Tumor necrosis factor-α inhibitors and chronic hepatitis C: A comprehensive literature review

Abstract

Tumor necrosis factor-α (TNF-α) inhibitors are known to increase reactivation of concurrent chronic hepatitis B, but their impact on the hepatitis C virus (HCV) is controversial. Some conditions of immunosuppression, such as liver transplantation, typically cause an increase in the rate of HCV evolution. Inhibition of TNF-α, a cytokine involved in the apoptotic signaling pathway of hepatocytes infected by HCV, could potentially increase viral replication. Currently available clinical data appear to contradict this hypothesis. A review of medical literature revealed that a total of 216 patients with HCV were exposed to one or more treatments with TNF-α inhibitors, with a median observation time of 1.2 years and 260 cumulative patient-years of exposure. Only three cases of drug withdrawal due to suspected HCV liver disease recrudescence were reported. Treatment with TNF-α inhibitors in patients with HCV infection appears to be safe in the short term, but there are insufficient data to assess their long-term safety. Universal screening for HCV before beginning treatment with TNF-α inhibitors is currently controversial. The presence of HCV is not a contraindication to therapy with TNF-α inhibitors, with the exception of cirrhotic patients. In cases of cirrhosis, the benefit/risk ratio should be evaluated at the individual level. Prior to treatment with TNF-α inhibitors, patients with HCV should be referred to a hepatologist to determine the necessity of hepatic disease assessment, using liver biopsy or non-invasive methods, and the potential indication for antiviral therapy. In patients with HCV infection who are treated with TNF-α inhibitors, liver function monitoring every three months is advised.

Keywords: Infliximab, Etanercept, Adalimumab, Hepatitis C virus, Rheumatoid arthritis, Inflammatory bowel disease, Psoriasis

Core tip: Our review summarizes data on patients with hepatitis C exposed to tumor necrosis factor-α (TNF-α) inhibitors, thus building a stronger safety profile than previously reported. A comprehensive paragraph on the pathway of TNF-α in hepatitis C virus (HCV) and an overview on immune-mediated damage induced by TNF-α inhibitors (cryoglobulins, autoimmune hepatitis) have been also included. Some controversies regarding the universal screening and monitoring of HCV-RNA were also addressed.