Liver Injury Secondary to Anti-TNF-Alpha Therapy in Inflammatory Bowel Disease: A Case Series and Review of the Literature

Abstract

Background. Biologic therapy to inhibit tumor necrosis factor-alpha (TNF-α) is an effective, safe treatment for patients with inflammatory bowel disease (IBD). All TNF-α inhibitors have been associated with liver toxicity, but many of these cases have been reported in patients receiving therapy for rheumatologic disease. Herein we report the first single-center case series of TNF-α antagonist related liver injury in patients with IBD. Methods. A retrospective case series was performed at the Henry Ford Inflammatory Bowel Diseases Center. IRB approval was obtained. Results. 2 patients were treated with infliximab, whereas the 3rd patient was treated with adalimumab for IBD. All 3 patients had negative viral markers, normal autoimmune serologies, and normal biliary imaging studies. Liver biopsy was performed in all 3 patients, and evidence of portal inflammation was seen. Liver enzymes normalized after discontinuation of therapy in all patients, and no long term effects have been observed. One patient was successfully transitioned from infliximab to adalimumab without relapse of either IBD or liver injury. Conclusion. Liver injury secondary to TNF-α antagonist is an underrecognized, important clinical entity with potentially serious consequences. The mechanism of drug-induced injury is idiosyncratic. Larger cohort studies are needed to establish risk factors and injury patterns related to hepatotoxicity in these patients.

Biologic and Checkpoint Inhibitor‐Induced Liver Injury: A Systematic Literature Review

“…Six of the nine cases went on to emergent transplantation, with the other three recovering liver function with steroid therapy. Given the wide range of latency, this may suggest an idiosyncratic DILI rather than a dose‐dependent toxicity, which has been described in other studies as well …”

Clinical Presentation and Outcomes of Autoimmune Hepatitis in Inflammatory Bowel Disease

“…In two of the reported cases, AIH resolved with switching to another biologic agent such as adalimumab suggesting an absence of cross-reactivity [38,39]. This phenomenon may be attributed to infliximab being a chimeric monoclonal antibody, whereas adalimumab is a fully human antibody [39,49]. However, there is one case of adalimumab-induced autoimmune hepatitis reported in a patient with Crohn's disease and psoriasis.…”

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

“…Case reports also emerged in the published literature, describing various types of liver injury, including both hepatocellular and cholestatic injury patterns associated with anti-TNF-α medications [22–25]. As the indications for the anti-TNF-α class of medications expanded and usage became more widespread, case series were collected, further providing evidence that there was an association between TNF-α antagonists and liver injury [26]. Over the past few years, several larger studies—including queries of large databases of patients on anti-TNF-α therapy and liver injury networks—have been published, and these have helped to better characterize the liver injury patterns that are encountered [8, 27–29].…”