence of three or more metabolic risk factors, a FibroScan vibration-controlled transient elastography (VCTE) score of 8.5 kPa or more, baseline MRI proton density fat fraction (MRI-PDFF) of 8% or more, and a NAS score of 4 or more with at least 1 in each NAS component. Around 65% of participants had type 2 diabetes, between 13% and 16% were taking glucagonlike peptide-1 (GLP-1) receptor agonists, and 46%-51% were taking statins.

Patients were randomized 1:1:1 to once-daily resmetirom 80 mg or 100 mg orally or to placebo and treated for 52 weeks.

Both liver histological improvement primary endpoints at week-52 were proposed by the U.S. Food and Drug Administration as reasonably likely to predict clinical benefit and as such support accelerated approval for the treatment of NASH with liver fibrosis. These primary endpoints were NASH resolution (ballooning 0, inflammation 0/1) with ≥ 2-point improvement in NAS with no worsening of fibrosis, and ≥ 1-stage reduction in fibrosis with no worsening of NAS.

Patients on resmetirom showed improvement in NAS components and fibrosis, and less worsening of NAS and fibrosis, compared with placebo. Percentage improvement was seen in 31%, 33%, and 15% of patients on 80 mg resmetirom, 100 mg resmetirom, and placebo respectively; no change was seen in 51%, 48%, and 51% respectively; and worsening was seen in 18%, 19%, and 34% respectively. 

The key secondary endpoint of LDL cholesterol lowering was also met. “There was a significant effect of resmetirom 80 and 100 mg on multiple atherogenic lipids/lipoproteins at both week 24 and 52,” reported Dr. Harrison. The 52-week percentage change from baseline in LDL cholesterol was –14%, –20%, and 0% for the 80-mg resmetirom group, the 100-mg group, and the placebo group respectively.

“We also saw a significant reduction in liver enzymes [alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase (GGT)] relative to placebo both in terms of percentage and absolute measures,” Dr. Harrison added. “[And] the change in liver enzymes was associated with the neutral biomarker that increases with resmetirom target engagement.”   

Resmetirom at both doses also resulted in a significant effect on MRI-PDFF and Fibroscan CAP. At week 52, 80 mg resmetirom, 100 mg, and placebo led to –42.1%, –51.4% and –10.4% change from baseline in MRI-PDFF, while Fibroscan CAP changed by –39.6%, –41.3%, and –14.5% respectively, reported Dr. Harrison. Liver volume dropped by –21.6% in the 80-mg group and –25.8% in the 100-mg group, compared with –1.0% in the placebo group. Spleen volume changed by –5.9%, –6.1%, and +3.2% respectively.

Liver stiffness, as measured by Fibroscan VCTE at week 52, changed from –3.7 KPa (F1B) to –2.0 KPa (F3) at 80 mg, and from –3.7 KPa (F1B) to –2.5 KPa (F2) and –3.3 KPa (F3) at the 100-mg dose.

Further analysis showed that improvements in fibrosis and NASH resolution were seen across all key subgroups, including baseline fibrosis stage (F2 or F3), NAS (< 6, ≥ 6), type 2 diabetes status, age (< 65 years, ≥ 65 years), and sex.
 

Safety profile

“The safety profile of resmetirom in the MAESTRO-NASH trial is consistent with previous phase 2/3 trials in which the most common adverse events were diarrhea and nausea at treatment initiation,” said Dr. Harrison.

Study discontinuations in the 100-mg group were increased relative to placebo during the first few weeks of treatment and were similar in all treatment groups up to 52 weeks. Discontinuations of patients on resmetirom 100 mg were mainly gastrointestinal related. 

Phase 2 results of the serial liver biopsy trial in adults with biopsy-confirmed NASH showed that resmetirom resolved NASH in a significantly greater percentage of patients and reduced liver enzymes, inflammatory biomarkers, and fibrosis, compared with placebo.

“We’ve been waiting for a long, long time for a therapy for these patients because until now, they have been challenged with lifestyle modifications to lose and maintain weight,” said Dr. Harrison. “There’s been a delay in identifying patients with this disease because we’ve had no treatment, but now that we are on the forefront of a treatment, it allows clinicians to open their minds to the possibility of identifying these patients.”

Dr. Harrison noted that a limitation of these data was the lack of clinical outcomes data to correlate with the biopsy data; however, the MAESTRO-NASH trial will continue to 54 months to accrue and evaluate clinical outcomes.

Milan Mishkovikj, MSc, board director of the European Liver Patients Association, Bitola, North Macedonia, commented on the potential benefit of this drug for patients. “Adhering to a healthy lifestyle is not always easy – not in all countries – so it’s encouraging to have a drug that hopefully is affordable and accessible to us. Now we need to manage the expectations of patients and caregivers.”

