Hepatology

SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.

Jim Kling/MDedge News

The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.

“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.

She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.

It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.

“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.

Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.

The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.

“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.

She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
 

SOURCE: AASLD 2018, Abstract 0249.

SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.

Jim Kling/MDedge News

The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.

“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.

She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.

It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.

“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.

Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.

The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.

“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.

She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
 

SOURCE: AASLD 2018, Abstract 0249.

SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.

Jim Kling/MDedge News

The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.

“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.

She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.

It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.

“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.

Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.

The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.

“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.

She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
 

SOURCE: AASLD 2018, Abstract 0249.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

SAN FRANCISCO – The risk of malignancy among patients with nonalcoholic fatty liver disease (NAFLD) is 91% higher than it is among age- and sex-matched control subjects, with gastrointestinal sites being the most commonly affected.

Doug Brunk/MDedge News

Those are key findings from a community cohort study with up to 21 years of follow-up, which one of the authors, Alina M. Allen, MD, discussed during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases.

“NAFLD is the most common chronic liver disease in the Western world,” said Dr. Allen, a gastroenterologist at the Mayo Clinic, Rochester, Minn. “It affects one in four adults in the U.S. It is related to fat accumulation in the liver in people who are overweight or obese and can lead to cirrhosis and liver-related mortality. However, the most common cause of death in this population is not liver disease but malignancy and cardiovascular disease. There is a paucity of epidemiologic studies of extrahepatic cancer in NAFLD. It is not clear what types of cancers and how much higher their cancer risk is in reference to the general population.”

In an effort to determine the incidence of cancer diagnoses in NALFD, compared with controls, in a U.S. community, Dr. Allen and her colleagues drew from the Rochester Epidemiology Project to evaluate 4,791 adults diagnosed with NAFLD and 14,432 age- and sex-matched control subjects in Olmstead County, Minn., during 1997-2017. The researchers obtained corresponding Surveillance, Epidemiology, and End Results Program (SEER) rates as a quality check and used a regression model to assess the malignancy risk in NAFLD overall and by cancer type, age, sex, and body mass index. They recorded all new diagnoses of cancers that developed in both groups until 2018, for a total possible follow-up of 21 years, and they reported results in incidence rate ratios, a risk estimate similar to hazard ratios.


The mean age of the study population was 53 years, 53% were female, and the mean follow-up was 8 years with a range from 1 to 21 years. New cancers were identified in 16% of subjects with NALFD and in 12% of control subjects. The overall risk of malignancy was 91% higher in NAFLD subjects, compared with control subjects; there were higher rates in the NAFLD subjects for most types of cancers, but the largest increases were in GI cancers. The greatest malignancy risk was for cancer of the liver (RR, 3.24), followed by cancer of the uterus (RR, 2.39), stomach (RR, 2.34), pancreas (RR, 2.09), and colon (RR, 1.75). “Interestingly, the risk of colon cancer increased only in men but not in women,” Dr. Allen said. “These data provide an important hierarchical overview of the top most important malignancy risks associated with NAFLD that the medical community should be aware of.”

When the researchers looked for differences in age at cancer diagnosis between NAFLD and controls, they found that pancreas cancer occurred at a younger age among subjects with NAFLD. They also observed that colon cancer occurred at a younger age in men with NAFLD, but not in women with the disease. “What was most interesting to us was the assessment of cancer risk in NAFLD versus obesity alone,” Dr. Allen said. “Previous studies from the general population have linked obesity to a higher risk of cancer. Whether the presence of fatty liver disease would impact that risk has not been assessed. We showed that obesity is associated with a higher risk of cancer only in those with NAFLD, not in those without. If validated in independent cohorts, these findings could change our understanding of the relationship between obesity and cancer and the importance of screening for NAFLD – not only to risk-stratify liver disease but also for the risk of extrahepatic malignancy.”

Dr. Allen concluded her presentation by noting that findings from large population-based studies such as the Rochester Epidemiology Project “can offer important epidemiologic data regarding the biggest threats to the health of a community,” she said. “Such data increase awareness, enable appropriate counseling, and could inform screening policies. There is a signal in the fact that the GI cancers are increased [in NAFLD]. It’s an interesting signal that needs to be studied further.”

Dr. Allen reported having no financial conflicts.

[email protected]

Source: Allen AM. Hepatol. 2018;68[S1]: Abstract 31.

SAN FRANCISCO – The risk of malignancy among patients with nonalcoholic fatty liver disease (NAFLD) is 91% higher than it is among age- and sex-matched control subjects, with gastrointestinal sites being the most commonly affected.

Doug Brunk/MDedge News

Those are key findings from a community cohort study with up to 21 years of follow-up, which one of the authors, Alina M. Allen, MD, discussed during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases.

“NAFLD is the most common chronic liver disease in the Western world,” said Dr. Allen, a gastroenterologist at the Mayo Clinic, Rochester, Minn. “It affects one in four adults in the U.S. It is related to fat accumulation in the liver in people who are overweight or obese and can lead to cirrhosis and liver-related mortality. However, the most common cause of death in this population is not liver disease but malignancy and cardiovascular disease. There is a paucity of epidemiologic studies of extrahepatic cancer in NAFLD. It is not clear what types of cancers and how much higher their cancer risk is in reference to the general population.”

In an effort to determine the incidence of cancer diagnoses in NALFD, compared with controls, in a U.S. community, Dr. Allen and her colleagues drew from the Rochester Epidemiology Project to evaluate 4,791 adults diagnosed with NAFLD and 14,432 age- and sex-matched control subjects in Olmstead County, Minn., during 1997-2017. The researchers obtained corresponding Surveillance, Epidemiology, and End Results Program (SEER) rates as a quality check and used a regression model to assess the malignancy risk in NAFLD overall and by cancer type, age, sex, and body mass index. They recorded all new diagnoses of cancers that developed in both groups until 2018, for a total possible follow-up of 21 years, and they reported results in incidence rate ratios, a risk estimate similar to hazard ratios.


The mean age of the study population was 53 years, 53% were female, and the mean follow-up was 8 years with a range from 1 to 21 years. New cancers were identified in 16% of subjects with NALFD and in 12% of control subjects. The overall risk of malignancy was 91% higher in NAFLD subjects, compared with control subjects; there were higher rates in the NAFLD subjects for most types of cancers, but the largest increases were in GI cancers. The greatest malignancy risk was for cancer of the liver (RR, 3.24), followed by cancer of the uterus (RR, 2.39), stomach (RR, 2.34), pancreas (RR, 2.09), and colon (RR, 1.75). “Interestingly, the risk of colon cancer increased only in men but not in women,” Dr. Allen said. “These data provide an important hierarchical overview of the top most important malignancy risks associated with NAFLD that the medical community should be aware of.”

When the researchers looked for differences in age at cancer diagnosis between NAFLD and controls, they found that pancreas cancer occurred at a younger age among subjects with NAFLD. They also observed that colon cancer occurred at a younger age in men with NAFLD, but not in women with the disease. “What was most interesting to us was the assessment of cancer risk in NAFLD versus obesity alone,” Dr. Allen said. “Previous studies from the general population have linked obesity to a higher risk of cancer. Whether the presence of fatty liver disease would impact that risk has not been assessed. We showed that obesity is associated with a higher risk of cancer only in those with NAFLD, not in those without. If validated in independent cohorts, these findings could change our understanding of the relationship between obesity and cancer and the importance of screening for NAFLD – not only to risk-stratify liver disease but also for the risk of extrahepatic malignancy.”

