Impact of <i>IFNL3</i> variants and baseline predictors on sustained virologic response (SVR).

<p>SVR rates in the evaluation (EC) and replication cohort (RC) with regard to (<b>A</b>) GGT/ALT ratio and HCV RNA concentration according to <i>IFNL3</i> rs12979860 and rs8099917 genotypes in combination and with (<b>B</b>) GGT/ALT ratio cutoff value of 0.70, (<b>C</b>) HCV RNA concentration cut-off value of 5.8log₁₀ (IU/mL). Pearson’s χ² test and Fischer’s exact test were used to compare the SVR rates.</p

Univariate and multivariate analyses of factors predictive for sustained virologic response (SVR).

<p>OR: odds ratio, CI: confidence interval, P = p-value, IU: international units.</p

Genotype frequencies and sustained virologic response (SVR) rates of <i>IFNL3</i> rs12979860 and rs8099917 SNPs in the evaluation and replication cohort.

<p>Genotype frequencies and sustained virologic response (SVR) rates of <i>IFNL3</i> rs12979860 and rs8099917 SNPs in the evaluation and replication cohort.</p

Patients’ characteristics of the evaluation and replication cohort.

a<p>median plus interquartile range (25^th, 75^th percentile), SVR: sustained virologic response, NR: non-response, IU: international units.</p

Hungarian

<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></div

Combined determination of <i>IFNL3</i> variants, GGT/ALT ratio and HCV RNA levels improved sustained virologic response (SVR) rates.

<p>SVR rates in the evaluation (EC) and replication cohort (RC) according to <i>IFNL3</i> (<b>A</b>) rs12979860 and (<b>B</b>) rs8099917 genotypes after adjustment for the GGT/ALT ratio (cut-off value 0.70) and HCV RNA concentration (cut-off value 5.8log₁₀).</p

Association of <i>IFNL3</i> variants with baseline predictors.

<p>Association of the <i>IFNL3</i> rs12979860 and rs8099917 genotypes with the levels of (<b>A</b>) GGT (IU/mL), (<b>B</b>) ALT (IU/mL), (<b>C</b>) GGT/ALT ratio, (<b>D</b>) pretreatment HCV RNA log₁₀ (IU/mL) and (<b>E</b>) cholesterol (mg/dL) concentration in the evaluation cohort (EC). Horizontal bars represent the median. Mann-Whitney U-test was used to compare the baseline parameter.</p