EASL’s vice secretary Aleksander Krag, MD, PhD, professor and head of hepatology at University of Southern Denmark, Odense, and Odense University Hospital remarked, “This is so exciting. This phase 3 trial is a real game-changer in the field of fatty liver disease because it has nearly 1,000 patients over 52 weeks of treatment.”

Madrigal Pharmaceuticals plans to submit an application to the FDA by end of the second quarter with a priority review.

Dr. Harrison is founder of Madrigal Pharmaceuticals. Dr. Krag has served as speaker for Norgine, Siemens, and Nordic Bioscience, and participated in advisory boards for Norgine and Siemens, all outside the submitted work. He receives royalties from Gyldendal and Echosens. Dr. Mishkovikj has declared no relevant financial relationships.

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

VIENNA – Resolution of nonalcoholic steatohepatitis (NASH), and reduction of fibrosis on liver biopsy were achieved with the oral, thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in patients with NASH and associated cirrhosis in a pivotal phase 3 clinical trial. The primary results of the MAESTRO-NASH (NCT03900429) trial were reported at the European Association for the Study of the Liver Congress 2023.

Both doses of resmetirom – 80 mg and 100 mg – met the primary endpoints of NASH resolution and no worsening of fibrosis on liver biopsy. The key secondary endpoint of LDL cholesterol lowering was also achieved with statistical significance. Likewise, improvement was seen in liver enzymes, and liver and spleen volumes.

In the intent-to-treat population, NASH resolution was achieved in 26% (P < .0001) in the 80-mg resmetirom group, 30% (P < .0001) in the 100-mg group, and 10% in those taking placebo. And ≥ 1-stage improvement in fibrosis with no worsening of the nonalcoholic fatty liver disease activity score (NAS) was achieved by 24% (P < .0002), 26% (P < .0001), and 14% in these groups respectively.

The investigational, liver-directed agent, designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity, was well tolerated overall with a favorable safety profile.

“This is an exciting time for NASH because we are at the forefront of having a drug to treat these patients, and the benefit to patients promises to be huge,” asserted Stephen Harrison, MD, principal investigator of the MAESTRO studies, gastroenterologist and hepatologist, and founder of Pinnacle Clinical Research, San Antonio, in reporting 52-week results.

“This is the first treatment to achieve meaningful effects on both primary liver biopsy endpoints – disease activity and fibrosis – which is absolutely critical because fibrosis pertains to a worse prognosis. [These results] are reasonably likely to predict clinical benefit in a phase 3 trial in patients with NASH,” he added.
 

FDA-chosen endpoints likely to predict clinical outcomes

The ongoing 54-month, phase 3, registrational, double-blind, placebo-controlled trial involved taking liver biopsies from 966 patients at around 200 global sites. Biopsy readings were taken by two pathologists that were then combined into a single treatment effect. 

Patients had biopsy-proven NASH with fibrosis stages F1B, F2, or F3, the presence of three or more metabolic risk factors, a FibroScan vibration-controlled transient elastography (VCTE) score of 8.5 kPa or more, baseline MRI proton density fat fraction (MRI-PDFF) of 8% or more, and a NAS score of 4 or more with at least 1 in each NAS component. Around 65% of participants had type 2 diabetes, between 13% and 16% were taking glucagonlike peptide-1 (GLP-1) receptor agonists, and 46%-51% were taking statins.

Patients were randomized 1:1:1 to once-daily resmetirom 80 mg or 100 mg orally or to placebo and treated for 52 weeks.

Both liver histological improvement primary endpoints at week-52 were proposed by the U.S. Food and Drug Administration as reasonably likely to predict clinical benefit and as such support accelerated approval for the treatment of NASH with liver fibrosis. These primary endpoints were NASH resolution (ballooning 0, inflammation 0/1) with ≥ 2-point improvement in NAS with no worsening of fibrosis, and ≥ 1-stage reduction in fibrosis with no worsening of NAS.

Patients on resmetirom showed improvement in NAS components and fibrosis, and less worsening of NAS and fibrosis, compared with placebo. Percentage improvement was seen in 31%, 33%, and 15% of patients on 80 mg resmetirom, 100 mg resmetirom, and placebo respectively; no change was seen in 51%, 48%, and 51% respectively; and worsening was seen in 18%, 19%, and 34% respectively. 

