Linkage of the hepatitis C virus genotype and interleukin-28B genetic polymorphisms in Asian patients (2010)

We read with great interest the report by Montes-Cano et al.1 in a recently published issue of Hepatology. They found different rates of hepatitis C virus (HCV) genotype distribution with respect to an interleukin-28B variant in Spanish individuals. The authors noted that the rs12979860 wild CC genotype, an independent predictor favoring a sustained virological response to peginterferon/ribavirin, was overrepresented among patients with a non-1 HCV genotype (HCV-non-1) versus hepatitis C virus genotype 1 (HCV-1)–infected patients (66.7% versus 39.1%, P < 0.001). However, the results require confirmation in a larger cohort and especially in Asian populations, in which HCV-non-1 is much more prevalent. To clarify the issue, we analyzed a large cohort in southern Taiwan, in which HCV infections are endemic2; more than 40% of the patients were infected with HCV-2.3 In all, 1005 patients were tested for associations between HCV characteristics and host genetic variants of rs8099917, a novel single nucleotide polymorphism that has a tremendous impact on the response to interferon-based therapy. For patients of Asian ethnicity, the carriage of the rs8099917 TT genotype could enhance the treatment outcomes of HCV-1 infection4 and improve the early viral kinetics of HCV-2 infection.5 With respect to the viral genotypes, 552 of the patients (54.9%) were infected with HCV-1, and 453 patients (45.1%) were infected with HCV-non-1 (43.4% with HCV-2, 0.1% with HCV-3, and 1.6% with an unclassified genotype). When patients were stratified according to their rs8099917 genotypes (TT versus TG/GG), the TT genotype was overrepresented among HCV-non-1–infected patients versus HCV-1 patients (91.4% versus 85.0%, P = 0.002; Table 1). Multivariate logistic regression analysis demonstrated that HCV-1 infection and baseline HCV RNA levels were independent factors negatively associated with the carriage of the rs8099917 TT genotype with odds ratios of 0.58 (95% confidence interval = 0.382-0.873, P = 0.009) and 0.81 (95% confidence interval = 0.652-0.997, P = 0.047), respectively. Our findings were in agreement with Montes-Cano and et al.'s discovery that HCV-1 patients carry a higher rate of unfavorable alleles that might compromise treatment responses. In addition, the frequency of the rs8099917 TT genotype in our study (88%) was substantially higher than that reported in Swiss Caucasians (58%),6 and this was in line with the finding that Asian populations had the highest rs12979860 C allelic frequency.7 The host genotype-specific selection of the viral genotype may contribute to the higher proportion of HCV-non-1 distribution in Asian areas.3 The divergence of the host genetic predisposition among patients with different HCV genotypes and ancestries might in part explain the substantially higher sustained virological response rates in Asian patients receiving peginterferon/ribavirin.8, 9 The real cause is not clear; it is postulated that there exists a selection pressure between the HCV viral genotype and host immune responses during evolution that might determine HCV genotype–specific treatment responses.10 Whether the driving force of selection applies to viral replication as well as the preference of the viral genotype distribution in terms of host genetic diversities warrants further molecular-based studies in the future. Chung-Feng Huang M.D* , Chia-Yen Dai M.D., Ph.D* § ¶, Jee-Fu Huang M.D.* ¶ **, Wan-Long Chuang M.D., Ph.D.* ¶, Ming-Lung Yu M.D., Ph.D.* ¶, * Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Departments of Occupational Medicine, Internal Medicine, Kaohsiung Municipal Ta- Tung Hospital, Kaohsiung, Taiwan, § Graduate Institute of Medicine, ¶ Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ** Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.