Dr. Allen concluded her presentation by noting that findings from large population-based studies such as the Rochester Epidemiology Project “can offer important epidemiologic data regarding the biggest threats to the health of a community,” she said. “Such data increase awareness, enable appropriate counseling, and could inform screening policies. There is a signal in the fact that the GI cancers are increased [in NAFLD]. It’s an interesting signal that needs to be studied further.”

Dr. Allen reported having no financial conflicts.

[email protected]

Source: Allen AM. Hepatol. 2018;68[S1]: Abstract 31.

SAN FRANCISCO – The risk of malignancy among patients with nonalcoholic fatty liver disease (NAFLD) is 91% higher than it is among age- and sex-matched control subjects, with gastrointestinal sites being the most commonly affected.

Doug Brunk/MDedge News

Those are key findings from a community cohort study with up to 21 years of follow-up, which one of the authors, Alina M. Allen, MD, discussed during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases.

“NAFLD is the most common chronic liver disease in the Western world,” said Dr. Allen, a gastroenterologist at the Mayo Clinic, Rochester, Minn. “It affects one in four adults in the U.S. It is related to fat accumulation in the liver in people who are overweight or obese and can lead to cirrhosis and liver-related mortality. However, the most common cause of death in this population is not liver disease but malignancy and cardiovascular disease. There is a paucity of epidemiologic studies of extrahepatic cancer in NAFLD. It is not clear what types of cancers and how much higher their cancer risk is in reference to the general population.”

In an effort to determine the incidence of cancer diagnoses in NALFD, compared with controls, in a U.S. community, Dr. Allen and her colleagues drew from the Rochester Epidemiology Project to evaluate 4,791 adults diagnosed with NAFLD and 14,432 age- and sex-matched control subjects in Olmstead County, Minn., during 1997-2017. The researchers obtained corresponding Surveillance, Epidemiology, and End Results Program (SEER) rates as a quality check and used a regression model to assess the malignancy risk in NAFLD overall and by cancer type, age, sex, and body mass index. They recorded all new diagnoses of cancers that developed in both groups until 2018, for a total possible follow-up of 21 years, and they reported results in incidence rate ratios, a risk estimate similar to hazard ratios.


The mean age of the study population was 53 years, 53% were female, and the mean follow-up was 8 years with a range from 1 to 21 years. New cancers were identified in 16% of subjects with NALFD and in 12% of control subjects. The overall risk of malignancy was 91% higher in NAFLD subjects, compared with control subjects; there were higher rates in the NAFLD subjects for most types of cancers, but the largest increases were in GI cancers. The greatest malignancy risk was for cancer of the liver (RR, 3.24), followed by cancer of the uterus (RR, 2.39), stomach (RR, 2.34), pancreas (RR, 2.09), and colon (RR, 1.75). “Interestingly, the risk of colon cancer increased only in men but not in women,” Dr. Allen said. “These data provide an important hierarchical overview of the top most important malignancy risks associated with NAFLD that the medical community should be aware of.”

When the researchers looked for differences in age at cancer diagnosis between NAFLD and controls, they found that pancreas cancer occurred at a younger age among subjects with NAFLD. They also observed that colon cancer occurred at a younger age in men with NAFLD, but not in women with the disease. “What was most interesting to us was the assessment of cancer risk in NAFLD versus obesity alone,” Dr. Allen said. “Previous studies from the general population have linked obesity to a higher risk of cancer. Whether the presence of fatty liver disease would impact that risk has not been assessed. We showed that obesity is associated with a higher risk of cancer only in those with NAFLD, not in those without. If validated in independent cohorts, these findings could change our understanding of the relationship between obesity and cancer and the importance of screening for NAFLD – not only to risk-stratify liver disease but also for the risk of extrahepatic malignancy.”

Dr. Allen concluded her presentation by noting that findings from large population-based studies such as the Rochester Epidemiology Project “can offer important epidemiologic data regarding the biggest threats to the health of a community,” she said. “Such data increase awareness, enable appropriate counseling, and could inform screening policies. There is a signal in the fact that the GI cancers are increased [in NAFLD]. It’s an interesting signal that needs to be studied further.”

Dr. Allen reported having no financial conflicts.

[email protected]

Source: Allen AM. Hepatol. 2018;68[S1]: Abstract 31.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

SAN FRANCISCO – In a phase 2 clinical trial of nonalcoholic steatohepatitis (NASH), the thyroid hormone receptor (THR)–beta agonist MCL-3196 improved various measures of liver function and led to significant levels of NASH resolution.

Jim Kling/MDedge News

“I think this is an ideal candidate to take into a registration trial for patients with NASH that have stage 2-3 fibrosis,” Stephen Harrison, MD, a visiting professor of hepatology at the University of Oxford (England), said in an interview. He presented the results at the annual meeting of the American Association for the Study of Liver Diseases.

THR-beta acts primarily through nuclear receptors, where it alters gene expression in target cells. THR-beta agonism can lead to a wide range of physiological effects, including reduction of LDL cholesterol, triglycerides, and liver fat. The latter activity has the potential to reduce lipotoxicity and improve NASH. According to a press release from drug sponsor Madrigal Pharmaceuticals, MCL-3196 is more selective for THR-beta than previous drug candidates and is also targeted to the liver, a combination the company hopes will avoid toxicities and nontarget effects that hampered previous THR-beta agonist development.

The study did not include patients with cirrhosis, and the researchers aren’t yet ready to test that population. “Everyone wants to jump into cirrhosis, but cirrhotic patients are a tougher nut to crack,” Dr. Harrison said. “There are a lot nuances – there is well-compensated cirrhosis, and cirrhosis with portal hypertension, and then there’s decompensation. We need to carefully, methodically, study the milder cirrhotics, and then those with portal hypertension that is clinically significant, and then decompensation as a last resort. But if you don’t show that in early phase development, then in my opinion we shouldn’t go to phase 3 in a cirrhotic population.”

The phase 2 study included 18 sites in the United States. The researchers randomly assigned 84 patients to MGL-3196 and 41 to placebo. The treatment group received 80 mg oral MGL-3196 once per day, with an option to adjust the dose 20 mg higher or lower at week 4. All patients underwent liver biopsy at baseline and again at 36 weeks.

At 12 weeks, there was a 36% relative reduction in fat across all patients taking MGL-3196, compared with a 10% reduction in the placebo group (P less than .0001). The difference at 36 weeks was 37% versus 8% (P less than .0001). In a predefined group who received high exposure to MCL-3196, the fat reduction was 42% at 12 weeks and 49% at 36 weeks.

At 36 weeks, 68% of all comers on the drug had lost at least 30% of liver fat, compared with 18% in the placebo group (P less than .0001). A total of 77% in the high-exposure group had a similar outcome (P less than .0001), as did 68% of patients with fibrosis stage 2 or 3 (P = .009).

The researchers also found a reduction at 36 weeks in liver enzyme levels among patients in the treatment group who had elevated levels at baseline, including a 40% reduction in ALT, compared with placebo (P = .01). There were smaller, but still significant, reductions in AST and gamma-glutamyltransferase at week 36 in the treatment group, compared with placebo (P = .002 for both).

