AASLD 2020: A Clinical News Roundup

Neil Osterweil

November 30, 2020

Studies that address fundamental questions in hepatology and have the potential to change or improve clinical practice were the focus of a clinical debrief session from the virtual annual meeting of the American Association for the Study of Liver Diseases.

"We chose papers that had the highest level of evidence, such as randomized controlled trials, controlled studies, and large data sets – and some small data sets too," said Tamar Taddei, MD, associate professor of medicine in the section of digestive disease at Yale University, New Haven, Conn.

Taddei and colleagues Silvia Vilarinho, MD, PhDSimona Jakab, MD; and Ariel Jaffe, MD, all also from Yale, selected the papers from among 197 oral and 1,769 poster abstracts presented at AASLD 2020.

They highlighted the most important findings from presentations on autoimmune and cholestatic disease, transplantation, cirrhosis and portal hypertension, alcoholic liver disease, neoplasia, drug-induced liver injury, and COVID-19. They did not review studies focused primarily on nonalcoholic steatohepatitis or nonalcoholic fatty liver disease, viral hepatitis, or basic science, all of which were covered in separate debriefing sessions.

Cirrhosis and Portal Hypertension

A study from the Department of Veterans Affairs looked at the prevalence of liver disease risk factors and rates of subsequent testing for and diagnosis of cirrhosis in the Veterans Health Administration system (VHA).

The authors found that, among more than 6.65 million VHA users in 2018 with no prior diagnosis of cirrhosis, approximately half were at risk for cirrhosis, of whom about 75% were screened, and approximately 5% of those who were screened were positive for possible cirrhosis (133,636). Of the patients who screened positive, about 10% (12,566) received a diagnosis of cirrhosis, including 4,120 with liver decompensation.

"This paper underscores the importance of population-level screening in uncovering unrecognized cirrhosis, enabling intervention earlier in the course of disease," Taddei said (Abstract #661).

A study looking at external validation of novel cirrhosis surgical risk models designed to improve prognostication for a range of common surgeries showed that the VOCAL-Penn score was superior to the Mayo Risk Score, Model for End-stage Liver Disease and MELD-sodium scores for discrimination of 30-day and 90-day postoperative mortality (Abstract #91).

"While these models are not a substitute for clinical acumen, they certainly improve our surgical risk prediction in patients with cirrhosis, a very common question in consultative hepatology," Taddei said.

She also cited three abstracts that address the important questions regarding performing studies in patients with varices or ascites, including whether it’s safe to perform transesophageal echocardiography in patients with cirrhosis without first screening for varices, and whether nonselective beta-blockers should be continued in patients with refractory ascites.

A retrospective study of 191 patients with cirrhosis who underwent upper endoscopy within 4 years of transesophageal echocardiography had no overt gastrointestinal bleeding regardless of the presence of esophageal varices, suggesting that routine preprocedure esophagogastroduodenoscopy "is of no utility," (Abstract #1872).

A study to determine risk of sepsis in 1,198 patients with cirrhosis found that 1-year risk of sepsis was reduced by 50% with the use of nonselective beta-blockers (Abstract #94).

The final abstract in this category touched on the use of an advance care planning video support tool to help transplant-ineligible patients with end-stage liver disease decide whether they want support measures such cardiopulmonary resuscitation or intubation. The authors found that the video decision tool was feasible and acceptable to patients, and improved their knowledge of end-of-life care. More patients randomized to the video arm opted against CPR or intubation, compared with those assigned to a verbal discussion of options (Abstract #712).


The reviewers highlighted two studies of alcohol use: The first was designed to determine the prevalence of early alcohol relapse (resumption within 3 months) in patients who presented with alcoholic hepatitis. The subjects included 478 patients enrolled in the STOPAH trial, and a validation set of 194 patients from the InTeam (Integrated Approaches for identifying Molecular Targets in Alcoholic Hepatitis) Consortium.

"They found that high-risk patients were younger, unemployed, and without a stable relationship. Intermediate risk were middle aged, employed, and in a stable relationship, and low-risk profiles were older, with known cirrhosis; they were mostly retired and in a stable relationship," Taddei said.

The identification of nongenetic factors that predict early relapse may aid in personalization of treatment strategies, she said (Abstract #232).

The second study looked at fecal microbial transplant (FMT) for reducing cravings in adults with alcohol use disorder (AUD) and cirrhosis. The investigators saw a nonsignificant trend toward greater total abstinence at 6 months in patients randomized to FMT versus placebo.

"Future trials should be performed to determine the impact of FMT on altering the gut-brain axis in patients with AUD," she said (Abstract #7).


