The Role of Polymorphisms Near IFNL3 Gene as Predictors of Residual HCV RNA in Buffy Coat after Successful Antiviral Therapy

Abstract

Background and Aims: The presence of the hepatitis C virus (HCV) in cells of extrahepatic organs like peripheral blood mononuclear cells (PBMCs) have important implications for transmission, disease progression, and effective treatment of HCV-infected patients. The impact of host genetics such as polymorphisms near Interferon lambda 3 (IFNL3) on clearance of HCV RNA from buffy coat (BC) following successful clearance of HCV from plasma using Pegylated-IFN (PegIFN) and Ribavirin (RBV) treatment was evaluated in our study. Methods: For detection of residual HCV RNA in BC samples, blood samples of 69 patients with sustained virologic response (SVR) after treatment with PegIFN and RBV were evaluated. Polymorphisms near IFNL3 gene including rs12979860 and rs8099917 were assessed using PCR-RFLP method. Results: The most prevalent rs12979860 and rs8099917 genotypes were CT (49.3%) and TT (62.3%), respectively. Nine (13.04%, 95%CI: 7.01% -22.96%) patients had HCV RNA in their BC samples. The favorable genotypes of the 2 polymorphisms (rs12979860 CC and rs8099917 TT) were more frequently observed in patients with undetectable HCV RNA in their BC samples than those with HCV RNA in their BC samples (rs12979860 CC, 45% vs. 22.2%, P = 0.016 and rs8099917 TT, 66.7% vs. 33.3%, P = 0.01). Conclusions:The polymorphisms of IFNL3 could play a crucial role not only in spontaneous clearance of HCV and SVR rate after PegIFN and RBV therapy, but also in the clearance of HCV from BC after PegIFN and RBV therapy.

Neutrocyte-to-lymphocyte ratio predicts the presence of a replicative hepatitis C virus strand after therapy with direct-acting antivirals

“…Additionally, among patients with this type of occult infection the presence of rs12979860 CC genotype associated with lower HCV-RNA load in liver tissue [18]. Polymorphisms in the IFNL3 - IFNL4 region also link with the presence of HCV-RNA in PBMCs both during chronic HCV infection and in patients who reached SVR after IFN treatment [19, 20]. We found no significant correlation between IFNL genotype and the occurrence of HCV-RNA in PBMCs.…”

Hepatitis C resistance to NS5A inhibitors: Is it going to be a problem?

“…While the IFN-based regimens result in suboptimal (30%-70%) virologic response, the DAA-based all-oral regimens have efficacy of > 95% in most patient groups[ 3 - 5 ]. Moreover, the treatment response to IFN-based regimens was modified by a large number of different host and virus parameters, such as age, sex, host genetics, liver fibrosis, HCV ribonucleic acid (RNA) level, HCV genotype, variations in HCV genes, etc [ 3 , 6 , 7 ].…”