A 2-point reduction in Nonalcoholic Fatty Liver Disease Activity Score occurred at week 36 in 32% of placebo subjects, compared with 51% (P = .09) of all patients in the treatment group and 61% of the high-exposure group (P = .02). Among patients judged to have been responders based on MRI, 65% had a 2-point reduction (P = .006). NASH resolution occurred in 6% of the placebo group, 27% of the treatment group (P = .02), and 39% of MRI responders (P = .003).

Adverse events were mild and similar between the treatment group and placebo, with the exception of loose stools, which were single events restricted to the initiation of therapy.

The study was funded by Madrigal Pharmaceuticals. Dr. Harrison is a consultant for Madrigal.

SAN FRANCISCO – Chronic liver disease (CLD) is independently associated with an increased risk of falls and fall injuries, results from a large study of nationally representative data showed.

Doug Brunk/MDedge News

“We have previously known that having cirrhosis, for example, is associated with the risk of falling, but we didn’t have any data from a nationally representative sample,” lead study author Maria Camila Pérez-Matos, MD, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases. “What surprised us is that just by having chronic liver disease – any subtype – you’re more likely to fall, and also to have a fracture after you have fallen.”

In an effort to define the association between CLD and fall history and its related injuries, Dr. Pérez-Matos of the division of gastroenterology and hepatology at Beth Israel Deaconess Medical Center, Boston, and her associates examined data from 5,363 subjects aged 60 years and older in the Third National Health and Nutrition Examination Survey, which represents the noninstitutionalized civilian population in the United States. Their outcomes of interest were one or more falls occurring in the previous 12 months and fall-related injuries. The main exposure was definitive CLD, defined by chronic viral hepatitis (hepatitis C RNA or hepatitis B surface antigen), nonalcoholic steatohepatitis (NASH; hepatosteatosis by ultrasound with abnormal transaminases), and alcohol-related liver disease (females consuming more than 7 drinks/week and males consuming 14 drinks/week among, plus having abnormal transaminases). Suspected CLD was defined as having abnormal alanine aminotransferase levels (males greater than 30 IU/L, females greater than 19 IU/L), aspartate aminotransferase levels above 33 IU/L, or alkaline phosphatase levels above 100 IU/L. The researchers used univariate and multivariate logistic regression to examine associations.

The average age of subjects was 70 years, and 59% were female. Of the 5,363 subjects, 340 had definitive CLD. Of these, 234 (69%) had NASH, 85 (25%) had viral hepatitis, and 21 (6%) had alcoholic liver disease. Subjects with definitive CLD were more likely to be female and have diabetes mellitus, a higher body mass index, and physical/functional impairment. Dr. Pérez-Matos and her colleagues found that definitive CLD was associated with a 52% increase in the odds of having a history of falls (odds ratio, 1.52; P = .01). The association remained significant after controlling for age, sex, smoking, race, physical or functional impairment, impaired vision, polypharmacy, and body mass index. The degree of excess falling risk posed by CLD was similar to that of having impaired vision (OR, 1.48; P less than .001).

Of the CLD subtypes, subjects with viral hepatitis had the strongest association with a history of falls (OR, 2.2; P = .001). In addition, definitive CLD was found to have significant association with any physical impairment, even after adjusting for relevant covariates (OR, 1.63; P = .001).

Finally, multivariate logistic regression revealed that both suspected and definitive CLD were associated with injurious falls (OR, 1.40 and OR of 1.67, respectively). “Everyone is interested in preventing falls because of its public health impact, and predictors of falls are relatively limited,” said Elliott B. Tapper, MD, the study’s principal investigator, who is with the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor. “Because chronic liver disease is increasingly common, our data is speaking to a hitherto unknown risk factor: one which if you apply it to other data sets might help figure out why more people are falling. The lesson is, there’s something about chronic liver disease; it’s a sign. If it’s fatty liver disease, it’s a sign that diabetes has taken its toll on the body – its nerves and muscles. There’s something about what’s going on in that person that’s worse than it is for other people. We don’t know cause or effect, but the association is strong and deserves further study, particularly when it comes to determining [which patients] in our clinics are at higher risk and making sure they’re doing physical therapy to prevent falls in the future.”

Dr. Tapper disclosed that she has a career development award from the National Institutes of Health. Dr. Pérez-Matos reported having no monetary conflicts.

[email protected]

Source: Hepatol. 2018;68[S1], Abstract 756.

SAN FRANCISCO – Chronic liver disease (CLD) is independently associated with an increased risk of falls and fall injuries, results from a large study of nationally representative data showed.

Doug Brunk/MDedge News

“We have previously known that having cirrhosis, for example, is associated with the risk of falling, but we didn’t have any data from a nationally representative sample,” lead study author Maria Camila Pérez-Matos, MD, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases. “What surprised us is that just by having chronic liver disease – any subtype – you’re more likely to fall, and also to have a fracture after you have fallen.”

In an effort to define the association between CLD and fall history and its related injuries, Dr. Pérez-Matos of the division of gastroenterology and hepatology at Beth Israel Deaconess Medical Center, Boston, and her associates examined data from 5,363 subjects aged 60 years and older in the Third National Health and Nutrition Examination Survey, which represents the noninstitutionalized civilian population in the United States. Their outcomes of interest were one or more falls occurring in the previous 12 months and fall-related injuries. The main exposure was definitive CLD, defined by chronic viral hepatitis (hepatitis C RNA or hepatitis B surface antigen), nonalcoholic steatohepatitis (NASH; hepatosteatosis by ultrasound with abnormal transaminases), and alcohol-related liver disease (females consuming more than 7 drinks/week and males consuming 14 drinks/week among, plus having abnormal transaminases). Suspected CLD was defined as having abnormal alanine aminotransferase levels (males greater than 30 IU/L, females greater than 19 IU/L), aspartate aminotransferase levels above 33 IU/L, or alkaline phosphatase levels above 100 IU/L. The researchers used univariate and multivariate logistic regression to examine associations.

The average age of subjects was 70 years, and 59% were female. Of the 5,363 subjects, 340 had definitive CLD. Of these, 234 (69%) had NASH, 85 (25%) had viral hepatitis, and 21 (6%) had alcoholic liver disease. Subjects with definitive CLD were more likely to be female and have diabetes mellitus, a higher body mass index, and physical/functional impairment. Dr. Pérez-Matos and her colleagues found that definitive CLD was associated with a 52% increase in the odds of having a history of falls (odds ratio, 1.52; P = .01). The association remained significant after controlling for age, sex, smoking, race, physical or functional impairment, impaired vision, polypharmacy, and body mass index. The degree of excess falling risk posed by CLD was similar to that of having impaired vision (OR, 1.48; P less than .001).

Of the CLD subtypes, subjects with viral hepatitis had the strongest association with a history of falls (OR, 2.2; P = .001). In addition, definitive CLD was found to have significant association with any physical impairment, even after adjusting for relevant covariates (OR, 1.63; P = .001).

Finally, multivariate logistic regression revealed that both suspected and definitive CLD were associated with injurious falls (OR, 1.40 and OR of 1.67, respectively). “Everyone is interested in preventing falls because of its public health impact, and predictors of falls are relatively limited,” said Elliott B. Tapper, MD, the study’s principal investigator, who is with the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor. “Because chronic liver disease is increasingly common, our data is speaking to a hitherto unknown risk factor: one which if you apply it to other data sets might help figure out why more people are falling. The lesson is, there’s something about chronic liver disease; it’s a sign. If it’s fatty liver disease, it’s a sign that diabetes has taken its toll on the body – its nerves and muscles. There’s something about what’s going on in that person that’s worse than it is for other people. We don’t know cause or effect, but the association is strong and deserves further study, particularly when it comes to determining [which patients] in our clinics are at higher risk and making sure they’re doing physical therapy to prevent falls in the future.”

