Hepatology

Living-donor liver transplant recipients gained an additional 13-17 years of life, compared with patients who remained on the wait list, according to a retrospective case-control study.

The data suggest that the life-years gained are comparable to or greater than those conferred by either other lifesaving procedures or liver transplant from a deceased donor, wrote the researchers, led by Whitney Jackson, MD, assistant professor of gastroenterology and medical director of living-donor liver transplantation at the University of Colorado Anschutz Medical Campus.

“Despite the acceptance of living-donor liver transplant as a lifesaving procedure for end-stage liver disease, it remains underused in the United States,” the authors wrote in JAMA Surgery. “This study’s findings challenge current perceptions regarding when the survival benefit of a living-donor transplant occurs.”

Dr. Jackson and colleagues conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database for 119,275 U.S. liver transplant candidates and recipients from January 2012 to September 2021. They assessed the survival benefit, life-years saved, and the Model for End-Stage Liver Disease incorporating sodium levels (MELD-Na) score at which the survival benefit was obtained, compared with those who remained on the wait list.

The research team included 116,455 liver transplant candidates who were 18 and older and assigned to the wait list, as well as 2,820 patients who received a living-donor liver transplant. Patients listed for retransplant or multiorgan transplant were excluded, as were those with prior kidney or liver transplants.

The mean age of the study participants was 55 years, and 63% were men. Overall, 70.2% were White, 15.8% were Hispanic or Latinx, 8.2% were Black or African American, 4.3% were Asian, 0.9% were American Indian or Alaska Native, and 0.2% were Native Hawaiian or Pacific Islander. The most common etiologies were alcoholic cirrhosis (23.8%) and nonalcoholic steatohepatitis (15.9%).

Compared with patients on the wait list, recipients of a living-donor liver transplant were younger, more often women, more educated, and more often White. A greater proportion of transplant recipients had a primary etiology of nonalcoholic steatohepatitis (19.8%) and cholestatic liver disease (24.1%). At wait list placement, one-third of candidates had a MELD-Na score of 14 or higher.

The research team found a significant survival benefit for patients receiving a living-donor liver transplant based on mortality risk and survival scores. The survival benefit was significant at a MELD-Na score as low as 11, with a 34% decrease(95% confidence interval [CI], 17.4%-52.0%) in mortality compared with the wait list. In addition, mortality risk models confirmed a survival benefit for patients with a MELD-Na score of 11 or higher at 1 year after transplant (adjusted hazard ratio, 0.64; 95% CI, 0.47-0.88; P = .006). At a MELD-Na score of 14-16, mortality decreased by about 50% (aHR, 0.47; 95% CI, 0.34-0.66; P < .001).

The probability of death from a living-donor liver transplant for patients with very low MELD-Na scores (between 6 and 10) was greater than that for patients on the wait list for the first 259 days, at which point the risk of death for both groups was equal. At 471 days, the probability of survival in both groups was equal. As the MELD-Na score increased, both the time to equal risk of death and the time to equal survival decreased, demonstrating that the survival benefit occurs much earlier for patients with a higher MELD-Na score.

Analysis of life-years from transplant showed living-donor transplant recipients gained 13-17 life-years compared to those who didn’t receive one.

“Living-donor liver transplantation is a valuable yet underutilized strategy to address the significant organ shortage and long waiting times on the transplant list in the U.S.,” said Renu Dhanasekaran, MD, PhD, assistant professor of gastroenterology and hepatology at Stanford (Calif.) University.

Dr. Dhanasekaran, who wasn’t involved with this study, also welcomed the finding that living-donor liver transplantation can benefit patients with low MELD-Na scores, even below the expected cutoff at 15. According to the study authors, previous research had suggested benefit would be seen only at MELD-Na 15 and above.

“In my practice, I have several patients whose symptoms are out of proportion to their MELD score, and data like this will convince them and their potential donors to avail a transplant at an earlier stage,” she said.

The findings challenge the current paradigm around the timing of referral for a liver transplant and may have ramifications for allocation policies for deceased donors, the study authors wrote. The data can also help to contextualize risk-benefit discussions for donors and recipients.

“Donating a part of one’s liver to save a patient suffering from end-stage liver disease is an incredible act of selfless love,” Dr. Dhanasekaran said. “I hope strong positive data from studies like this one encourage more donors, patients, and transplant centers to expand the use of [living-donor liver transplant].”

The authors reported no grant support or funding sources for this study. One author disclosed being married to the current chair of the United Network for Organ Sharing’s Liver and Intestinal Organ Transplantation Committee. No other conflicts of interest were reported. Dr. Dhanasekaran reported no relevant disclosures.

Living-donor liver transplant recipients gained an additional 13-17 years of life, compared with patients who remained on the wait list, according to a retrospective case-control study.

The data suggest that the life-years gained are comparable to or greater than those conferred by either other lifesaving procedures or liver transplant from a deceased donor, wrote the researchers, led by Whitney Jackson, MD, assistant professor of gastroenterology and medical director of living-donor liver transplantation at the University of Colorado Anschutz Medical Campus.

“Despite the acceptance of living-donor liver transplant as a lifesaving procedure for end-stage liver disease, it remains underused in the United States,” the authors wrote in JAMA Surgery. “This study’s findings challenge current perceptions regarding when the survival benefit of a living-donor transplant occurs.”

Dr. Jackson and colleagues conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database for 119,275 U.S. liver transplant candidates and recipients from January 2012 to September 2021. They assessed the survival benefit, life-years saved, and the Model for End-Stage Liver Disease incorporating sodium levels (MELD-Na) score at which the survival benefit was obtained, compared with those who remained on the wait list.

The research team included 116,455 liver transplant candidates who were 18 and older and assigned to the wait list, as well as 2,820 patients who received a living-donor liver transplant. Patients listed for retransplant or multiorgan transplant were excluded, as were those with prior kidney or liver transplants.

The mean age of the study participants was 55 years, and 63% were men. Overall, 70.2% were White, 15.8% were Hispanic or Latinx, 8.2% were Black or African American, 4.3% were Asian, 0.9% were American Indian or Alaska Native, and 0.2% were Native Hawaiian or Pacific Islander. The most common etiologies were alcoholic cirrhosis (23.8%) and nonalcoholic steatohepatitis (15.9%).

Compared with patients on the wait list, recipients of a living-donor liver transplant were younger, more often women, more educated, and more often White. A greater proportion of transplant recipients had a primary etiology of nonalcoholic steatohepatitis (19.8%) and cholestatic liver disease (24.1%). At wait list placement, one-third of candidates had a MELD-Na score of 14 or higher.

The research team found a significant survival benefit for patients receiving a living-donor liver transplant based on mortality risk and survival scores. The survival benefit was significant at a MELD-Na score as low as 11, with a 34% decrease(95% confidence interval [CI], 17.4%-52.0%) in mortality compared with the wait list. In addition, mortality risk models confirmed a survival benefit for patients with a MELD-Na score of 11 or higher at 1 year after transplant (adjusted hazard ratio, 0.64; 95% CI, 0.47-0.88; P = .006). At a MELD-Na score of 14-16, mortality decreased by about 50% (aHR, 0.47; 95% CI, 0.34-0.66; P < .001).

The probability of death from a living-donor liver transplant for patients with very low MELD-Na scores (between 6 and 10) was greater than that for patients on the wait list for the first 259 days, at which point the risk of death for both groups was equal. At 471 days, the probability of survival in both groups was equal. As the MELD-Na score increased, both the time to equal risk of death and the time to equal survival decreased, demonstrating that the survival benefit occurs much earlier for patients with a higher MELD-Na score.

Analysis of life-years from transplant showed living-donor transplant recipients gained 13-17 life-years compared to those who didn’t receive one.

“Living-donor liver transplantation is a valuable yet underutilized strategy to address the significant organ shortage and long waiting times on the transplant list in the U.S.,” said Renu Dhanasekaran, MD, PhD, assistant professor of gastroenterology and hepatology at Stanford (Calif.) University.

Dr. Dhanasekaran, who wasn’t involved with this study, also welcomed the finding that living-donor liver transplantation can benefit patients with low MELD-Na scores, even below the expected cutoff at 15. According to the study authors, previous research had suggested benefit would be seen only at MELD-Na 15 and above.

“In my practice, I have several patients whose symptoms are out of proportion to their MELD score, and data like this will convince them and their potential donors to avail a transplant at an earlier stage,” she said.

The findings challenge the current paradigm around the timing of referral for a liver transplant and may have ramifications for allocation policies for deceased donors, the study authors wrote. The data can also help to contextualize risk-benefit discussions for donors and recipients.

“Donating a part of one’s liver to save a patient suffering from end-stage liver disease is an incredible act of selfless love,” Dr. Dhanasekaran said. “I hope strong positive data from studies like this one encourage more donors, patients, and transplant centers to expand the use of [living-donor liver transplant].”

The authors reported no grant support or funding sources for this study. One author disclosed being married to the current chair of the United Network for Organ Sharing’s Liver and Intestinal Organ Transplantation Committee. No other conflicts of interest were reported. Dr. Dhanasekaran reported no relevant disclosures.

Living-donor liver transplant recipients gained an additional 13-17 years of life, compared with patients who remained on the wait list, according to a retrospective case-control study.

The data suggest that the life-years gained are comparable to or greater than those conferred by either other lifesaving procedures or liver transplant from a deceased donor, wrote the researchers, led by Whitney Jackson, MD, assistant professor of gastroenterology and medical director of living-donor liver transplantation at the University of Colorado Anschutz Medical Campus.

“Despite the acceptance of living-donor liver transplant as a lifesaving procedure for end-stage liver disease, it remains underused in the United States,” the authors wrote in JAMA Surgery. “This study’s findings challenge current perceptions regarding when the survival benefit of a living-donor transplant occurs.”

Dr. Jackson and colleagues conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database for 119,275 U.S. liver transplant candidates and recipients from January 2012 to September 2021. They assessed the survival benefit, life-years saved, and the Model for End-Stage Liver Disease incorporating sodium levels (MELD-Na) score at which the survival benefit was obtained, compared with those who remained on the wait list.

The research team included 116,455 liver transplant candidates who were 18 and older and assigned to the wait list, as well as 2,820 patients who received a living-donor liver transplant. Patients listed for retransplant or multiorgan transplant were excluded, as were those with prior kidney or liver transplants.

The mean age of the study participants was 55 years, and 63% were men. Overall, 70.2% were White, 15.8% were Hispanic or Latinx, 8.2% were Black or African American, 4.3% were Asian, 0.9% were American Indian or Alaska Native, and 0.2% were Native Hawaiian or Pacific Islander. The most common etiologies were alcoholic cirrhosis (23.8%) and nonalcoholic steatohepatitis (15.9%).

Compared with patients on the wait list, recipients of a living-donor liver transplant were younger, more often women, more educated, and more often White. A greater proportion of transplant recipients had a primary etiology of nonalcoholic steatohepatitis (19.8%) and cholestatic liver disease (24.1%). At wait list placement, one-third of candidates had a MELD-Na score of 14 or higher.

The research team found a significant survival benefit for patients receiving a living-donor liver transplant based on mortality risk and survival scores. The survival benefit was significant at a MELD-Na score as low as 11, with a 34% decrease(95% confidence interval [CI], 17.4%-52.0%) in mortality compared with the wait list. In addition, mortality risk models confirmed a survival benefit for patients with a MELD-Na score of 11 or higher at 1 year after transplant (adjusted hazard ratio, 0.64; 95% CI, 0.47-0.88; P = .006). At a MELD-Na score of 14-16, mortality decreased by about 50% (aHR, 0.47; 95% CI, 0.34-0.66; P < .001).

