title: 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.
authors.affiliation: Section on Gastroenterology and Hepatology, Department of Internal Medicine, Wake Forest Health Sciences, Winston-Salem, NC, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: French
authors.affiliation: Liver Center, Sutter Health, San Francisco, CA, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bonacini
authors.affiliation: Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Suite 225, 702 Rotary Circle, Indianapolis, IN, USA. MGhabril@iu.edu.
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghabril
authors.affiliation: Department of Research, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Foureau
authors.affiliation: Section on Gastroenterology and Hepatology, Department of Internal Medicine, Wake Forest Health Sciences, Winston-Salem, NC, USA.|Department of Medicine, University of Connecticut Health Science Center, Farmington, CT, USA.|Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000378:metabolism*; D000068800:Etanercept / Q000009:adverse effects; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept