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RESEARCH PRODUCT

AB0438 Safety of tnf blockers in case of non-alcoholic fatty liver disease and cirrhosisa systematic review

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Background The management of inflammatory rheumatisms and psoriasis has largely evolved over the last 15 years with the emergence of biotherapies whose main adverse effect is the increased infection risk. The prevalence of metabolic syndrome is increasing and has been estimated at 30% in patients with rheumatoid arthritis with an excess of 45% compared to healthy subjects. One of the major complications of the metabolic syndrome is the Non Alcoholic Fatty Liver Disease (NAFLD), which prevalence is 25% in the global population, and 30% in a cohort of patients with rheumatoid arthritis. The main complication of NAFLD is the development of cirrhosis, known to increase infectious risk. Surprisingly, there are no data on the safety of TNF antagonists in patients with chronic inflammatory disease and NAFLD or cirrhosis. Objectives To assess infectious and liver safety of the main TNF blockers used in chronic inflammatory diseases in patients with cirrhosis or NAFLD. Methods A systematic review of the literature, following the Prisma recommendations, was conducted on the Pubmed and Embase databases with the following keywords: ”adalimumab”, ”infliximab”, ”etanercept”, ”certolizumab”, ”golimumab” ”TNF -blockers “AND” liver cirrhosis ”,” non alcoholic fatty liver disease “. We selected only studies including patients treated with TNF blockers and with cirrhosis or ultrasonically characterised NAFLD. We excluded animal models and non-English articles. Results We identified 39 articles and only 11 fulfilled the inclusion criteria. 9 Case Reports have reported the tolerance of TNF-blockers in patients with cirrhosis and one controlled study (44 patients) assessed the safety of etanercept in case of NAFLD. One study (7 patients) investigated the impact of infliximab in refractory autoimmune hepatitis. The cause of cirrhosis was primary biliary cholangitis (5 cases), alpha1 antitrypsin deficiency (4 cases) and post hepatitis B cirrhosis (2 cases). All cirrhosis were compensated. Inflammatory diseases requiring the introduction of TNF blocker were rheumatoid arthritis (n=5), psoriatic arthritis (n=4), ulcerative colitis (n=2) and psoriasis (n=44). The TNF-blockers prescribed were adalimumab in 2 patients, infliximab in 11 patients and etanercept in 49 patients. The duration of treatment ranged from 6 to 24 months. For the 9 cirrhotic patients with an inflammatory disorder, no infection was reported and two of them (2 cases of primary biliary cholangitis) even had an improvement in liver function secondary to the introduction of biotherapy. For the 7 patients receiving infliximab to treat auto-immune hepatitis, 5 patients presented recurrent infections. For patients with NAFLD, no infectious event was reported and an improvement of the hepatic biological parameters was observed, suggesting an improvement in liver function. Conclusions The results of this review suggest that in case of compensated cirrhosis, TNF-blockers were not deleterious for the liver and did not increase the infectious risk. In case of auto-immune cirrhosis, TNF-blockers increased the infectious risk. In case of NAFLD, TNF-blockers might improve liver function and prevent fibrosis. Disclosure of Interest None declared