The key secondary endpoint of LDL cholesterol lowering was also met. “There was a significant effect of resmetirom 80 and 100 mg on multiple atherogenic lipids/lipoproteins at both week 24 and 52,” reported Dr. Harrison. The 52-week percentage change from baseline in LDL cholesterol was –14%, –20%, and 0% for the 80-mg resmetirom group, the 100-mg group, and the placebo group respectively.

“We also saw a significant reduction in liver enzymes [alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase (GGT)] relative to placebo both in terms of percentage and absolute measures,” Dr. Harrison added. “[And] the change in liver enzymes was associated with the neutral biomarker that increases with resmetirom target engagement.”   

Resmetirom at both doses also resulted in a significant effect on MRI-PDFF and Fibroscan CAP. At week 52, 80 mg resmetirom, 100 mg, and placebo led to –42.1%, –51.4% and –10.4% change from baseline in MRI-PDFF, while Fibroscan CAP changed by –39.6%, –41.3%, and –14.5% respectively, reported Dr. Harrison. Liver volume dropped by –21.6% in the 80-mg group and –25.8% in the 100-mg group, compared with –1.0% in the placebo group. Spleen volume changed by –5.9%, –6.1%, and +3.2% respectively.

Liver stiffness, as measured by Fibroscan VCTE at week 52, changed from –3.7 KPa (F1B) to –2.0 KPa (F3) at 80 mg, and from –3.7 KPa (F1B) to –2.5 KPa (F2) and –3.3 KPa (F3) at the 100-mg dose.

Further analysis showed that improvements in fibrosis and NASH resolution were seen across all key subgroups, including baseline fibrosis stage (F2 or F3), NAS (< 6, ≥ 6), type 2 diabetes status, age (< 65 years, ≥ 65 years), and sex.
 

Safety profile

“The safety profile of resmetirom in the MAESTRO-NASH trial is consistent with previous phase 2/3 trials in which the most common adverse events were diarrhea and nausea at treatment initiation,” said Dr. Harrison.

Study discontinuations in the 100-mg group were increased relative to placebo during the first few weeks of treatment and were similar in all treatment groups up to 52 weeks. Discontinuations of patients on resmetirom 100 mg were mainly gastrointestinal related. 

Phase 2 results of the serial liver biopsy trial in adults with biopsy-confirmed NASH showed that resmetirom resolved NASH in a significantly greater percentage of patients and reduced liver enzymes, inflammatory biomarkers, and fibrosis, compared with placebo.

“We’ve been waiting for a long, long time for a therapy for these patients because until now, they have been challenged with lifestyle modifications to lose and maintain weight,” said Dr. Harrison. “There’s been a delay in identifying patients with this disease because we’ve had no treatment, but now that we are on the forefront of a treatment, it allows clinicians to open their minds to the possibility of identifying these patients.”

Dr. Harrison noted that a limitation of these data was the lack of clinical outcomes data to correlate with the biopsy data; however, the MAESTRO-NASH trial will continue to 54 months to accrue and evaluate clinical outcomes.

Milan Mishkovikj, MSc, board director of the European Liver Patients Association, Bitola, North Macedonia, commented on the potential benefit of this drug for patients. “Adhering to a healthy lifestyle is not always easy – not in all countries – so it’s encouraging to have a drug that hopefully is affordable and accessible to us. Now we need to manage the expectations of patients and caregivers.”

EASL’s vice secretary Aleksander Krag, MD, PhD, professor and head of hepatology at University of Southern Denmark, Odense, and Odense University Hospital remarked, “This is so exciting. This phase 3 trial is a real game-changer in the field of fatty liver disease because it has nearly 1,000 patients over 52 weeks of treatment.”

Madrigal Pharmaceuticals plans to submit an application to the FDA by end of the second quarter with a priority review.

Dr. Harrison is founder of Madrigal Pharmaceuticals. Dr. Krag has served as speaker for Norgine, Siemens, and Nordic Bioscience, and participated in advisory boards for Norgine and Siemens, all outside the submitted work. He receives royalties from Gyldendal and Echosens. Dr. Mishkovikj has declared no relevant financial relationships.

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

VIENNA – Resolution of nonalcoholic steatohepatitis (NASH), and reduction of fibrosis on liver biopsy were achieved with the oral, thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in patients with NASH and associated cirrhosis in a pivotal phase 3 clinical trial. The primary results of the MAESTRO-NASH (NCT03900429) trial were reported at the European Association for the Study of the Liver Congress 2023.

Both doses of resmetirom – 80 mg and 100 mg – met the primary endpoints of NASH resolution and no worsening of fibrosis on liver biopsy. The key secondary endpoint of LDL cholesterol lowering was also achieved with statistical significance. Likewise, improvement was seen in liver enzymes, and liver and spleen volumes.