Dr. Tapper disclosed that she has a career development award from the National Institutes of Health. Dr. Pérez-Matos reported having no monetary conflicts.

[email protected]

Source: Hepatol. 2018;68[S1], Abstract 756.

SAN FRANCISCO – Chronic liver disease (CLD) is independently associated with an increased risk of falls and fall injuries, results from a large study of nationally representative data showed.

Doug Brunk/MDedge News

“We have previously known that having cirrhosis, for example, is associated with the risk of falling, but we didn’t have any data from a nationally representative sample,” lead study author Maria Camila Pérez-Matos, MD, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases. “What surprised us is that just by having chronic liver disease – any subtype – you’re more likely to fall, and also to have a fracture after you have fallen.”

In an effort to define the association between CLD and fall history and its related injuries, Dr. Pérez-Matos of the division of gastroenterology and hepatology at Beth Israel Deaconess Medical Center, Boston, and her associates examined data from 5,363 subjects aged 60 years and older in the Third National Health and Nutrition Examination Survey, which represents the noninstitutionalized civilian population in the United States. Their outcomes of interest were one or more falls occurring in the previous 12 months and fall-related injuries. The main exposure was definitive CLD, defined by chronic viral hepatitis (hepatitis C RNA or hepatitis B surface antigen), nonalcoholic steatohepatitis (NASH; hepatosteatosis by ultrasound with abnormal transaminases), and alcohol-related liver disease (females consuming more than 7 drinks/week and males consuming 14 drinks/week among, plus having abnormal transaminases). Suspected CLD was defined as having abnormal alanine aminotransferase levels (males greater than 30 IU/L, females greater than 19 IU/L), aspartate aminotransferase levels above 33 IU/L, or alkaline phosphatase levels above 100 IU/L. The researchers used univariate and multivariate logistic regression to examine associations.

The average age of subjects was 70 years, and 59% were female. Of the 5,363 subjects, 340 had definitive CLD. Of these, 234 (69%) had NASH, 85 (25%) had viral hepatitis, and 21 (6%) had alcoholic liver disease. Subjects with definitive CLD were more likely to be female and have diabetes mellitus, a higher body mass index, and physical/functional impairment. Dr. Pérez-Matos and her colleagues found that definitive CLD was associated with a 52% increase in the odds of having a history of falls (odds ratio, 1.52; P = .01). The association remained significant after controlling for age, sex, smoking, race, physical or functional impairment, impaired vision, polypharmacy, and body mass index. The degree of excess falling risk posed by CLD was similar to that of having impaired vision (OR, 1.48; P less than .001).

Of the CLD subtypes, subjects with viral hepatitis had the strongest association with a history of falls (OR, 2.2; P = .001). In addition, definitive CLD was found to have significant association with any physical impairment, even after adjusting for relevant covariates (OR, 1.63; P = .001).

Finally, multivariate logistic regression revealed that both suspected and definitive CLD were associated with injurious falls (OR, 1.40 and OR of 1.67, respectively). “Everyone is interested in preventing falls because of its public health impact, and predictors of falls are relatively limited,” said Elliott B. Tapper, MD, the study’s principal investigator, who is with the division of gastroenterology and hepatology at the University of Michigan, Ann Arbor. “Because chronic liver disease is increasingly common, our data is speaking to a hitherto unknown risk factor: one which if you apply it to other data sets might help figure out why more people are falling. The lesson is, there’s something about chronic liver disease; it’s a sign. If it’s fatty liver disease, it’s a sign that diabetes has taken its toll on the body – its nerves and muscles. There’s something about what’s going on in that person that’s worse than it is for other people. We don’t know cause or effect, but the association is strong and deserves further study, particularly when it comes to determining [which patients] in our clinics are at higher risk and making sure they’re doing physical therapy to prevent falls in the future.”

Dr. Tapper disclosed that she has a career development award from the National Institutes of Health. Dr. Pérez-Matos reported having no monetary conflicts.

[email protected]

Source: Hepatol. 2018;68[S1], Abstract 756.

SAN FRANCISCO – The prevalence of PTSD among adult liver transplant recipients is about twice that of the general population and on par with other chronic diseases, results from a pilot study suggest.

Doug Brunk/MDedge News

“Serving the emotional and mental health of these patients is just as important as [improving] liver function and their immunosuppression,” study author Meg O’Meara, NP, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases.

Recent data suggests that patients who undergo significant medical events like solid organ transplantation face a risk of developing PTSD, but limited information exists regarding the psychological effects following adult liver transplantation, said Ms. O’Meara, a nurse practitioner in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. In an effort to determine the prevalence of and risk factors for PTSD in adult liver transplant recipients, she and her associates used the PCL-5 to screen 71 patients seen at the university’s posttransplant clinic from Dec. 1, 2017, to May 31, 2018. The PCL-5 is a validated 20-item questionnaire that corresponds to the DSM-5 symptom criteria for PTSD.

The researchers also collected clinical and demographic information including pretransplant disease severity, history of psychiatric disease, duration of transplant hospitalization, and need for rehospitalization. They used a multivariable regression model to evaluate associations between clinical and demographic variables and a positive screen for PTSD.

The median age of the 71 patients was 58 years; 61% were male. A preexisting diagnosis of depression was present in 25 patients (35%), their mean Model for End-Stage Liver Disease (MELD) score at time of transplant was 31, and their median time from transplant was 1,163 days. In all, nine patients (12.7%) tested positive for PTSD on the PCL-5, and all met criteria for a provisional diagnosis of PTSD based on the DSM-5 criteria. This prevalence is about two times higher than the prevalence of PTSD in the general population (6.7%), comparable with that reported for heart transplant recipients (10.8%) and coronary artery disease (9%), but lower than that reported for ICU patients (38%), HIV patients (35.3%), and in those with Crohn’s disease (19.1%).

On multivariable logistic regression, only three factors were found to be significantly associated with the development of PTSD: younger age at transplant (P = .019), history of depression (P = .008), and a history of PTSD (P less than .001). “What I found surprising was that the MELD score at the time of transplant and the number of readmissions or complications around the time of transplant were not predictive of PTSD,” Ms. O’Meara said.

One possible explanation for the finding of younger age being a predictor of PTSD, she continued, is that younger liver transplant patients may lack certain coping skills, compared with their older counterparts. “Maybe patients who have had more years to deal with their disease are more accepting of it and they learn how to use productive tools to manage it.”

In their abstract, the researchers acknowledged certain limitations of the study, including its cross-sectional design, small sample size, and lack of corresponding pretransplant data.

The researchers reported having no financial disclosures.

[email protected]

SAN FRANCISCO – The prevalence of PTSD among adult liver transplant recipients is about twice that of the general population and on par with other chronic diseases, results from a pilot study suggest.

Doug Brunk/MDedge News

“Serving the emotional and mental health of these patients is just as important as [improving] liver function and their immunosuppression,” study author Meg O’Meara, NP, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases.

