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American Association for the Study of Liver Disease (AASLD): The Liver Meeting
VIDEO: Liver transplant center competition tied to delisting patients
WASHINGTON – Low market competition among liver transplant centers may affect which patients are considered too sick to transplant, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
With 20% of patients dying while on the transplant wait list, including those who were delisted, understanding the distribution of organs among donor service areas (DSAs) is crucial to lowering mortality during the current organ shortage, according to presenter Yanik Babekov, MD, of Massachusetts General Hospital, Boston.
Investigators studied 3,131 patients who were delisted after being classified as “too sick” from 116 centers in 51 DSAs, between 2002 and 2012.
Researchers used the Herfindahl-Hirschman Index (HHI), which analyzes the market share of each participant to determine the overall level of competition. Measurements on the HHI range between 0 and 1, with 0 being the most competitive and 1 being the least.
Mean delisting Model for End-Stage Liver Disease (MELD) scores considered to be “too sick to transplant” were 26.1, and average HHI among DSAs was 0.46, according to investigators. They found that, for every 1% increase in HHI, the delisting MELD score increased by 0.06, according to a risk-adjustment analysis.
“In other words, more competitive DSAs delist patients for [being] ‘too sick’ at lower MELD scores,” Dr. Babekov explained in a video interview. “Interestingly, race, education, citizenship, and other DSA factors also impacted delisting MELD for ‘too sick.’ ”
While market competition may not be the only factor to explain the phenomenon of patients delisted for being ‘too sick,’ it is important to identify how having more transplant centers in DSAs can help more patients be added to, and stay on, these wait lists, according to investigators.
Dr. Babekov had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – Low market competition among liver transplant centers may affect which patients are considered too sick to transplant, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
With 20% of patients dying while on the transplant wait list, including those who were delisted, understanding the distribution of organs among donor service areas (DSAs) is crucial to lowering mortality during the current organ shortage, according to presenter Yanik Babekov, MD, of Massachusetts General Hospital, Boston.
Investigators studied 3,131 patients who were delisted after being classified as “too sick” from 116 centers in 51 DSAs, between 2002 and 2012.
Researchers used the Herfindahl-Hirschman Index (HHI), which analyzes the market share of each participant to determine the overall level of competition. Measurements on the HHI range between 0 and 1, with 0 being the most competitive and 1 being the least.
Mean delisting Model for End-Stage Liver Disease (MELD) scores considered to be “too sick to transplant” were 26.1, and average HHI among DSAs was 0.46, according to investigators. They found that, for every 1% increase in HHI, the delisting MELD score increased by 0.06, according to a risk-adjustment analysis.
“In other words, more competitive DSAs delist patients for [being] ‘too sick’ at lower MELD scores,” Dr. Babekov explained in a video interview. “Interestingly, race, education, citizenship, and other DSA factors also impacted delisting MELD for ‘too sick.’ ”
While market competition may not be the only factor to explain the phenomenon of patients delisted for being ‘too sick,’ it is important to identify how having more transplant centers in DSAs can help more patients be added to, and stay on, these wait lists, according to investigators.
Dr. Babekov had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – Low market competition among liver transplant centers may affect which patients are considered too sick to transplant, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
With 20% of patients dying while on the transplant wait list, including those who were delisted, understanding the distribution of organs among donor service areas (DSAs) is crucial to lowering mortality during the current organ shortage, according to presenter Yanik Babekov, MD, of Massachusetts General Hospital, Boston.
Investigators studied 3,131 patients who were delisted after being classified as “too sick” from 116 centers in 51 DSAs, between 2002 and 2012.
Researchers used the Herfindahl-Hirschman Index (HHI), which analyzes the market share of each participant to determine the overall level of competition. Measurements on the HHI range between 0 and 1, with 0 being the most competitive and 1 being the least.
Mean delisting Model for End-Stage Liver Disease (MELD) scores considered to be “too sick to transplant” were 26.1, and average HHI among DSAs was 0.46, according to investigators. They found that, for every 1% increase in HHI, the delisting MELD score increased by 0.06, according to a risk-adjustment analysis.
“In other words, more competitive DSAs delist patients for [being] ‘too sick’ at lower MELD scores,” Dr. Babekov explained in a video interview. “Interestingly, race, education, citizenship, and other DSA factors also impacted delisting MELD for ‘too sick.’ ”
While market competition may not be the only factor to explain the phenomenon of patients delisted for being ‘too sick,’ it is important to identify how having more transplant centers in DSAs can help more patients be added to, and stay on, these wait lists, according to investigators.
Dr. Babekov had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
AT THE LIVER MEETING 2017
VIDEO: Huge database analysis affirms genes associated with NAFLD
WASHINGTON – A genome-wide association study of the Million Veteran Program confirmed three specific genes associated with nonalcoholic fatty liver disease, underscoring the robustness of those loci as well as the clinical phenotyping in the program.
Marina Serper, MD, of the Cpl. Michael J. Crescenz Veterans Affairs Medical Center, and University of Pennsylvania, both in Philadelphia, and her colleagues looked at patients with NAFLD in the Million Veterans Program (MVP), a project of the federal Precision Medicine Initiative designed to leverage the data and experience associated with the Veterans Health Care Administration, Dr. Serper said at the annual meeting of the American Association for the Study of Liver Diseases. Currently, more than 600,000 veterans have been enrolled at over 50 sites across the United States, with a goal of 1 million participants by 2020.
About one-third (108,458) of 352,953 MVP enrollees whose DNA has been analyzed met the study definition of NAFLD. In their study, Dr. Serper and her associates defined the clinical phenotype of NAFLD as patients having abnormal alanine aminotransferase levels (greater than 30 U/L for men and greater than 20 U/L for women) detected twice in a 2-year period, plus at least 1 metabolic risk factor, such as body mass index of 30 kg/m2 or greater, type 2 diabetes or prediabetes, hypertension, or dyslipidemia. Further, included patients did not have alcohol misuse disorders or viral hepatitis.
Most patients were male (90%) and white (72%), with a median age of 64 years. More than half (56%) had a BMI of 30 or greater, 30% were diagnosed with type 2 diabetes, and 71% with dyslipidemia – aligning the cohort closely with rest of the MVP population, Dr. Serper said.
Logistic regression analysis adjusted for age, sex, and principal components stratified by ancestry (European, African American, and Hispanic). On initial analysis, 21 genetic loci met the criteria for genome-wide significant association; specifically, investigators successfully replicated three key variants that have been previously seen associated with NAFLD – PNPLA3, ERLIN1, and TRIB1.
“We were able to use clinical VA data to come up with a robust and clinically relevant definition and validate that definition because the genes we found associated with our definition of NAFLD have previously been shown by others who used biopsy data and imaging data for steatosis,” Dr. Serper said in a video interview. “This is important because the diagnosis of fatty liver disease is really a clinical diagnosis.”
Panel moderator Elizabeth K. Speliotes, MD, of the University of Michigan, Ann Arbor, said, “Really what makes us unique is our genetics and our exposures and the environment, and if we can capture that better, then we can use that to more precisely tailor diagnoses and treatments for patients. That’s really the hope of the next generation.”
The study was supported by the VA Office of Research and Development award 1I01BX003362. Dr. Serper disclosed no relevant conflicts of interest.
Watch this video interview with Dr. Serper and Dr. Chang for more information on the Million Veteran Program.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
WASHINGTON – A genome-wide association study of the Million Veteran Program confirmed three specific genes associated with nonalcoholic fatty liver disease, underscoring the robustness of those loci as well as the clinical phenotyping in the program.
Marina Serper, MD, of the Cpl. Michael J. Crescenz Veterans Affairs Medical Center, and University of Pennsylvania, both in Philadelphia, and her colleagues looked at patients with NAFLD in the Million Veterans Program (MVP), a project of the federal Precision Medicine Initiative designed to leverage the data and experience associated with the Veterans Health Care Administration, Dr. Serper said at the annual meeting of the American Association for the Study of Liver Diseases. Currently, more than 600,000 veterans have been enrolled at over 50 sites across the United States, with a goal of 1 million participants by 2020.
About one-third (108,458) of 352,953 MVP enrollees whose DNA has been analyzed met the study definition of NAFLD. In their study, Dr. Serper and her associates defined the clinical phenotype of NAFLD as patients having abnormal alanine aminotransferase levels (greater than 30 U/L for men and greater than 20 U/L for women) detected twice in a 2-year period, plus at least 1 metabolic risk factor, such as body mass index of 30 kg/m2 or greater, type 2 diabetes or prediabetes, hypertension, or dyslipidemia. Further, included patients did not have alcohol misuse disorders or viral hepatitis.
