Liver Disease

MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.

M. Alexander Otto/MDedge News

“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.

For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.

One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
 

A newly recognized cancer risk

Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.

A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.

The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”

This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
 

Entecavir versus tenofovir

Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.

A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.

Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.

Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.

So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
 

A drug holiday?

Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.

“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).

It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.

Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.

[email protected]

MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.

M. Alexander Otto/MDedge News

“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.

For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.

One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
 

A newly recognized cancer risk

Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.

A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.

The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”

This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
 

Entecavir versus tenofovir

Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.

A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.

Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.

Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.

So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
 

A drug holiday?

Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.

“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).

It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.

Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.

[email protected]

MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.

M. Alexander Otto/MDedge News

“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.

For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.

One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
 

A newly recognized cancer risk

Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.

A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.

The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”

This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
 

Entecavir versus tenofovir

Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.

A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.

Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.

Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.

So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
 

A drug holiday?

Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.

“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).

It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.

Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.

[email protected]

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

[email protected]

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

[email protected]

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

[email protected]

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

[email protected]

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

[email protected]

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

[email protected]

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

[email protected]

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

[email protected]

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

[email protected]

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

While initial case reports and series provided preliminarily encouraging results, a larger retrospective study has provided no clear-cut evidence of biochemical response to vedolizumab in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease, investigators report.

A subset of patients in the retrospective analysis did experience a substantial drop in alkaline phosphatase (ALP), according to investigators with the International Primary Sclerosing Cholangitis Study Group.

Overall, however, levels of that cholestasis marker rose by a small but statistically significant amount in this study, which included more than 100 patients with PSC and inflammatory bowel disease (IBD).

Responses were more likely in patients with cirrhosis and in those with elevated ALP at baseline, both of which are indicators of more aggressive disease, according to investigator Kate D. Lynch, MD, PhD, of the University of Oxford (England) and her coauthors.

The rate of liver outcomes was in line with the natural history of the disease, according to Dr. Lynch and coinvestigators, who added that most patients had an endoscopic IBD response, as might be expected based on studies of IBD-only patients treated with vedolizumab.

“Despite the disappointment with lack of a uniform response, further evaluation of vedolizumab as a beneficial treatment in PSC may be warranted in a subset of patients via a stratified randomized clinical trial,” Dr. Lynch and coauthors said in their report, which was published in Clinical Gastroenterology and Hepatology.

Vedolizumab, a monoclonal antibody against integrin alpha4beta7, is effective in Crohn’s disease and ulcerative colitis, according to investigators, who added that the “gut-homing pathway” it targets has also been implicated in the pathophysiology of PSC.

“It is possible that vedolizumab may play a role in reducing lymphocyte infiltration into the liver in patients with PSC and thereby in reducing hepatic and biliary inflammation, authors of the retrospective analysis said.

Their analysis included 102 patients with PSC and IBD at 20 centers in Europe and North America. All patients had received at least three doses of vedolizumab for their IBD, given according to the usual dosing schedule. Most of the patients were male (64 patients, or 62.8%) and about 90% had classical large-duct PSC. About one-fifth had cirrhosis, and the majority (about 65%) had ulcerative colitis. Patients were followed until death, liver transplant, or 56 days after the last vedolizumab dose.

The median ALP increased from 1.53 times the upper limit of normal at baseline to 1.64 times the upper limit of normal by the last follow-up, an increase that was statistically significant (P = .018) but not clinically significant, according to investigators. Likewise, they said, statistically significant increases were seen overall in median alanine transaminase and aspartate aminotransferase levels.

However, 21 patients (20.6%) had a drop in ALP of at least 20% from baseline to last follow-up, and another 39 patients (38.2%) had stable ALP over that period, data show, while the remaining 42 (41.2%) had an increase of 20% or more.

Cirrhosis was associated with a near fivefold odds of a 20% or greater ALP drop from baseline to follow-up (odds ratio, 4.70, 95% confidence interval, 1.61-13.76), according to results of univariate analysis, which investigators said were “reproduced” in multivariate analysis.

While no other variables were so clearly linked to a 20% or greater drop in ALP, Dr. Lynch and colleagues said there was a “trend toward an association” in patients with ALP raised at baseline, and in those who had Crohn’s disease or IBD-unspecified instead of ulcerative colitis.

Endoscopic IBD responses were seen in 42 out of 74 patients (56.8%) for whom those data were available, investigators added.

A total of 22 patients (20.9%) had a liver-related outcome over median follow-up of 561 days; however, that outcome may be “slightly overrepresented” by an incidence of cholangitis in 8.8%, which in and of itself is not necessarily an indicator of advanced liver disease, said Dr. Lynch and coauthors in their report.