The probability of death from a living-donor liver transplant for patients with very low MELD-Na scores (between 6 and 10) was greater than that for patients on the wait list for the first 259 days, at which point the risk of death for both groups was equal. At 471 days, the probability of survival in both groups was equal. As the MELD-Na score increased, both the time to equal risk of death and the time to equal survival decreased, demonstrating that the survival benefit occurs much earlier for patients with a higher MELD-Na score.

Analysis of life-years from transplant showed living-donor transplant recipients gained 13-17 life-years compared to those who didn’t receive one.

“Living-donor liver transplantation is a valuable yet underutilized strategy to address the significant organ shortage and long waiting times on the transplant list in the U.S.,” said Renu Dhanasekaran, MD, PhD, assistant professor of gastroenterology and hepatology at Stanford (Calif.) University.

Dr. Dhanasekaran, who wasn’t involved with this study, also welcomed the finding that living-donor liver transplantation can benefit patients with low MELD-Na scores, even below the expected cutoff at 15. According to the study authors, previous research had suggested benefit would be seen only at MELD-Na 15 and above.

“In my practice, I have several patients whose symptoms are out of proportion to their MELD score, and data like this will convince them and their potential donors to avail a transplant at an earlier stage,” she said.

The findings challenge the current paradigm around the timing of referral for a liver transplant and may have ramifications for allocation policies for deceased donors, the study authors wrote. The data can also help to contextualize risk-benefit discussions for donors and recipients.

“Donating a part of one’s liver to save a patient suffering from end-stage liver disease is an incredible act of selfless love,” Dr. Dhanasekaran said. “I hope strong positive data from studies like this one encourage more donors, patients, and transplant centers to expand the use of [living-donor liver transplant].”

The authors reported no grant support or funding sources for this study. One author disclosed being married to the current chair of the United Network for Organ Sharing’s Liver and Intestinal Organ Transplantation Committee. No other conflicts of interest were reported. Dr. Dhanasekaran reported no relevant disclosures.

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – run an increased risk of hepatocellular carcinoma, researchers say.

The correlation does not prove that PFOS causes this cancer, and more research is needed, but in the meantime, people should limit their exposure to it and others in its class, said Jesse Goodrich, PhD, a postdoctoral scholar in environmental medicine at the University of Southern California, Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to kind of send you over the edge,” he told this news organization.

Dr. Goodrich and colleagues published their research online in JHEP Reports.

Dubbed “forever chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) figure in makeup, food packaging, waterproof clothing, nonstick cookware, firefighting foams, and groundwater. They have spread through the atmosphere into rain and can be found in the blood of most Americans. PFOS is one of the most widely used PFAS.

“You can’t really escape them,” Dr. Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavioral problems in children, immune system issues, and higher cholesterol, as well as other cancers. Some experiments in animals suggested PFAS could cause liver cancer, and others showed a correlation between PFAS serum levels and biomarkers associated with liver cancer. But many of these health effects take a long time to develop.

“It wasn’t until we started to get really highly exposed groups of people that we started, as scientists, to be able to figure out what was going on,” said Dr. Goodrich.
 

High exposure, increased incidence

To measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma more definitively, Dr. Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latin, Native Hawaiian, Japanese, and European ancestry tracked since the early 1990s in California and Hawaii. About 67,000 participants provided blood samples from 2001 to 2007.

From this cohort, the researchers found 50 people who later developed hepatocellular carcinoma. The researchers matched these patients with 50 controls of similar age at blood collection, sex, race, ethnicity, and study area who did not develop the cancer.

They found that people with more than 54.9 mcg/L of PFOS in their blood before any diagnosis of hepatocellular carcinoma were almost five times more likely to get the cancer (odds ratio 4.5; 95% confidence interval, 1.2-16.0), which was statistically significant (P = .02).

This level of PFOS corresponds to the 90th percentile found in the U.S. National Health and Nutrition Examination Survey (NHANES).

To get some idea of the mechanism by which PFOS might do its damage, the researchers also looked for linkage to levels of metabolites.

They found an overlap among high PFOS levels, hepatocellular carcinoma, and high levels of glucose, butyric acid (a short chain fatty acid), alpha-Ketoisovaleric acid (alpha branched-chain alpha-keto acid), and 7alpha-Hydroxy-3-oxo-4-cholestenoate (a bile acid). These metabolites have been associated in previous studies with metabolic disorders and liver disease.

Similarly, the researchers identified an association among the cancer, PFOS, and alterations in amino acid and glycan biosynthesis pathways.
 

Risk mitigation

The half-life of PFAS in the human body is about 3-7 years, said Dr. Goodrich.

“There’s not much you can do once they’re in there,” he said. “So, the focus needs to be on preventing the exposure in the first place.”

People can limit exposure by avoiding water contaminated with PFAS or filtering it out, Dr. Goodrich said. He recommended avoiding fish from contaminated waterways and nonstick cookware. The Environmental Protection Agency has more detailed recommendations.

But giving patients individualized recommendations is difficult, said Vincent Chen, MD, MS, a clinical instructor in gastroenterology at the University of Michigan, Ann Arbor, who was not involved in the study. Most clinicians don’t know their patients’ PFOS levels.

“It’s not that easy to get a test,” Dr. Chen told this news organization.

People can also mitigate their risk factors for hepatocellular carcinoma, such as a poor diet, a lack of exercise, and smoking, said Dr. Goodrich.

The researchers found that patients with hepatocellular carcinoma were more likely to be overweight and have diabetes, and PFOS was associated with higher fasting glucose levels. This raises the possibility that PFOS increases the risk for hepatocellular carcinoma by causing diabetes and obesity.

Dr. Goodrich and his colleagues tried to address this question by adjusting for baseline body mass index (BMI) and diabetes diagnosis in their statistical analysis.

After adjusting for BMI, they found that the association between PFOS and hepatocellular carcinoma diminished to a threefold risk (OR, 2.90; 95% CI, 0.78-10.00) and was no longer statistically significant (P = .11).

On the other hand, adjusting for diabetes did not change the significance of the relationship between PFOS and the cancer (OR, 5.7; 95% CI, 1.10-30.00; P = .04).

The sample size was probably too small to adequately tease out this relationship, Dr. Chen said. Still, he said, “I thought it was a very, very important study.”

The levels of PFOS found in the blood of Americans has been declining since the 1999-2000 NHANES, Dr. Chen pointed out. But that’s not as reassuring as it sounds.

“The problem is that if you put a regulation limiting the use of one PFAS, what people can do is just substitute with another PFAS or another molecule, which for all we know could be equally harmful,” Dr. Chen said.

Funding was provided by the Southern California Environmental Health Science Center supported by the National Institutes of Health. Dr. Goodrich and Dr. Chen report no relevant financial relationships.

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

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – run an increased risk of hepatocellular carcinoma, researchers say.

The correlation does not prove that PFOS causes this cancer, and more research is needed, but in the meantime, people should limit their exposure to it and others in its class, said Jesse Goodrich, PhD, a postdoctoral scholar in environmental medicine at the University of Southern California, Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to kind of send you over the edge,” he told this news organization.

Dr. Goodrich and colleagues published their research online in JHEP Reports.

Dubbed “forever chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) figure in makeup, food packaging, waterproof clothing, nonstick cookware, firefighting foams, and groundwater. They have spread through the atmosphere into rain and can be found in the blood of most Americans. PFOS is one of the most widely used PFAS.

“You can’t really escape them,” Dr. Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavioral problems in children, immune system issues, and higher cholesterol, as well as other cancers. Some experiments in animals suggested PFAS could cause liver cancer, and others showed a correlation between PFAS serum levels and biomarkers associated with liver cancer. But many of these health effects take a long time to develop.

“It wasn’t until we started to get really highly exposed groups of people that we started, as scientists, to be able to figure out what was going on,” said Dr. Goodrich.
 

High exposure, increased incidence

To measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma more definitively, Dr. Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latin, Native Hawaiian, Japanese, and European ancestry tracked since the early 1990s in California and Hawaii. About 67,000 participants provided blood samples from 2001 to 2007.

From this cohort, the researchers found 50 people who later developed hepatocellular carcinoma. The researchers matched these patients with 50 controls of similar age at blood collection, sex, race, ethnicity, and study area who did not develop the cancer.

They found that people with more than 54.9 mcg/L of PFOS in their blood before any diagnosis of hepatocellular carcinoma were almost five times more likely to get the cancer (odds ratio 4.5; 95% confidence interval, 1.2-16.0), which was statistically significant (P = .02).

This level of PFOS corresponds to the 90th percentile found in the U.S. National Health and Nutrition Examination Survey (NHANES).

To get some idea of the mechanism by which PFOS might do its damage, the researchers also looked for linkage to levels of metabolites.

They found an overlap among high PFOS levels, hepatocellular carcinoma, and high levels of glucose, butyric acid (a short chain fatty acid), alpha-Ketoisovaleric acid (alpha branched-chain alpha-keto acid), and 7alpha-Hydroxy-3-oxo-4-cholestenoate (a bile acid). These metabolites have been associated in previous studies with metabolic disorders and liver disease.

Similarly, the researchers identified an association among the cancer, PFOS, and alterations in amino acid and glycan biosynthesis pathways.
 

Risk mitigation

The half-life of PFAS in the human body is about 3-7 years, said Dr. Goodrich.

“There’s not much you can do once they’re in there,” he said. “So, the focus needs to be on preventing the exposure in the first place.”

People can limit exposure by avoiding water contaminated with PFAS or filtering it out, Dr. Goodrich said. He recommended avoiding fish from contaminated waterways and nonstick cookware. The Environmental Protection Agency has more detailed recommendations.

But giving patients individualized recommendations is difficult, said Vincent Chen, MD, MS, a clinical instructor in gastroenterology at the University of Michigan, Ann Arbor, who was not involved in the study. Most clinicians don’t know their patients’ PFOS levels.

“It’s not that easy to get a test,” Dr. Chen told this news organization.

People can also mitigate their risk factors for hepatocellular carcinoma, such as a poor diet, a lack of exercise, and smoking, said Dr. Goodrich.

The researchers found that patients with hepatocellular carcinoma were more likely to be overweight and have diabetes, and PFOS was associated with higher fasting glucose levels. This raises the possibility that PFOS increases the risk for hepatocellular carcinoma by causing diabetes and obesity.

Dr. Goodrich and his colleagues tried to address this question by adjusting for baseline body mass index (BMI) and diabetes diagnosis in their statistical analysis.

After adjusting for BMI, they found that the association between PFOS and hepatocellular carcinoma diminished to a threefold risk (OR, 2.90; 95% CI, 0.78-10.00) and was no longer statistically significant (P = .11).

On the other hand, adjusting for diabetes did not change the significance of the relationship between PFOS and the cancer (OR, 5.7; 95% CI, 1.10-30.00; P = .04).

The sample size was probably too small to adequately tease out this relationship, Dr. Chen said. Still, he said, “I thought it was a very, very important study.”

The levels of PFOS found in the blood of Americans has been declining since the 1999-2000 NHANES, Dr. Chen pointed out. But that’s not as reassuring as it sounds.

“The problem is that if you put a regulation limiting the use of one PFAS, what people can do is just substitute with another PFAS or another molecule, which for all we know could be equally harmful,” Dr. Chen said.

Funding was provided by the Southern California Environmental Health Science Center supported by the National Institutes of Health. Dr. Goodrich and Dr. Chen report no relevant financial relationships.

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

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – run an increased risk of hepatocellular carcinoma, researchers say.

The correlation does not prove that PFOS causes this cancer, and more research is needed, but in the meantime, people should limit their exposure to it and others in its class, said Jesse Goodrich, PhD, a postdoctoral scholar in environmental medicine at the University of Southern California, Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to kind of send you over the edge,” he told this news organization.

Dr. Goodrich and colleagues published their research online in JHEP Reports.

Dubbed “forever chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) figure in makeup, food packaging, waterproof clothing, nonstick cookware, firefighting foams, and groundwater. They have spread through the atmosphere into rain and can be found in the blood of most Americans. PFOS is one of the most widely used PFAS.

