FRI0251 Liver Injury in Patients Receiving Infliximab: A Systematic Review
Authors: F. Medina, D. Mulleman, Y. Bacq, P. Goupille, T. Bejan-Angoulvan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> 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]. <h3>Objectives</h3> To identify and describe different patterns of liver injury in infliximab-treated patients. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusions</h3> 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. <h3>References</h3> Important drug warning. http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM166923.pdf Briefing document. 2003. http://www.fda.gov/ohrms/dockets/ac/03/transcripts/3930t1.htm <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2602