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

Abstract

Medications to inhibit the actions of tumour necrosis factor alpha have revolutionized the treatment of several pro-inflammatory autoimmune conditions. Despite their many benefits, several serious side effects exist and adverse reactions do occur from these medications. While many of the medications' potential adverse effects were anticipated and recognized in clinical trials prior to drug approval, several more rare adverse reactions were recorded in the literature as the popularity, availability and distribution of these medications grew. Of these potential adverse reactions, liver injury, although uncommon, has been observed in some patients. As case reports accrued over time and ultimately case series developed, the link became better established between this family of medicines and various patterns of liver injury. Interestingly, it appears that the majority of cases exhibit an autoimmune hepatitis profile both in serological markers of autoimmune liver disease and in classic autoimmune features seen on hepatic histopathology. Despite the growing evidence of this relationship, the pathogenesis of this reaction remains incompletely understood, but it appears to depend on characteristics of the medications and the genetic composition of the patients; it is likely more complicated than a simple medication class effect. Because of this still incomplete understanding and the infrequency of the occurrence, treatments have also been limited, although it is clear that most patients improve with cessation of the offending agent and, in certain cases, glucocorticoid use. However, more needs to be done in the future to unveil the underlying mechanisms of this adverse reaction.

Fig. 1

a Indications for use of anti-tumour necrosis factor alpha (anti-TNF-α) agents among subjects who developed drug-induced liver injury (DILI): reported underlying conditions of the patients who developed liver injury secondarily to anti-TNF therapy. The numbers of subjects in each category are displayed on the chart. CD Crohn’s disease, JIA juvenile inflammatory arthritis, Ps psoriasis, PsA psoriatic arthritis, RA rheumatoid arthritis, S spondylitis, UC ulcerative colitis. b Anti-TNF-α medications cited in the cases as the cause of liver injury, represented as percentages of the total cases presented (note: in the reports by Titos-Arcos et al. [39] and Rösner et al. [43], a patient from each report had two separate incidents of liver injury due to both adalimumab and etanercept, and both are counted in this figure)