“You can’t really escape them,” Dr. Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavioral problems in children, immune system issues, and higher cholesterol, as well as other cancers. Some experiments in animals suggested PFAS could cause liver cancer, and others showed a correlation between PFAS serum levels and biomarkers associated with liver cancer. But many of these health effects take a long time to develop.

“It wasn’t until we started to get really highly exposed groups of people that we started, as scientists, to be able to figure out what was going on,” said Dr. Goodrich.
 

High exposure, increased incidence

To measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma more definitively, Dr. Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latin, Native Hawaiian, Japanese, and European ancestry tracked since the early 1990s in California and Hawaii. About 67,000 participants provided blood samples from 2001 to 2007.

From this cohort, the researchers found 50 people who later developed hepatocellular carcinoma. The researchers matched these patients with 50 controls of similar age at blood collection, sex, race, ethnicity, and study area who did not develop the cancer.

They found that people with more than 54.9 mcg/L of PFOS in their blood before any diagnosis of hepatocellular carcinoma were almost five times more likely to get the cancer (odds ratio 4.5; 95% confidence interval, 1.2-16.0), which was statistically significant (P = .02).

This level of PFOS corresponds to the 90th percentile found in the U.S. National Health and Nutrition Examination Survey (NHANES).

To get some idea of the mechanism by which PFOS might do its damage, the researchers also looked for linkage to levels of metabolites.

They found an overlap among high PFOS levels, hepatocellular carcinoma, and high levels of glucose, butyric acid (a short chain fatty acid), alpha-Ketoisovaleric acid (alpha branched-chain alpha-keto acid), and 7alpha-Hydroxy-3-oxo-4-cholestenoate (a bile acid). These metabolites have been associated in previous studies with metabolic disorders and liver disease.

Similarly, the researchers identified an association among the cancer, PFOS, and alterations in amino acid and glycan biosynthesis pathways.
 

Risk mitigation

The half-life of PFAS in the human body is about 3-7 years, said Dr. Goodrich.

“There’s not much you can do once they’re in there,” he said. “So, the focus needs to be on preventing the exposure in the first place.”

People can limit exposure by avoiding water contaminated with PFAS or filtering it out, Dr. Goodrich said. He recommended avoiding fish from contaminated waterways and nonstick cookware. The Environmental Protection Agency has more detailed recommendations.

But giving patients individualized recommendations is difficult, said Vincent Chen, MD, MS, a clinical instructor in gastroenterology at the University of Michigan, Ann Arbor, who was not involved in the study. Most clinicians don’t know their patients’ PFOS levels.

“It’s not that easy to get a test,” Dr. Chen told this news organization.

People can also mitigate their risk factors for hepatocellular carcinoma, such as a poor diet, a lack of exercise, and smoking, said Dr. Goodrich.

The researchers found that patients with hepatocellular carcinoma were more likely to be overweight and have diabetes, and PFOS was associated with higher fasting glucose levels. This raises the possibility that PFOS increases the risk for hepatocellular carcinoma by causing diabetes and obesity.

Dr. Goodrich and his colleagues tried to address this question by adjusting for baseline body mass index (BMI) and diabetes diagnosis in their statistical analysis.

After adjusting for BMI, they found that the association between PFOS and hepatocellular carcinoma diminished to a threefold risk (OR, 2.90; 95% CI, 0.78-10.00) and was no longer statistically significant (P = .11).

On the other hand, adjusting for diabetes did not change the significance of the relationship between PFOS and the cancer (OR, 5.7; 95% CI, 1.10-30.00; P = .04).

The sample size was probably too small to adequately tease out this relationship, Dr. Chen said. Still, he said, “I thought it was a very, very important study.”

The levels of PFOS found in the blood of Americans has been declining since the 1999-2000 NHANES, Dr. Chen pointed out. But that’s not as reassuring as it sounds.

“The problem is that if you put a regulation limiting the use of one PFAS, what people can do is just substitute with another PFAS or another molecule, which for all we know could be equally harmful,” Dr. Chen said.

Funding was provided by the Southern California Environmental Health Science Center supported by the National Institutes of Health. Dr. Goodrich and Dr. Chen report no relevant financial relationships.

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

People are more likely to die of alcohol-associated liver disease (ALD) when there are fewer gastroenterologists in their state, researchers say.

The finding raises questions about steps that policymakers could take to increase the number of gastroenterologists and spread them more evenly around the United States.

“We found that there’s a fivefold difference in density of gastroenterologists through different states,” said Brian P. Lee, MD, MAS, an assistant professor of clinical medicine at the University of Southern California, Los Angeles.

Dr. Lee and colleagues published their findings in Clinical Gastroenterology and Hepatology.

ALD is becoming more common, and it is killing more people. Research among veterans has linked visits to gastroenterologists to a lower risk for death from liver disease.

To see whether that correlation applies more broadly, Dr. Lee and colleagues compared multiple datasets. One from the U.S. Health Resources & Service Administration provided the number of gastroenterologists per 100,000 population. The other from the U.S. Centers for Disease Control and Prevention provided ALD-related deaths per 1,000,000 adults for each state and the District of Columbia.

The researchers adjusted for many variables that could affect the relationship between the availability of gastroenterologists and deaths related to ALD, including the age distribution of the population in each state, the gender balance, race and ethnicity, binge drinking, household income, obesity, and the proportion of rural residents.

They found that for every additional gastroenterologist, there is almost one fewer ALD-related death each year per 100,000 population (9.0 [95% confidence interval, 1.3-16.7] fewer ALD-related deaths per 1,000,000 population for each additional gastroenterologist per 100,000 population).

The strength of the association appeared to plateau when there were at least 7.5 gastroenterologists per 100,000 people.

From these findings, the researchers calculated that as many as 40% of deaths from ALD nationwide could be prevented by providing more gastroenterologists in the places where they are lacking.

The mean number of gastroenterologists per 100,000 people in the United States was 4.6, and the annual ALD-related death rate was 85.6 per 1,000,000 people.

The Atlantic states had the greatest concentration of gastroenterologists and the lowest ALD-related mortality, whereas the Mountain states had the lowest concentration of gastroenterologists and the highest ALD-related mortality.

The lowest mortality related to ALD was in New Jersey, Maryland, and Hawaii, with 52 per 1,000,000 people, and the highest was in Wyoming, with 289.
 

Study shines spotlight on general GI care

Access to liver transplants did not make a statistically significant difference in mortality from ALD.

“It makes you realize that transplant will only be accessible for really just a small fraction of the population who needs it,” Dr. Lee told this news organization.

General gastroenterologic care appears to make a bigger difference in saving patients’ lives. “Are they getting endoscopy for bleeding from varices?” Dr. Lee asked. “Are they getting appropriate antibiotics prescribed to prevent bacterial infection of ascites?”

The concentration of primary care physicians did not reduce mortality from ALD, and neither did the concentration of substance use, behavioral disorder, and mental health counselors.

Previous research has shown that substance abuse therapy is effective. But many people do not want to undertake it, or they face barriers of transportation, language, or insurance, said Dr. Lee.

“I have many patients whose insurance will provide them access to medical visits to me but will not to substance-use rehab, for example,” he said.

To see whether the effect was more generally due to the concentration of medical specialists, the researchers examined the state-level density of ophthalmologists and dermatologists. They found no significant difference in ALD-related mortality.

The finding builds on reports by the American Gastroenterological Association and the American Association for the Study of Liver Diseases that the number of gastroenterologists has not kept up with the U.S. population nor the burden of digestive diseases, and that predicts a critical shortage in the future.
 

Overcoming barriers to care for liver disease

The overall supply of gastroenterologists could be increased by reducing the educational requirements and increasing the funding for fellowships, said Dr. Lee.

“We have to have a better understanding as to the barriers to gastroenterology practice in certain areas, then interventions to address those barriers and also incentives to attract gastroenterologists to those areas,” Dr. Lee said.

The study underscores the importance of access to gastroenterological care, said George Cholankeril, MD, assistant professor of medicine at Baylor College of Medicine, Houston, who was not involved in the study. That urgency has only grown as ALD has spiraled up with the COVID-19 pandemic, he said.

“Anyone in clinical practice right now will be able to say that there’s been a clear rising tide of patients with alcohol-related liver disease,” he told this news organization. “There’s an urgent need to address this and provide the necessary resources.”

Prevention remains essential, Dr. Cholankeril said.

Gastroenterologists and primary care physicians can help stem the tide of ALD by screening their patients for the disease through a tool like AUDIT (Alcohol Use Disorders Identification Test), he said. They can then refer patients to substance abuse treatment centers or to psychologists and psychiatrists.

Dr. Lee and Dr. Cholankeril report no relevant financial relationships.

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

People are more likely to die of alcohol-associated liver disease (ALD) when there are fewer gastroenterologists in their state, researchers say.

The finding raises questions about steps that policymakers could take to increase the number of gastroenterologists and spread them more evenly around the United States.

“We found that there’s a fivefold difference in density of gastroenterologists through different states,” said Brian P. Lee, MD, MAS, an assistant professor of clinical medicine at the University of Southern California, Los Angeles.

Dr. Lee and colleagues published their findings in Clinical Gastroenterology and Hepatology.

ALD is becoming more common, and it is killing more people. Research among veterans has linked visits to gastroenterologists to a lower risk for death from liver disease.

To see whether that correlation applies more broadly, Dr. Lee and colleagues compared multiple datasets. One from the U.S. Health Resources & Service Administration provided the number of gastroenterologists per 100,000 population. The other from the U.S. Centers for Disease Control and Prevention provided ALD-related deaths per 1,000,000 adults for each state and the District of Columbia.

The researchers adjusted for many variables that could affect the relationship between the availability of gastroenterologists and deaths related to ALD, including the age distribution of the population in each state, the gender balance, race and ethnicity, binge drinking, household income, obesity, and the proportion of rural residents.

They found that for every additional gastroenterologist, there is almost one fewer ALD-related death each year per 100,000 population (9.0 [95% confidence interval, 1.3-16.7] fewer ALD-related deaths per 1,000,000 population for each additional gastroenterologist per 100,000 population).

The strength of the association appeared to plateau when there were at least 7.5 gastroenterologists per 100,000 people.

From these findings, the researchers calculated that as many as 40% of deaths from ALD nationwide could be prevented by providing more gastroenterologists in the places where they are lacking.

The mean number of gastroenterologists per 100,000 people in the United States was 4.6, and the annual ALD-related death rate was 85.6 per 1,000,000 people.

The Atlantic states had the greatest concentration of gastroenterologists and the lowest ALD-related mortality, whereas the Mountain states had the lowest concentration of gastroenterologists and the highest ALD-related mortality.

The lowest mortality related to ALD was in New Jersey, Maryland, and Hawaii, with 52 per 1,000,000 people, and the highest was in Wyoming, with 289.
 

Study shines spotlight on general GI care

Access to liver transplants did not make a statistically significant difference in mortality from ALD.

“It makes you realize that transplant will only be accessible for really just a small fraction of the population who needs it,” Dr. Lee told this news organization.

General gastroenterologic care appears to make a bigger difference in saving patients’ lives. “Are they getting endoscopy for bleeding from varices?” Dr. Lee asked. “Are they getting appropriate antibiotics prescribed to prevent bacterial infection of ascites?”

The concentration of primary care physicians did not reduce mortality from ALD, and neither did the concentration of substance use, behavioral disorder, and mental health counselors.

Previous research has shown that substance abuse therapy is effective. But many people do not want to undertake it, or they face barriers of transportation, language, or insurance, said Dr. Lee.

“I have many patients whose insurance will provide them access to medical visits to me but will not to substance-use rehab, for example,” he said.

To see whether the effect was more generally due to the concentration of medical specialists, the researchers examined the state-level density of ophthalmologists and dermatologists. They found no significant difference in ALD-related mortality.

