IL28B Genetic Variants and Gender Are Associated With Spontaneous Clearance of Hepatitis C Virus Infection

H.-Y. Rao; D.-G. Sun; D. Jiang; R.-F. Yang; F. Guo; J.-H. Wang; F. Liu; H.-Y. Zhang; H.-H. Zhang; S.-C. Du; Q. Jin; H. Qin; A.-S.-F. Lok; L. Wei


J Viral Hepat. 2012;19(3):173-181. 

In This Article

Abstract and Introduction


Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus (HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV-infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY® SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07–112.50), 14.88 (2.02–109.72), 7.92 (1.88–33.32) and 2.32 (1.22–4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men [56/213 (26.3%) vs 24/163 (14.6%), P = 0.007], and this was true even after stratification for IL28B genotypes with OR of 1.9–2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.


Hepatitis C virus (HCV) infection is rated by the World Health Organization as a global health problem, based on its prevalence, the high rate (50–85%) of chronicity, the rate of severe complications such as cirrhosis and hepatocellular carcinoma, as well as the high costs of antiviral therapy and liver transplantation.[1–3]

There is a significant difference in response to treatment with pegylated interferon plus ribavirin in patients of different race or ethnicity, with sustained virological response rates of 28%, 34%, 52% and 76% in African American, Hispanic, Caucasian American and Asian patients respectively with genotype 1 HCV infection.[4–7] Likewise, racial differences in the rate of spontaneous viral clearance have been reported.[8,9] These racial differences suggest a genetic influence on HCV outcome.

Ge et al.[10] identified a key role for variation in a region close to the interleukin-28B (IL28B) gene on chromosome 19, which codes for interferon-lambda-3, in predicting response to pegylated interferon plus ribavirin therapy in patients with genotype 1 chronic HCV infection. This finding has been confirmed in other independent cohorts.[11–13] In addition, the IL28B single nucleotide polymorphism (SNP) most strongly associated with treatment response, rs12979860, has also been shown to be significantly associated with spontaneous hepatitis C clearance.[14–16] Tanaka et al.[17] found other SNPs in close proximity to IL28B that were associated with treatment response in Japanese patients, with rs8099917 and rs12980275 having the strongest association. Rauch et al.[12] also reported that rs8099917 was significantly associated with treatment response as well as with spontaneous clearance of HCV infection in Swiss and German patients. An association between rs8099917 and spontaneous HCV clearance was also shown in a study of Spanish patients.[18]

Data on the association between IL28B genetic variants and treatment response or spontaneous viral clearance in Chinese patients with HCV infection are limited. In a study of 2371 persons from different continents, Thomas et al.[14] found that the frequency of the C allele at rs12979860 was roughly 95% among Chinese, 70% among Caucasians and 25–40% among Africans. Ge et al.[10] noted that the linkage between rs12979860 and rs8099917 is high among Caucasians but low among African Americans. These data suggest that the IL28B variants that have the strongest association with spontaneous HCV clearance and response to HCV treatment in different racial/ethnic groups may be different.

Between 1972 and 1990, several outbreaks of non-A, non-B hepatitis linked to plasma donation occurred at plasmapheresis centres in Hebei Province Guan County, China. These donors have been followed for 12–19 years after initial documentation of HCV infection and roughly 20% have cleared HCV infection spontaneously. This cohort provided a unique opportunity to evaluate the role of host genetics in the outcome of HCV infection in a population with fairly homogenous ethnic background. Here, we present data on the association between IL28B genetic variation and spontaneous HCV clearance in these HCV-infected plasma donors.


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