Recent data suggests that patients who undergo significant medical events like solid organ transplantation face a risk of developing PTSD, but limited information exists regarding the psychological effects following adult liver transplantation, said Ms. O’Meara, a nurse practitioner in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. In an effort to determine the prevalence of and risk factors for PTSD in adult liver transplant recipients, she and her associates used the PCL-5 to screen 71 patients seen at the university’s posttransplant clinic from Dec. 1, 2017, to May 31, 2018. The PCL-5 is a validated 20-item questionnaire that corresponds to the DSM-5 symptom criteria for PTSD.

The researchers also collected clinical and demographic information including pretransplant disease severity, history of psychiatric disease, duration of transplant hospitalization, and need for rehospitalization. They used a multivariable regression model to evaluate associations between clinical and demographic variables and a positive screen for PTSD.

The median age of the 71 patients was 58 years; 61% were male. A preexisting diagnosis of depression was present in 25 patients (35%), their mean Model for End-Stage Liver Disease (MELD) score at time of transplant was 31, and their median time from transplant was 1,163 days. In all, nine patients (12.7%) tested positive for PTSD on the PCL-5, and all met criteria for a provisional diagnosis of PTSD based on the DSM-5 criteria. This prevalence is about two times higher than the prevalence of PTSD in the general population (6.7%), comparable with that reported for heart transplant recipients (10.8%) and coronary artery disease (9%), but lower than that reported for ICU patients (38%), HIV patients (35.3%), and in those with Crohn’s disease (19.1%).

On multivariable logistic regression, only three factors were found to be significantly associated with the development of PTSD: younger age at transplant (P = .019), history of depression (P = .008), and a history of PTSD (P less than .001). “What I found surprising was that the MELD score at the time of transplant and the number of readmissions or complications around the time of transplant were not predictive of PTSD,” Ms. O’Meara said.

One possible explanation for the finding of younger age being a predictor of PTSD, she continued, is that younger liver transplant patients may lack certain coping skills, compared with their older counterparts. “Maybe patients who have had more years to deal with their disease are more accepting of it and they learn how to use productive tools to manage it.”

In their abstract, the researchers acknowledged certain limitations of the study, including its cross-sectional design, small sample size, and lack of corresponding pretransplant data.

The researchers reported having no financial disclosures.

[email protected]

SAN FRANCISCO – The prevalence of PTSD among adult liver transplant recipients is about twice that of the general population and on par with other chronic diseases, results from a pilot study suggest.

Doug Brunk/MDedge News

“Serving the emotional and mental health of these patients is just as important as [improving] liver function and their immunosuppression,” study author Meg O’Meara, NP, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases.

Recent data suggests that patients who undergo significant medical events like solid organ transplantation face a risk of developing PTSD, but limited information exists regarding the psychological effects following adult liver transplantation, said Ms. O’Meara, a nurse practitioner in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. In an effort to determine the prevalence of and risk factors for PTSD in adult liver transplant recipients, she and her associates used the PCL-5 to screen 71 patients seen at the university’s posttransplant clinic from Dec. 1, 2017, to May 31, 2018. The PCL-5 is a validated 20-item questionnaire that corresponds to the DSM-5 symptom criteria for PTSD.

The researchers also collected clinical and demographic information including pretransplant disease severity, history of psychiatric disease, duration of transplant hospitalization, and need for rehospitalization. They used a multivariable regression model to evaluate associations between clinical and demographic variables and a positive screen for PTSD.

The median age of the 71 patients was 58 years; 61% were male. A preexisting diagnosis of depression was present in 25 patients (35%), their mean Model for End-Stage Liver Disease (MELD) score at time of transplant was 31, and their median time from transplant was 1,163 days. In all, nine patients (12.7%) tested positive for PTSD on the PCL-5, and all met criteria for a provisional diagnosis of PTSD based on the DSM-5 criteria. This prevalence is about two times higher than the prevalence of PTSD in the general population (6.7%), comparable with that reported for heart transplant recipients (10.8%) and coronary artery disease (9%), but lower than that reported for ICU patients (38%), HIV patients (35.3%), and in those with Crohn’s disease (19.1%).

On multivariable logistic regression, only three factors were found to be significantly associated with the development of PTSD: younger age at transplant (P = .019), history of depression (P = .008), and a history of PTSD (P less than .001). “What I found surprising was that the MELD score at the time of transplant and the number of readmissions or complications around the time of transplant were not predictive of PTSD,” Ms. O’Meara said.

One possible explanation for the finding of younger age being a predictor of PTSD, she continued, is that younger liver transplant patients may lack certain coping skills, compared with their older counterparts. “Maybe patients who have had more years to deal with their disease are more accepting of it and they learn how to use productive tools to manage it.”

In their abstract, the researchers acknowledged certain limitations of the study, including its cross-sectional design, small sample size, and lack of corresponding pretransplant data.

The researchers reported having no financial disclosures.

[email protected]

SAN FRANCISCO – A novel therapeutic strategy shows initial promise in dampening hepatic cell injury in mice caused by overexposure to acetaminophen. The approach relies on a synthetic version of heparan sulfate, which is believed to interfere with recruitment of neutrophils to the site of hepatic injury. That reduces harm caused by inflammation and may offer a longer therapeutic window than N-acetyl cysteine, which is the current standard therapy but is only effective if given within 8 hours of the injury.

The endogenous syndecan-1, which is a heparan sulfate, is also known to act as a native defense mechanism against inflammatory injury to hepatocytes. “It looks like heparan sulfate attenuates inflammatory responses,” said Jian Liu, PhD, during a presentation of his research at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Liu is a professor of chemical biology and medicinal chemistry at the University of North Carolina at Chapel Hill.

The heparan sulfate analogue heparin has long been used as an anticoagulant, of course, which suggests that a novel heparan sulfate has a good chance of also being safe.

Dr. Liu’s team had to identify a heparan sulfate that had a hepatoprotective effect, but a heparan sulfate’s unique biological activity depends on the specific pattern of sulfation on the heparan molecule. Heparans isolated from natural sources are generally a complex mixture, which makes them difficult to study and produce in large enough quantities to be therapeutically useful.

Dr. Liu’s team used a combinatory approach, harnessing various enzymes to produce hundreds of different heparan sulfate variants, and then screened them for hepatoprotective activity. That process identified an 18-chain heparan sulfate with hepatoprotective activity. With an active formula in hand, they could employ the enzymes to create enough of the pure compound to further the research. “It’s probably two to three hundred times more efficient than the traditional chemical synthesis,” said Dr. Liu.

In mice, researchers injected the 18-mer 30 minutes after a hepatotoxic dose of acetaminophen and again after 12 hours. Tissue staining showed less migration of neutrophils, as well as lower concentrations of tumor necrosis factor–alpha. The animals also had lower alanine transferase levels than did the untreated animals, as well as greater survival after 4 days.

The pathological process surrounding acetaminophen overdose involves release of the high mobility group box 1 (HMGB1) protein from necrotic hepatocytes, which in turn binds to the receptor for advanced glycation end-products (RAGE). The HMGB1/RAGE complex then binds to neutrophils, recruiting them to the site of the injury and initiating inflammation.

To better understand the molecule’s role in the pathological process, the researchers studied RAGE knockout mice, and found that the 18-mer had no protective effect in these animals, suggesting that it relies on RAGE for its biological activity.

Heparan sulfates are widely present in the body, which prompted the researchers to investigate their endogenous effect. In the liver, the primary heparan sulfate is syndecan-1. The researchers demonstrated that the molecule is shed from cell surfaces in response to acetaminophen toxicity and that the levels correlate with HMGB1 release.