Most patients were male (90%) and white (72%), with a median age of 64 years. More than half (56%) had a BMI of 30 or greater, 30% were diagnosed with type 2 diabetes, and 71% with dyslipidemia – aligning the cohort closely with rest of the MVP population, Dr. Serper said.
Logistic regression analysis adjusted for age, sex, and principal components stratified by ancestry (European, African American, and Hispanic). On initial analysis, 21 genetic loci met the criteria for genome-wide significant association; specifically, investigators successfully replicated three key variants that have been previously seen associated with NAFLD – PNPLA3, ERLIN1, and TRIB1.
“We were able to use clinical VA data to come up with a robust and clinically relevant definition and validate that definition because the genes we found associated with our definition of NAFLD have previously been shown by others who used biopsy data and imaging data for steatosis,” Dr. Serper said in a video interview. “This is important because the diagnosis of fatty liver disease is really a clinical diagnosis.”
Panel moderator Elizabeth K. Speliotes, MD, of the University of Michigan, Ann Arbor, said, “Really what makes us unique is our genetics and our exposures and the environment, and if we can capture that better, then we can use that to more precisely tailor diagnoses and treatments for patients. That’s really the hope of the next generation.”
The study was supported by the VA Office of Research and Development award 1I01BX003362. Dr. Serper disclosed no relevant conflicts of interest.
Watch this video interview with Dr. Serper and Dr. Chang for more information on the Million Veteran Program.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
WASHINGTON – A genome-wide association study of the Million Veteran Program confirmed three specific genes associated with nonalcoholic fatty liver disease, underscoring the robustness of those loci as well as the clinical phenotyping in the program.
Marina Serper, MD, of the Cpl. Michael J. Crescenz Veterans Affairs Medical Center, and University of Pennsylvania, both in Philadelphia, and her colleagues looked at patients with NAFLD in the Million Veterans Program (MVP), a project of the federal Precision Medicine Initiative designed to leverage the data and experience associated with the Veterans Health Care Administration, Dr. Serper said at the annual meeting of the American Association for the Study of Liver Diseases. Currently, more than 600,000 veterans have been enrolled at over 50 sites across the United States, with a goal of 1 million participants by 2020.
About one-third (108,458) of 352,953 MVP enrollees whose DNA has been analyzed met the study definition of NAFLD. In their study, Dr. Serper and her associates defined the clinical phenotype of NAFLD as patients having abnormal alanine aminotransferase levels (greater than 30 U/L for men and greater than 20 U/L for women) detected twice in a 2-year period, plus at least 1 metabolic risk factor, such as body mass index of 30 kg/m2 or greater, type 2 diabetes or prediabetes, hypertension, or dyslipidemia. Further, included patients did not have alcohol misuse disorders or viral hepatitis.
Most patients were male (90%) and white (72%), with a median age of 64 years. More than half (56%) had a BMI of 30 or greater, 30% were diagnosed with type 2 diabetes, and 71% with dyslipidemia – aligning the cohort closely with rest of the MVP population, Dr. Serper said.
Logistic regression analysis adjusted for age, sex, and principal components stratified by ancestry (European, African American, and Hispanic). On initial analysis, 21 genetic loci met the criteria for genome-wide significant association; specifically, investigators successfully replicated three key variants that have been previously seen associated with NAFLD – PNPLA3, ERLIN1, and TRIB1.
“We were able to use clinical VA data to come up with a robust and clinically relevant definition and validate that definition because the genes we found associated with our definition of NAFLD have previously been shown by others who used biopsy data and imaging data for steatosis,” Dr. Serper said in a video interview. “This is important because the diagnosis of fatty liver disease is really a clinical diagnosis.”
Panel moderator Elizabeth K. Speliotes, MD, of the University of Michigan, Ann Arbor, said, “Really what makes us unique is our genetics and our exposures and the environment, and if we can capture that better, then we can use that to more precisely tailor diagnoses and treatments for patients. That’s really the hope of the next generation.”
The study was supported by the VA Office of Research and Development award 1I01BX003362. Dr. Serper disclosed no relevant conflicts of interest.
Watch this video interview with Dr. Serper and Dr. Chang for more information on the Million Veteran Program.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
AT THE LIVER MEETING 2017
Key clinical point:
Major finding: About one-third (108,458) of 352,953 Million Veteran Program enrollees whose DNA has been analyzed met the study definition of NAFLD.
Data source: Genome-wide association study of more than 100,000 patients.
Disclosures: The study was supported by the Veterans Administration Office of Research and Development award 1I01BX003362. Dr. Serper disclosed no relevant conflicts of interest.
Carvedilol fails to reduce variceal bleeds in acute-on-chronic liver failure
WASHINGTON – Treatment with carvedilol reduced the incidence of sepsis and acute kidney injury and improved survival at 28 days but did not significantly reduce the progression of esophageal varices in patients with acute-on-chronic liver failure.
A total of 136 patients with acute-on-chronic liver failure with small or no esophageal varices and a hepatic venous pressure gradient (HVPG) of 12 mm Hg or greater were enrolled in a single center, prospective, open-label, randomized controlled trial: 66 were randomized to carvedilol and 70 to placebo, according to Sumeet Kainth, MD, of the Institute of Liver and Biliary Sciences in New Delhi.
More than 90% of patients were men with a mean age of 44 years, and composition of the treatment and placebo groups was similar. About 70% in each group had alcoholic hepatitis (the reason for acute liver failure in most). Mean Model for End-Stage Liver Disease (MELD) scores were about 25. Hemodynamic parameters also were comparable, with a mean HVPG of about 19, Dr. Kainth said at the annual meeting of the American Association for the Study of Liver Diseases.
Patients in the treatment group received a median maximum tolerated dose of carvedilol of 12.5 mg, with a range of 3.13 mg to 25 mg.
Morbidity and mortality were high, as is expected with acute-on-chronic liver failure, he noted. A total of 36 patients died before the end of the 90-day study period. Another 23 experienced adverse events and 2 progressed to liver transplant.
HVPG at 90 days decreased significantly in both groups. In the carvedilol group, 90-day HVPG was 16 mm Hg, compared with 19.7 mm Hg at baseline (P less than .01). For placebo patients, 90-day HVPG spontaneously improved to 14.8 mm Hg, compared with a baseline of 17.2 mm Hg (P less than .01).
Carvedilol did not significantly slow the development or growth of varices, however, Dr. Kainth said. At 90 days, varices had progressed in 9 of 40 patients (22.5%) of patients on carvedilol and 8 of 31 (25.8%) of placebo patients.
Significantly fewer patients in the carvedilol group developed acute kidney injury at 28 days (14% vs. 38% on placebo) and sepsis (5% vs. 20%). Mortality also was reduced significantly at 28 days (11% vs. 24%), he reported.
Treatment with carvedilol did not achieve significant reductions in variceal bleeding, “possibly due to the low number of bleeds seen in the study [because of] the exclusion of patients with large varices,” Dr. Kainth said.
The study was sponsored by Institute of Liver and Biliary Sciences. Dr. Kainth reported no relevant conflicts of interest.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
WASHINGTON – Treatment with carvedilol reduced the incidence of sepsis and acute kidney injury and improved survival at 28 days but did not significantly reduce the progression of esophageal varices in patients with acute-on-chronic liver failure.
A total of 136 patients with acute-on-chronic liver failure with small or no esophageal varices and a hepatic venous pressure gradient (HVPG) of 12 mm Hg or greater were enrolled in a single center, prospective, open-label, randomized controlled trial: 66 were randomized to carvedilol and 70 to placebo, according to Sumeet Kainth, MD, of the Institute of Liver and Biliary Sciences in New Delhi.
More than 90% of patients were men with a mean age of 44 years, and composition of the treatment and placebo groups was similar. About 70% in each group had alcoholic hepatitis (the reason for acute liver failure in most). Mean Model for End-Stage Liver Disease (MELD) scores were about 25. Hemodynamic parameters also were comparable, with a mean HVPG of about 19, Dr. Kainth said at the annual meeting of the American Association for the Study of Liver Diseases.
Patients in the treatment group received a median maximum tolerated dose of carvedilol of 12.5 mg, with a range of 3.13 mg to 25 mg.