The finding builds on reports by the American Gastroenterological Association and the American Association for the Study of Liver Diseases that the number of gastroenterologists has not kept up with the U.S. population nor the burden of digestive diseases, and that predicts a critical shortage in the future.
 

Overcoming barriers to care for liver disease

The overall supply of gastroenterologists could be increased by reducing the educational requirements and increasing the funding for fellowships, said Dr. Lee.

“We have to have a better understanding as to the barriers to gastroenterology practice in certain areas, then interventions to address those barriers and also incentives to attract gastroenterologists to those areas,” Dr. Lee said.

The study underscores the importance of access to gastroenterological care, said George Cholankeril, MD, assistant professor of medicine at Baylor College of Medicine, Houston, who was not involved in the study. That urgency has only grown as ALD has spiraled up with the COVID-19 pandemic, he said.

“Anyone in clinical practice right now will be able to say that there’s been a clear rising tide of patients with alcohol-related liver disease,” he told this news organization. “There’s an urgent need to address this and provide the necessary resources.”

Prevention remains essential, Dr. Cholankeril said.

Gastroenterologists and primary care physicians can help stem the tide of ALD by screening their patients for the disease through a tool like AUDIT (Alcohol Use Disorders Identification Test), he said. They can then refer patients to substance abuse treatment centers or to psychologists and psychiatrists.

Dr. Lee and Dr. Cholankeril report no relevant financial relationships.

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

People are more likely to die of alcohol-associated liver disease (ALD) when there are fewer gastroenterologists in their state, researchers say.

The finding raises questions about steps that policymakers could take to increase the number of gastroenterologists and spread them more evenly around the United States.

“We found that there’s a fivefold difference in density of gastroenterologists through different states,” said Brian P. Lee, MD, MAS, an assistant professor of clinical medicine at the University of Southern California, Los Angeles.

Dr. Lee and colleagues published their findings in Clinical Gastroenterology and Hepatology.

ALD is becoming more common, and it is killing more people. Research among veterans has linked visits to gastroenterologists to a lower risk for death from liver disease.

To see whether that correlation applies more broadly, Dr. Lee and colleagues compared multiple datasets. One from the U.S. Health Resources & Service Administration provided the number of gastroenterologists per 100,000 population. The other from the U.S. Centers for Disease Control and Prevention provided ALD-related deaths per 1,000,000 adults for each state and the District of Columbia.

The researchers adjusted for many variables that could affect the relationship between the availability of gastroenterologists and deaths related to ALD, including the age distribution of the population in each state, the gender balance, race and ethnicity, binge drinking, household income, obesity, and the proportion of rural residents.

They found that for every additional gastroenterologist, there is almost one fewer ALD-related death each year per 100,000 population (9.0 [95% confidence interval, 1.3-16.7] fewer ALD-related deaths per 1,000,000 population for each additional gastroenterologist per 100,000 population).

The strength of the association appeared to plateau when there were at least 7.5 gastroenterologists per 100,000 people.

From these findings, the researchers calculated that as many as 40% of deaths from ALD nationwide could be prevented by providing more gastroenterologists in the places where they are lacking.

The mean number of gastroenterologists per 100,000 people in the United States was 4.6, and the annual ALD-related death rate was 85.6 per 1,000,000 people.

The Atlantic states had the greatest concentration of gastroenterologists and the lowest ALD-related mortality, whereas the Mountain states had the lowest concentration of gastroenterologists and the highest ALD-related mortality.

The lowest mortality related to ALD was in New Jersey, Maryland, and Hawaii, with 52 per 1,000,000 people, and the highest was in Wyoming, with 289.
 

Study shines spotlight on general GI care

Access to liver transplants did not make a statistically significant difference in mortality from ALD.

“It makes you realize that transplant will only be accessible for really just a small fraction of the population who needs it,” Dr. Lee told this news organization.

General gastroenterologic care appears to make a bigger difference in saving patients’ lives. “Are they getting endoscopy for bleeding from varices?” Dr. Lee asked. “Are they getting appropriate antibiotics prescribed to prevent bacterial infection of ascites?”

The concentration of primary care physicians did not reduce mortality from ALD, and neither did the concentration of substance use, behavioral disorder, and mental health counselors.

Previous research has shown that substance abuse therapy is effective. But many people do not want to undertake it, or they face barriers of transportation, language, or insurance, said Dr. Lee.

“I have many patients whose insurance will provide them access to medical visits to me but will not to substance-use rehab, for example,” he said.

To see whether the effect was more generally due to the concentration of medical specialists, the researchers examined the state-level density of ophthalmologists and dermatologists. They found no significant difference in ALD-related mortality.

The finding builds on reports by the American Gastroenterological Association and the American Association for the Study of Liver Diseases that the number of gastroenterologists has not kept up with the U.S. population nor the burden of digestive diseases, and that predicts a critical shortage in the future.
 

Overcoming barriers to care for liver disease

The overall supply of gastroenterologists could be increased by reducing the educational requirements and increasing the funding for fellowships, said Dr. Lee.

“We have to have a better understanding as to the barriers to gastroenterology practice in certain areas, then interventions to address those barriers and also incentives to attract gastroenterologists to those areas,” Dr. Lee said.

The study underscores the importance of access to gastroenterological care, said George Cholankeril, MD, assistant professor of medicine at Baylor College of Medicine, Houston, who was not involved in the study. That urgency has only grown as ALD has spiraled up with the COVID-19 pandemic, he said.

“Anyone in clinical practice right now will be able to say that there’s been a clear rising tide of patients with alcohol-related liver disease,” he told this news organization. “There’s an urgent need to address this and provide the necessary resources.”

Prevention remains essential, Dr. Cholankeril said.

Gastroenterologists and primary care physicians can help stem the tide of ALD by screening their patients for the disease through a tool like AUDIT (Alcohol Use Disorders Identification Test), he said. They can then refer patients to substance abuse treatment centers or to psychologists and psychiatrists.

Dr. Lee and Dr. Cholankeril report no relevant financial relationships.

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

Rare gene variants are associated with a reduced risk for multiple types of liver disease, including cirrhosis, researchers say.

People with certain variants in the gene CIDEB are one-third less likely to develop any sort of liver disease, according to Aris Baras, MD, a senior vice president at Regeneron, and colleagues.

“The unprecedented protective effect that these CIDEB genetic variants have against liver disease provides us with one of our most exciting targets and potential therapeutic approaches for a notoriously hard-to-treat disease where there are currently no approved treatments,” said Dr. Baras in a press release.

Dr. Baras and colleagues published the finding in The New England Journal of Medicine.

The finding follows on a similar discovery about a common variant in the gene HSD17B13. Treatments targeting this gene are being tested in clinical trials.

To search for more such genes, the researchers analyzed human exomes – the part of the genome that codes for proteins – to look for associations between gene variants and liver function.

The researchers used exome sequencing on 542,904 people from the UK Biobank, the Geisinger Health System MyCode cohort, and other datasets.

They found that coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk for liver disease.

But variants in CIDEB were associated with decreased levels of alanine aminotransferase, a biomarker of hepatocellular injury. And they were associated with a decreased risk for liver disease of any cause (odds ratio per allele, 0.67; 95% confidence interval, 0.57-0.79).

The CIDEB variants were present in only 0.7% of the persons in the study.

Zeroing in on various kinds of liver disease, the researchers found that the CIDEB variants were associated with a reduced risk for alcoholic liver disease, nonalcoholic liver disease, any liver cirrhosis, alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and viral hepatitis.

In 3,599 patients who had undergone bariatric surgery, variants in CIDEB were associated with a reduced nonalcoholic fatty liver disease activity score of –0.98 beta per allele in score units, where scores range from 0-8, with a higher score indicating more severe disease.

In patients for whom MRI data were available, those with rare coding variants in CIDEB had lower proportions of liver fat. However, percentage of liver fat did not fully explain the reduced risk for liver disease.

Pursuing another line of investigation, the researchers found that they could prevent the buildup of large lipid droplets in oleic acid-treated human hepatoma cell lines by silencing the CIDEB gene using small interfering RNA.

The association was particularly strong among people with higher body mass indices and type 2 diabetes.

The associations with the rare protective CIDEB variants were consistent across ancestries, but people of non-European ancestry, who might be disproportionately affected by liver disease, were underrepresented in the database, the researchers note.

The study was supported by Regeneron Pharmaceuticals, which also employed several of the researchers.

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

Rare gene variants are associated with a reduced risk for multiple types of liver disease, including cirrhosis, researchers say.

People with certain variants in the gene CIDEB are one-third less likely to develop any sort of liver disease, according to Aris Baras, MD, a senior vice president at Regeneron, and colleagues.

“The unprecedented protective effect that these CIDEB genetic variants have against liver disease provides us with one of our most exciting targets and potential therapeutic approaches for a notoriously hard-to-treat disease where there are currently no approved treatments,” said Dr. Baras in a press release.

Dr. Baras and colleagues published the finding in The New England Journal of Medicine.

The finding follows on a similar discovery about a common variant in the gene HSD17B13. Treatments targeting this gene are being tested in clinical trials.

To search for more such genes, the researchers analyzed human exomes – the part of the genome that codes for proteins – to look for associations between gene variants and liver function.

The researchers used exome sequencing on 542,904 people from the UK Biobank, the Geisinger Health System MyCode cohort, and other datasets.

They found that coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk for liver disease.

But variants in CIDEB were associated with decreased levels of alanine aminotransferase, a biomarker of hepatocellular injury. And they were associated with a decreased risk for liver disease of any cause (odds ratio per allele, 0.67; 95% confidence interval, 0.57-0.79).

The CIDEB variants were present in only 0.7% of the persons in the study.

Zeroing in on various kinds of liver disease, the researchers found that the CIDEB variants were associated with a reduced risk for alcoholic liver disease, nonalcoholic liver disease, any liver cirrhosis, alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and viral hepatitis.

In 3,599 patients who had undergone bariatric surgery, variants in CIDEB were associated with a reduced nonalcoholic fatty liver disease activity score of –0.98 beta per allele in score units, where scores range from 0-8, with a higher score indicating more severe disease.

In patients for whom MRI data were available, those with rare coding variants in CIDEB had lower proportions of liver fat. However, percentage of liver fat did not fully explain the reduced risk for liver disease.

Pursuing another line of investigation, the researchers found that they could prevent the buildup of large lipid droplets in oleic acid-treated human hepatoma cell lines by silencing the CIDEB gene using small interfering RNA.

The association was particularly strong among people with higher body mass indices and type 2 diabetes.

The associations with the rare protective CIDEB variants were consistent across ancestries, but people of non-European ancestry, who might be disproportionately affected by liver disease, were underrepresented in the database, the researchers note.

The study was supported by Regeneron Pharmaceuticals, which also employed several of the researchers.

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

Rare gene variants are associated with a reduced risk for multiple types of liver disease, including cirrhosis, researchers say.

People with certain variants in the gene CIDEB are one-third less likely to develop any sort of liver disease, according to Aris Baras, MD, a senior vice president at Regeneron, and colleagues.

“The unprecedented protective effect that these CIDEB genetic variants have against liver disease provides us with one of our most exciting targets and potential therapeutic approaches for a notoriously hard-to-treat disease where there are currently no approved treatments,” said Dr. Baras in a press release.

Dr. Baras and colleagues published the finding in The New England Journal of Medicine.

The finding follows on a similar discovery about a common variant in the gene HSD17B13. Treatments targeting this gene are being tested in clinical trials.

To search for more such genes, the researchers analyzed human exomes – the part of the genome that codes for proteins – to look for associations between gene variants and liver function.

The researchers used exome sequencing on 542,904 people from the UK Biobank, the Geisinger Health System MyCode cohort, and other datasets.

They found that coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk for liver disease.

