Correlation of interferon-lambda 4 ss469415590 with the hepatitis C virus treatment response and its comparison with interleukin 28b polymorphisms in predicting a sustained virological response: a meta-analysis.

Background: Interferon-lambda 4 (IFNL4) ss469415590 is a newly discovered polymorphism that could predict the treatment response in hepatitis C virus (HCV)-infected patients. This meta-analysis was performed in order to clarify its specific effect on the treatment response and to compare it with interleukin 28b (IL28B).

Method: The commonly used literature databases were searched. Meta-analyses were performed with fixed/random-effects models using Stata 12.0. The sustained virological response (SVR) rate was summarized using R software. Publication bias was examined through Egger's test.

Results: A total of seven studies were finally included in this meta-analysis. IFNL4 ss469415590 was demonstrated to be associated with SVR (odds ratio (OR) 3.83, 95% confidence interval (CI) 3.22-4.56, p<0.001). Asians had a higher likelihood of achieving SVR than Caucasians (OR=7.36 vs. 3.54). When stratifying all the patients according to HCV genotype, a significant association was observed in HCV genotype 1 patients (OR 4.5, 95% CI 2.91-6.95, p<0.001). In HCV genotype 2/3 patients, the favorable TT/TT genotype patients tended to have a statistically higher SVR rate than the non-TT/TT genotype patients (84.4% vs. 78.3%, p=0.058). Compared with IL28B rs12979860 (OR 3.45) and rs8099917 (OR 3.50), ss469415590 TT/TT genotype patients showed a slightly higher probability of achieving a SVR (OR 3.61 calculated from studies investigating both IFNL4 and rs12979860; OR 4.86 for studies investigating both IFNL4 and rs8099917). Furthermore, ss469415590 showed a slightly higher predictive value than rs12979860 using the diagnostic test tool (area under the curve=0.71 vs. 0.70). IFNL4 was also correlated with rapid virological response (RVR) (OR 4.35, 95% CI 1.43-13.20, p=0.01), viral clearance (OR 0.31, 95% CI 0.24-0.39, p<0.001), and HCV susceptibility (OR 0.76, 95% CI 0.65-0.89, p=0.001).

Conclusions: IFNL4 ss469415590 is significantly associated with SVR in HCV genotype 1 patients, irrespective of race; there is a tendency towards an association in HCV genotype 2/3 patients. Comparable to IL28B, IFNL4 is correlated with natural viral clearance and HCV susceptibility, additionally IFNL4 ss469415590 has a slightly higher predictive performance over IL28B polymorphisms in regard to SVR.