Morbidity and mortality were high, as is expected with acute-on-chronic liver failure, he noted. A total of 36 patients died before the end of the 90-day study period. Another 23 experienced adverse events and 2 progressed to liver transplant.
HVPG at 90 days decreased significantly in both groups. In the carvedilol group, 90-day HVPG was 16 mm Hg, compared with 19.7 mm Hg at baseline (P less than .01). For placebo patients, 90-day HVPG spontaneously improved to 14.8 mm Hg, compared with a baseline of 17.2 mm Hg (P less than .01).
Carvedilol did not significantly slow the development or growth of varices, however, Dr. Kainth said. At 90 days, varices had progressed in 9 of 40 patients (22.5%) of patients on carvedilol and 8 of 31 (25.8%) of placebo patients.
Significantly fewer patients in the carvedilol group developed acute kidney injury at 28 days (14% vs. 38% on placebo) and sepsis (5% vs. 20%). Mortality also was reduced significantly at 28 days (11% vs. 24%), he reported.
Treatment with carvedilol did not achieve significant reductions in variceal bleeding, “possibly due to the low number of bleeds seen in the study [because of] the exclusion of patients with large varices,” Dr. Kainth said.
The study was sponsored by Institute of Liver and Biliary Sciences. Dr. Kainth reported no relevant conflicts of interest.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
WASHINGTON – Treatment with carvedilol reduced the incidence of sepsis and acute kidney injury and improved survival at 28 days but did not significantly reduce the progression of esophageal varices in patients with acute-on-chronic liver failure.
A total of 136 patients with acute-on-chronic liver failure with small or no esophageal varices and a hepatic venous pressure gradient (HVPG) of 12 mm Hg or greater were enrolled in a single center, prospective, open-label, randomized controlled trial: 66 were randomized to carvedilol and 70 to placebo, according to Sumeet Kainth, MD, of the Institute of Liver and Biliary Sciences in New Delhi.
More than 90% of patients were men with a mean age of 44 years, and composition of the treatment and placebo groups was similar. About 70% in each group had alcoholic hepatitis (the reason for acute liver failure in most). Mean Model for End-Stage Liver Disease (MELD) scores were about 25. Hemodynamic parameters also were comparable, with a mean HVPG of about 19, Dr. Kainth said at the annual meeting of the American Association for the Study of Liver Diseases.
Patients in the treatment group received a median maximum tolerated dose of carvedilol of 12.5 mg, with a range of 3.13 mg to 25 mg.
Morbidity and mortality were high, as is expected with acute-on-chronic liver failure, he noted. A total of 36 patients died before the end of the 90-day study period. Another 23 experienced adverse events and 2 progressed to liver transplant.
HVPG at 90 days decreased significantly in both groups. In the carvedilol group, 90-day HVPG was 16 mm Hg, compared with 19.7 mm Hg at baseline (P less than .01). For placebo patients, 90-day HVPG spontaneously improved to 14.8 mm Hg, compared with a baseline of 17.2 mm Hg (P less than .01).
Carvedilol did not significantly slow the development or growth of varices, however, Dr. Kainth said. At 90 days, varices had progressed in 9 of 40 patients (22.5%) of patients on carvedilol and 8 of 31 (25.8%) of placebo patients.
Significantly fewer patients in the carvedilol group developed acute kidney injury at 28 days (14% vs. 38% on placebo) and sepsis (5% vs. 20%). Mortality also was reduced significantly at 28 days (11% vs. 24%), he reported.
Treatment with carvedilol did not achieve significant reductions in variceal bleeding, “possibly due to the low number of bleeds seen in the study [because of] the exclusion of patients with large varices,” Dr. Kainth said.
The study was sponsored by Institute of Liver and Biliary Sciences. Dr. Kainth reported no relevant conflicts of interest.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
AT THE LIVER MEETING 2017
Key clinical point:
Major finding: At 90 days, varices had progressed in 9 of 40 (22.5%) patients on carvedilol vs. 8 of 31 (25.8%) of placebo patients.
Data source: A single-center, prospective, open-label, randomized controlled trial of 136 patients with acute-on-chronic liver failure.
Disclosures: The study was sponsored by the Institute of Liver and Biliary Sciences. Dr. Kainth reported no relevant conflicts of interest.
New biomarkers improve DILI predictability
WASHINGTON – Researchers have identified six new biomarkers of drug-induced liver injury (DILI) that, when combined with traditional measurements, seemed to better predict the disease course, compared with traditional biomarkers alone, according to a presentation at the annual meeting of the American Association for the Study of Liver Diseases.
In addition, some of these biomarkers may provide a “liquid biopsy” to assess degree of inflammation and mode of hepatocyte death, said Rachel Church, PhD, of the University of North Carolina, Chapel Hill.
“The motivation behind this research is that the standard biomarkers for DILI have several shortcomings,” Dr. Church said. “They’re not entirely liver specific, they’re not mechanistically informative, and they’re not sufficiently predictive of outcome.”
The researchers found that elevated levels of these six candidate biomarkers were predictive for adverse outcome in DILI: total keratin18 (K18); caspase-cleaved K18 (ccK18); alpha-fetoprotein (AFP); osteopontin (OPN); fatty acid–binding protein 1 (FABP1); and macrophage colony-stimulating factor receptor (MCSFR) determined by immunoassay. “We believe that using some of these candidate biomarkers in combination with the standard tests may be the best way to identify individuals at risk for an adverse outcome,” Dr. Church said.
While their analysis found that the traditional international normalized ratio had the overall best predictive value, measured as area under the curve (AUC) of 0.922, the candidate biomarker OPN was second best with an AUC of 0.871, “and actually performed better than total bilirubin,” Dr. Church said.
The study evaluated mechanistic candidate biomarkers by obtaining biopsies in a cohort of 27 patients within 2 weeks of diagnosis, focusing on three physiological reactions: inflammation, necrosis, and apoptosis.
With regard to inflammation, Dr. Church said, “What we found was that MCSFR actually was significantly elevated in patients who had a high score for inflammation; however, there was no significant difference in OPN, although there was a slight elevation.”
They evaluated necrosis using a semiquantitative confluent coagulative necrosis score, and found no difference in the typical biomarkers of cell necrosis, such as alanine transminase, aspartate aminotransferase, and K18. “So we also looked at the regenerative biomarkers, OPN and AFP, and indeed, we observed that both were significantly elevated with high confluent coagulative necrosis scores,” she said.
To evaluate apoptosis, the researchers used the semiquantitative apoptosis score. “We found there was a small but significant elevation in ccK18 in individuals with a high apoptosis score,” she said. They then evaluated the ratio of ccK18 to K18. “The closer the score is to 1, the more apoptosis you have; and the closer the score is to 0, the more necrosis you have,” Dr. Church said.
They also developed a predictive model that combined the traditional biomarkers INR, total bilirubin, and aspartate aminotransferase with the candidate biomarkers OPN and K18, which had an AUC of 0.97. “Some analysis of candidate biomarkers in combination with tests such as MELD score [Model for End-Stage Liver Disease] and ‘Hy’s Law’ saw that incorporating candidate biomarkers was useful,” Dr. Church said.
Dr. Church reported having no financial disclosures.
WASHINGTON – Researchers have identified six new biomarkers of drug-induced liver injury (DILI) that, when combined with traditional measurements, seemed to better predict the disease course, compared with traditional biomarkers alone, according to a presentation at the annual meeting of the American Association for the Study of Liver Diseases.
In addition, some of these biomarkers may provide a “liquid biopsy” to assess degree of inflammation and mode of hepatocyte death, said Rachel Church, PhD, of the University of North Carolina, Chapel Hill.
“The motivation behind this research is that the standard biomarkers for DILI have several shortcomings,” Dr. Church said. “They’re not entirely liver specific, they’re not mechanistically informative, and they’re not sufficiently predictive of outcome.”
The researchers found that elevated levels of these six candidate biomarkers were predictive for adverse outcome in DILI: total keratin18 (K18); caspase-cleaved K18 (ccK18); alpha-fetoprotein (AFP); osteopontin (OPN); fatty acid–binding protein 1 (FABP1); and macrophage colony-stimulating factor receptor (MCSFR) determined by immunoassay. “We believe that using some of these candidate biomarkers in combination with the standard tests may be the best way to identify individuals at risk for an adverse outcome,” Dr. Church said.