“This proportion of liver-related outcomes is consistent with the natural history of PSC and does not by itself indicate that vedolizumab treatment is harmful in PSC,” they said, adding that the findings were similar to a study of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2, in patients with PSC, of whom 20.1% had a PSC-related event and the incidence of cholangitis was 13.2%.

The retrospective study was supported by the Birmingham National Institute for Health Research (NIHR) Biomedical Research Centre in the United Kingdom. Authors of the report provided disclosures related to Takeda, AbbVie, Dr. Falk Pharma, Intercept, MSD, Janssen, Vifor, Gilead, and Novartis, among others.

SOURCE: Lynch KD et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.013.

While initial case reports and series provided preliminarily encouraging results, a larger retrospective study has provided no clear-cut evidence of biochemical response to vedolizumab in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease, investigators report.

A subset of patients in the retrospective analysis did experience a substantial drop in alkaline phosphatase (ALP), according to investigators with the International Primary Sclerosing Cholangitis Study Group.

Overall, however, levels of that cholestasis marker rose by a small but statistically significant amount in this study, which included more than 100 patients with PSC and inflammatory bowel disease (IBD).

Responses were more likely in patients with cirrhosis and in those with elevated ALP at baseline, both of which are indicators of more aggressive disease, according to investigator Kate D. Lynch, MD, PhD, of the University of Oxford (England) and her coauthors.

The rate of liver outcomes was in line with the natural history of the disease, according to Dr. Lynch and coinvestigators, who added that most patients had an endoscopic IBD response, as might be expected based on studies of IBD-only patients treated with vedolizumab.

“Despite the disappointment with lack of a uniform response, further evaluation of vedolizumab as a beneficial treatment in PSC may be warranted in a subset of patients via a stratified randomized clinical trial,” Dr. Lynch and coauthors said in their report, which was published in Clinical Gastroenterology and Hepatology.

Vedolizumab, a monoclonal antibody against integrin alpha4beta7, is effective in Crohn’s disease and ulcerative colitis, according to investigators, who added that the “gut-homing pathway” it targets has also been implicated in the pathophysiology of PSC.

“It is possible that vedolizumab may play a role in reducing lymphocyte infiltration into the liver in patients with PSC and thereby in reducing hepatic and biliary inflammation, authors of the retrospective analysis said.

Their analysis included 102 patients with PSC and IBD at 20 centers in Europe and North America. All patients had received at least three doses of vedolizumab for their IBD, given according to the usual dosing schedule. Most of the patients were male (64 patients, or 62.8%) and about 90% had classical large-duct PSC. About one-fifth had cirrhosis, and the majority (about 65%) had ulcerative colitis. Patients were followed until death, liver transplant, or 56 days after the last vedolizumab dose.

The median ALP increased from 1.53 times the upper limit of normal at baseline to 1.64 times the upper limit of normal by the last follow-up, an increase that was statistically significant (P = .018) but not clinically significant, according to investigators. Likewise, they said, statistically significant increases were seen overall in median alanine transaminase and aspartate aminotransferase levels.

However, 21 patients (20.6%) had a drop in ALP of at least 20% from baseline to last follow-up, and another 39 patients (38.2%) had stable ALP over that period, data show, while the remaining 42 (41.2%) had an increase of 20% or more.

Cirrhosis was associated with a near fivefold odds of a 20% or greater ALP drop from baseline to follow-up (odds ratio, 4.70, 95% confidence interval, 1.61-13.76), according to results of univariate analysis, which investigators said were “reproduced” in multivariate analysis.

While no other variables were so clearly linked to a 20% or greater drop in ALP, Dr. Lynch and colleagues said there was a “trend toward an association” in patients with ALP raised at baseline, and in those who had Crohn’s disease or IBD-unspecified instead of ulcerative colitis.

Endoscopic IBD responses were seen in 42 out of 74 patients (56.8%) for whom those data were available, investigators added.

A total of 22 patients (20.9%) had a liver-related outcome over median follow-up of 561 days; however, that outcome may be “slightly overrepresented” by an incidence of cholangitis in 8.8%, which in and of itself is not necessarily an indicator of advanced liver disease, said Dr. Lynch and coauthors in their report.

“This proportion of liver-related outcomes is consistent with the natural history of PSC and does not by itself indicate that vedolizumab treatment is harmful in PSC,” they said, adding that the findings were similar to a study of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2, in patients with PSC, of whom 20.1% had a PSC-related event and the incidence of cholangitis was 13.2%.

