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      Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection

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          Abstract

          Background and Aim

          Chronic hepatitis C virus (HCV) infection is relatively frequent in China. This study investigated the clinical, demographic, and viral and host genetic characteristics that may influence disease manifestations and clinical management.

          Methods

          In this cross-sectional observational study, treatment-naïve Han ethnic adults with recently confirmed chronic HCV infection were enrolled at 28 hospitals across China. HCV genotype and host interleukin 28B (IL28B) genotypes were determined and compared with patient demographic parameters and medical status.

          Results

          Among the 997 HCV-positive patients analyzed, 56.8% were infected with HCV genotype 1b, followed in prevalence by genotypes 2, 3, and 6, with substantial regional variation. Overall, 84.1% of patients were IL28B genotype CC (rs12979860), with little regional variation. Cirrhosis was reported in 10.1% of patients and was significantly associated with hepatitis B virus coinfection, low HCV viral load, low serum alanine aminotransferase, high serum aspartate aminotransferase, diabetes, and high pickled food consumption. Medical procedures were common transmission risk factors; however, lifestyle-associated risk factors, including intravenous drug abuse and tattoos or piercings, were more common in patients with HCV genotype 3 or 6.

          Conclusions

          Most HCV-infected Han Chinese patients were IL28B genotype CC (rs12979860). HCV genotypes varied by geographic region, and disease characteristics differed according to HCV genotype. Relatively frequent detection of advanced liver disease may reflect limitations on access to antiviral therapy, and suggests that greater awareness of factors that influence HCV-associated disease may help avoid clinical complications and improve patient outcomes.

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          Most cited references34

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          Management of hepatocellular carcinoma.

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            Diagnosis, management, and treatment of hepatitis C: an update.

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              Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

              The recommended treatment for patients with chronic hepatitis C, pegylated interferon-alpha (PEG-IFN-alpha) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 x 10(-13), and rs8099917, 3.11 x 10(-15)). We replicated these associations in an independent cohort (combined P values, 2.84 x 10(-27) (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 x 10(-32) (OR = 27.1; 95% CI = 14.6-50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 x 10(-24), and rs8099917, P = 1.11 x 10(-27)). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 x 10(-28)-2.68 x 10(-32); OR = 22.3-27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).
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                Author and article information

                Journal
                J Gastroenterol Hepatol
                J. Gastroenterol. Hepatol
                jgh
                Journal of Gastroenterology and Hepatology
                BlackWell Publishing Ltd (Oxford, UK )
                0815-9319
                1440-1746
                March 2014
                19 February 2014
                : 29
                : 3
                : 545-553
                Affiliations
                [1 ]Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease Beijing, China
                [2 ]Beijing Friendship Hospital, Capital Medical University Beijing, China
                [3 ]Peking University Health Science Center Beijing, China
                [4 ]Henan Provincial People's Hospital Zhengzhou, China
                [5 ]First Affiliated Hospital of Zhengzhou University Zhengzhou, China
                [6 ]First Hospital of Lanzhou University Lanzhou, China
                [7 ]First Affiliated Hospital with Nanjing Medical University Nanjing, China
                [8 ]Shanghai Ruijin Hospital Shanghai, China
                [9 ]Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China
                [10 ]Third Affiliated Hospital of Sun Yat-sen University Guangzhou, China
                [11 ]Nanfang Hospital, Southern Medical University Guangzhou, China
                [12 ]Second Hospital of Shandong University Jinan, China
                [13 ]First Affiliated Hospital of Kunming Medical College Kunming, China
                [14 ]First Affiliated Hospital of Guangxi Medical University Nanning, China
                [15 ]Fourth Military Medical University, Tangdu Hospital Xi'an, China
                [16 ]People's Hospital of Hubei Wuhan University Wuhan, China
                [17 ]Affiliated Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology Wuhan, China
                [18 ]First Affiliated Hospital of Nanchang University Nanchang, China
                [19 ]First Affiliated Hospital of Shanxi Medical University Taiyuan, China
                [20 ]Shengjing Hospital of China Medical University Shenyang, China
                [21 ]First Hospital of Jilin University Changchun, China
                [22 ]First Affiliated Hospital of Medical College ZheJiang University Hangzhou, China
                [23 ]Second Xiangya Hospital of Central South University Changsha, China
                [24 ]Ningxia People's Hospital Yinchuan, China
                [25 ]Southwest Hospital Chongqing, China
                [26 ]West China Hospital Chengdu, China
                [27 ]Second Affiliated Hospital of Harbin Medical University Harbin, China
                [28 ]First Affiliated Hospital of Anhui Medical University Hefei, China
                [29 ]First Affiliated Hospital of Fujian Medical University Fuzhou, China
                [30 ]Bristol-Myers Squibb Wallingford, Connecticut, USA
                Author notes
                Correspondence, Dr Lai Wei, Peking University People's Hospital, Peking University Hepatology Institute, 11 Xizhimen South Street, Beijing 100044, China. Email: weilai@ 123456pkuph.edu.cn
                Article
                10.1111/jgh.12398
                4272577
                24090188
                dd176d1a-4aa9-49a1-9dfa-53d57908edb7
                © 2013 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing and Wiley Publishing Asia Pty Ltd.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 17 August 2013
                Categories
                Hepatology

                Gastroenterology & Hepatology
                china,cirrhosis,epidemiology,hpv,il28b,natural history
                Gastroenterology & Hepatology
                china, cirrhosis, epidemiology, hpv, il28b, natural history

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