While their analysis found that the traditional international normalized ratio had the overall best predictive value, measured as area under the curve (AUC) of 0.922, the candidate biomarker OPN was second best with an AUC of 0.871, “and actually performed better than total bilirubin,” Dr. Church said.
The study evaluated mechanistic candidate biomarkers by obtaining biopsies in a cohort of 27 patients within 2 weeks of diagnosis, focusing on three physiological reactions: inflammation, necrosis, and apoptosis.
With regard to inflammation, Dr. Church said, “What we found was that MCSFR actually was significantly elevated in patients who had a high score for inflammation; however, there was no significant difference in OPN, although there was a slight elevation.”
They evaluated necrosis using a semiquantitative confluent coagulative necrosis score, and found no difference in the typical biomarkers of cell necrosis, such as alanine transminase, aspartate aminotransferase, and K18. “So we also looked at the regenerative biomarkers, OPN and AFP, and indeed, we observed that both were significantly elevated with high confluent coagulative necrosis scores,” she said.
To evaluate apoptosis, the researchers used the semiquantitative apoptosis score. “We found there was a small but significant elevation in ccK18 in individuals with a high apoptosis score,” she said. They then evaluated the ratio of ccK18 to K18. “The closer the score is to 1, the more apoptosis you have; and the closer the score is to 0, the more necrosis you have,” Dr. Church said.
They also developed a predictive model that combined the traditional biomarkers INR, total bilirubin, and aspartate aminotransferase with the candidate biomarkers OPN and K18, which had an AUC of 0.97. “Some analysis of candidate biomarkers in combination with tests such as MELD score [Model for End-Stage Liver Disease] and ‘Hy’s Law’ saw that incorporating candidate biomarkers was useful,” Dr. Church said.
Dr. Church reported having no financial disclosures.
WASHINGTON – Researchers have identified six new biomarkers of drug-induced liver injury (DILI) that, when combined with traditional measurements, seemed to better predict the disease course, compared with traditional biomarkers alone, according to a presentation at the annual meeting of the American Association for the Study of Liver Diseases.
In addition, some of these biomarkers may provide a “liquid biopsy” to assess degree of inflammation and mode of hepatocyte death, said Rachel Church, PhD, of the University of North Carolina, Chapel Hill.
“The motivation behind this research is that the standard biomarkers for DILI have several shortcomings,” Dr. Church said. “They’re not entirely liver specific, they’re not mechanistically informative, and they’re not sufficiently predictive of outcome.”
The researchers found that elevated levels of these six candidate biomarkers were predictive for adverse outcome in DILI: total keratin18 (K18); caspase-cleaved K18 (ccK18); alpha-fetoprotein (AFP); osteopontin (OPN); fatty acid–binding protein 1 (FABP1); and macrophage colony-stimulating factor receptor (MCSFR) determined by immunoassay. “We believe that using some of these candidate biomarkers in combination with the standard tests may be the best way to identify individuals at risk for an adverse outcome,” Dr. Church said.
While their analysis found that the traditional international normalized ratio had the overall best predictive value, measured as area under the curve (AUC) of 0.922, the candidate biomarker OPN was second best with an AUC of 0.871, “and actually performed better than total bilirubin,” Dr. Church said.
The study evaluated mechanistic candidate biomarkers by obtaining biopsies in a cohort of 27 patients within 2 weeks of diagnosis, focusing on three physiological reactions: inflammation, necrosis, and apoptosis.
With regard to inflammation, Dr. Church said, “What we found was that MCSFR actually was significantly elevated in patients who had a high score for inflammation; however, there was no significant difference in OPN, although there was a slight elevation.”
They evaluated necrosis using a semiquantitative confluent coagulative necrosis score, and found no difference in the typical biomarkers of cell necrosis, such as alanine transminase, aspartate aminotransferase, and K18. “So we also looked at the regenerative biomarkers, OPN and AFP, and indeed, we observed that both were significantly elevated with high confluent coagulative necrosis scores,” she said.
To evaluate apoptosis, the researchers used the semiquantitative apoptosis score. “We found there was a small but significant elevation in ccK18 in individuals with a high apoptosis score,” she said. They then evaluated the ratio of ccK18 to K18. “The closer the score is to 1, the more apoptosis you have; and the closer the score is to 0, the more necrosis you have,” Dr. Church said.
They also developed a predictive model that combined the traditional biomarkers INR, total bilirubin, and aspartate aminotransferase with the candidate biomarkers OPN and K18, which had an AUC of 0.97. “Some analysis of candidate biomarkers in combination with tests such as MELD score [Model for End-Stage Liver Disease] and ‘Hy’s Law’ saw that incorporating candidate biomarkers was useful,” Dr. Church said.
Dr. Church reported having no financial disclosures.
AT THE LIVER MEETING 2017
Key clinical point: Combining six candidate biomarkers with traditional biomarkers may improve prediction of adverse outcomes in drug-induced liver injury.
Major finding: Candidate biomarker osteopontin had an area under the cure measure of 0.871, second only to the traditional biomarker international normalized ratio and exceeding that of total bilirubin.
Data source: Analysis of serum samples collected by the DILI Network from 145 patients with a greater than 50% likelihood of having DILI.
Disclosures: Dr. Church reported having no financial disclosures.
Nutrition status predicts outcomes in liver transplant
WASHINGTON – Efforts to improve nutritional status prior to transplant may lead to improved patient outcomes and economic benefits after orthotopic liver transplant.
Clinicians at Austin Health, a tertiary health center in Melbourne, reviewed prospectively acquired data on 390 adult patients who underwent orthotopic liver transplant at their institution between January 2009 and June 2016, according to Brooke Chapman, a dietitian on the center’s transplant team.
“Hand-grip strength test is a functional measure of upper-body strength,” Ms. Chapman said at the annual meeting of the American Association for the Study of Liver Diseases. “It’s quick and cheap and reliable but importantly, it does respond quite readily to changes in nutritional intake and nutrition status.”
Assessments were made as patients were wait listed for liver transplant. Hand-grip strength and subjective global assessment were repeated at the time of transplant.
Patients with fulminant liver failure and those requiring retransplantation were excluded from the final analysis, leaving 321 patients in the cohort. More than two-thirds (69%) were men and the median age was 52 years old. About half of patients had a diagnosis of hepatocellular carcinoma or hepatitis C infection. The median MELD (Model for Endstage Liver Disease) score was 18, with a range of 6-40, and the median time on the wait list was 140 days.
We saw a “high prevalence of malnutrition in patients undergoing liver transplant and the deterioration in nutritional status despite our best efforts while they are on the waiting list,” Ms. Chapman said.
At baseline, two-thirds of patients were malnourished – either mildly to moderately or severely; by transplantation, 77% were malnourished.
“At assessment, we are prescribing and educating patients on a high-calorie, high-protein diet initially, and we give oral nutrition support therapies,” she said. “We really try to get them to improve oral intake, but for patients who do require more aggressive intervention, we will feed them via nasogastric tube.”
Just over half (55%) of patients fell below the cutoff for sarcopenia on the hand-grip test at baseline and at transplant. More than a quarter of patients (27%) were not able to complete the 6-minute walk test.
“On univariate analysis, we saw malnutrition to be strongly associated with increased ICU and hospital length of stay,” Ms. Chapman noted. Severely malnourished patients spent significantly more time in the ICU than did well-nourished patients – a mean 147 hours vs. 89 hours (P = .001). Mean length of stay also was significantly longer at 40 days vs. 16 days (P = .003).
There was also an increased incidence of infection in severely malnourished patients as compared with well-nourished patients – 55.2% vs. 33.8%, she said.
“Aggressive strategies to combat malnutrition and deconditioning in the pretransplant period may lead to improved outcomes after transplant,” Ms. Chapman concluded.
The study was funded by Austin Health. Ms. Chapman declared no relevant conflicts of interest.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
WASHINGTON – Efforts to improve nutritional status prior to transplant may lead to improved patient outcomes and economic benefits after orthotopic liver transplant.
Clinicians at Austin Health, a tertiary health center in Melbourne, reviewed prospectively acquired data on 390 adult patients who underwent orthotopic liver transplant at their institution between January 2009 and June 2016, according to Brooke Chapman, a dietitian on the center’s transplant team.
“Hand-grip strength test is a functional measure of upper-body strength,” Ms. Chapman said at the annual meeting of the American Association for the Study of Liver Diseases. “It’s quick and cheap and reliable but importantly, it does respond quite readily to changes in nutritional intake and nutrition status.”
