Article Text

PDF
FRI0251 Liver Injury in Patients Receiving Infliximab: A Systematic Review
  1. F. Medina1,
  2. D. Mulleman1,2,
  3. Y. Bacq2,3,
  4. P. Goupille1,2,
  5. T. Bejan-Angoulvan2,4
  1. 1Rheumatology, University Hospital of Tours
  2. 2François Rabelais University
  3. 3Hepatology
  4. 4Pharmacology, University Hospital of Tours, Tours, France

Abstract

Background Infliximab is a therapeutic monoclonal antibody that specifically targets Tumor Necrosis Factor alpha. In December 2004, the FDA conveyed an important drug warning on infliximab potential hepatotoxicity[1]. Several serious hepatic reactions had been reported in postmarketing reports worldwide[2].

Objectives To identify and describe different patterns of liver injury in infliximab-treated patients.

Methods A systematic review was performed in MEDLINE and Cochrane databases. Articles were included if they mentioned liver injury in infliximab-treated patients. References of the selected articles were also reviewed to identify additional articles. Whenever possible, results of clinical trials were pooled using a meta-analytical approach.

Results From 3069 articles retrieved, we included 60 articles: 12 randomized controlled trials, 7 extended reports of clinical trials, and 47 reported cases in 41 articles. In randomized controlled trials, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were more often increased in infliximab-treated patients than in controls with a significant result for ALT: RR 2.1 [1,36 to 3,37] (p=0.001) and RR 1.8 [0,92 to 3,62] (p=0.09) respectively. In trials that reported both, increases in ALT levels were more frequent than increases in AST levels.

Twenty-six cases of non viral hepatitis were retrieved, confirmed by liver biopsy in 19 cases: 18 cases of autoimmune hepatitis (AIH), 5 cases of increased aminotransferase levels (no biopsy), 1 case of cytolysis confirmed by biopsy without autoimmunity, 1 case of acute toxic hepatitis and 1 case of bland cholestasis. Anti-nuclear, anti-double-stranded DNA and anti-smooth muscle-cell antibodies were mainly implicated in AIH suggesting a process of type 1 AIH. After infliximab discontinuation and corticosteroid treatment the liver injury usually improved within a few weeks. In one case, AIH led to liver transplantation.

Twenty-one cases of patients with hepatitis B infection (HBV) and treated with infliximab were retrieved. Nine patients received a concomitant anti-viral therapy and had no HBV reactivation. Eleven out of twelve patients without concomitant anti-viral therapy had HBV reactivation. The time to onset of reactivation was variable from a single infusion of infliximab to several years of treatment. Two patients with viral reactivation died and one patient required liver transplantation. In this way, a prophylactic treatment seems to be effective in preventing HBV reactivation in patients receiving infliximab.

Conclusions This systematic review retrieved several patterns of liver injury in infliximab-treated patients: increased aminotransferase levels isolated or possibly related with AIH, cholestasis, and potential fatal hepatitis B reactivations. In light of these observations, aminotransferase levels should be monitored in patients treated by infliximab, and hepatitis B markers should be tested before treatment initiation.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2602

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.