IFNL3 (IL28B)andIFNL4polymorphisms are associated with treatment response in Thai patients infected with HCV genotype 1, but not with genotypes 3 and 6

Abstract

Recent studies have shown an association between single nucleotide polymorphisms (SNPs) in the interferon lambda-3 (IFNL3 or IL-28B) and IFNL4 genes and treatment response to hepatitis C virus genotype 1 (HCV-1) infection. The importance of these SNPs for HCV genotype 3 (HCV-3), and particularly HCV genotype 6 (HCV-6), remains to be elucidated. We analyzed a cohort of 225 Thai individuals with chronic HCV infection treated with pegylated-interferon and ribavirin, of whom 69 (30.7%), 114 (50.7%) and 42 (18.6%) patients were infected with HCV-1, HCV-3, and HCV-6, respectively. DNA extracted from blood samples was analyzed for the SNPs rs12979860 and ss469415590. The distribution of CC, CT, and TT genotypes of rs12979860 was 189 (84%), 28 (12.4%) and 8 (3.6%), respectively, while the distribution of TT/TT, ΔG/TT, and ΔG/ΔG genotypes of ss469415590 was 192(85.3%), 28(12.5%), and 5(2.2%), respectively. Significantly lower frequencies of the favorable genotypes CC (for rs12979860) and TT/TT (for ss469415590) were found in the HCV-1 group in comparison with the other groups. The favorable genotypes were associated significantly with rapid and sustained virological response in the HCV-1 group. However, they were only associated with rapid virological response in the HCV-3 and HCV-6 groups. Furthermore, both SNPs were associated equally with the treatment outcome in the HCV-1 group. In contrast, the role of these SNPs in predicting treatment response was attenuated in the HCV-3 and HCV-6 groups. Thus, identification of these SNPs may be useful only in patients with refractory HCV-1 infection.

Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis

“…The modified process employed for study search and selection is summarized in figure 1. After the titles were screened and abstracts read, 193 studies were removed based on exclusion criteria and 14 potentially eligible articles included [17,18,19,20,21,22,23,24,25,26,27,28,29,30]. Among these studies, some studies were only included on the treatment efficacy of PEG-IFN+RBV for HCV-6 in a previous study [31].…”

“…Two studies involving 102 patients assessed SVR in relation to IL28B polymorphisms while 1 study focused on IFNL4 polymorphisms [23,29]. Among the 2 studies on IL28B polymorphisms, 1 study investigating 60 HCV-6 patients [52 (90%) TT and 8 (10%) GT/GG] assessed SVR in rs8099917 TT compared with GT/GG.…”

“…A total of 7 studies involving patients with mild and advanced fibrosis were included to evaluate the influence of fibrosis on treatment response [23,24,25,26,27,29,30]. Mild and advanced fibrosis were defined as F0-F2 and F3-F4 based on the METAVIR scoring system, respectively.…”

“…Six trials assessed treatment response in patients infected with HCV-6 compared with those infected with HCV-1 [18,19,21,27,29,30]. Among these, 3 were direct comparisons of response to antiviral therapy by HCV-6 versus HCV-3 and/or HCV-2 patients.…”

The Correlation between Hepatitis C Core Antigen and Hepatitis C Virus RNA Levels with Respect to Human Immunodeficiency Virus Status, Hepatitis C Virus Genotype and Interferon-Lambda-4 Polymorphism

“…The presence of IFNL4 polymorphism ss469415590 was identified by reverse transcription PCR assay using TaqMan genotyping assay with MGB probes (Applied Biosystems, USA) as described previously [25]. Briefly, genomic DNA of patients with chronic HCV infection was extracted from 100 μl of peripheral blood mononuclear cells using the QIAamp DNA Mini Kit (Qiagen, Germany).…”