Association of <i>IFNL3</i> rs12979860 and rs8099917 with Biochemical Predictors of Interferon Responsiveness in Chronic Hepatitis C Virus Infection

<div><p>Background & Aims</p><p>Genetic variations near the interferon lambda 3 gene (<i>IFNL3, IL28B</i>) are the most powerful predictors for sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, compared to other biochemical or histological baseline parameters. We evaluated whether the interplay of both <i>IFNL3</i> polymorphisms rs12979860 and rs8099917 together with non-genetic clinical factors contributes to the predictive role of these genetic variants.</p><p>Methods</p><p>The cohort comprised 1,402 patients of European descent with chronic HCV type 1 infection. 1,298 patients received interferon-based antiviral therapy, and 719 (55%) achieved SVR. The <i>IFNL3</i> polymorphisms were genotyped by polymerase chain reaction and melting curve analysis.</p><p>Results</p><p>A significant correlation was found between the <i>IFNL3</i> polymorphisms and biochemical as well as virologic predictors of treatment outcome such as ALT, GGT, cholesterol, and HCV RNA levels. In multivariate regression analysis, <i>IFLN3</i> SNPs, HCV RNA levels, and the GGT/ALT ratio were independent predictors of SVR. Dependent on the GGT/ALT ratio and on the HCV RNA concentration, significant variations in the likelihood for achieving SVR were observed in both, carriers of the responder as well as non-responder alleles.</p><p>Conclusions</p><p>Our data support a clear association between <i>IFNL3</i> genotypes and baseline parameters known to impact interferon responsiveness. Improved treatment outcome prediction was achieved when these predictors were considered in combination with the <i>IFNL3</i> genotype.</p>