Dr. Liu believes that syndecan-1 acts as a natural buffer to inflammation, helping to neutralize HMGB1 and limit damage. “The problem is that when the damage is massive, the shed of syndecan-1 is not enough,” said Dr. Liu. He hopes that something like his team’s heparan sulfate 18-mer can be used therapeutically to bolster these endogenous controls and prevent further damage.

The research was funded by Glycan Therapeutics. Dr. Liu founded Glycan, which offers custom-synthesized heparan sulfates and chondroitin sulfates for research purposes.

SOURCE: Liu J. AASLD 2018, Abstract 0040.

SAN FRANCISCO – A novel therapeutic strategy shows initial promise in dampening hepatic cell injury in mice caused by overexposure to acetaminophen. The approach relies on a synthetic version of heparan sulfate, which is believed to interfere with recruitment of neutrophils to the site of hepatic injury. That reduces harm caused by inflammation and may offer a longer therapeutic window than N-acetyl cysteine, which is the current standard therapy but is only effective if given within 8 hours of the injury.

The endogenous syndecan-1, which is a heparan sulfate, is also known to act as a native defense mechanism against inflammatory injury to hepatocytes. “It looks like heparan sulfate attenuates inflammatory responses,” said Jian Liu, PhD, during a presentation of his research at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Liu is a professor of chemical biology and medicinal chemistry at the University of North Carolina at Chapel Hill.

The heparan sulfate analogue heparin has long been used as an anticoagulant, of course, which suggests that a novel heparan sulfate has a good chance of also being safe.

Dr. Liu’s team had to identify a heparan sulfate that had a hepatoprotective effect, but a heparan sulfate’s unique biological activity depends on the specific pattern of sulfation on the heparan molecule. Heparans isolated from natural sources are generally a complex mixture, which makes them difficult to study and produce in large enough quantities to be therapeutically useful.

Dr. Liu’s team used a combinatory approach, harnessing various enzymes to produce hundreds of different heparan sulfate variants, and then screened them for hepatoprotective activity. That process identified an 18-chain heparan sulfate with hepatoprotective activity. With an active formula in hand, they could employ the enzymes to create enough of the pure compound to further the research. “It’s probably two to three hundred times more efficient than the traditional chemical synthesis,” said Dr. Liu.

In mice, researchers injected the 18-mer 30 minutes after a hepatotoxic dose of acetaminophen and again after 12 hours. Tissue staining showed less migration of neutrophils, as well as lower concentrations of tumor necrosis factor–alpha. The animals also had lower alanine transferase levels than did the untreated animals, as well as greater survival after 4 days.

The pathological process surrounding acetaminophen overdose involves release of the high mobility group box 1 (HMGB1) protein from necrotic hepatocytes, which in turn binds to the receptor for advanced glycation end-products (RAGE). The HMGB1/RAGE complex then binds to neutrophils, recruiting them to the site of the injury and initiating inflammation.

To better understand the molecule’s role in the pathological process, the researchers studied RAGE knockout mice, and found that the 18-mer had no protective effect in these animals, suggesting that it relies on RAGE for its biological activity.

Heparan sulfates are widely present in the body, which prompted the researchers to investigate their endogenous effect. In the liver, the primary heparan sulfate is syndecan-1. The researchers demonstrated that the molecule is shed from cell surfaces in response to acetaminophen toxicity and that the levels correlate with HMGB1 release.

Dr. Liu believes that syndecan-1 acts as a natural buffer to inflammation, helping to neutralize HMGB1 and limit damage. “The problem is that when the damage is massive, the shed of syndecan-1 is not enough,” said Dr. Liu. He hopes that something like his team’s heparan sulfate 18-mer can be used therapeutically to bolster these endogenous controls and prevent further damage.

The research was funded by Glycan Therapeutics. Dr. Liu founded Glycan, which offers custom-synthesized heparan sulfates and chondroitin sulfates for research purposes.

SOURCE: Liu J. AASLD 2018, Abstract 0040.

SAN FRANCISCO – A novel therapeutic strategy shows initial promise in dampening hepatic cell injury in mice caused by overexposure to acetaminophen. The approach relies on a synthetic version of heparan sulfate, which is believed to interfere with recruitment of neutrophils to the site of hepatic injury. That reduces harm caused by inflammation and may offer a longer therapeutic window than N-acetyl cysteine, which is the current standard therapy but is only effective if given within 8 hours of the injury.

The endogenous syndecan-1, which is a heparan sulfate, is also known to act as a native defense mechanism against inflammatory injury to hepatocytes. “It looks like heparan sulfate attenuates inflammatory responses,” said Jian Liu, PhD, during a presentation of his research at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Liu is a professor of chemical biology and medicinal chemistry at the University of North Carolina at Chapel Hill.

The heparan sulfate analogue heparin has long been used as an anticoagulant, of course, which suggests that a novel heparan sulfate has a good chance of also being safe.

Dr. Liu’s team had to identify a heparan sulfate that had a hepatoprotective effect, but a heparan sulfate’s unique biological activity depends on the specific pattern of sulfation on the heparan molecule. Heparans isolated from natural sources are generally a complex mixture, which makes them difficult to study and produce in large enough quantities to be therapeutically useful.

Dr. Liu’s team used a combinatory approach, harnessing various enzymes to produce hundreds of different heparan sulfate variants, and then screened them for hepatoprotective activity. That process identified an 18-chain heparan sulfate with hepatoprotective activity. With an active formula in hand, they could employ the enzymes to create enough of the pure compound to further the research. “It’s probably two to three hundred times more efficient than the traditional chemical synthesis,” said Dr. Liu.

In mice, researchers injected the 18-mer 30 minutes after a hepatotoxic dose of acetaminophen and again after 12 hours. Tissue staining showed less migration of neutrophils, as well as lower concentrations of tumor necrosis factor–alpha. The animals also had lower alanine transferase levels than did the untreated animals, as well as greater survival after 4 days.

The pathological process surrounding acetaminophen overdose involves release of the high mobility group box 1 (HMGB1) protein from necrotic hepatocytes, which in turn binds to the receptor for advanced glycation end-products (RAGE). The HMGB1/RAGE complex then binds to neutrophils, recruiting them to the site of the injury and initiating inflammation.

To better understand the molecule’s role in the pathological process, the researchers studied RAGE knockout mice, and found that the 18-mer had no protective effect in these animals, suggesting that it relies on RAGE for its biological activity.

Heparan sulfates are widely present in the body, which prompted the researchers to investigate their endogenous effect. In the liver, the primary heparan sulfate is syndecan-1. The researchers demonstrated that the molecule is shed from cell surfaces in response to acetaminophen toxicity and that the levels correlate with HMGB1 release.

Dr. Liu believes that syndecan-1 acts as a natural buffer to inflammation, helping to neutralize HMGB1 and limit damage. “The problem is that when the damage is massive, the shed of syndecan-1 is not enough,” said Dr. Liu. He hopes that something like his team’s heparan sulfate 18-mer can be used therapeutically to bolster these endogenous controls and prevent further damage.

The research was funded by Glycan Therapeutics. Dr. Liu founded Glycan, which offers custom-synthesized heparan sulfates and chondroitin sulfates for research purposes.

SOURCE: Liu J. AASLD 2018, Abstract 0040.

SAN FRANCISCO – Patients with chronic liver disease are prescribed opioids and benzodiazepines at very high rates, despite risk for adverse consequences because of hepatic metabolism, according to results from a large longitudinal study of national data.

