Occult hepatitis C virus infection in hemophilia patients and its correlation with interferon lambda 3 and 4 polymorphisms

Abstract

Occult HCV infection (OCI) is described as the presence of HCV RNA in the liver and peripheral blood mononuclear cells (PBMCs), with no HCV RNA in the serum. Single-nucleotide polymorphisms (SNPs) near interferon lambda 3/4 (IFNL3/4) gene are associated with spontaneous clearance and treatment response in patients with hepatitis C virus (HCV) infection. In this study, we evaluated the frequency of OCI in hemophilia patients and determined the association of three IFNL3 SNPs (rs12979860, rs12980275, and rs8099917) and IFNL4 ss469415590 with OCI positivity. A total of 450 hemophilia patients with HCV negative markers were included in this study. Positive- and negative-stranded HCV-RNA was determined in peripheral blood mononuclear cells (PBMCs) samples by reverse-transcription polymerase chain reaction (RT-PCR) method. IFNL3 SNPs and IFNL4 ss469415590 were genotyped by PCR-RFLP and TaqMan® Real-Time PCR methods, respectively. The frequency of OCI was estimated at 10.2%. Among 46 OCI patients, 56.5%, 23.9%, and 19.6% were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. Compared to patients without OCI, unfavorable IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ∆G/∆G genotypes were more frequently reported in OCI patients. The multivariate logistic regression analysis showed that alanine aminotransferase (ALT), cholesterol, triglyceride, IFNL3 rs12979860 (TT), IFNL3 rs8099917 (GG), IFNL3 rs12980275 (GG), and IFNL4 ss469415590 (∆G/∆G) were associated with OCI positivity. In conclusion, we studied the incidence of OCI in Iranian patients with hemophilia for the first time. Our results demonstrated that unfavorable genotypes of IFNL3 SNPs and IFNL4 ss469415590 have a strong relationship with OCI positivity. It seems that the host immune response plays a vital role in OCI positivity.