The retrospective study was supported by the Birmingham National Institute for Health Research (NIHR) Biomedical Research Centre in the United Kingdom. Authors of the report provided disclosures related to Takeda, AbbVie, Dr. Falk Pharma, Intercept, MSD, Janssen, Vifor, Gilead, and Novartis, among others.

SOURCE: Lynch KD et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.013.

While initial case reports and series provided preliminarily encouraging results, a larger retrospective study has provided no clear-cut evidence of biochemical response to vedolizumab in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease, investigators report.

A subset of patients in the retrospective analysis did experience a substantial drop in alkaline phosphatase (ALP), according to investigators with the International Primary Sclerosing Cholangitis Study Group.

Overall, however, levels of that cholestasis marker rose by a small but statistically significant amount in this study, which included more than 100 patients with PSC and inflammatory bowel disease (IBD).

Responses were more likely in patients with cirrhosis and in those with elevated ALP at baseline, both of which are indicators of more aggressive disease, according to investigator Kate D. Lynch, MD, PhD, of the University of Oxford (England) and her coauthors.

The rate of liver outcomes was in line with the natural history of the disease, according to Dr. Lynch and coinvestigators, who added that most patients had an endoscopic IBD response, as might be expected based on studies of IBD-only patients treated with vedolizumab.

“Despite the disappointment with lack of a uniform response, further evaluation of vedolizumab as a beneficial treatment in PSC may be warranted in a subset of patients via a stratified randomized clinical trial,” Dr. Lynch and coauthors said in their report, which was published in Clinical Gastroenterology and Hepatology.

Vedolizumab, a monoclonal antibody against integrin alpha4beta7, is effective in Crohn’s disease and ulcerative colitis, according to investigators, who added that the “gut-homing pathway” it targets has also been implicated in the pathophysiology of PSC.

“It is possible that vedolizumab may play a role in reducing lymphocyte infiltration into the liver in patients with PSC and thereby in reducing hepatic and biliary inflammation, authors of the retrospective analysis said.

Their analysis included 102 patients with PSC and IBD at 20 centers in Europe and North America. All patients had received at least three doses of vedolizumab for their IBD, given according to the usual dosing schedule. Most of the patients were male (64 patients, or 62.8%) and about 90% had classical large-duct PSC. About one-fifth had cirrhosis, and the majority (about 65%) had ulcerative colitis. Patients were followed until death, liver transplant, or 56 days after the last vedolizumab dose.

The median ALP increased from 1.53 times the upper limit of normal at baseline to 1.64 times the upper limit of normal by the last follow-up, an increase that was statistically significant (P = .018) but not clinically significant, according to investigators. Likewise, they said, statistically significant increases were seen overall in median alanine transaminase and aspartate aminotransferase levels.

However, 21 patients (20.6%) had a drop in ALP of at least 20% from baseline to last follow-up, and another 39 patients (38.2%) had stable ALP over that period, data show, while the remaining 42 (41.2%) had an increase of 20% or more.

Cirrhosis was associated with a near fivefold odds of a 20% or greater ALP drop from baseline to follow-up (odds ratio, 4.70, 95% confidence interval, 1.61-13.76), according to results of univariate analysis, which investigators said were “reproduced” in multivariate analysis.

While no other variables were so clearly linked to a 20% or greater drop in ALP, Dr. Lynch and colleagues said there was a “trend toward an association” in patients with ALP raised at baseline, and in those who had Crohn’s disease or IBD-unspecified instead of ulcerative colitis.

Endoscopic IBD responses were seen in 42 out of 74 patients (56.8%) for whom those data were available, investigators added.

A total of 22 patients (20.9%) had a liver-related outcome over median follow-up of 561 days; however, that outcome may be “slightly overrepresented” by an incidence of cholangitis in 8.8%, which in and of itself is not necessarily an indicator of advanced liver disease, said Dr. Lynch and coauthors in their report.

“This proportion of liver-related outcomes is consistent with the natural history of PSC and does not by itself indicate that vedolizumab treatment is harmful in PSC,” they said, adding that the findings were similar to a study of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2, in patients with PSC, of whom 20.1% had a PSC-related event and the incidence of cholangitis was 13.2%.

The retrospective study was supported by the Birmingham National Institute for Health Research (NIHR) Biomedical Research Centre in the United Kingdom. Authors of the report provided disclosures related to Takeda, AbbVie, Dr. Falk Pharma, Intercept, MSD, Janssen, Vifor, Gilead, and Novartis, among others.

SOURCE: Lynch KD et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.013.