Interferon Lambda-3 rs12979860 Variants and Response to Pegylated Interferon in Chronic Hepatitis-C Genotype-3.

Abstract

To assess the role of single nucleotide polymorphisms (SNPs) near the interferon lambda-3 (IFNλ3) (formal IL-28B) gene rs12979860 in predicting sustained virologic response (SVR) in hepatitis-C virus genotype-3 (HCV-3). Descriptive, analytical study. Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014. Patients with HCV-3 were classified as sustained virologic response (SVR), relapsers and non-responders. SNPrs12979860 was determined by PCR-RFLPprotocol. Differences between categorical variables were assessed by chi-square or Fisher's exact test, while those between continuous variables were evaluated using the Mann-Whitney U-test. Binary logistic regression analysis by forward conditional method was performed by using significant variables with p-values less than 0.05 as the criteria for model inclusion. Out of 115 patients, rs12979860 genotype-CC, CT, TTwas found in 37 (32.2%), 70 (60.9%), and 8 (7%) patients. 72 patients were male with median age of 45 years. Cirrhosis was present in 32 patients. Patients with response failures (no response and relapse, n=36 and 29, respectively) had higher baseline gamma glutamyl transferase (GGT) level (p < 0.001), higher alanine aminotransferase (p=0.027) and cirrhosis (p=0.001) than patients with SVR. Genotype-CC was present in 16/65 in response failures compared to 21/50 who achieved SVR (p=0.048). Rapid virologic response (RVR) (p < 0.001), low GGT(p=0.001) and absence of cirrhosis (p=0.039) were the independent predictive factors for SVR. In patients who could not achieve RVR and in patients with cirrhosis, SVR was seen more in with genotype-CC (p=0.007 and 0.038). In patients infected with HCV-3, IFNλ3 rs12979860, SNPhas less impact on SVR.