But variants in CIDEB were associated with decreased levels of alanine aminotransferase, a biomarker of hepatocellular injury. And they were associated with a decreased risk for liver disease of any cause (odds ratio per allele, 0.67; 95% confidence interval, 0.57-0.79).

The CIDEB variants were present in only 0.7% of the persons in the study.

Zeroing in on various kinds of liver disease, the researchers found that the CIDEB variants were associated with a reduced risk for alcoholic liver disease, nonalcoholic liver disease, any liver cirrhosis, alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and viral hepatitis.

In 3,599 patients who had undergone bariatric surgery, variants in CIDEB were associated with a reduced nonalcoholic fatty liver disease activity score of –0.98 beta per allele in score units, where scores range from 0-8, with a higher score indicating more severe disease.

In patients for whom MRI data were available, those with rare coding variants in CIDEB had lower proportions of liver fat. However, percentage of liver fat did not fully explain the reduced risk for liver disease.

Pursuing another line of investigation, the researchers found that they could prevent the buildup of large lipid droplets in oleic acid-treated human hepatoma cell lines by silencing the CIDEB gene using small interfering RNA.

The association was particularly strong among people with higher body mass indices and type 2 diabetes.

The associations with the rare protective CIDEB variants were consistent across ancestries, but people of non-European ancestry, who might be disproportionately affected by liver disease, were underrepresented in the database, the researchers note.

The study was supported by Regeneron Pharmaceuticals, which also employed several of the researchers.

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

Factors operating at the community level may help explain disparities in rates of hepatocellular carcinoma (HCC) across Texas.

Researchers found that the risk for HCC is higher in neighborhoods characterized by minority populations, socioeconomic disadvantage, and blue-collar workers from specific industries.

However, these relationships are not uniform across the state, report researchers from Baylor College of Medicine, Houston.

“HCC is a serious health concern in Texas, and our foundational work is a step forward to better prevent this deadly disease,” study investigator Hashem El-Serag, MD, PhD, said in a news release.

The study was published online in Clinical Gastroenterology and Hepatology.

HCC is the most common type of liver cancer in the United States, and Texas has the highest rate of HCC. Yet, within Texas, incidence rates vary by race, ethnicity, and geographic location.

The Baylor team examined these disparities at the neighborhood level, with a focus on measures of social determinants of health and the industries where most neighborhood residents work.

They identified 11,547 Texas residents diagnosed with HCC between 2011 and 2015, at a mean age of 63 years. Roughly three-quarters were men, and 44% were non-Hispanic White, 14% non-Hispanic Black, 37% Hispanic, and 5% other.

The researchers used demographics, socioeconomic status, and employment provided by the U.S. Census Bureau to characterize the neighborhoods where these people lived when they were diagnosed with HCC.

Among their key findings, the risk for HCC among African American and Hispanic residents was highest in West Texas, South Texas, and the panhandle. However, some factors, like age and socioeconomic status, were not affected by location.

Across the entire state, however, people older than 60 years and those of low socioeconomic status had a higher relative risk for HCC.

Two areas of employment – construction and service occupations – also stood out as being associated with a higher risk for HCC, whereas employment in agriculture was associated with lower risk.

The authors caution that the ecological nature of the study precludes any firm conclusions regarding a causal link between working in these industries and HCC.

“Further research, including longitudinal studies, [is] needed to clarify the roles of specific occupations in HCC risk,” corresponding author Abiodun Oluyomi, PhD, said in the news release.

“Our findings validate factors previously associated with HCC, and our geographic analysis shows areas of Texas where specific intervention strategies may be most relevant,” Dr. Oluyomi added.

This research was supported by the Cancer Prevention & Research Institute of Texas. The authors have no relevant disclosures.

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

Factors operating at the community level may help explain disparities in rates of hepatocellular carcinoma (HCC) across Texas.

Researchers found that the risk for HCC is higher in neighborhoods characterized by minority populations, socioeconomic disadvantage, and blue-collar workers from specific industries.

However, these relationships are not uniform across the state, report researchers from Baylor College of Medicine, Houston.

“HCC is a serious health concern in Texas, and our foundational work is a step forward to better prevent this deadly disease,” study investigator Hashem El-Serag, MD, PhD, said in a news release.

The study was published online in Clinical Gastroenterology and Hepatology.

HCC is the most common type of liver cancer in the United States, and Texas has the highest rate of HCC. Yet, within Texas, incidence rates vary by race, ethnicity, and geographic location.

The Baylor team examined these disparities at the neighborhood level, with a focus on measures of social determinants of health and the industries where most neighborhood residents work.

They identified 11,547 Texas residents diagnosed with HCC between 2011 and 2015, at a mean age of 63 years. Roughly three-quarters were men, and 44% were non-Hispanic White, 14% non-Hispanic Black, 37% Hispanic, and 5% other.

The researchers used demographics, socioeconomic status, and employment provided by the U.S. Census Bureau to characterize the neighborhoods where these people lived when they were diagnosed with HCC.

Among their key findings, the risk for HCC among African American and Hispanic residents was highest in West Texas, South Texas, and the panhandle. However, some factors, like age and socioeconomic status, were not affected by location.

Across the entire state, however, people older than 60 years and those of low socioeconomic status had a higher relative risk for HCC.

Two areas of employment – construction and service occupations – also stood out as being associated with a higher risk for HCC, whereas employment in agriculture was associated with lower risk.

The authors caution that the ecological nature of the study precludes any firm conclusions regarding a causal link between working in these industries and HCC.

“Further research, including longitudinal studies, [is] needed to clarify the roles of specific occupations in HCC risk,” corresponding author Abiodun Oluyomi, PhD, said in the news release.

“Our findings validate factors previously associated with HCC, and our geographic analysis shows areas of Texas where specific intervention strategies may be most relevant,” Dr. Oluyomi added.

This research was supported by the Cancer Prevention & Research Institute of Texas. The authors have no relevant disclosures.

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

Factors operating at the community level may help explain disparities in rates of hepatocellular carcinoma (HCC) across Texas.

Researchers found that the risk for HCC is higher in neighborhoods characterized by minority populations, socioeconomic disadvantage, and blue-collar workers from specific industries.

However, these relationships are not uniform across the state, report researchers from Baylor College of Medicine, Houston.

“HCC is a serious health concern in Texas, and our foundational work is a step forward to better prevent this deadly disease,” study investigator Hashem El-Serag, MD, PhD, said in a news release.

The study was published online in Clinical Gastroenterology and Hepatology.

HCC is the most common type of liver cancer in the United States, and Texas has the highest rate of HCC. Yet, within Texas, incidence rates vary by race, ethnicity, and geographic location.

The Baylor team examined these disparities at the neighborhood level, with a focus on measures of social determinants of health and the industries where most neighborhood residents work.

They identified 11,547 Texas residents diagnosed with HCC between 2011 and 2015, at a mean age of 63 years. Roughly three-quarters were men, and 44% were non-Hispanic White, 14% non-Hispanic Black, 37% Hispanic, and 5% other.

The researchers used demographics, socioeconomic status, and employment provided by the U.S. Census Bureau to characterize the neighborhoods where these people lived when they were diagnosed with HCC.

Among their key findings, the risk for HCC among African American and Hispanic residents was highest in West Texas, South Texas, and the panhandle. However, some factors, like age and socioeconomic status, were not affected by location.

Across the entire state, however, people older than 60 years and those of low socioeconomic status had a higher relative risk for HCC.

Two areas of employment – construction and service occupations – also stood out as being associated with a higher risk for HCC, whereas employment in agriculture was associated with lower risk.

The authors caution that the ecological nature of the study precludes any firm conclusions regarding a causal link between working in these industries and HCC.

“Further research, including longitudinal studies, [is] needed to clarify the roles of specific occupations in HCC risk,” corresponding author Abiodun Oluyomi, PhD, said in the news release.

“Our findings validate factors previously associated with HCC, and our geographic analysis shows areas of Texas where specific intervention strategies may be most relevant,” Dr. Oluyomi added.

This research was supported by the Cancer Prevention & Research Institute of Texas. The authors have no relevant disclosures.

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

A reduction in portal hepatic pressure gradient (PPG) soon after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) greater than 60% was associated with improved ascites control at 6 weeks in a study published in Hepatology.

“The probability of ascites resolution is much higher if PPG reduction exceeded 60% of PPG before TIPS,” wrote the researchers, led by co–first authors Alexander Queck, MD, a postdoctoral researcher in the department of internal medicine at University Hospital Frankfurt (Germany) and Goethe University Frankfurt, and Louise Schwierz, MD, of the department of internal medicine in the University Hospital Bonn (Germany). “This study suggests that, even in patients with uncomplicated TIPS insertion, a short-term follow-up 6 weeks after TIPS should be scheduled to be able to predict their course of disease.”

Alexander Raths/Fotolia

The authors investigated the decrease of PPG in a single-center, retrospective analysis of 341 patients with liver cirrhosis undergoing TIPS insertion for recurrent or refractory ascites between March 1994 and July 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients’ outcomes and ascites progression over time. In 241 patients, or 71%, chronic alcohol consumption was the reason for cirrhosis development, followed by 13% with chronic viral hepatitis (n = 43). Median survival after TIPS insertion was 102 weeks, and 19 patients received liver transplants over time.

Median portal pressure before TIPS placement was 28 mm Hg, which decreased to a median of 21 mm Hg after TIPS. Median PPG levels were 19 mm Hg before TIPS and 8 mm Hg immediately after TIPS placement.

At the time of TIPS placement, 65 patients, or 19%, had hepatic encephalopathy, and nine had severe hepatic encephalopathy. Six weeks after TIPS, two had episodes of hepatic encephalopathy.

After 6 weeks, ascites significantly improved through TIPS insertion. About 47% had a complete resolution of ascites at 6 weeks, whereas 29% had ascites detectable only by ultrasound and 24% of patients still needed large-volume paracentesis. There was an association between extent of PPG reduction and ascites resolution: Median PPG reduction was 55% of initial PPG in patients with persistence of severe ascites, 58% in patients with ascites detected by ultrasound, and 65% in patients with complete resolution of ascites at 6 weeks after TIPS.

Ascites resolved in 54% of patients with higher PPG reduction (60% or above), compared with 39% of patients with lower PPG reduction (below 60%). Ascites that was detected by ultrasound in another 27% of patients with higher PPG reduction, compared with 31% of patients with lower PPG reduction. In addition, persistent severe ascites was seen in 19% of patients with higher PPG reduction, compared with 30% of patients with lower PPG reduction.

The authors also noted the importance of timing follow-up evaluation: They noted that post-TIPS follow-up is a frequent question and not yet standardized; in this study, they found that, with follow-up at 6 weeks, they could “clearly stratify the course post TIPS” and this could “detect patients at high risk of unstable course of disease.”

PPG reduction of more than 60% after TIPS correlated with resolution of severe ascites 6 weeks after TIPS, the study authors concluded.

A reduction in portal hepatic pressure gradient (PPG) soon after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) greater than 60% was associated with improved ascites control at 6 weeks in a study published in Hepatology.

“The probability of ascites resolution is much higher if PPG reduction exceeded 60% of PPG before TIPS,” wrote the researchers, led by co–first authors Alexander Queck, MD, a postdoctoral researcher in the department of internal medicine at University Hospital Frankfurt (Germany) and Goethe University Frankfurt, and Louise Schwierz, MD, of the department of internal medicine in the University Hospital Bonn (Germany). “This study suggests that, even in patients with uncomplicated TIPS insertion, a short-term follow-up 6 weeks after TIPS should be scheduled to be able to predict their course of disease.”

Alexander Raths/Fotolia

The authors investigated the decrease of PPG in a single-center, retrospective analysis of 341 patients with liver cirrhosis undergoing TIPS insertion for recurrent or refractory ascites between March 1994 and July 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients’ outcomes and ascites progression over time. In 241 patients, or 71%, chronic alcohol consumption was the reason for cirrhosis development, followed by 13% with chronic viral hepatitis (n = 43). Median survival after TIPS insertion was 102 weeks, and 19 patients received liver transplants over time.

