THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Liver a concern when picking drug therapies

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the United States and a leading cause of liver disease worldwide, so it is no surprise when rheumatologists and hepatologists confer.

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Jacquelyn Maher, MD

“We get a fair number of consultation requests from rheumatologists who note that their patients have abnormal liver function tests and want to follow up,” said Jacquelyn Maher, MD, Professor of Medicine and Director of the Liver Center at the University of California San Francisco School of Medicine. “NAFLD has become so prevalent that it is appearing on everyone’s radar screens. We have to make sure that the treatment decisions we are making for other diseases don’t overlap with preexisting liver problems.”

Dr. Maher will discuss the nexus of rheumatology and nonalcoholic steatohepatitis (NASH) during the clinical symposium Fatty Liver and the Rheumatology Patient at 9:00 am Monday. Certain drugs commonly used in rheumatology may exacerbate risks for fatty liver disease and a significant number of patients with fatty liver disease also manifest abnormal autoantibodies.

“One of the more frequent conundrums in our practice is patients who have fatty liver disease, who are overweight and may have type 2 diabetes along with abnormal liver function test results, often have a positive antinuclear antibody or high IgG,” Dr. Maher said. “Based on test results, there is a real question whether they also have an autoimmune liver disease.”

Population studies suggest that as many as 25 percent of patients with NAFLD show some sort of abnormal autoimmune test results, she said. The majority of positive autoantibody tests in these patients are determined to be false positives, based on liver biopsy results, but the concern is genuine. Many autoimmune diseases include a systemic component that can involve the liver.

“Because patients are on potentially hepatotoxic drugs or because liver abnormalities can be part of their syndrome, rheumatologists tend to check liver enzymes on a regular basis,” Dr. Maher said. “From the hepatologist’s perspective, rheumatologists tend to screen their patients for liver disorders very effectively.”

Most of the drugs commonly used in rheumatology are relatively safe from the liver perspective, she said. The most obvious problem agents are prednisone and other corticosteroids that can exacerbate existing metabolic problems and methotrexate, which may confound underlying fatty liver disease.

“You need to be aware if someone who needs to be on a corticosteroid has fatty liver disease,” she explained. “It doesn’t mean the person can’t take prednisone, but it does require careful consideration of the need for a steroid and the severity of the person’s liver disease. Prednisone would clearly be appropriate for some patients, while in others you should be looking for an alternative.”

Major risk factors for fatty liver disease include central obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome, Dr. Maher said. Some common rheumatologic agents, including tofacitinib and tocilizumab, are associated with an increased risk for dyslipidemia, which could influence the risk of progression in patients with existing NAFLD.

Clinicians must determine the nature of the patient’s liver disease. While the name comes from its similarity in many respects to alcoholic hepatitis, NASH does not have the tendency to manifest as an acute severe illness in the same fashion as alcoholic hepatitis. Some of the concern over using etanercept, infliximab, and other biologics in patients with fatty liver disease may stem from negative clinical trial experiences with these compounds in the treatment of alcoholic hepatitis.

“Patients who were treated with anti-TNF agents for alcoholic hepatitis did poorly because they developed infectious complications,” Dr. Maher said. “The important difference is that patients with alcoholic hepatitis are already severely ill with liver disease and immunocompromised, so they can get into trouble with biologics and other agents. For the large part, patients with NAFLD or NASH are not going to have disease of the same severity or acuity as patients with alcoholic hepatitis. Giving anti-TNF agents or other biologics should be reasonably safe as far as the liver is concerned.”