Assessments were made as patients were wait listed for liver transplant. Hand-grip strength and subjective global assessment were repeated at the time of transplant.
Patients with fulminant liver failure and those requiring retransplantation were excluded from the final analysis, leaving 321 patients in the cohort. More than two-thirds (69%) were men and the median age was 52 years old. About half of patients had a diagnosis of hepatocellular carcinoma or hepatitis C infection. The median MELD (Model for Endstage Liver Disease) score was 18, with a range of 6-40, and the median time on the wait list was 140 days.
We saw a “high prevalence of malnutrition in patients undergoing liver transplant and the deterioration in nutritional status despite our best efforts while they are on the waiting list,” Ms. Chapman said.
At baseline, two-thirds of patients were malnourished – either mildly to moderately or severely; by transplantation, 77% were malnourished.
“At assessment, we are prescribing and educating patients on a high-calorie, high-protein diet initially, and we give oral nutrition support therapies,” she said. “We really try to get them to improve oral intake, but for patients who do require more aggressive intervention, we will feed them via nasogastric tube.”
Just over half (55%) of patients fell below the cutoff for sarcopenia on the hand-grip test at baseline and at transplant. More than a quarter of patients (27%) were not able to complete the 6-minute walk test.
“On univariate analysis, we saw malnutrition to be strongly associated with increased ICU and hospital length of stay,” Ms. Chapman noted. Severely malnourished patients spent significantly more time in the ICU than did well-nourished patients – a mean 147 hours vs. 89 hours (P = .001). Mean length of stay also was significantly longer at 40 days vs. 16 days (P = .003).
There was also an increased incidence of infection in severely malnourished patients as compared with well-nourished patients – 55.2% vs. 33.8%, she said.
“Aggressive strategies to combat malnutrition and deconditioning in the pretransplant period may lead to improved outcomes after transplant,” Ms. Chapman concluded.
The study was funded by Austin Health. Ms. Chapman declared no relevant conflicts of interest.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
WASHINGTON – Efforts to improve nutritional status prior to transplant may lead to improved patient outcomes and economic benefits after orthotopic liver transplant.
Clinicians at Austin Health, a tertiary health center in Melbourne, reviewed prospectively acquired data on 390 adult patients who underwent orthotopic liver transplant at their institution between January 2009 and June 2016, according to Brooke Chapman, a dietitian on the center’s transplant team.
“Hand-grip strength test is a functional measure of upper-body strength,” Ms. Chapman said at the annual meeting of the American Association for the Study of Liver Diseases. “It’s quick and cheap and reliable but importantly, it does respond quite readily to changes in nutritional intake and nutrition status.”
Assessments were made as patients were wait listed for liver transplant. Hand-grip strength and subjective global assessment were repeated at the time of transplant.
Patients with fulminant liver failure and those requiring retransplantation were excluded from the final analysis, leaving 321 patients in the cohort. More than two-thirds (69%) were men and the median age was 52 years old. About half of patients had a diagnosis of hepatocellular carcinoma or hepatitis C infection. The median MELD (Model for Endstage Liver Disease) score was 18, with a range of 6-40, and the median time on the wait list was 140 days.
We saw a “high prevalence of malnutrition in patients undergoing liver transplant and the deterioration in nutritional status despite our best efforts while they are on the waiting list,” Ms. Chapman said.
At baseline, two-thirds of patients were malnourished – either mildly to moderately or severely; by transplantation, 77% were malnourished.
“At assessment, we are prescribing and educating patients on a high-calorie, high-protein diet initially, and we give oral nutrition support therapies,” she said. “We really try to get them to improve oral intake, but for patients who do require more aggressive intervention, we will feed them via nasogastric tube.”
Just over half (55%) of patients fell below the cutoff for sarcopenia on the hand-grip test at baseline and at transplant. More than a quarter of patients (27%) were not able to complete the 6-minute walk test.
“On univariate analysis, we saw malnutrition to be strongly associated with increased ICU and hospital length of stay,” Ms. Chapman noted. Severely malnourished patients spent significantly more time in the ICU than did well-nourished patients – a mean 147 hours vs. 89 hours (P = .001). Mean length of stay also was significantly longer at 40 days vs. 16 days (P = .003).
There was also an increased incidence of infection in severely malnourished patients as compared with well-nourished patients – 55.2% vs. 33.8%, she said.
“Aggressive strategies to combat malnutrition and deconditioning in the pretransplant period may lead to improved outcomes after transplant,” Ms. Chapman concluded.
The study was funded by Austin Health. Ms. Chapman declared no relevant conflicts of interest.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
AT THE LIVER MEETING 2017
Key clinical point:
Major finding: Severely malnourished patients spent a mean of 147 hours in the ICU vs. 89 hours for well-nourished patients. Mean length of stay also was significantly longer at 40 days vs. 16 days (P = .003).
Data source: Retrospective review of data on 390 adults awaiting liver transplantation between Jan. 2009 and June 2016.
Disclosures: The study was funded by the institutions. The authors reported no relevant conflicts of interest.
Post–liver transplant results similar in acute alcoholic hepatitis, stage 1a
WASHINGTON – Patients with acute alcoholic hepatitis (AAH) have similar early post–liver transplant outcomes to those listed with fulminant hepatic failure, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Patients with severe AAH have high mortality, but many are unable to survive the 6 months of sobriety required to be accepted as liver transplant candidates, said George Cholankeril, MD, of the gastroenterology and hepatology department at Stanford (Calif.) University.
He and his associates studied wait-list mortality and post–liver transplant survival among 1,912 patients listed for either AAH or fulminant hepatic failure on the United Network for Organ Sharing (UNOS) registry between 2011 and 2016.
A total of 193 patients were listed with AAH, 314 were listed with drug-induced liver injury including acetaminophen (DILI-APAP), and 1,405 were listed as non-DILI patients.
One-year post–liver transplant survival among AAH patients was 93.3%, compared with 87.75% for DILI-APAP patients and 88.4% among non-DILI patients (P less than .001). Survival remained the same among AAH patients 3 years following transplantation, but rates dropped for both the DILI-APAP group (80.8%) and the non-DILI group (81.4%), Dr. Cholankeril reported.
Patients were a median age of 45, 33, and 46 years among the AAH, DILI-APAP, and non-DILI, groups respectively. Patients were majority white among all three groups, with a significantly larger female population among the DILI-APAP group (80.6%) than the AAH (34.7%) or non-DILI (59.4%) groups. Patients in the AAH group had a median Model for End-Stage Liver Disease (MELD) score of 32, compared with 34 for DILI-APAP and 21 for non-DILI.
AAH patients could potentially see significant improvement with a liver transplant, according to investigators; however, the current standards for candidacy have created treatment barriers.
“Patients with AAH have comparable early post-transplant outcomes to those with hepatic liver failure,” said Dr. Cholankeril. “However, there is no consensus or national guidelines for liver transplantation within this patient population.”
Wait-list trends have already started to shift toward more AAH patient acceptance. The number of AAH patients added to the transplant wait lists increased from 14 in 2011 to 58 in 2016. Investigators also found that the number of liver transplant centers accepting AAH patients to their transplant lists increased from 3 to 26.
Investigators were limited by the variations in protocols for each transplant center, as well as by the inconsistency of pre–liver transplant psychosocial metrics. The diagnostic criteria of AAH through UNOS was also a limitation for investigators, according to Dr. Cholankeril.
Although liver transplantation may be able to help some patients, it is only a small fix for a much larger problem. “This is only a solution for a minority of patients with the rising epidemic of alcoholic intoxication in the U.S.,” he said. “As the increasing mortality trends show alcohol-related mortality, and alcoholic liver disease is a contributor to it, we must recognize alcoholic liver disease remains an orphan disease and there is still an unmet need.”
Dr. Cholankeril reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
Transplanting patients with alcohol induced liver disease has been controversial since the earliest days of liver transplantation. Initially some programs were reluctant to transplant patients with a disease that was “self-inflicted” based on an ethical concern about using a scarce resource to save the lives of those whose disease was their own fault, while other patients may die waiting. There was also a concern that transplanting alcoholics would be bad publicity for organ donation and reduce the public’s willingness to donate organs. The highly publicized transplantation of baseball legend and known alcoholic Mickey Mantle in 1995 intensified this debate.