“Middle-aged individuals and those with a background of substance abuse and mental health conditions appear to have highest rates of use and represent populations for which targeted interventions to curb use could be highest yield,” lead study author Monica Konerman, MD, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases.

In an effort to better understand the rates of prescription opioid and benzodiazepine use in chronic liver disease, Dr. Konerman, director of the Michigan Medicine NAFLD Clinic at the University of Michigan, Ann Arbor, and her colleagues drew from the Truven Health Analytics Marketscan databases from 2009 to 2015. They limited the analysis to individuals with drug coverage who had chronic hepatitis C (HCV) without cirrhosis, cirrhosis, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD), and examined pharmacy files for outpatient prescriptions.

Dr. Konerman reported data from 210,191 patients with HCV, 79,332 with cirrhosis, 766,840 with CHF, and 1,438,798 with COPD. Their median age was 59 years, and 51% were female. In per person-years, the prevalence of prescription opioid use was 25% among patients with chronic HCV, 53% among patients with cirrhosis, 26% among those with CHF, and 24% among those with COPD. At the same time, in per person-years, the prevalence of benzodiazepine use was 12% among patients with chronic HCV, 21% among patients with cirrhosis, 12% among those with CHF, and 13% among those with COPD. Use of opioids was greatest in adults 40-59 years of age (P less than .001). High-dose opioid use, defined as 100 opioid morphine equivalents per day or greater, occurred in 23% of those with cirrhosis and in 22% of those with HCV.

“The significant increase in rates of use in chronic liver disease, compared to other chronic conditions was remarkable, particularly given that patients with liver disease are at higher risk for adverse consequences of use due to hepatic metabolism of these medications,” Dr. Konerman said.

She went on to acknowledge “inherent limitations to studies that are secondary database analyses that rely on diagnosis codes for categorization of disease with potential for both over and under classification. We also did not capture inpatient prescriptions,” she said.

Dr. Konerman reported having no financial disclosures.

[email protected]

SAN FRANCISCO – Patients with chronic liver disease are prescribed opioids and benzodiazepines at very high rates, despite risk for adverse consequences because of hepatic metabolism, according to results from a large longitudinal study of national data.

“Middle-aged individuals and those with a background of substance abuse and mental health conditions appear to have highest rates of use and represent populations for which targeted interventions to curb use could be highest yield,” lead study author Monica Konerman, MD, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases.

In an effort to better understand the rates of prescription opioid and benzodiazepine use in chronic liver disease, Dr. Konerman, director of the Michigan Medicine NAFLD Clinic at the University of Michigan, Ann Arbor, and her colleagues drew from the Truven Health Analytics Marketscan databases from 2009 to 2015. They limited the analysis to individuals with drug coverage who had chronic hepatitis C (HCV) without cirrhosis, cirrhosis, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD), and examined pharmacy files for outpatient prescriptions.

Dr. Konerman reported data from 210,191 patients with HCV, 79,332 with cirrhosis, 766,840 with CHF, and 1,438,798 with COPD. Their median age was 59 years, and 51% were female. In per person-years, the prevalence of prescription opioid use was 25% among patients with chronic HCV, 53% among patients with cirrhosis, 26% among those with CHF, and 24% among those with COPD. At the same time, in per person-years, the prevalence of benzodiazepine use was 12% among patients with chronic HCV, 21% among patients with cirrhosis, 12% among those with CHF, and 13% among those with COPD. Use of opioids was greatest in adults 40-59 years of age (P less than .001). High-dose opioid use, defined as 100 opioid morphine equivalents per day or greater, occurred in 23% of those with cirrhosis and in 22% of those with HCV.

“The significant increase in rates of use in chronic liver disease, compared to other chronic conditions was remarkable, particularly given that patients with liver disease are at higher risk for adverse consequences of use due to hepatic metabolism of these medications,” Dr. Konerman said.

She went on to acknowledge “inherent limitations to studies that are secondary database analyses that rely on diagnosis codes for categorization of disease with potential for both over and under classification. We also did not capture inpatient prescriptions,” she said.

Dr. Konerman reported having no financial disclosures.

[email protected]

SAN FRANCISCO – Patients with chronic liver disease are prescribed opioids and benzodiazepines at very high rates, despite risk for adverse consequences because of hepatic metabolism, according to results from a large longitudinal study of national data.

“Middle-aged individuals and those with a background of substance abuse and mental health conditions appear to have highest rates of use and represent populations for which targeted interventions to curb use could be highest yield,” lead study author Monica Konerman, MD, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases.

In an effort to better understand the rates of prescription opioid and benzodiazepine use in chronic liver disease, Dr. Konerman, director of the Michigan Medicine NAFLD Clinic at the University of Michigan, Ann Arbor, and her colleagues drew from the Truven Health Analytics Marketscan databases from 2009 to 2015. They limited the analysis to individuals with drug coverage who had chronic hepatitis C (HCV) without cirrhosis, cirrhosis, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD), and examined pharmacy files for outpatient prescriptions.

Dr. Konerman reported data from 210,191 patients with HCV, 79,332 with cirrhosis, 766,840 with CHF, and 1,438,798 with COPD. Their median age was 59 years, and 51% were female. In per person-years, the prevalence of prescription opioid use was 25% among patients with chronic HCV, 53% among patients with cirrhosis, 26% among those with CHF, and 24% among those with COPD. At the same time, in per person-years, the prevalence of benzodiazepine use was 12% among patients with chronic HCV, 21% among patients with cirrhosis, 12% among those with CHF, and 13% among those with COPD. Use of opioids was greatest in adults 40-59 years of age (P less than .001). High-dose opioid use, defined as 100 opioid morphine equivalents per day or greater, occurred in 23% of those with cirrhosis and in 22% of those with HCV.

“The significant increase in rates of use in chronic liver disease, compared to other chronic conditions was remarkable, particularly given that patients with liver disease are at higher risk for adverse consequences of use due to hepatic metabolism of these medications,” Dr. Konerman said.

She went on to acknowledge “inherent limitations to studies that are secondary database analyses that rely on diagnosis codes for categorization of disease with potential for both over and under classification. We also did not capture inpatient prescriptions,” she said.

Dr. Konerman reported having no financial disclosures.

[email protected]

SAN DIEGO – There’s good news and bad news about hepatitis C virus (HCV) in patients with chronic kidney disease (CKD): The new generation of drugs that cures HCV is effective in this population, but outbreaks of infection are still plaguing the nation’s dialysis clinics.

These perspectives came in a presentation about infections in CKD at Kidney Week 2018, sponsored by the American Society of Nephrology.

First, the good news about HCV. “Treatment is now feasible for all stages of chronic kidney disease,” said gastroenterologist Paul Martin, MD, of the University of Miami. “It was possible to achieve biological cure in 99% of patients, which is truly remarkable considering what a problem kidney patients were for hepatitis C until very recently.”

The key is to treat HCV with drug combinations that lower the risk of viral resistance. “These drugs are extremely well tolerated. They’re not like interferon or ribavirin,” he said, referring to a drug combo that was formerly used to treat HCV. “We can anticipate curing hepatitis C with a finite amount of therapy in virtually every patient we see, including those with kidney disease.”

In patients with CKD, all the new drugs are approved for glomerular filtration rates greater than 30 mL/min. Sofosbuvir (Sovaldi) is not approved for patients with a filtration rate under 30 mL/min, he said, but other options are available.