In the intent-to-treat population, NASH resolution was achieved in 26% (P < .0001) in the 80-mg resmetirom group, 30% (P < .0001) in the 100-mg group, and 10% in those taking placebo. And ≥ 1-stage improvement in fibrosis with no worsening of the nonalcoholic fatty liver disease activity score (NAS) was achieved by 24% (P < .0002), 26% (P < .0001), and 14% in these groups respectively.

The investigational, liver-directed agent, designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity, was well tolerated overall with a favorable safety profile.

“This is an exciting time for NASH because we are at the forefront of having a drug to treat these patients, and the benefit to patients promises to be huge,” asserted Stephen Harrison, MD, principal investigator of the MAESTRO studies, gastroenterologist and hepatologist, and founder of Pinnacle Clinical Research, San Antonio, in reporting 52-week results.

“This is the first treatment to achieve meaningful effects on both primary liver biopsy endpoints – disease activity and fibrosis – which is absolutely critical because fibrosis pertains to a worse prognosis. [These results] are reasonably likely to predict clinical benefit in a phase 3 trial in patients with NASH,” he added.
 

FDA-chosen endpoints likely to predict clinical outcomes

The ongoing 54-month, phase 3, registrational, double-blind, placebo-controlled trial involved taking liver biopsies from 966 patients at around 200 global sites. Biopsy readings were taken by two pathologists that were then combined into a single treatment effect. 

Patients had biopsy-proven NASH with fibrosis stages F1B, F2, or F3, the presence of three or more metabolic risk factors, a FibroScan vibration-controlled transient elastography (VCTE) score of 8.5 kPa or more, baseline MRI proton density fat fraction (MRI-PDFF) of 8% or more, and a NAS score of 4 or more with at least 1 in each NAS component. Around 65% of participants had type 2 diabetes, between 13% and 16% were taking glucagonlike peptide-1 (GLP-1) receptor agonists, and 46%-51% were taking statins.

Patients were randomized 1:1:1 to once-daily resmetirom 80 mg or 100 mg orally or to placebo and treated for 52 weeks.

Both liver histological improvement primary endpoints at week-52 were proposed by the U.S. Food and Drug Administration as reasonably likely to predict clinical benefit and as such support accelerated approval for the treatment of NASH with liver fibrosis. These primary endpoints were NASH resolution (ballooning 0, inflammation 0/1) with ≥ 2-point improvement in NAS with no worsening of fibrosis, and ≥ 1-stage reduction in fibrosis with no worsening of NAS.

Patients on resmetirom showed improvement in NAS components and fibrosis, and less worsening of NAS and fibrosis, compared with placebo. Percentage improvement was seen in 31%, 33%, and 15% of patients on 80 mg resmetirom, 100 mg resmetirom, and placebo respectively; no change was seen in 51%, 48%, and 51% respectively; and worsening was seen in 18%, 19%, and 34% respectively. 

The key secondary endpoint of LDL cholesterol lowering was also met. “There was a significant effect of resmetirom 80 and 100 mg on multiple atherogenic lipids/lipoproteins at both week 24 and 52,” reported Dr. Harrison. The 52-week percentage change from baseline in LDL cholesterol was –14%, –20%, and 0% for the 80-mg resmetirom group, the 100-mg group, and the placebo group respectively.

“We also saw a significant reduction in liver enzymes [alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase (GGT)] relative to placebo both in terms of percentage and absolute measures,” Dr. Harrison added. “[And] the change in liver enzymes was associated with the neutral biomarker that increases with resmetirom target engagement.”   

Resmetirom at both doses also resulted in a significant effect on MRI-PDFF and Fibroscan CAP. At week 52, 80 mg resmetirom, 100 mg, and placebo led to –42.1%, –51.4% and –10.4% change from baseline in MRI-PDFF, while Fibroscan CAP changed by –39.6%, –41.3%, and –14.5% respectively, reported Dr. Harrison. Liver volume dropped by –21.6% in the 80-mg group and –25.8% in the 100-mg group, compared with –1.0% in the placebo group. Spleen volume changed by –5.9%, –6.1%, and +3.2% respectively.

Liver stiffness, as measured by Fibroscan VCTE at week 52, changed from –3.7 KPa (F1B) to –2.0 KPa (F3) at 80 mg, and from –3.7 KPa (F1B) to –2.5 KPa (F2) and –3.3 KPa (F3) at the 100-mg dose.

Further analysis showed that improvements in fibrosis and NASH resolution were seen across all key subgroups, including baseline fibrosis stage (F2 or F3), NAS (< 6, ≥ 6), type 2 diabetes status, age (< 65 years, ≥ 65 years), and sex.
 