Over time it became clear that the concerns regarding transplanting alcoholics were unfounded. The outcomes were equal or better than for other diseases. Liver transplantation was termed “the ultimate eye opening experience” as serious recidivism turned out to be very uncommon. It was realized that a large percentage of all reasons for seeking medical care can be attributed to self-inflicted harm when one considers cigarette induced malignancy and cardiovascular disease and dietary indiscretion leading to obesity and diabetes. It also became clear that from a practical standpoint prohibiting transplantation of alcoholics simply drove patients to programs that would accept such patients, or caused them and their family to withhold disclosure of alcohol use.
While transplantation of patients with chronic liver disease due to alcohol use has become standard of care, transplanting patients with acute alcoholic hepatitis remains controversial and relatively uncommon. Many programs require a period of abstinence, which is impossible in the setting of acute alcoholic hepatitis. The concern is that it is impossible to discern among actively drinking candidates which ones will be able to achieve sobriety after the transplant. The report by Cholankeril and colleagues documents that the tide is changing. There are increasing numbers of patients being transplanted for acute alcoholic hepatitis, and outcomes are acceptable. However, as the authors point out, the numbers are small and represent a highly selected group of patients. Nevertheless, the pressure on programs to modify rigid abstinence criteria is likely to grow as the evidence accumulates showing selected patients with acute alcoholic hepatitis can do well.
Jeffrey Punch, MD, FACS, is transplant specialist at the University of Michigan in Ann Arbor, and on the Editorial Advisory Board of ACS Surgery News.
Transplanting patients with alcohol induced liver disease has been controversial since the earliest days of liver transplantation. Initially some programs were reluctant to transplant patients with a disease that was “self-inflicted” based on an ethical concern about using a scarce resource to save the lives of those whose disease was their own fault, while other patients may die waiting. There was also a concern that transplanting alcoholics would be bad publicity for organ donation and reduce the public’s willingness to donate organs. The highly publicized transplantation of baseball legend and known alcoholic Mickey Mantle in 1995 intensified this debate.
Over time it became clear that the concerns regarding transplanting alcoholics were unfounded. The outcomes were equal or better than for other diseases. Liver transplantation was termed “the ultimate eye opening experience” as serious recidivism turned out to be very uncommon. It was realized that a large percentage of all reasons for seeking medical care can be attributed to self-inflicted harm when one considers cigarette induced malignancy and cardiovascular disease and dietary indiscretion leading to obesity and diabetes. It also became clear that from a practical standpoint prohibiting transplantation of alcoholics simply drove patients to programs that would accept such patients, or caused them and their family to withhold disclosure of alcohol use.
While transplantation of patients with chronic liver disease due to alcohol use has become standard of care, transplanting patients with acute alcoholic hepatitis remains controversial and relatively uncommon. Many programs require a period of abstinence, which is impossible in the setting of acute alcoholic hepatitis. The concern is that it is impossible to discern among actively drinking candidates which ones will be able to achieve sobriety after the transplant. The report by Cholankeril and colleagues documents that the tide is changing. There are increasing numbers of patients being transplanted for acute alcoholic hepatitis, and outcomes are acceptable. However, as the authors point out, the numbers are small and represent a highly selected group of patients. Nevertheless, the pressure on programs to modify rigid abstinence criteria is likely to grow as the evidence accumulates showing selected patients with acute alcoholic hepatitis can do well.
Jeffrey Punch, MD, FACS, is transplant specialist at the University of Michigan in Ann Arbor, and on the Editorial Advisory Board of ACS Surgery News.
Transplanting patients with alcohol induced liver disease has been controversial since the earliest days of liver transplantation. Initially some programs were reluctant to transplant patients with a disease that was “self-inflicted” based on an ethical concern about using a scarce resource to save the lives of those whose disease was their own fault, while other patients may die waiting. There was also a concern that transplanting alcoholics would be bad publicity for organ donation and reduce the public’s willingness to donate organs. The highly publicized transplantation of baseball legend and known alcoholic Mickey Mantle in 1995 intensified this debate.
Over time it became clear that the concerns regarding transplanting alcoholics were unfounded. The outcomes were equal or better than for other diseases. Liver transplantation was termed “the ultimate eye opening experience” as serious recidivism turned out to be very uncommon. It was realized that a large percentage of all reasons for seeking medical care can be attributed to self-inflicted harm when one considers cigarette induced malignancy and cardiovascular disease and dietary indiscretion leading to obesity and diabetes. It also became clear that from a practical standpoint prohibiting transplantation of alcoholics simply drove patients to programs that would accept such patients, or caused them and their family to withhold disclosure of alcohol use.
While transplantation of patients with chronic liver disease due to alcohol use has become standard of care, transplanting patients with acute alcoholic hepatitis remains controversial and relatively uncommon. Many programs require a period of abstinence, which is impossible in the setting of acute alcoholic hepatitis. The concern is that it is impossible to discern among actively drinking candidates which ones will be able to achieve sobriety after the transplant. The report by Cholankeril and colleagues documents that the tide is changing. There are increasing numbers of patients being transplanted for acute alcoholic hepatitis, and outcomes are acceptable. However, as the authors point out, the numbers are small and represent a highly selected group of patients. Nevertheless, the pressure on programs to modify rigid abstinence criteria is likely to grow as the evidence accumulates showing selected patients with acute alcoholic hepatitis can do well.
Jeffrey Punch, MD, FACS, is transplant specialist at the University of Michigan in Ann Arbor, and on the Editorial Advisory Board of ACS Surgery News.
WASHINGTON – Patients with acute alcoholic hepatitis (AAH) have similar early post–liver transplant outcomes to those listed with fulminant hepatic failure, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Patients with severe AAH have high mortality, but many are unable to survive the 6 months of sobriety required to be accepted as liver transplant candidates, said George Cholankeril, MD, of the gastroenterology and hepatology department at Stanford (Calif.) University.
He and his associates studied wait-list mortality and post–liver transplant survival among 1,912 patients listed for either AAH or fulminant hepatic failure on the United Network for Organ Sharing (UNOS) registry between 2011 and 2016.
A total of 193 patients were listed with AAH, 314 were listed with drug-induced liver injury including acetaminophen (DILI-APAP), and 1,405 were listed as non-DILI patients.
One-year post–liver transplant survival among AAH patients was 93.3%, compared with 87.75% for DILI-APAP patients and 88.4% among non-DILI patients (P less than .001). Survival remained the same among AAH patients 3 years following transplantation, but rates dropped for both the DILI-APAP group (80.8%) and the non-DILI group (81.4%), Dr. Cholankeril reported.
Patients were a median age of 45, 33, and 46 years among the AAH, DILI-APAP, and non-DILI, groups respectively. Patients were majority white among all three groups, with a significantly larger female population among the DILI-APAP group (80.6%) than the AAH (34.7%) or non-DILI (59.4%) groups. Patients in the AAH group had a median Model for End-Stage Liver Disease (MELD) score of 32, compared with 34 for DILI-APAP and 21 for non-DILI.
AAH patients could potentially see significant improvement with a liver transplant, according to investigators; however, the current standards for candidacy have created treatment barriers.
“Patients with AAH have comparable early post-transplant outcomes to those with hepatic liver failure,” said Dr. Cholankeril. “However, there is no consensus or national guidelines for liver transplantation within this patient population.”
Wait-list trends have already started to shift toward more AAH patient acceptance. The number of AAH patients added to the transplant wait lists increased from 14 in 2011 to 58 in 2016. Investigators also found that the number of liver transplant centers accepting AAH patients to their transplant lists increased from 3 to 26.
Investigators were limited by the variations in protocols for each transplant center, as well as by the inconsistency of pre–liver transplant psychosocial metrics. The diagnostic criteria of AAH through UNOS was also a limitation for investigators, according to Dr. Cholankeril.
Although liver transplantation may be able to help some patients, it is only a small fix for a much larger problem. “This is only a solution for a minority of patients with the rising epidemic of alcoholic intoxication in the U.S.,” he said. “As the increasing mortality trends show alcohol-related mortality, and alcoholic liver disease is a contributor to it, we must recognize alcoholic liver disease remains an orphan disease and there is still an unmet need.”
Dr. Cholankeril reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – Patients with acute alcoholic hepatitis (AAH) have similar early post–liver transplant outcomes to those listed with fulminant hepatic failure, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Patients with severe AAH have high mortality, but many are unable to survive the 6 months of sobriety required to be accepted as liver transplant candidates, said George Cholankeril, MD, of the gastroenterology and hepatology department at Stanford (Calif.) University.
