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Chronic Liver Conditions Raise Risk of Death in COVID-19 Patients

— Alcohol appears to play major role, researcher says

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Patients with chronic liver disease were at increased risk for poor COVID-19 outcomes, and liver-specific risk factors included alcoholic liver disease, hepatocellular carcinoma, and decompensated cirrhosis, a researcher said.

In a multicenter study, liver-specific risk factors associated with independent risk of all-cause mortality were hepatocellular carcinoma (OR 6.90, 95% CI 2.14-22.26), decompensated cirrhosis (OR 3.97, 95% CI 2.01-7.84), and alcoholic liver disease (OR 3.25, 95% CI 1.40-7.53), reported Nia Adeniji, M.Ed, of Stanford University School of Medicine, at a presentation at the virtual annual meeting of the American Association for the Study of Liver Diseases (AASLD).

Origins of the study "developed from a Twitter conversation," Adeniji said, as only a couple studies in the spring suggested chronic liver disease was a risk factor for poor COVID-19 outcomes.

The COVID-19 in Chronic Liver Diseases (COLD) study was comprised of data from a review of electronic medical records at 23 centers across the U.S., retrospective prior to April 14, and prospective going forward. Participants had a laboratory-confirmed SARS-CoV-2 positive test, and an ICD-10 diagnosis of any chronic liver disease.

Overall, they examined data from 867 patients, who were a median age of 59; 31% were non-Hispanic white, 31% were non-Hispanic Black, and 25% were Hispanic.

The most common etiology of chronic liver disease was nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH), followed by hepatitis C, and alcoholic liver disease. About 26% of patients had cirrhosis, and of those, 59% had compensated cirrhosis and 41% had decompensated cirrhosis.

In total, 61% of patients were hospitalized, 23% were admitted to the ICU, 18% were on mechanical ventilation, and 12% died, the majority of which were older than age 50. Gastrointestinal symptoms, such as diarrhea and nausea/vomiting, were associated with severe disease, but not with higher rates of mortality.

Adeniji noted that when examining liver-specific factors, decompensated cirrhosis was associated with a higher risk of COVID-19 mortality compared with patients with compensated cirrhosis and no cirrhosis. The same was "surprisingly" true for alcoholic liver disease, with higher mortality risk versus patients without alcoholic liver disease.

But she added that independent modeling did not find any interaction between alcoholic liver disease and decompensated cirrhosis, "emphasizing the independent predictive power of alcoholic liver disease in this study."

Raymond Chung, MD, of Massachusetts General Hospital in Boston, who moderated the session but was not involved with the research, asked Adeniji to speculate how alcohol specifically put these patients at risk.

She said that while researchers did not stratify for whether or not patients were actively drinking in the survival analysis, about half of patients with alcoholic liver disease reported daily alcohol use (defined as one or more drinks per day for women and two or more drinks per day for men).

"As for all liver-specific risk factors found in the study" it raises the concept of "immune dysregulation," Adeniji said, adding, "a hypothesis could be posed related to immune dysfunction caused by these diseases."

Adeniji noted that COVID-19 is creating "a lot of stress in many different areas," which can lead to increased alcohol use. She urged clinicians to "encourage your patients to abstain from excessive alcohol use during the pandemic, especially since alcoholic liver disease is associated with worse COVID-19 mortality."

Patients with hepatocellular carcinoma also had higher rates of death, Adeniji said, pointing to prior research suggesting cancer was a risk factor for COVID-19-related mortality, and said immunosuppression may play a part in "cancer-mediated immune dysregulation."

She urged physicians to encourage telemedicine in this high-risk cohort of patients with chronic liver disease to reduce the risk of COVID-19 in healthcare settings.

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    Molly Walker is deputy managing editor and covers infectious diseases for 鶹ý. She is a 2020 J2 Achievement Award winner for her COVID-19 coverage.

Disclosures

Adeniji disclosed no conflicts of interest.

Other co-authors disclosed support from Synlogic Inc, Intercept Pharmaceuticals, Inc, Boehringer Ingelheim, and Gilead Sciences, Inc.

Primary Source

American Association for the Study of Liver Diseases

Adeniji N, et al "Predictors of outcomes of COVID-19 with chronic liver disease: U.S. multicenter study" AASLD 2020; Abstract 9.