Safety profile

“The safety profile of resmetirom in the MAESTRO-NASH trial is consistent with previous phase 2/3 trials in which the most common adverse events were diarrhea and nausea at treatment initiation,” said Dr. Harrison.

Study discontinuations in the 100-mg group were increased relative to placebo during the first few weeks of treatment and were similar in all treatment groups up to 52 weeks. Discontinuations of patients on resmetirom 100 mg were mainly gastrointestinal related. 

Phase 2 results of the serial liver biopsy trial in adults with biopsy-confirmed NASH showed that resmetirom resolved NASH in a significantly greater percentage of patients and reduced liver enzymes, inflammatory biomarkers, and fibrosis, compared with placebo.

“We’ve been waiting for a long, long time for a therapy for these patients because until now, they have been challenged with lifestyle modifications to lose and maintain weight,” said Dr. Harrison. “There’s been a delay in identifying patients with this disease because we’ve had no treatment, but now that we are on the forefront of a treatment, it allows clinicians to open their minds to the possibility of identifying these patients.”

Dr. Harrison noted that a limitation of these data was the lack of clinical outcomes data to correlate with the biopsy data; however, the MAESTRO-NASH trial will continue to 54 months to accrue and evaluate clinical outcomes.

Milan Mishkovikj, MSc, board director of the European Liver Patients Association, Bitola, North Macedonia, commented on the potential benefit of this drug for patients. “Adhering to a healthy lifestyle is not always easy – not in all countries – so it’s encouraging to have a drug that hopefully is affordable and accessible to us. Now we need to manage the expectations of patients and caregivers.”

EASL’s vice secretary Aleksander Krag, MD, PhD, professor and head of hepatology at University of Southern Denmark, Odense, and Odense University Hospital remarked, “This is so exciting. This phase 3 trial is a real game-changer in the field of fatty liver disease because it has nearly 1,000 patients over 52 weeks of treatment.”

Madrigal Pharmaceuticals plans to submit an application to the FDA by end of the second quarter with a priority review.

Dr. Harrison is founder of Madrigal Pharmaceuticals. Dr. Krag has served as speaker for Norgine, Siemens, and Nordic Bioscience, and participated in advisory boards for Norgine and Siemens, all outside the submitted work. He receives royalties from Gyldendal and Echosens. Dr. Mishkovikj has declared no relevant financial relationships.

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

People with nonalcoholic fatty liver disease (NAFLD) are more likely to develop severe infections requiring hospitalization, according to findings from a large Swedish cohort study.

The increased risk was equal to one extra severe infection in every six patients with NAFLD by 20 years after diagnosis, wrote Fahim Ebrahimi, MD, of the Karolinska Institute in Stockholm, and coauthors.

“Accumulating evidence suggests that NAFLD can affect multiple organ systems, which is not surprising, as the liver has multiple functions – regulating metabolism and being a central organ of the immune system,” Dr. Ebrahimi said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

“Up to a fifth of cells in the liver are immune cells that process numerous antigens and pathogens from the gastrointestinal tract,” Dr. Ebrahimi noted. “We were intrigued by experimental studies showing that, in NAFLD, many of these key immune cells become dysfunctional at various levels, which may affect disease progression, but at the same time also increase the susceptibility to viral, bacterial, and fungal infections.”

Patients with NAFLD have metabolic risk factors known to increase infection risk, but a smaller study by a different research group had found that NAFLD could independently predispose patients to bacterial infections.

To further explore a connection between NAFLD and infection risk, the researchers looked at data for 12,133 Swedish adults with simple steatosis, nonfibrotic steatohepatitis, noncirrhotic fibrosis, or cirrhosis caused by NAFLD confirmed by liver biopsies performed between 1969 and 2017.

Each patient was matched to five or more contemporary controls from the general population by age, sex, and region of residence. The authors conducted an additional analysis that also adjusted for education, country of birth, and baseline clinical comorbidities, including diabetes, obesity, dyslipidemia, and hypertension, as well as hospitalization preceding the biopsy and chronic obstructive pulmonary disease.

The primary endpoint was severe infections requiring hospital admission. Secondary endpoints included seven prespecified infection subgroups: sepsis; respiratory tract; most gastrointestinal infections; bacterial peritonitis; urogenital; muscle, skin, and soft tissue; and other infections.
 

Elevated risk at all NAFLD stages

Dr. Ebrahimi and colleagues found that over a median follow-up of 14 years, patients with NAFLD had a higher incidence of severe infections – most often respiratory or urinary tract infections – compared with those without NAFLD (32% vs. 17%, respectively).