The prospective controlled QUICKTRANS study by French and Belgian researchers found that patients who underwent early liver transplantation for severe alcoholic hepatitis had numerically but not significantly higher rates of relapse than patients who were transplanted after at least 6 months of abstinence, although heavy drinking was more frequent in patients who underwent early transplant.

The 2-year survival rates for both patients who underwent early transplant and those who underwent transplant after 6 months of sobriety were "identical, and excellent." In addition, the 2-year survival rate for patients with severe alcoholic hepatitis who underwent transplant was 82.8%, compared with 28.2% for patients who were deemed ineligible for transplant according to a selection algorithm ( < .001).

"Perhaps most important is that studies in this population can be conducted in a controlled fashion across centers with reproducible transplant eligibility algorithms," Taddei commented (Abstract #6).

The place of honor – Abstract # 1 – was reserved for a study looking at the effects on liver transplant practice of a new "safety net" policy from the Organ Procurement and Transplantation Network and United Network for Organ Sharing stating that patients awaiting liver transplantation who develop kidney failure may be given priority on the kidney transplant waiting list.

The investigators found that the new policy significantly increased the number of adult primary liver transplant alone candidates who where on dialysis at the time of listing, and did not affect either waiting list mortality or posttransplant outcomes.

The authors also saw a significant increase in kidney transplant listing after liver transplant, especially for patients who were on hemodialysis at the time of list.

In the period after implementation of the policy, there was a significantly higher probability of kidney transplant, and significant reduction in waiting list mortality.

Autoimmune & Cholestatic Diseases

Investigators performed an analysis of the phase 3 randomized controlled ENHANCE trial of seladelpar in patients with primary biliary cholangitis. The trial was stopped because of an adverse event ultimately deemed to be unrelated to the drug, so the analysis looked at the composite responder rate at month 3.

"The key takeaway from this study is that at the 10-mg dosage of seladelpar, 78% met a composite endpoint, 27% of patients normalized their alkaline phosphatase, and 50% normalized their ALT. There was significant improvement in pruritus," Taddei said.

The drug was generally safe and well tolerated. A 52-week phase 3 global registration study will begin enrolling patients in early 2021 (Abstract #LO11).

In a pediatric study, investigators looked at differences in primary sclerosing cholangitis (PSC) among various population, and found that "Black and Hispanic patients have dramatically worse clinical outcomes, compared to White and Asian patients. They are more likely to be diagnosed with PSC at an advanced stage with extensive fibrosis and portal hypertensive manifestations."

The authors suggested that the differences may be explained in part by socioeconomic disparities leading to delay in diagnosis, to a more aggressive phenotype, or both (Abstract #66).

A meta-analysis of maternal and fetal outcomes in women with autoimmune hepatitis showed that the disease is associated with increased risk of gestational diabetes, premature births, and small-for-gestational age or low-birth-weight babies.

"Pregnant women should be monitored closely before, during and after pregnancy. It’s important to know that, in the prevalence data, flares were most prevalent postpartum at 41%. These finds will help us counsel our patients with autoimmune hepatitis who become pregnant," Taddei said (Abstract #97).

Drug-Induced Liver Injury

A study of clinical outcomes following immune checkpoint inhibitor rechallenge in melanoma patients with resolved higher grade 3 or higher checkpoint inhibitor–induced hepatitis showed that 4 of 31 patients (13%) developed recurrence of grade 2 or greater hepatitis, and 15 of 31 (48%) developed an immune-related adverse event after rechallenge.

There was no difference in time to death between patients who were rechallenged and those who were not, and immune-related liver toxicities requiring drug discontinuation after rechallenge were uncommon.

"High-grade immune checkpoint inhibitor hepatitis should be reconsidered as an absolute contraindication for immune checkpoint inhibitor rechallenge," Taddei said (Abstract # 116).


The investigators also highlighted an abstract describing significant urban-rural and racial ethnic differences in hepatocellular carcinoma rates. A fuller description of this study can be found here (Abstract #136).


Finally, the reviewer highlighted a study of the clinical course of COVID-19 in patients with chronic liver disease, and to determine factors associated with adverse outcomes in patients with chronic liver disease who acquire COVID-19.

The investigators found that patients with chronic liver disease and COVID-19 have a 14% morality rate, and that alcohol-related liver disease, decompensated cirrhosis, and hepatocellular carcinoma are all risk factors for increased mortality from COVID-19.

They recommended emphasizing telemedicine, prioritizing patients with chronic liver disease for vaccination, and including these patients in prospective studies and drug trials for COVID-19 therapies.

Taddei reported having no disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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