Median portal pressure before TIPS placement was 28 mm Hg, which decreased to a median of 21 mm Hg after TIPS. Median PPG levels were 19 mm Hg before TIPS and 8 mm Hg immediately after TIPS placement.

At the time of TIPS placement, 65 patients, or 19%, had hepatic encephalopathy, and nine had severe hepatic encephalopathy. Six weeks after TIPS, two had episodes of hepatic encephalopathy.

After 6 weeks, ascites significantly improved through TIPS insertion. About 47% had a complete resolution of ascites at 6 weeks, whereas 29% had ascites detectable only by ultrasound and 24% of patients still needed large-volume paracentesis. There was an association between extent of PPG reduction and ascites resolution: Median PPG reduction was 55% of initial PPG in patients with persistence of severe ascites, 58% in patients with ascites detected by ultrasound, and 65% in patients with complete resolution of ascites at 6 weeks after TIPS.

Ascites resolved in 54% of patients with higher PPG reduction (60% or above), compared with 39% of patients with lower PPG reduction (below 60%). Ascites that was detected by ultrasound in another 27% of patients with higher PPG reduction, compared with 31% of patients with lower PPG reduction. In addition, persistent severe ascites was seen in 19% of patients with higher PPG reduction, compared with 30% of patients with lower PPG reduction.

The authors also noted the importance of timing follow-up evaluation: They noted that post-TIPS follow-up is a frequent question and not yet standardized; in this study, they found that, with follow-up at 6 weeks, they could “clearly stratify the course post TIPS” and this could “detect patients at high risk of unstable course of disease.”

PPG reduction of more than 60% after TIPS correlated with resolution of severe ascites 6 weeks after TIPS, the study authors concluded.

A reduction in portal hepatic pressure gradient (PPG) soon after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) greater than 60% was associated with improved ascites control at 6 weeks in a study published in Hepatology.

“The probability of ascites resolution is much higher if PPG reduction exceeded 60% of PPG before TIPS,” wrote the researchers, led by co–first authors Alexander Queck, MD, a postdoctoral researcher in the department of internal medicine at University Hospital Frankfurt (Germany) and Goethe University Frankfurt, and Louise Schwierz, MD, of the department of internal medicine in the University Hospital Bonn (Germany). “This study suggests that, even in patients with uncomplicated TIPS insertion, a short-term follow-up 6 weeks after TIPS should be scheduled to be able to predict their course of disease.”

Alexander Raths/Fotolia

The authors investigated the decrease of PPG in a single-center, retrospective analysis of 341 patients with liver cirrhosis undergoing TIPS insertion for recurrent or refractory ascites between March 1994 and July 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients’ outcomes and ascites progression over time. In 241 patients, or 71%, chronic alcohol consumption was the reason for cirrhosis development, followed by 13% with chronic viral hepatitis (n = 43). Median survival after TIPS insertion was 102 weeks, and 19 patients received liver transplants over time.

Median portal pressure before TIPS placement was 28 mm Hg, which decreased to a median of 21 mm Hg after TIPS. Median PPG levels were 19 mm Hg before TIPS and 8 mm Hg immediately after TIPS placement.

At the time of TIPS placement, 65 patients, or 19%, had hepatic encephalopathy, and nine had severe hepatic encephalopathy. Six weeks after TIPS, two had episodes of hepatic encephalopathy.

After 6 weeks, ascites significantly improved through TIPS insertion. About 47% had a complete resolution of ascites at 6 weeks, whereas 29% had ascites detectable only by ultrasound and 24% of patients still needed large-volume paracentesis. There was an association between extent of PPG reduction and ascites resolution: Median PPG reduction was 55% of initial PPG in patients with persistence of severe ascites, 58% in patients with ascites detected by ultrasound, and 65% in patients with complete resolution of ascites at 6 weeks after TIPS.

Ascites resolved in 54% of patients with higher PPG reduction (60% or above), compared with 39% of patients with lower PPG reduction (below 60%). Ascites that was detected by ultrasound in another 27% of patients with higher PPG reduction, compared with 31% of patients with lower PPG reduction. In addition, persistent severe ascites was seen in 19% of patients with higher PPG reduction, compared with 30% of patients with lower PPG reduction.

The authors also noted the importance of timing follow-up evaluation: They noted that post-TIPS follow-up is a frequent question and not yet standardized; in this study, they found that, with follow-up at 6 weeks, they could “clearly stratify the course post TIPS” and this could “detect patients at high risk of unstable course of disease.”

PPG reduction of more than 60% after TIPS correlated with resolution of severe ascites 6 weeks after TIPS, the study authors concluded.

Using ultrasound (US) to evaluate sarcopenic obesity in patients with cirrhosis may offer accuracy on par with computed tomography (CT), according to investigators.

US-based assessment presents a more affordable point-of-care strategy that limits radiation exposure, which enables sequential monitoring, reported lead author Sukhpal Dhariwal, MBBS, MD, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India.

“Preliminary data in patients with liver disease ... suggest that US muscle assessment–derived indices, especially thigh muscle thickness, identify sarcopenia CT-skeletal muscle index (SMI) and also predict hospitalization and mortality,” the investigators wrote in Journal of Clinical Gastroenterology. “However, the applicability of US-based techniques to measure muscle mass in the high-risk group of patients with cirrhosis and sarcopenic obesity has not been evaluated.”

To address this knowledge gap, the investigators performed both US- and CT-based muscle assessments in 52 patients with obesity and evidence of cirrhosis; 40 patients were male and the mean age was 50.9 years. In all, 20 (38.5%) were diagnosed with sarcopenia based on CT-determined SMI scores of less than 39 cm²/m² for women and 50 cm²/m² for men.

US showed that it was similarly capable of categorizing patients. The modality significantly differentiated individuals with or without sarcopenia based on high area under the curve values in four muscle indices: quadriceps muscle thickness (0.98), quadriceps muscle feather index (0.95), forearm muscle thickness (0.85), and forearm feather index (0.80).

Direct comparison of US-based assessment against CT-based SMI revealed positive correlations, with significant r values ranging from 0.40 to 0.58. These correlations were stronger in a male-only subgroup analysis, in which r values ranged from 0.52 to 0.70. R values were not calculated in the female subgroup because of the small sample size (n = 12).

The investigators adjusted indices for height, which may pose bias for overestimating muscle mass. Another limitation is the small sample size.

“US-based assessment of sarcopenia has excellent diagnostic accuracy and correlates highly with cross-sectional imaging-based SMI in cirrhosis patients with sarcopenic obesity,” the investigators concluded. “US may serve as an easy-to-use, point-of-care tool for assessing sarcopenia in sarcopenic obesity with the advantage of repeated sequential assessment.”

According to Jamile Wakim-Fleming, MD, of the Cleveland Clinic, “US-based muscle mass assessment seems to be reliable, reproducible, and simple to perform and should be encouraged along with nutrition assessments in all patients with cirrhosis and obesity.”

In a written comment, Dr. Wakim-Fleming noted the importance of timely monitoring and intervention in this patient population.

“Considering the morbidity and the poor outcomes associated with sarcopenic obesity and its frequency in cirrhosis, it is important to make early diagnosis and institute a management plan to improve muscle mass and function,” she said.

The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Wakim-Fleming reported no relevant conflicts of interest.

Using ultrasound (US) to evaluate sarcopenic obesity in patients with cirrhosis may offer accuracy on par with computed tomography (CT), according to investigators.

US-based assessment presents a more affordable point-of-care strategy that limits radiation exposure, which enables sequential monitoring, reported lead author Sukhpal Dhariwal, MBBS, MD, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India.

“Preliminary data in patients with liver disease ... suggest that US muscle assessment–derived indices, especially thigh muscle thickness, identify sarcopenia CT-skeletal muscle index (SMI) and also predict hospitalization and mortality,” the investigators wrote in Journal of Clinical Gastroenterology. “However, the applicability of US-based techniques to measure muscle mass in the high-risk group of patients with cirrhosis and sarcopenic obesity has not been evaluated.”

To address this knowledge gap, the investigators performed both US- and CT-based muscle assessments in 52 patients with obesity and evidence of cirrhosis; 40 patients were male and the mean age was 50.9 years. In all, 20 (38.5%) were diagnosed with sarcopenia based on CT-determined SMI scores of less than 39 cm²/m² for women and 50 cm²/m² for men.

US showed that it was similarly capable of categorizing patients. The modality significantly differentiated individuals with or without sarcopenia based on high area under the curve values in four muscle indices: quadriceps muscle thickness (0.98), quadriceps muscle feather index (0.95), forearm muscle thickness (0.85), and forearm feather index (0.80).

Direct comparison of US-based assessment against CT-based SMI revealed positive correlations, with significant r values ranging from 0.40 to 0.58. These correlations were stronger in a male-only subgroup analysis, in which r values ranged from 0.52 to 0.70. R values were not calculated in the female subgroup because of the small sample size (n = 12).

The investigators adjusted indices for height, which may pose bias for overestimating muscle mass. Another limitation is the small sample size.

“US-based assessment of sarcopenia has excellent diagnostic accuracy and correlates highly with cross-sectional imaging-based SMI in cirrhosis patients with sarcopenic obesity,” the investigators concluded. “US may serve as an easy-to-use, point-of-care tool for assessing sarcopenia in sarcopenic obesity with the advantage of repeated sequential assessment.”

According to Jamile Wakim-Fleming, MD, of the Cleveland Clinic, “US-based muscle mass assessment seems to be reliable, reproducible, and simple to perform and should be encouraged along with nutrition assessments in all patients with cirrhosis and obesity.”

In a written comment, Dr. Wakim-Fleming noted the importance of timely monitoring and intervention in this patient population.

“Considering the morbidity and the poor outcomes associated with sarcopenic obesity and its frequency in cirrhosis, it is important to make early diagnosis and institute a management plan to improve muscle mass and function,” she said.

The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Wakim-Fleming reported no relevant conflicts of interest.

Using ultrasound (US) to evaluate sarcopenic obesity in patients with cirrhosis may offer accuracy on par with computed tomography (CT), according to investigators.

US-based assessment presents a more affordable point-of-care strategy that limits radiation exposure, which enables sequential monitoring, reported lead author Sukhpal Dhariwal, MBBS, MD, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India.

“Preliminary data in patients with liver disease ... suggest that US muscle assessment–derived indices, especially thigh muscle thickness, identify sarcopenia CT-skeletal muscle index (SMI) and also predict hospitalization and mortality,” the investigators wrote in Journal of Clinical Gastroenterology. “However, the applicability of US-based techniques to measure muscle mass in the high-risk group of patients with cirrhosis and sarcopenic obesity has not been evaluated.”

To address this knowledge gap, the investigators performed both US- and CT-based muscle assessments in 52 patients with obesity and evidence of cirrhosis; 40 patients were male and the mean age was 50.9 years. In all, 20 (38.5%) were diagnosed with sarcopenia based on CT-determined SMI scores of less than 39 cm²/m² for women and 50 cm²/m² for men.

US showed that it was similarly capable of categorizing patients. The modality significantly differentiated individuals with or without sarcopenia based on high area under the curve values in four muscle indices: quadriceps muscle thickness (0.98), quadriceps muscle feather index (0.95), forearm muscle thickness (0.85), and forearm feather index (0.80).

Direct comparison of US-based assessment against CT-based SMI revealed positive correlations, with significant r values ranging from 0.40 to 0.58. These correlations were stronger in a male-only subgroup analysis, in which r values ranged from 0.52 to 0.70. R values were not calculated in the female subgroup because of the small sample size (n = 12).

The investigators adjusted indices for height, which may pose bias for overestimating muscle mass. Another limitation is the small sample size.