Biopsy-confirmed NAFLD was also associated with a 71% higher hazard and a 20-year absolute excess risk of 17.3% for severe infections requiring hospital admission versus comparators. The elevated risk showed up in patients with steatosis and increased with the severity of NAFLD. Simple steatosis saw a 64% higher risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.55-1.73), whereas patients with cirrhosis saw a more than twofold higher risk, compared with controls (aHR, 2.32; 95% CI, 1.92-2.82).

When Dr. Ebrahimi and colleagues adjusted for parameters of the metabolic syndrome, they found an independent increased risk for severe infection. For patients with NAFLD, the increased risk may come from greater susceptibility to infections in general or to a more severe course of infections.

“Our study clearly demonstrates the complexity and high disease burden associated with NAFLD,” Dr. Ebrahimi said. “We are beginning to understand the different layers involved and will eventually move away from a liver-centric view to a more holistic view of the disease.”

Clinicians caring for patients with NAFLD need to be aware of the increased risk for infection, Dr. Ebrahimi said. They also should assess their patients’ vaccination status, and seek to control modifiable risk factors, such as diabetes.

Nancy Reau, MD, of Rush University, Chicago, described the study’s message as important.

“Patients with NAFLD and advancing liver disease are at risk for severe infections,” Dr. Reau said. “When we consider the fact that patients with advanced liver disease tend to die from infectious complications, awareness leading to early recognition and efficient treatment is imperative.”

The authors acknowledged the following limitations: only severe infections requiring hospitalization could be captured; whether infection led to decompensation or vice versa among patients with cirrhosis could not be determined; and detailed data on smoking, alcohol, vaccinations, body mass, and other potentially relevant measures were not available.

The Swiss National Science Foundation, Syskonen Svensson Foundation, and Bengt Ihre Foundation provided grants to Dr. Ebrahimi or coauthors. One coauthor disclosed previous research funding from Janssen and MSD. Dr. Reau disclosed receiving research support and consulting fees from AbbVie and Gilead, as well as consulting fees from Arbutus, Intercept, and Salix.

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

People with nonalcoholic fatty liver disease (NAFLD) are more likely to develop severe infections requiring hospitalization, according to findings from a large Swedish cohort study.

The increased risk was equal to one extra severe infection in every six patients with NAFLD by 20 years after diagnosis, wrote Fahim Ebrahimi, MD, of the Karolinska Institute in Stockholm, and coauthors.

“Accumulating evidence suggests that NAFLD can affect multiple organ systems, which is not surprising, as the liver has multiple functions – regulating metabolism and being a central organ of the immune system,” Dr. Ebrahimi said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

“Up to a fifth of cells in the liver are immune cells that process numerous antigens and pathogens from the gastrointestinal tract,” Dr. Ebrahimi noted. “We were intrigued by experimental studies showing that, in NAFLD, many of these key immune cells become dysfunctional at various levels, which may affect disease progression, but at the same time also increase the susceptibility to viral, bacterial, and fungal infections.”

Patients with NAFLD have metabolic risk factors known to increase infection risk, but a smaller study by a different research group had found that NAFLD could independently predispose patients to bacterial infections.

To further explore a connection between NAFLD and infection risk, the researchers looked at data for 12,133 Swedish adults with simple steatosis, nonfibrotic steatohepatitis, noncirrhotic fibrosis, or cirrhosis caused by NAFLD confirmed by liver biopsies performed between 1969 and 2017.

Each patient was matched to five or more contemporary controls from the general population by age, sex, and region of residence. The authors conducted an additional analysis that also adjusted for education, country of birth, and baseline clinical comorbidities, including diabetes, obesity, dyslipidemia, and hypertension, as well as hospitalization preceding the biopsy and chronic obstructive pulmonary disease.

The primary endpoint was severe infections requiring hospital admission. Secondary endpoints included seven prespecified infection subgroups: sepsis; respiratory tract; most gastrointestinal infections; bacterial peritonitis; urogenital; muscle, skin, and soft tissue; and other infections.
 

Elevated risk at all NAFLD stages

Dr. Ebrahimi and colleagues found that over a median follow-up of 14 years, patients with NAFLD had a higher incidence of severe infections – most often respiratory or urinary tract infections – compared with those without NAFLD (32% vs. 17%, respectively).

Biopsy-confirmed NAFLD was also associated with a 71% higher hazard and a 20-year absolute excess risk of 17.3% for severe infections requiring hospital admission versus comparators. The elevated risk showed up in patients with steatosis and increased with the severity of NAFLD. Simple steatosis saw a 64% higher risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.55-1.73), whereas patients with cirrhosis saw a more than twofold higher risk, compared with controls (aHR, 2.32; 95% CI, 1.92-2.82).

