The Role of Interferon Lambda 3 Genetic Polymorphisms in Response to Interferon Therapy in Chronic Hepatitis B Patients: An Updated Meta-Analysis

CONTEXT: Polymorphisms of the interferon lambda 3 (IFNL3) gene have been proposed to be associated with drug-induced clearance of the hepatitis C virus (HCV). However, the role of IFNL3 polymorphisms in the prediction of treatment on chronic hepatitis B (CHB) patients have yielded controversial results. The aim of this study was to clarify the role of IFNL3 polymorphisms (rs12979860, rs8099917, and rs12980275) in the treatment response of CHB patients to interferon (IFN). EVIDENCE ACQUISITION: EMBASE and PUBMED/MEDLINE were searched to identify relevant studies from January 2009 to March 2015. The search used the keyword “interferon lambda 3” or “IFNL3,” combined with the following terms: “interferon therapy,” “hepatitis,” and “polymorphisms.” Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were used to assess the strength of the associations between the polymorphisms and the response to IFN therapy. RESULTS: Nine studies of 1602 CHB patients receiving IFN treatment were included. Under the random-effects model, patients expressing the variant rs12980275 showed a significantly increased response to IFN therapy (OR = 2.85; 95% CI = 1.14 - 4.60). In the subgroup analyses by antiviral agents, the patients carrying the rs8099917T allele in the IFN-only treatment group showed a significantly increased response to IFN therapy (OR for the dominant model = 2.03; 95% CI = 1.24 - 3.31), whereas those in the mixed treatment group showed a significantly decreased response (OR for the dominant model = 0.30; 95% CI = 0.10 - 0.90). CONCLUSIONS: This study supports the idea that the IFNL3 gene is an important predictor of the response of CHB patients to IFN therapy.