“US-based assessment of sarcopenia has excellent diagnostic accuracy and correlates highly with cross-sectional imaging-based SMI in cirrhosis patients with sarcopenic obesity,” the investigators concluded. “US may serve as an easy-to-use, point-of-care tool for assessing sarcopenia in sarcopenic obesity with the advantage of repeated sequential assessment.”

According to Jamile Wakim-Fleming, MD, of the Cleveland Clinic, “US-based muscle mass assessment seems to be reliable, reproducible, and simple to perform and should be encouraged along with nutrition assessments in all patients with cirrhosis and obesity.”

In a written comment, Dr. Wakim-Fleming noted the importance of timely monitoring and intervention in this patient population.

“Considering the morbidity and the poor outcomes associated with sarcopenic obesity and its frequency in cirrhosis, it is important to make early diagnosis and institute a management plan to improve muscle mass and function,” she said.

The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Wakim-Fleming reported no relevant conflicts of interest.

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

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

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

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

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

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

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

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

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

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

The risk of developing incident heart failure is 1.5-times higher in people with nonalcoholic fatty liver disease (NAFLD) during a median follow-up of 10 years, according to a new meta-analysis.

The risk appears to increase with greater liver disease severity and was independent of age, sex, ethnicity, obesity, and the presence of diabetes, hypertension, and other common cardiovascular risk factors.

“Health care professionals should be aware that the risk of new-onset heart failure is moderately higher in patients with NAFLD,” senior author Giovanni Targher, MD, said in an interview.

“Because of the link between the two conditions, more careful surveillance of these patients will be needed,” said Dr. Targher, who is an associate professor of diabetes and endocrinology at the University of Verona (Italy). “In particular, the results of this meta-analysis highlight the need for a patient-centered, multidisciplinary, and holistic approach to manage both liver disease and cardiovascular risk in patients with NAFLD.”

The study was published online in Gut.
 

Risk calculations

NAFLD has become one of the most common causes of chronic liver disease worldwide (affecting up to about 30% of the world’s adults), and is expected to rise sharply in the next decade, the study authors write. The disease is linked with liver-related conditions, such as nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, as well as complications in other organs.

Previous meta-analyses have found an association between NAFLD and a higher risk of heart failure, though the analyses included a relatively small number of studies and a relatively modest sample size, Dr. Targher and colleagues write.

Since then, several new cohort studies have examined the association, which inspired a new meta-analysis.

The research team analyzed 11 observational cohort studies with aggregate data on more than 11 million middle-aged people from different countries, including nearly 3 million with NAFLD and nearly 98,000 cases of incident heart failure over a median follow-up of 10 years.

In the studies, NAFLD was diagnosed by serum liver enzyme levels, serum biomarkers or scores, diagnostic codes, imaging techniques, or liver histology. Four studies were conducted in the United States, three were conducted in South Korea, and four were carried out in Europe, including Finland, Sweden, and the United Kingdom.

Dr. Targher and colleagues found that the presence of NAFLD was associated with a moderately higher risk of new-onset heart failure, with a pooled random-effects hazard ratio of 1.5. The risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other typical cardiovascular risk factors.

The association between NAFLD and heart failure risk was consistent even when the comparison was stratified by study country, follow-up length, modality of heart failure diagnosis, and modality of NAFLD diagnosis.

In addition, sensitivity analyses didn’t change the results, and a funnel plot suggested that publication bias was unlikely.

“Accumulating evidence supports that NAFLD is part of a multisystem disease that adversely affects several extrahepatic organs, including the heart,” Dr. Targher said.

“NAFLD not only promotes accelerated coronary atherosclerosis but also confers a higher risk of myocardial abnormalities (cardiac remodeling and hypertrophy) and certain arrhythmias (mostly atrial fibrillation), which may precede and promote the development of new-onset heart failure over time,” he said.
 

Future research

Dr. Targher and colleagues also found that the risk of incident heart failure appeared to further increase with more advanced liver disease, particularly with higher levels of liver fibrosis, as assessed by noninvasive fibrosis biomarkers or histology. With only two cohort studies that examined the association, the authors judged there was insufficient data available to combine the studies into a meta-analysis.

But the observations are consistent with other recent meta-analyses that reported a significant association between the presence and severity of NAFLD and the risk of developing adverse cardiovascular outcomes, atrial fibrillation, chronic kidney disease, or other non-liver complications.

“It’s reassuring that the observations that have come from single studies hold true when you look at the totality of evidence,” Ambarish Pandey, MD, a cardiologist and assistant professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas, told this news organization.

Dr. Pandey, who wasn’t involved with this study, conducted one of the recent meta-analyses that found a 1.6-times increased risk of heart failure associated with NAFLD, as well as a further increased risk with more advanced liver disease.

Now Dr. Pandey and colleagues are studying the underlying mechanisms for the link between NAFLD and heart failure risk, including cardiac structure and function, biomarkers of injury and stress, and how proportions of liver fat influence risk. Additional studies should investigate whether resolving NAFLD could reduce the risk of heart failure, he said.

“It’s really important to look for patients with NAFLD in primary care and think about cardiovascular disease in our liver patients,” he said. “Early strategies to implement the prevention of heart failure would go a long way in reducing long-term risks for these patients.”

The study authors did not declare a specific grant for this research from any funding agency in the public, commercial, or nonprofit sectors. Dr. Targher and Dr. Pandey report no relevant financial relationships.

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

Reinfection rates are low after treating hepatitis C virus in people taking opioid agonist therapy (OAT), even among those who still inject drugs, according to a new study.

The findings, which are based on prospective data from 13 countries, including the United States, and were published in Annals of Internal Medicine (2022 Aug 8. doi: 10.7326/M21-4119), should encourage physicians to treat HCV in people with a history of injection drug use, said lead author Jason Grebely, PhD. They should also pressure payers to lift reimbursement restrictions on the same population.

“Direct-acting antiviral medications for HCV infection are safe and effective among people receiving OAT and people with recent injecting-drug use,” the investigators wrote. “Concerns remain, however, that HCV reinfection may reduce the benefits of cure among people who inject drugs and compromise HCV elimination efforts.”

They explored these concerns through a 3-year extension of the phase 3 CO-STAR trial that evaluated elbasvir and grazoprevir in people consistently taking OAT. Participants in the CO-STAR trial, which had a 96% sustained virologic response rate among those who completed therapy, could elect to participate in the present study, offering a prospective look at long-term reinfection.

Out of 296 participants in the CO-STAR trial, 286 were evaluable for reinfection and 199 enrolled in the present extension. The majority were White (79.4%) and male (75.9%), with most taking methadone (79%), followed by buprenorphine (20%). At 6 months, 40 out of 191 respondents (21%) reported injection-drug use in the previous month. At the 3-year mark, 26 out of 142 respondents (18%) disclosed injection-drug use in the previous month.

For all participants in the CO-STAR trial, the overall rate of reinfection at 3 years was 1.7 per 100 person-years (95% confidence interval, 0.8-3.0), which is lower than the rate reported in systematic reviews (3.8 per 100 person-years), according to the investigators.

In the extension analysis, the 3-year reinfection rate was lower still, at 1.2 per 100 person-years. The rate was slightly higher among people who reported injection-drug use in the previous month (1.9 per 100 person-years), and slightly lower among those who did not report injection-drug use in the prior month (0.5 per 100 person-years). More pronounced differences in reinfection were observed among participants who shared needles (6.4 per 100 person-years), versus those who didn’t share needles (1.5 per 100 person years).
 

Low reinfection rate may help facilitate removal of reimbursement restrictions

“Most of the reinfections in this study occurred within 24 weeks of completing treatment, suggesting that this is a key period for optimizing treatment of opioid use disorder and for providing access to needle and syringe programs that have documented benefits in preventing HCV transmission,” the investigators wrote.

This is one of the largest observational studies of its kind to date, bolstered by “excellent study retention” and a “well-characterized cohort,” with findings that should prompt real-world action, said Dr. Grebely, who is head of the hepatitis C and drug use group in the viral hepatitis clinical research program at the Kirby Institute, University of New South Wales, Sydney.

“Given that reinfection has often been cited ... by some providers as a reason for not offering treatment to people receiving OAT, the low reinfection rate in this study will be incredibly important for guiding practice and ensuring therapy is not withheld from this group,” Dr. Grebely said in an interview. “In terms of policy implications, these data may also help to facilitate the removal of reimbursement restrictions based on recent drug/alcohol use criteria that are in place among many payers in the United States.”
 

More research needed to determine optimal intervention strategies

Carl Latkin, PhD, professor and vice chair of the department of health, behavior, and society at Johns Hopkins University, Baltimore, called the present publication a “great article and well-done study with long-term follow-up.”

Dr. Latkin, who investigates biobehavioral interventions for disadvantaged communities, said the reported rate of reinfection is “very low among a group of current and former injectors.”

Affirming Dr. Grebely’s call for supportive practices by physicians and payers, Dr. Latkin said: “The study highlights the importance of improving access to medication for opioid use disorder. This level of treatment adherence in this group is much higher than for many other medications. Given these data, it would be difficult for payers to have a rational reason for blanket restrictions for HCV treatment among people who use drugs.”

Dr. Latkin explained that “it isn’t simply injection drug use per se” that drives HCV reinfection; instead, he cited social factors, such as lack of housing, as well as withdrawal symptoms, especially among those without access to medications for opioid use disorder (MOUD).

Dr. Latkin and Grebely also agreed that more research is needed to determine optimal intervention strategies.

Dr. Grebely called for one to enhance HCV testing and linkage to care, a topic he covered in a recent review article (Lancet Gastroenterol Hepatol. 2022 May;7[5]:426-45.).

Dr. Latkin said that, while it’s clear that “syringe services programs, accessible HCV treatment, and MOUD are needed,” it is unclear how much coverage is necessary for a given population.

Findings support critical nature of needle and syringe exchange programs

Sarah M. Kattakuzhy, MD, an associate professor in the division of clinical care & research at the Institute of Human Virology, University of Maryland, Baltimore, agreed that the findings “support the critical nature of needle and syringe exchange programs.”

“As most cities in the United States fall well below the high coverage needle and syringe program threshold required to maximally prevent disease transmission, the study serves as a push toward an evidence-based harm reduction policy,” she said.

Dr. Kattakuzhy he added that the study “supports the need to longitudinally engage individuals after HCV treatment to monitor reinfection risk behaviors and test for reinfection,” she continued.

When it came to translating all the data to populations in the United States, she offered a more guarded view.

“Critically, the study population included only individuals who were engaged with OAT and adherent for 3 or more months, selecting to a population of individuals with high adherence and engagement in care,” Dr. Kattakuzhy said in an interview. “As such, the study findings are not applicable to other cross sections of the drug-using community, including individuals not engaged in OAT, and cohorts with higher rates of ongoing injection drug use. Furthermore, there are known genetic impacts on spontaneous clearance, and emerging data on the immunology of reinfection.

“Studies with a focus on less engaged, higher-risk, and minority populations with active drug use are required to answer the remaining questions in HCV reinfection,” she said.

The study was supported by Merck, the Australian Government Department of Health, and the Australian National Health and Medical Research Council. Dr. Grebely disclosed receiving funding from Cepheid, the manufacturer of the Xpert HCV assay. The other investigators disclosed additional relationships with Gilead, AbbVie, Cepheid, and others. Dr. Latkin and Dr. Kattakuzhy disclosed no relevant conflicts of interest.

Reinfection rates are low after treating hepatitis C virus in people taking opioid agonist therapy (OAT), even among those who still inject drugs, according to a new study.

The findings, which are based on prospective data from 13 countries, including the United States, and were published in Annals of Internal Medicine (2022 Aug 8. doi: 10.7326/M21-4119), should encourage physicians to treat HCV in people with a history of injection drug use, said lead author Jason Grebely, PhD. They should also pressure payers to lift reimbursement restrictions on the same population.

