Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy: A single center report of 8 cases

Abstract

This article describes cases of anti-tumor necrosis factor (TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis (AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

Differential characteristics in drug‐induced autoimmune hepatitis

“…They have recently begun to constitute an important cause of DIAIH according to the findings of Rodrigues et al . in a series of eight cases (seven with infliximab and one with adalimumab) in a single center in Portugal19 and Björnsson et al . in a cohort in Iceland, where 11 of 15 cases were secondary to infliximab 20.…”

Infliximab‐induced autoimmune hepatitis requiring liver transplantation

“…Other TNF‐α inhibitors including etanercept and adalimumab have reportedly also resulted in autoimmune hepatitis. Some of the mechanisms proposed include underlying genetic susceptibility, a selective effect of T helper cells and immune complex formation, and the induction of an immune system imbalance from cytokine blockade .…”

Hepatotoxicity Associated with the Use of Anti-TNF-α Agents

“…Furthermore, Rodrigues et al [36] recently described eight cases of an autoimmune pattern of liver injury, many relatively mild in severity, based on biopsy and serological data attributed to anti-TNF-α therapy (Table 2). …”

“…Interestingly, there has also been a report of a patient developing an autoimmune type of liver injury from infliximab and, after recovery, being retreated with infliximab once again without recurrence of the liver injury [36]. Until the mechanism of liver injury induced by the anti-TNF-α class of medications is fully elucidated, it will be difficult to understand the presence or absence of cross-reactions among medications within this class, or even the risk of repeated use of the same agent after anti-TNF-α liver injury has occurred in a patient.…”

“…These data would suggest that the majority of incidents of liver injury that occur secondarily to anti-TNF-α therapy occur within the first 20 weeks of therapy (Table 2). However, Rodrigues et al [36] noted a mean onset of liver injury after eight doses of anti-TNF-α therapy in their series of eight patients, which would be a longer latency of approximately 46 weeks, assuming standard loading and dosing of infliximab. Long latencies (up to ~156 weeks) also were recently described by Rösner et al [43].…”