Ribavirin, he added, is no longer needed with current regimens.

Dr. Martin pointed to two studies that reveal the power of the new regimens against HCV in patients with CKD. One of the studies, a 2015 industry-funded report in the Lancet, found that “once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease.” The other study, also funded by industry and published in 2017 in the New England Journal of Medicine, found that “treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection.”

Meanwhile, there are signs that HCV treatment may boost survival in CKD patients on dialysis, Dr. Martin said.

In terms of bad news, Priti R. Patel, MD, MPH, a medical officer with the Centers for Disease Control and Prevention, warned that dialysis clinics are still seeing HCV outbreaks. “It’s a continuing problem,” she said. “What we hear about at the CDC is the tip of the iceberg.”

The CDC says it received word of 21 HCV outbreaks of two or more cases in dialysis clinics during 2008-2017. These affected 102 patients, and more than 3,000 patients were notified that they were at risk and should be screened.

One dialysis clinic in Philadelphia had 18 cases of HCV during 2008-2013; they were blamed on “multiple lapses in infection control ... including hand hygiene and glove use, vascular access care, medication preparation, cleaning, and disinfection.”

“There should be no more than one case that has to happen for a facility to detect that it has a problem and identify a solution,” Dr. Patel said.

Since acute HCV can appear without symptoms, every dialysis patients should be tested for HCV antibodies, she added. “If it’s positive, confirm it. If confirmed, they should be informed of their infection status and have an evaluation for treatment.”

Dr. Martin reported consulting for Bristol-Myers Squibb and AbbVie and receiving research funding from Gilead, Bristol-Myers Squibb, AbbVie, and Merck. Dr. Patel reported no disclosures.
 

SAN DIEGO – There’s good news and bad news about hepatitis C virus (HCV) in patients with chronic kidney disease (CKD): The new generation of drugs that cures HCV is effective in this population, but outbreaks of infection are still plaguing the nation’s dialysis clinics.

These perspectives came in a presentation about infections in CKD at Kidney Week 2018, sponsored by the American Society of Nephrology.

First, the good news about HCV. “Treatment is now feasible for all stages of chronic kidney disease,” said gastroenterologist Paul Martin, MD, of the University of Miami. “It was possible to achieve biological cure in 99% of patients, which is truly remarkable considering what a problem kidney patients were for hepatitis C until very recently.”

The key is to treat HCV with drug combinations that lower the risk of viral resistance. “These drugs are extremely well tolerated. They’re not like interferon or ribavirin,” he said, referring to a drug combo that was formerly used to treat HCV. “We can anticipate curing hepatitis C with a finite amount of therapy in virtually every patient we see, including those with kidney disease.”

In patients with CKD, all the new drugs are approved for glomerular filtration rates greater than 30 mL/min. Sofosbuvir (Sovaldi) is not approved for patients with a filtration rate under 30 mL/min, he said, but other options are available.

Ribavirin, he added, is no longer needed with current regimens.

Dr. Martin pointed to two studies that reveal the power of the new regimens against HCV in patients with CKD. One of the studies, a 2015 industry-funded report in the Lancet, found that “once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease.” The other study, also funded by industry and published in 2017 in the New England Journal of Medicine, found that “treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection.”

Meanwhile, there are signs that HCV treatment may boost survival in CKD patients on dialysis, Dr. Martin said.

In terms of bad news, Priti R. Patel, MD, MPH, a medical officer with the Centers for Disease Control and Prevention, warned that dialysis clinics are still seeing HCV outbreaks. “It’s a continuing problem,” she said. “What we hear about at the CDC is the tip of the iceberg.”

The CDC says it received word of 21 HCV outbreaks of two or more cases in dialysis clinics during 2008-2017. These affected 102 patients, and more than 3,000 patients were notified that they were at risk and should be screened.

One dialysis clinic in Philadelphia had 18 cases of HCV during 2008-2013; they were blamed on “multiple lapses in infection control ... including hand hygiene and glove use, vascular access care, medication preparation, cleaning, and disinfection.”

“There should be no more than one case that has to happen for a facility to detect that it has a problem and identify a solution,” Dr. Patel said.

Since acute HCV can appear without symptoms, every dialysis patients should be tested for HCV antibodies, she added. “If it’s positive, confirm it. If confirmed, they should be informed of their infection status and have an evaluation for treatment.”

Dr. Martin reported consulting for Bristol-Myers Squibb and AbbVie and receiving research funding from Gilead, Bristol-Myers Squibb, AbbVie, and Merck. Dr. Patel reported no disclosures.
 

SAN DIEGO – There’s good news and bad news about hepatitis C virus (HCV) in patients with chronic kidney disease (CKD): The new generation of drugs that cures HCV is effective in this population, but outbreaks of infection are still plaguing the nation’s dialysis clinics.

These perspectives came in a presentation about infections in CKD at Kidney Week 2018, sponsored by the American Society of Nephrology.

First, the good news about HCV. “Treatment is now feasible for all stages of chronic kidney disease,” said gastroenterologist Paul Martin, MD, of the University of Miami. “It was possible to achieve biological cure in 99% of patients, which is truly remarkable considering what a problem kidney patients were for hepatitis C until very recently.”

The key is to treat HCV with drug combinations that lower the risk of viral resistance. “These drugs are extremely well tolerated. They’re not like interferon or ribavirin,” he said, referring to a drug combo that was formerly used to treat HCV. “We can anticipate curing hepatitis C with a finite amount of therapy in virtually every patient we see, including those with kidney disease.”

In patients with CKD, all the new drugs are approved for glomerular filtration rates greater than 30 mL/min. Sofosbuvir (Sovaldi) is not approved for patients with a filtration rate under 30 mL/min, he said, but other options are available.

Ribavirin, he added, is no longer needed with current regimens.

Dr. Martin pointed to two studies that reveal the power of the new regimens against HCV in patients with CKD. One of the studies, a 2015 industry-funded report in the Lancet, found that “once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease.” The other study, also funded by industry and published in 2017 in the New England Journal of Medicine, found that “treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection.”

Meanwhile, there are signs that HCV treatment may boost survival in CKD patients on dialysis, Dr. Martin said.

In terms of bad news, Priti R. Patel, MD, MPH, a medical officer with the Centers for Disease Control and Prevention, warned that dialysis clinics are still seeing HCV outbreaks. “It’s a continuing problem,” she said. “What we hear about at the CDC is the tip of the iceberg.”

The CDC says it received word of 21 HCV outbreaks of two or more cases in dialysis clinics during 2008-2017. These affected 102 patients, and more than 3,000 patients were notified that they were at risk and should be screened.

One dialysis clinic in Philadelphia had 18 cases of HCV during 2008-2013; they were blamed on “multiple lapses in infection control ... including hand hygiene and glove use, vascular access care, medication preparation, cleaning, and disinfection.”

“There should be no more than one case that has to happen for a facility to detect that it has a problem and identify a solution,” Dr. Patel said.

Since acute HCV can appear without symptoms, every dialysis patients should be tested for HCV antibodies, she added. “If it’s positive, confirm it. If confirmed, they should be informed of their infection status and have an evaluation for treatment.”

Dr. Martin reported consulting for Bristol-Myers Squibb and AbbVie and receiving research funding from Gilead, Bristol-Myers Squibb, AbbVie, and Merck. Dr. Patel reported no disclosures.