“Direct-acting antiviral medications for HCV infection are safe and effective among people receiving OAT and people with recent injecting-drug use,” the investigators wrote. “Concerns remain, however, that HCV reinfection may reduce the benefits of cure among people who inject drugs and compromise HCV elimination efforts.”

They explored these concerns through a 3-year extension of the phase 3 CO-STAR trial that evaluated elbasvir and grazoprevir in people consistently taking OAT. Participants in the CO-STAR trial, which had a 96% sustained virologic response rate among those who completed therapy, could elect to participate in the present study, offering a prospective look at long-term reinfection.

Out of 296 participants in the CO-STAR trial, 286 were evaluable for reinfection and 199 enrolled in the present extension. The majority were White (79.4%) and male (75.9%), with most taking methadone (79%), followed by buprenorphine (20%). At 6 months, 40 out of 191 respondents (21%) reported injection-drug use in the previous month. At the 3-year mark, 26 out of 142 respondents (18%) disclosed injection-drug use in the previous month.

For all participants in the CO-STAR trial, the overall rate of reinfection at 3 years was 1.7 per 100 person-years (95% confidence interval, 0.8-3.0), which is lower than the rate reported in systematic reviews (3.8 per 100 person-years), according to the investigators.

In the extension analysis, the 3-year reinfection rate was lower still, at 1.2 per 100 person-years. The rate was slightly higher among people who reported injection-drug use in the previous month (1.9 per 100 person-years), and slightly lower among those who did not report injection-drug use in the prior month (0.5 per 100 person-years). More pronounced differences in reinfection were observed among participants who shared needles (6.4 per 100 person-years), versus those who didn’t share needles (1.5 per 100 person years).
 

Low reinfection rate may help facilitate removal of reimbursement restrictions

“Most of the reinfections in this study occurred within 24 weeks of completing treatment, suggesting that this is a key period for optimizing treatment of opioid use disorder and for providing access to needle and syringe programs that have documented benefits in preventing HCV transmission,” the investigators wrote.

This is one of the largest observational studies of its kind to date, bolstered by “excellent study retention” and a “well-characterized cohort,” with findings that should prompt real-world action, said Dr. Grebely, who is head of the hepatitis C and drug use group in the viral hepatitis clinical research program at the Kirby Institute, University of New South Wales, Sydney.

“Given that reinfection has often been cited ... by some providers as a reason for not offering treatment to people receiving OAT, the low reinfection rate in this study will be incredibly important for guiding practice and ensuring therapy is not withheld from this group,” Dr. Grebely said in an interview. “In terms of policy implications, these data may also help to facilitate the removal of reimbursement restrictions based on recent drug/alcohol use criteria that are in place among many payers in the United States.”
 

More research needed to determine optimal intervention strategies

Carl Latkin, PhD, professor and vice chair of the department of health, behavior, and society at Johns Hopkins University, Baltimore, called the present publication a “great article and well-done study with long-term follow-up.”

Dr. Latkin, who investigates biobehavioral interventions for disadvantaged communities, said the reported rate of reinfection is “very low among a group of current and former injectors.”

Affirming Dr. Grebely’s call for supportive practices by physicians and payers, Dr. Latkin said: “The study highlights the importance of improving access to medication for opioid use disorder. This level of treatment adherence in this group is much higher than for many other medications. Given these data, it would be difficult for payers to have a rational reason for blanket restrictions for HCV treatment among people who use drugs.”

Dr. Latkin explained that “it isn’t simply injection drug use per se” that drives HCV reinfection; instead, he cited social factors, such as lack of housing, as well as withdrawal symptoms, especially among those without access to medications for opioid use disorder (MOUD).

Dr. Latkin and Grebely also agreed that more research is needed to determine optimal intervention strategies.

Dr. Grebely called for one to enhance HCV testing and linkage to care, a topic he covered in a recent review article (Lancet Gastroenterol Hepatol. 2022 May;7[5]:426-45.).

Dr. Latkin said that, while it’s clear that “syringe services programs, accessible HCV treatment, and MOUD are needed,” it is unclear how much coverage is necessary for a given population.

Findings support critical nature of needle and syringe exchange programs

Sarah M. Kattakuzhy, MD, an associate professor in the division of clinical care & research at the Institute of Human Virology, University of Maryland, Baltimore, agreed that the findings “support the critical nature of needle and syringe exchange programs.”

“As most cities in the United States fall well below the high coverage needle and syringe program threshold required to maximally prevent disease transmission, the study serves as a push toward an evidence-based harm reduction policy,” she said.

Dr. Kattakuzhy he added that the study “supports the need to longitudinally engage individuals after HCV treatment to monitor reinfection risk behaviors and test for reinfection,” she continued.

When it came to translating all the data to populations in the United States, she offered a more guarded view.

“Critically, the study population included only individuals who were engaged with OAT and adherent for 3 or more months, selecting to a population of individuals with high adherence and engagement in care,” Dr. Kattakuzhy said in an interview. “As such, the study findings are not applicable to other cross sections of the drug-using community, including individuals not engaged in OAT, and cohorts with higher rates of ongoing injection drug use. Furthermore, there are known genetic impacts on spontaneous clearance, and emerging data on the immunology of reinfection.

“Studies with a focus on less engaged, higher-risk, and minority populations with active drug use are required to answer the remaining questions in HCV reinfection,” she said.

The study was supported by Merck, the Australian Government Department of Health, and the Australian National Health and Medical Research Council. Dr. Grebely disclosed receiving funding from Cepheid, the manufacturer of the Xpert HCV assay. The other investigators disclosed additional relationships with Gilead, AbbVie, Cepheid, and others. Dr. Latkin and Dr. Kattakuzhy disclosed no relevant conflicts of interest.

Reinfection rates are low after treating hepatitis C virus in people taking opioid agonist therapy (OAT), even among those who still inject drugs, according to a new study.

The findings, which are based on prospective data from 13 countries, including the United States, and were published in Annals of Internal Medicine (2022 Aug 8. doi: 10.7326/M21-4119), should encourage physicians to treat HCV in people with a history of injection drug use, said lead author Jason Grebely, PhD. They should also pressure payers to lift reimbursement restrictions on the same population.

“Direct-acting antiviral medications for HCV infection are safe and effective among people receiving OAT and people with recent injecting-drug use,” the investigators wrote. “Concerns remain, however, that HCV reinfection may reduce the benefits of cure among people who inject drugs and compromise HCV elimination efforts.”

They explored these concerns through a 3-year extension of the phase 3 CO-STAR trial that evaluated elbasvir and grazoprevir in people consistently taking OAT. Participants in the CO-STAR trial, which had a 96% sustained virologic response rate among those who completed therapy, could elect to participate in the present study, offering a prospective look at long-term reinfection.

Out of 296 participants in the CO-STAR trial, 286 were evaluable for reinfection and 199 enrolled in the present extension. The majority were White (79.4%) and male (75.9%), with most taking methadone (79%), followed by buprenorphine (20%). At 6 months, 40 out of 191 respondents (21%) reported injection-drug use in the previous month. At the 3-year mark, 26 out of 142 respondents (18%) disclosed injection-drug use in the previous month.

For all participants in the CO-STAR trial, the overall rate of reinfection at 3 years was 1.7 per 100 person-years (95% confidence interval, 0.8-3.0), which is lower than the rate reported in systematic reviews (3.8 per 100 person-years), according to the investigators.

In the extension analysis, the 3-year reinfection rate was lower still, at 1.2 per 100 person-years. The rate was slightly higher among people who reported injection-drug use in the previous month (1.9 per 100 person-years), and slightly lower among those who did not report injection-drug use in the prior month (0.5 per 100 person-years). More pronounced differences in reinfection were observed among participants who shared needles (6.4 per 100 person-years), versus those who didn’t share needles (1.5 per 100 person years).
 

Low reinfection rate may help facilitate removal of reimbursement restrictions

“Most of the reinfections in this study occurred within 24 weeks of completing treatment, suggesting that this is a key period for optimizing treatment of opioid use disorder and for providing access to needle and syringe programs that have documented benefits in preventing HCV transmission,” the investigators wrote.

This is one of the largest observational studies of its kind to date, bolstered by “excellent study retention” and a “well-characterized cohort,” with findings that should prompt real-world action, said Dr. Grebely, who is head of the hepatitis C and drug use group in the viral hepatitis clinical research program at the Kirby Institute, University of New South Wales, Sydney.

“Given that reinfection has often been cited ... by some providers as a reason for not offering treatment to people receiving OAT, the low reinfection rate in this study will be incredibly important for guiding practice and ensuring therapy is not withheld from this group,” Dr. Grebely said in an interview. “In terms of policy implications, these data may also help to facilitate the removal of reimbursement restrictions based on recent drug/alcohol use criteria that are in place among many payers in the United States.”
 

More research needed to determine optimal intervention strategies

Carl Latkin, PhD, professor and vice chair of the department of health, behavior, and society at Johns Hopkins University, Baltimore, called the present publication a “great article and well-done study with long-term follow-up.”

Dr. Latkin, who investigates biobehavioral interventions for disadvantaged communities, said the reported rate of reinfection is “very low among a group of current and former injectors.”

Affirming Dr. Grebely’s call for supportive practices by physicians and payers, Dr. Latkin said: “The study highlights the importance of improving access to medication for opioid use disorder. This level of treatment adherence in this group is much higher than for many other medications. Given these data, it would be difficult for payers to have a rational reason for blanket restrictions for HCV treatment among people who use drugs.”

Dr. Latkin explained that “it isn’t simply injection drug use per se” that drives HCV reinfection; instead, he cited social factors, such as lack of housing, as well as withdrawal symptoms, especially among those without access to medications for opioid use disorder (MOUD).

Dr. Latkin and Grebely also agreed that more research is needed to determine optimal intervention strategies.

Dr. Grebely called for one to enhance HCV testing and linkage to care, a topic he covered in a recent review article (Lancet Gastroenterol Hepatol. 2022 May;7[5]:426-45.).

Dr. Latkin said that, while it’s clear that “syringe services programs, accessible HCV treatment, and MOUD are needed,” it is unclear how much coverage is necessary for a given population.

Findings support critical nature of needle and syringe exchange programs

Sarah M. Kattakuzhy, MD, an associate professor in the division of clinical care & research at the Institute of Human Virology, University of Maryland, Baltimore, agreed that the findings “support the critical nature of needle and syringe exchange programs.”

“As most cities in the United States fall well below the high coverage needle and syringe program threshold required to maximally prevent disease transmission, the study serves as a push toward an evidence-based harm reduction policy,” she said.

Dr. Kattakuzhy he added that the study “supports the need to longitudinally engage individuals after HCV treatment to monitor reinfection risk behaviors and test for reinfection,” she continued.

When it came to translating all the data to populations in the United States, she offered a more guarded view.

“Critically, the study population included only individuals who were engaged with OAT and adherent for 3 or more months, selecting to a population of individuals with high adherence and engagement in care,” Dr. Kattakuzhy said in an interview. “As such, the study findings are not applicable to other cross sections of the drug-using community, including individuals not engaged in OAT, and cohorts with higher rates of ongoing injection drug use. Furthermore, there are known genetic impacts on spontaneous clearance, and emerging data on the immunology of reinfection.

“Studies with a focus on less engaged, higher-risk, and minority populations with active drug use are required to answer the remaining questions in HCV reinfection,” she said.

The study was supported by Merck, the Australian Government Department of Health, and the Australian National Health and Medical Research Council. Dr. Grebely disclosed receiving funding from Cepheid, the manufacturer of the Xpert HCV assay. The other investigators disclosed additional relationships with Gilead, AbbVie, Cepheid, and others. Dr. Latkin and Dr. Kattakuzhy disclosed no relevant conflicts of interest.