Abstract
Background/AimsSingle-nucleotide polymorphisms (SNPs) near the interleukin 28B gene (IL28B; interferon [IFN]-λ-3) are associated with outcomes of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection treated with peginterferon (PEG-IFN) alpha-based antiviral therapy. In this study, we investigated the influence of IL28B polymorphisms on spontaneous clearance of HBV infection in a large Korean cohort.MethodsBetween January 2007 and June 2010, a total of 208 patients with chronic HBV infection and newly diagnosed HBV-related hepatocellular carcinoma were recruited as the CC group [HBsAg(+) for >6 months, anti-HBc(+), and anti-HBs(-)]. In addition, 351 organ donors were stratified into the UE group [n = 106; HBsAg(-), anti-HBc(-), and anti-HBs(-)] or the SC group [n = 245; HBsAg(-), anti-HBc(+), and anti-HBs(+)]. The SNaPshot ddNTP Primer Extension Kit (Applied Biosystems, Foster City, CA) was used for SNP detection. Direct full sequencing of the IL28B coding region was attempted.ResultsRegardless of group, rs12979860 CC was most frequently identified (85.0% in UE, 85.9% in SC, and 93.5% in CC, respectively), whereas rs12979860 TT was not identified in any group. Similarly, rs12980275 AA and rs8099917 TT were most frequently identified (≥85%) regardless of group, whereas rs12980275 GG was identified in only one subject in the SC group. In addition, rs8099917 GG was not identified. The prevalences of CC in rs12979860, AA in rs12980275, and TT in rs8099917 were significantly higher in the CC group when compared with the UE and SC group (all P<0.05). Among 19 novel SNPs in the IL28B coding region, the proportions of 6 SNPs were significantly different among the UE, SC, and CC groups (all P<0.05).ConclusionsThe SNP upstream of IL28B that has the strongest genetic association with HCV recovery has an inverse influence on HBV recovery. Additional studies are needed to understand the mechanisms of this SNP in HBV infection.
Highlights
Several independent genome-wide association studies have shown that genetic polymorphisms at or near the interleukin 28B gene (IL28B; known as interferon [IFN]-l-3), including rs12979860, rs12980275, and rs8099917, are associated with higher rates of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) treated with peginterferon (PEG-IFN) alpha and ribavirin [1,2,3,4]
A human study demonstrated that IL28B polymorphisms were independently related to serological responses to PEG-IFN in a large global cohort of patients with hepatitis B e antigen positive chronic hepatitis B (CHB), similar to the results from chronic hepatitis C virus (HCV) infection [7,8]
Because IFN-a and IFN-stimulated genes (ISGs) are thought to be important in the immune response to hepatitis B virus (HBV), and PEG-IFN-a is used to treat chronic HBV infection similar to HCV infection, we can assume that IL28B may be important in treatment and recovery from HBV infection
Summary
Several independent genome-wide association studies have shown that genetic polymorphisms at or near the interleukin 28B gene (IL28B; known as interferon [IFN]-l-3), including rs12979860, rs12980275, and rs8099917, are associated with higher rates of sustained virologic response (SVR) in patients with chronic hepatitis C (CHC) treated with peginterferon (PEG-IFN) alpha and ribavirin [1,2,3,4]. A human study demonstrated that IL28B polymorphisms were independently related to serological responses to PEG-IFN in a large global cohort of patients with hepatitis B e antigen positive chronic hepatitis B (CHB), similar to the results from chronic HCV infection [7,8]. In addition to this association between IL28B polymorphisms and treatment responses to PEG-IFN, the relationship between IL28B polymorphism and spontaneous clearance of HCV infection has been reported in several previous studies [1,4,9,10,11].
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