Role of Interleukin-28B Genetic Polymorphisms in Korean Patients with Hepatitis C Virus Infection
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Background/Aims: This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. Methods: Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. Results: The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. Conclusions: The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.
Abstract
Background/Aims: This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. Methods: Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. Results: The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. Conclusions: The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.
참고문헌 (28)
- Lavanchy D., "The global burden of hepatitis C", Liver Int, 29(Suppl 1), pp.74~81 (2009)
- Perz JF, "The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide", J Hepatol, 45, pp.529~538 (2006)
- Lauer GM, "Hepatitis C virus infection", N Engl J Med, 345, pp.41~52 (2001)
- European Association for the Study of the Liver, "EASL Clinical Practice Guidelines: management of hepatitis C virus infection", J Hepatol, 55, pp.245~264 (2011)
- Ghany MG, "American Association for Study of Liver Diseases. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases", Hepatology, 54, pp.1433~1444 (2011)
- Kim JY, "Acute hepatitis C in Korea: different modes of infection, high rate of spontaneous recovery, and low rate of seroconversion", J Med Virol, 83, pp.1195~1202 (2011)
- Yu ML, "Treatment of chronic hepatitis C in Asia: when East meets West", J Gastroenterol Hepatol, 24, pp.336~345 (2009)
- Ge D, "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance", Nature, 461, pp.399~401 (2009)
- Tanaka Y, "Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C", Nat Genet, 41, pp.1105~1109 (2009)
- Suppiah V, "IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy", Nat Genet, 41, pp.1100~1104 (2009)
- Rauch A, "Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study", Gastroenterology, 138, pp.1338~1345 (2010)
- Jensen DM, "IL28B genetic polymorphism testing in the era of direct acting antivirals therapy for chronic hepatitis C: ten years too late?", Liver Int, 32(Suppl 1), pp.74~78 (2012)
- Bruix J, "American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update", Hepatology, 53, pp.1020~1022 (2011)
- Sinn DH, "Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in Asian patients", J Gastroenterol Hepatol, 26, pp.1374~1379 (2011)
- Lyoo K, "Polymorphism near the IL28B gene in Korean hepatitis C virus-infected patients treated with peg-interferon plus ribavirin", J Clin Virol, 52, pp.363~366 (2011)
- Thomas DL, "Genetic variation in IL28B and spontaneous clearance of hepatitis C virus", Nature, 461, pp.798~801 (2009)
- Tillmann HL, "A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice", Gastroenterology, 139, pp.1586~1592 (2010)
- Grebely J, "Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection", Hepatology, 52, pp.1216~1224 (2010)
- Santantonio T, "Acute hepatitis C: current status and remaining challenges", J Hepatol, 49, pp.625~633 (2008)
- Fabris C, "IL-28B rs12979860 C", T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC, 2011, pp.54, 716~722
- McCarthy JJ, "Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin", Gastroenterology, 138, pp.2307~2314 (2010)
- Kawaoka T, "Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b", J Hepatol, 54, pp.408~414 (2011)
- Yu ML, "Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients", Hepatology, 53, pp.7~13 (2011)
- Shiffman M, "PEG-IFN-l: antiviral activity and safety profile in a 4-week phase 1b study in relapsed genotype 1 hepatitis C infection", J Hepatol, 50(Suppl 1), pp.S237~ (2009)
- Zeuzem S, "Pegylated interferon-lambda (PEGIFN-λ) shows superior viral response with improved safety and tolerability versus PEGIFNα-2a in HCV patients (Gl", 2, 4): emerge phase IIB through week 12, pp.J Hepatol, 2011[DOI]
- Abushahba W, "Antitumor activity of type I and type III interferons in BNL hepatoma model", Cancer Immunol Immunother, 59, pp.1059~1071 (2010)
- Li Q, "Interferon-lambda induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents", Eur J Cancer, 46, pp.180~190 (2010)
- Kurosaki M, "Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors", J Hepatol, 54, pp.439~448 (2011)