Could Steroid Treatment Speed Recovery From Infliximab-Induced Liver Injury?

NEW YORK (Reuters Health) – Corticosteroid treatment might speed the recovery of patients who sustained liver injury from infliximab use, but the finding is not statistically robust, researchers in Iceland report.

Their observational study, published in the Journal of Hepatology, also shows that patients with more-prolonged elevations in liver enzymes were likelier to have been treated with corticosteroids. No relapses of liver injury were seen after corticosteroids were tapered, and the majority of patients who were switched to a second biologic agent did not see a return of liver injury.

Dr. Helgi Kristinn Bjornsson of Landspitali, the National University Hospital, in Reykjavik, told Reuters Health by email that the frequency of infliximab-induced liver injury “has been estimated to be 1 in every 148 to 1 in every 120 patients” and that most cases have a favorable prognosis.

“Infliximab is an effective treatment against various autoimmune diseases,” he said, “and the overall use of infliximab should not be reconsidered based solely on the risk of liver injury. However, it is the treating physician’s task to estimate the risk-benefit ratio in each case.”

This reportedly was the largest study cohort to include only patients with infliximab-induced liver injury.

Dr. Bjornsson and his colleagues identified 36 patients (median age 46; median body mass index 28) who sustained infliximab-induced liver injury between 2009 and 2020. The commonest type of liver injury was hepatocellular.

The conditions for which patients had been receiving infliximab were diverse and included psoriasis, ankylosing spondylitis, seronegative arthritis and inflammatory bowel disease.

Seventeen patients (47%) received the corticosteroid prednisolone, with this decision made by one of the authors of the report, based on liver test findings escalating and/or not improving despite infliximab discontinuation. Patients whose liver functions showed improvement after discontinuation of infliximab did not receive corticosteroids.

The median duration of corticosteroid treatment was 84 days, and the median dose of prednisolone was 30 mg.

The time from peak alanine aminotransferase to normalization of liver enzymes was numerically shorter in patients treated with corticosteroids: 45 vs. 77 days (P=0.062).

In an email to Reuters Health, Dr. Guilherme Macedo, head of the gastroenterology and hepatology department at the University Hospital Center of Sao Joao, in Porto, Portugal, called the Icelandic report “another cautionary note on the use of infliximab. It is important that prescribers should be fully aware of these potential liver problems, especially if they are recognized early in the process and they are promptly tackled by . . . immunosuppression with steroids.”

He added that liver function should be assessed regularly, from the very start of infliximab use, and that autoantibodies should be evaluated before administering infliximab. Dr. Macedo was not involved in the new research.

Dr. Jay H. Hoofnagle, director of the Liver Disease Research Branch at the National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Maryland, told Reuters Health by email that these findings “may not be completely new, but this is the largest and most representative study of infliximab-induced liver injury. And it represents an unbiased and ‘population-based’ study, most others being samples from specialized centers.”

He highlighted the report’s observation that liver injury “appears to be caused by the immune changes induced by infliximab, rather than the direct action of the drug on the liver.”

This is why a steroid seems to be helpful, explained Dr. Hoofnagle, who also was not involved in the study, as “it dampens the immune response, rather than being liver-protective.”

SOURCE: Journal of Hepatology, online September 3, 2021.

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