When Dr. Ebrahimi and colleagues adjusted for parameters of the metabolic syndrome, they found an independent increased risk for severe infection. For patients with NAFLD, the increased risk may come from greater susceptibility to infections in general or to a more severe course of infections.

“Our study clearly demonstrates the complexity and high disease burden associated with NAFLD,” Dr. Ebrahimi said. “We are beginning to understand the different layers involved and will eventually move away from a liver-centric view to a more holistic view of the disease.”

Clinicians caring for patients with NAFLD need to be aware of the increased risk for infection, Dr. Ebrahimi said. They also should assess their patients’ vaccination status, and seek to control modifiable risk factors, such as diabetes.

Nancy Reau, MD, of Rush University, Chicago, described the study’s message as important.

“Patients with NAFLD and advancing liver disease are at risk for severe infections,” Dr. Reau said. “When we consider the fact that patients with advanced liver disease tend to die from infectious complications, awareness leading to early recognition and efficient treatment is imperative.”

The authors acknowledged the following limitations: only severe infections requiring hospitalization could be captured; whether infection led to decompensation or vice versa among patients with cirrhosis could not be determined; and detailed data on smoking, alcohol, vaccinations, body mass, and other potentially relevant measures were not available.

The Swiss National Science Foundation, Syskonen Svensson Foundation, and Bengt Ihre Foundation provided grants to Dr. Ebrahimi or coauthors. One coauthor disclosed previous research funding from Janssen and MSD. Dr. Reau disclosed receiving research support and consulting fees from AbbVie and Gilead, as well as consulting fees from Arbutus, Intercept, and Salix.

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

People with nonalcoholic fatty liver disease (NAFLD) are more likely to develop severe infections requiring hospitalization, according to findings from a large Swedish cohort study.

The increased risk was equal to one extra severe infection in every six patients with NAFLD by 20 years after diagnosis, wrote Fahim Ebrahimi, MD, of the Karolinska Institute in Stockholm, and coauthors.

“Accumulating evidence suggests that NAFLD can affect multiple organ systems, which is not surprising, as the liver has multiple functions – regulating metabolism and being a central organ of the immune system,” Dr. Ebrahimi said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

“Up to a fifth of cells in the liver are immune cells that process numerous antigens and pathogens from the gastrointestinal tract,” Dr. Ebrahimi noted. “We were intrigued by experimental studies showing that, in NAFLD, many of these key immune cells become dysfunctional at various levels, which may affect disease progression, but at the same time also increase the susceptibility to viral, bacterial, and fungal infections.”

Patients with NAFLD have metabolic risk factors known to increase infection risk, but a smaller study by a different research group had found that NAFLD could independently predispose patients to bacterial infections.

To further explore a connection between NAFLD and infection risk, the researchers looked at data for 12,133 Swedish adults with simple steatosis, nonfibrotic steatohepatitis, noncirrhotic fibrosis, or cirrhosis caused by NAFLD confirmed by liver biopsies performed between 1969 and 2017.

Each patient was matched to five or more contemporary controls from the general population by age, sex, and region of residence. The authors conducted an additional analysis that also adjusted for education, country of birth, and baseline clinical comorbidities, including diabetes, obesity, dyslipidemia, and hypertension, as well as hospitalization preceding the biopsy and chronic obstructive pulmonary disease.

The primary endpoint was severe infections requiring hospital admission. Secondary endpoints included seven prespecified infection subgroups: sepsis; respiratory tract; most gastrointestinal infections; bacterial peritonitis; urogenital; muscle, skin, and soft tissue; and other infections.
 

Elevated risk at all NAFLD stages

Dr. Ebrahimi and colleagues found that over a median follow-up of 14 years, patients with NAFLD had a higher incidence of severe infections – most often respiratory or urinary tract infections – compared with those without NAFLD (32% vs. 17%, respectively).

Biopsy-confirmed NAFLD was also associated with a 71% higher hazard and a 20-year absolute excess risk of 17.3% for severe infections requiring hospital admission versus comparators. The elevated risk showed up in patients with steatosis and increased with the severity of NAFLD. Simple steatosis saw a 64% higher risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.55-1.73), whereas patients with cirrhosis saw a more than twofold higher risk, compared with controls (aHR, 2.32; 95% CI, 1.92-2.82).

When Dr. Ebrahimi and colleagues adjusted for parameters of the metabolic syndrome, they found an independent increased risk for severe infection. For patients with NAFLD, the increased risk may come from greater susceptibility to infections in general or to a more severe course of infections.

