Interferon-λ rs12979860 genotype association with liver fibrosis in chronic hepatitis C (CHC) patients in the Pakistani population.

Risk and progression of liver fibrosis and cirrhosis in chronic hepatitis C (CHC) patients is significantly influenced by host genetic factors in a polygenic manner. The rs12979860 genetic polymorphism in the interferon-λ3-interferon-λ4 (IFNL3-IFNL4) region has been found to be a major determinant of hepatic inflammatory and fibrotic progression in CHC patients of mainly Caucasian origin; however, it is not known if this association applies to other ethnicities, including Pakistani CHC patients. Here, we genotyped IFNL3-IFNL4 rs12979860 genetic variants in a sample set of 502 Pakistani patients with CHC and used logistic regression analysis to determine its association with the risk and progression of HCV-related fibrosis and cirrhosis. We demonstrate that the rs12979860 major (CC) genotype, despite not determining the risk of stage-specific hepatic fibrosis independently, is associated with a marginally significant risk of liver cirrhosis (OR: 1.64, p = 0.049) after an adjustment for age, gender, body mass index, HCV viral load, and liver enzymes. In a subgroup of CHC patients with sustained ALT levels of <60 IU/L, a more pronounced impact of the IFNL3-IFNL4 rs12979860 major (CC) genotype on advanced liver fibrosis (OR: 4.99, p = 0.017) and cirrhosis (OR: 3.34, p = 0.005) was seen. The present study suggests that IFNL3-IFNL4 rs12979860 polymorphism may also be a significant predictor of hepatic fibrosis and cirrhosis in Pakistani CHC patients, especially in those with normal or near-normal liver enzyme levels.