He and his associates studied wait-list mortality and post–liver transplant survival among 1,912 patients listed for either AAH or fulminant hepatic failure on the United Network for Organ Sharing (UNOS) registry between 2011 and 2016.
A total of 193 patients were listed with AAH, 314 were listed with drug-induced liver injury including acetaminophen (DILI-APAP), and 1,405 were listed as non-DILI patients.
One-year post–liver transplant survival among AAH patients was 93.3%, compared with 87.75% for DILI-APAP patients and 88.4% among non-DILI patients (P less than .001). Survival remained the same among AAH patients 3 years following transplantation, but rates dropped for both the DILI-APAP group (80.8%) and the non-DILI group (81.4%), Dr. Cholankeril reported.
Patients were a median age of 45, 33, and 46 years among the AAH, DILI-APAP, and non-DILI, groups respectively. Patients were majority white among all three groups, with a significantly larger female population among the DILI-APAP group (80.6%) than the AAH (34.7%) or non-DILI (59.4%) groups. Patients in the AAH group had a median Model for End-Stage Liver Disease (MELD) score of 32, compared with 34 for DILI-APAP and 21 for non-DILI.
AAH patients could potentially see significant improvement with a liver transplant, according to investigators; however, the current standards for candidacy have created treatment barriers.
“Patients with AAH have comparable early post-transplant outcomes to those with hepatic liver failure,” said Dr. Cholankeril. “However, there is no consensus or national guidelines for liver transplantation within this patient population.”
Wait-list trends have already started to shift toward more AAH patient acceptance. The number of AAH patients added to the transplant wait lists increased from 14 in 2011 to 58 in 2016. Investigators also found that the number of liver transplant centers accepting AAH patients to their transplant lists increased from 3 to 26.
Investigators were limited by the variations in protocols for each transplant center, as well as by the inconsistency of pre–liver transplant psychosocial metrics. The diagnostic criteria of AAH through UNOS was also a limitation for investigators, according to Dr. Cholankeril.
Although liver transplantation may be able to help some patients, it is only a small fix for a much larger problem. “This is only a solution for a minority of patients with the rising epidemic of alcoholic intoxication in the U.S.,” he said. “As the increasing mortality trends show alcohol-related mortality, and alcoholic liver disease is a contributor to it, we must recognize alcoholic liver disease remains an orphan disease and there is still an unmet need.”
Dr. Cholankeril reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
AT THE LIVER MEETING 2017
Key clinical point:
Major finding: Survival 1 and 3 years after liver transplant was comparable in patients with drug-induced liver injury including acetaminophen (P = .10) and significantly higher than other chronic alcoholic liver disease patients (P less that .001).
Data source: Retrospective study of 1,912 liver transplant patients listed for either AAH or status 1A registered on the UNOS registry between 2011 and 2016.
Disclosures: Presenter reported no relevant financial disclosures.
VIDEO: Fibrosis biomarkers show promise to replace liver biopsy
WASHINGTON – The concentrations of three biomarkers successfully identified the severity of fibrosis in patients with nonalcoholic steatohepatitis (NASH), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
This noninvasive diagnostic method could replace liver biopsy, the current standard used to diagnose patients with NASH.
Liver biopsies are associated with high cost, high rates of complications like infection, and minimal association with morbidity and mortality, Manal Abdelmalek, MD, a hepatologist and liver transplant specialist at Duke University, Durham, N.C., said in a video interview.
Investigators measured serum concentrations of a2-macroglobulin, hyaluronic acid, and metalloproteinase-1 collected from 792 patients with NASH on the same day as patients’ liver biopsies.
Dr. Abdelmalek and her fellow investigators randomly assigned half of the samples to a training group and half the samples to a validation group.
Investigators found that samples in the training group showed a sensitivity of 84.4% (95% confidence interval, 75.5%-91.0%), compared with 81.1% (95% CI, 71.7%-88.4%) in the validation group. Among patients with liver fibrosis, the biomarker test correctly diagnosed 76.5%-100% of patients, with variations depending on placement in the four classifications based on severity.
Investigators feel optimistic that, with more testing, this biomarker test can be used in collaboration with imaging or used independently, minimizing possible patient complications.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – The concentrations of three biomarkers successfully identified the severity of fibrosis in patients with nonalcoholic steatohepatitis (NASH), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
This noninvasive diagnostic method could replace liver biopsy, the current standard used to diagnose patients with NASH.
Liver biopsies are associated with high cost, high rates of complications like infection, and minimal association with morbidity and mortality, Manal Abdelmalek, MD, a hepatologist and liver transplant specialist at Duke University, Durham, N.C., said in a video interview.
Investigators measured serum concentrations of a2-macroglobulin, hyaluronic acid, and metalloproteinase-1 collected from 792 patients with NASH on the same day as patients’ liver biopsies.
Dr. Abdelmalek and her fellow investigators randomly assigned half of the samples to a training group and half the samples to a validation group.
Investigators found that samples in the training group showed a sensitivity of 84.4% (95% confidence interval, 75.5%-91.0%), compared with 81.1% (95% CI, 71.7%-88.4%) in the validation group. Among patients with liver fibrosis, the biomarker test correctly diagnosed 76.5%-100% of patients, with variations depending on placement in the four classifications based on severity.
Investigators feel optimistic that, with more testing, this biomarker test can be used in collaboration with imaging or used independently, minimizing possible patient complications.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – The concentrations of three biomarkers successfully identified the severity of fibrosis in patients with nonalcoholic steatohepatitis (NASH), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
This noninvasive diagnostic method could replace liver biopsy, the current standard used to diagnose patients with NASH.
Liver biopsies are associated with high cost, high rates of complications like infection, and minimal association with morbidity and mortality, Manal Abdelmalek, MD, a hepatologist and liver transplant specialist at Duke University, Durham, N.C., said in a video interview.
Investigators measured serum concentrations of a2-macroglobulin, hyaluronic acid, and metalloproteinase-1 collected from 792 patients with NASH on the same day as patients’ liver biopsies.
Dr. Abdelmalek and her fellow investigators randomly assigned half of the samples to a training group and half the samples to a validation group.
Investigators found that samples in the training group showed a sensitivity of 84.4% (95% confidence interval, 75.5%-91.0%), compared with 81.1% (95% CI, 71.7%-88.4%) in the validation group. Among patients with liver fibrosis, the biomarker test correctly diagnosed 76.5%-100% of patients, with variations depending on placement in the four classifications based on severity.
Investigators feel optimistic that, with more testing, this biomarker test can be used in collaboration with imaging or used independently, minimizing possible patient complications.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
AT THE LIVER MEETING 2017
Bilirubin levels associated with transplant-free survival in PBC patients
Normal serum bilirubin concentrations in patients with primary biliary cholangitis (PBC) were associated with improved odds of transplant-free survival, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
In a retrospective analysis of data from the Global PBC Study group, PBC patients who had bilirubin levels between normal and the upper limit of normal at baseline (n = 2,795), at 1 year (n = 3,082), at 3 years (n = 1,657), or at 5 years (n = 1,339) were included in the study. Both ursodeoxycholic acid–treated and untreated patients were included, according to Carla Murillo Perez of Toronto General Hospital and her associates.
Each cohort was organized into quartiles, with Q1 having the lowest bilirubin levels and Q4 having the highest. In the baseline cohort, 5-year transplant-free survival rates were 97% in Q1, 95% in Q2, 96% in Q3, and 91% in Q4; similarly improved odds for transplant-free survival in lower quartiles were seen in the later cohorts.
Higher bilirubin (per 0.1 × upper limit of normal increase) was associated with an increased chance for death or transplantation, with hazard ratios of 1.14 in the baseline cohort, 1.21 in the 1-year cohort, 1.19 in the 3-year cohort, and 1.17 in the 5-year cohort, Ms. Perez and her associates said.
Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
Normal serum bilirubin concentrations in patients with primary biliary cholangitis (PBC) were associated with improved odds of transplant-free survival, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
In a retrospective analysis of data from the Global PBC Study group, PBC patients who had bilirubin levels between normal and the upper limit of normal at baseline (n = 2,795), at 1 year (n = 3,082), at 3 years (n = 1,657), or at 5 years (n = 1,339) were included in the study. Both ursodeoxycholic acid–treated and untreated patients were included, according to Carla Murillo Perez of Toronto General Hospital and her associates.