“Our study clearly demonstrates the complexity and high disease burden associated with NAFLD,” Dr. Ebrahimi said. “We are beginning to understand the different layers involved and will eventually move away from a liver-centric view to a more holistic view of the disease.”

Clinicians caring for patients with NAFLD need to be aware of the increased risk for infection, Dr. Ebrahimi said. They also should assess their patients’ vaccination status, and seek to control modifiable risk factors, such as diabetes.

Nancy Reau, MD, of Rush University, Chicago, described the study’s message as important.

“Patients with NAFLD and advancing liver disease are at risk for severe infections,” Dr. Reau said. “When we consider the fact that patients with advanced liver disease tend to die from infectious complications, awareness leading to early recognition and efficient treatment is imperative.”

The authors acknowledged the following limitations: only severe infections requiring hospitalization could be captured; whether infection led to decompensation or vice versa among patients with cirrhosis could not be determined; and detailed data on smoking, alcohol, vaccinations, body mass, and other potentially relevant measures were not available.

The Swiss National Science Foundation, Syskonen Svensson Foundation, and Bengt Ihre Foundation provided grants to Dr. Ebrahimi or coauthors. One coauthor disclosed previous research funding from Janssen and MSD. Dr. Reau disclosed receiving research support and consulting fees from AbbVie and Gilead, as well as consulting fees from Arbutus, Intercept, and Salix.

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

Having a fatty liver raises a patient’s risk of colorectal cancer liver metastasis via an immunosuppressive tumor microenvironment, yes-associated protein (YAP) signaling, and extracellular vesicle-microRNAs, according to the authors of new research.

These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.

“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”

To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.

Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.

“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”

One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.

Having a fatty liver raises a patient’s risk of colorectal cancer liver metastasis via an immunosuppressive tumor microenvironment, yes-associated protein (YAP) signaling, and extracellular vesicle-microRNAs, according to the authors of new research.

These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.

“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”

To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.

Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.

“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”

One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.

Having a fatty liver raises a patient’s risk of colorectal cancer liver metastasis via an immunosuppressive tumor microenvironment, yes-associated protein (YAP) signaling, and extracellular vesicle-microRNAs, according to the authors of new research.

These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.

“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”

To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.

Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.

“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”

One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.

Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.

The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.

“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.

Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.

The prevalence of liver disease in women of reproductive age is rising, leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.

The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.

“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
 

Similar outcomes

Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.

The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.

The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.

Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.

A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.

“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
 

Data for patient counseling

The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.

“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.

The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.

Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.

The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.

“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
 

Differences in oocyte numbers

Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.

“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”

The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.

“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”

As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.

Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.

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

Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.

The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.

“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.

Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.

The prevalence of liver disease in women of reproductive age is rising, leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.

The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.

“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
 

Similar outcomes

Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.

The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.

The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.

Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.

A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.

“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
 

Data for patient counseling

The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.

“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.

The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.

Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.

The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.

“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
 

Differences in oocyte numbers

Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.

“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”

The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.

“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”

As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.

Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.

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

Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.

The study, published online in the American Journal of Gastroenterology, compared women with and those without chronic liver disease who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.

“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers wrote.

Women with liver disease may experience impaired fertility. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.

The prevalence of liver disease in women of reproductive age is rising, leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease,” the authors wrote.

The literature about ART treatment outcomes for women with liver disease was limited and may not reflect current therapy protocols, researchers found.

“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with liver disease,” they wrote.
 

Similar outcomes

Researchers identified 295 women with liver disease (mean age, 37.8 ± 5.2 years) who underwent 1,033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.

The control group consisted of all the women at the treatment center without liver disease who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.

The mean age of the patients with liver disease was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with liver disease, and there were differences in baseline levels of selected hormones, compared with control participants. In addition, among those with liver disease, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs. 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs. 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs. 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs. 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs. 2.7 ± 2.4; P < .05), compared with control participants.

Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.

A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the liver disease group and the control group.

“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers wrote.
 

Data for patient counseling

The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai, New York, said.

“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she said.

The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in liver diseases at the Icahn School.

Women with liver disease whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.

The study’s findings are “encouraging,” said Monika Sarkar, MD, associate professor of medicine in gastroenterology at the University of California, San Francisco.

“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients – namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
 

Differences in oocyte numbers

Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the liver disease group, compared with 609 in the control group, noted Dr. Sarkar, who was not involved with the study.

“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Dr. Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”

The data suggest that fewer eggs are retrieved per cycle from patients with liver disease, “which ultimately will lower the success per cycle,” Dr. Sarkar said.

“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”

As more research on ART outcomes in women with liver disease is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Dr. Sarkar said.

Ms. Lee, Dr. Kushner, and Dr. Sarkar report no relevant financial relationships.

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