Each cohort was organized into quartiles, with Q1 having the lowest bilirubin levels and Q4 having the highest. In the baseline cohort, 5-year transplant-free survival rates were 97% in Q1, 95% in Q2, 96% in Q3, and 91% in Q4; similarly improved odds for transplant-free survival in lower quartiles were seen in the later cohorts.
Higher bilirubin (per 0.1 × upper limit of normal increase) was associated with an increased chance for death or transplantation, with hazard ratios of 1.14 in the baseline cohort, 1.21 in the 1-year cohort, 1.19 in the 3-year cohort, and 1.17 in the 5-year cohort, Ms. Perez and her associates said.
Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
Normal serum bilirubin concentrations in patients with primary biliary cholangitis (PBC) were associated with improved odds of transplant-free survival, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
In a retrospective analysis of data from the Global PBC Study group, PBC patients who had bilirubin levels between normal and the upper limit of normal at baseline (n = 2,795), at 1 year (n = 3,082), at 3 years (n = 1,657), or at 5 years (n = 1,339) were included in the study. Both ursodeoxycholic acid–treated and untreated patients were included, according to Carla Murillo Perez of Toronto General Hospital and her associates.
Each cohort was organized into quartiles, with Q1 having the lowest bilirubin levels and Q4 having the highest. In the baseline cohort, 5-year transplant-free survival rates were 97% in Q1, 95% in Q2, 96% in Q3, and 91% in Q4; similarly improved odds for transplant-free survival in lower quartiles were seen in the later cohorts.
Higher bilirubin (per 0.1 × upper limit of normal increase) was associated with an increased chance for death or transplantation, with hazard ratios of 1.14 in the baseline cohort, 1.21 in the 1-year cohort, 1.19 in the 3-year cohort, and 1.17 in the 5-year cohort, Ms. Perez and her associates said.
Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
FROM THE LIVER MEETING 2017
Key clinical point:
Major finding: In a baseline cohort, 5-year transplant-free survival rates were 97% in patients with the lowest bilirubin levels and 91% in patients with the highest.
Data source: A retrospective analysis of data from the Global PBC Study group database.
Disclosures: Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
Early liver transplant good for patients with severe alcoholic hepatitis
Early liver transplantation was associated with good short-term survival in patients with severe alcoholic hepatitis, but a significant number of patients started consuming alcohol again, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
The study was a retrospective review of the ACCELERATE-AH trial, utilizing a cohort of 147 patients with severe AH who underwent liver transplant prior to a 6-month abstinence period and were discharged home after surgery, said Dr. Brian Lee of the University of California, San Francisco, and his colleagues. Patients also underwent a follow-up period with a median time of 1.6 years.
Pretransplant abstinence time was a median of 55 days, and 54% received steroids for alcoholic hepatitis before the surgery. A total of 141 patients were discharged home after surgery, and 132 survived past 3 months. Of the nine patients who died within 3 months of their liver transplant, eight had received steroid therapy, and five died from sepsis.
No deaths were reported between 3 months and 1 year post transplant, but nine deaths were reported after 1 year, seven of which were alcohol related. The probability of alcohol use after 1 year was 25% and was 34% after 3 years.
After adjustment, a lack of self-admission into a hospital was associated with alcohol usage post transplant, with a hazard ratio of 4.3. In multivariate analysis, any alcohol use post transplant was associated with death, with a hazard ratio of 3.9, Dr. Lee and his colleagues noted.
Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
Early liver transplantation was associated with good short-term survival in patients with severe alcoholic hepatitis, but a significant number of patients started consuming alcohol again, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
The study was a retrospective review of the ACCELERATE-AH trial, utilizing a cohort of 147 patients with severe AH who underwent liver transplant prior to a 6-month abstinence period and were discharged home after surgery, said Dr. Brian Lee of the University of California, San Francisco, and his colleagues. Patients also underwent a follow-up period with a median time of 1.6 years.
Pretransplant abstinence time was a median of 55 days, and 54% received steroids for alcoholic hepatitis before the surgery. A total of 141 patients were discharged home after surgery, and 132 survived past 3 months. Of the nine patients who died within 3 months of their liver transplant, eight had received steroid therapy, and five died from sepsis.
No deaths were reported between 3 months and 1 year post transplant, but nine deaths were reported after 1 year, seven of which were alcohol related. The probability of alcohol use after 1 year was 25% and was 34% after 3 years.
After adjustment, a lack of self-admission into a hospital was associated with alcohol usage post transplant, with a hazard ratio of 4.3. In multivariate analysis, any alcohol use post transplant was associated with death, with a hazard ratio of 3.9, Dr. Lee and his colleagues noted.
Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
Early liver transplantation was associated with good short-term survival in patients with severe alcoholic hepatitis, but a significant number of patients started consuming alcohol again, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
The study was a retrospective review of the ACCELERATE-AH trial, utilizing a cohort of 147 patients with severe AH who underwent liver transplant prior to a 6-month abstinence period and were discharged home after surgery, said Dr. Brian Lee of the University of California, San Francisco, and his colleagues. Patients also underwent a follow-up period with a median time of 1.6 years.
Pretransplant abstinence time was a median of 55 days, and 54% received steroids for alcoholic hepatitis before the surgery. A total of 141 patients were discharged home after surgery, and 132 survived past 3 months. Of the nine patients who died within 3 months of their liver transplant, eight had received steroid therapy, and five died from sepsis.
No deaths were reported between 3 months and 1 year post transplant, but nine deaths were reported after 1 year, seven of which were alcohol related. The probability of alcohol use after 1 year was 25% and was 34% after 3 years.
After adjustment, a lack of self-admission into a hospital was associated with alcohol usage post transplant, with a hazard ratio of 4.3. In multivariate analysis, any alcohol use post transplant was associated with death, with a hazard ratio of 3.9, Dr. Lee and his colleagues noted.
Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
FROM THE LIVER MEETING 2017
Key clinical point:
Major finding: The survival rate post transplant was 94% after 1 year.
Data source: A retrospective review from the ACCELERATE-AH trial of 147 alcoholic hepatitis patients who received liver transplants.
Disclosures: Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
Asians have highest rate of herbal dietary supplement DILI liver transplantations
There is a significant relationship between race/ethnicity and drug-induced liver disease requiring liver transplantation caused by herbal and dietary supplements (HDS), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Asian people had significantly higher rates of HDS DILI that required transplant than did blacks, Hispanics, whites, and others (American Indian/Alaskan native, multiracial, and native Hawaii/Pacific Islander). White people had significantly lower rates of HDS DILI than did blacks, Hispanics, and others.
While the proportion of white people with HDS DILI requiring transplant was much lower than other races/ethnicities, the rate from 2005 to 2015 was significantly higher in this population than in 1995-2005, Dr. Kesar and his colleagues noted.
Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.
There is a significant relationship between race/ethnicity and drug-induced liver disease requiring liver transplantation caused by herbal and dietary supplements (HDS), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Asian people had significantly higher rates of HDS DILI that required transplant than did blacks, Hispanics, whites, and others (American Indian/Alaskan native, multiracial, and native Hawaii/Pacific Islander). White people had significantly lower rates of HDS DILI than did blacks, Hispanics, and others.
While the proportion of white people with HDS DILI requiring transplant was much lower than other races/ethnicities, the rate from 2005 to 2015 was significantly higher in this population than in 1995-2005, Dr. Kesar and his colleagues noted.
Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.
There is a significant relationship between race/ethnicity and drug-induced liver disease requiring liver transplantation caused by herbal and dietary supplements (HDS), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Asian people had significantly higher rates of HDS DILI that required transplant than did blacks, Hispanics, whites, and others (American Indian/Alaskan native, multiracial, and native Hawaii/Pacific Islander). White people had significantly lower rates of HDS DILI than did blacks, Hispanics, and others.
While the proportion of white people with HDS DILI requiring transplant was much lower than other races/ethnicities, the rate from 2005 to 2015 was significantly higher in this population than in 1995-2005, Dr. Kesar and his colleagues noted.
Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.
FROM THE LIVER MEETING 2017
Key clinical point:
Major finding: People of Asian descent were most likely to require transplantation because of drug-induced liver injury from herbal dietary supplements.
Data source: Retrospective data analysis of 645 patients from the Organ Procurement and Transplantation Network database.
Disclosures: Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.