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      Polymorphisms of HLA-DM on Treatment Response to Interferon/Ribavirin in Patients with Chronic Hepatitis C Virus Type 1 Infection

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          Abstract

          Background: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in HLA-DM gene in HCV treatment outcomes. Methods: We genotyped four SNPs from the candidate genes ( HLA-DMA and DMB) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV). Multivariate analysis of factors predicting sustained virological response (SVR) was conducted. Results: HLA-DMA rs1063478 and DMB rs23544 were independent factors of HCV treatment outcomes in Chinese Han population. Individuals who carried favorable genotypes of rs1063478TT and rs23544GG were more likely to achieve SVR {Dominant model: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.24–3.41; OR = 2.04, 95% CI =1.23–3.35, respectively}. Rs23544, rs1063478, baseline glucose, baseline platelet and T4 level were independent predictors of SVR. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.740. Conclusions: The genetic variation of rs1063478 and rs23544 are associated with the treatment outcomes in the Chinese Han population.

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          Epidemiology of hepatitis C virus infection.

          Miriam J Alter (2007)
          Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.
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            Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection.

            Angelique Zeringue, Fasiha Kanwal, Peter Richardson … (2011)
            Patients with hepatitis C virus (HCV) infection are at risk for developing costly and morbid complications, although the actual prevalence of these complications is unknown. We examined time trends in the prevalence of cirrhosis and its related complications, such as hepatic decompensation and hepatocellular carcinoma (HCC). We calculated the annual prevalence of cirrhosis, decompensated cirrhosis, and HCC in a national sample of veterans diagnosed with HCV between 1996 and 2006. Patients with HCV who had at least one physician visit in a given calendar year were included in the analysis of prevalence for that year. We used direct standardization to adjust the prevalence of cirrhosis and related complications for increasing age of the cohort as well as sex and changes in clinical characteristics. In this cohort, the number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006. The prevalence of cirrhosis increased from 9% in 1996 to 18.5% in 2006. The prevalence of patients with decompensated cirrhosis doubled, from 5% in 1996 to 11% in 2006, whereas the prevalence of HCC increased approximately 20-fold (0.07% in 1996 to 1.3% in 2006). After adjustment, the time trend in the prevalence of cirrhosis (and its complications) was lower than the crude trend, although it still increased significantly. The prevalence of cirrhosis and HCC in HCV-infected patients has increased significantly over the past 10 years. An aging cohort of patients with HCV could partly explain our findings. Clinicians and health care systems should develop strategies to provide timely and effective care to this high-risk population of patients. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Antiviral strategies in hepatitis C virus infection.

              Christoph Sarrazin, Christophe Hézode, Stefan Zeuzem … (2012)
              Resolution of the three-dimensional structures of several hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral (DAA) agents. Numerous families of drugs that potently inhibit the HCV lifecycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1, in both treatment-naïve and treatment-experienced patients. Sustained virological response rates in the range of 6675% and 5966% (2988% if the response to the first course of therapy is taken into account) have been achieved in these two patient populations, respectively, with treatment durations of 24 to 48 weeks. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-α and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3/4A protease inhibitors, nucleoside/nucleotide analogue inhibitors and non-nucleoside inhibitorsof HCVRNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A (NS5A) and host-targeted compounds, such as cyclophilin inhibitors and silibinin. The proof of concept that IFN-free regimens may lead to HCV eradication has recently been brought. However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Paul B. Tchounwou: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Int J Environ Res Public Health
                Journal ID (iso-abbrev): Int J Environ Res Public Health
                Journal ID (publisher-id): ijerph
                Title: International Journal of Environmental Research and Public Health
                Publisher: MDPI
                ISSN (Print): 1661-7827
                ISSN (Electronic): 1660-4601
                Publication date (Electronic): 20 October 2016
                Publication date (Print): October 2016
                Volume: 13
                Issue: 10
                Electronic Location Identifier: 1030
                Affiliations
                [1 ]Department of Infectious Disease, the Jurong People’s Hospital, Jurong 212400, China; chb2180@ 123456126.com (H.C.); yifanwang333@ 123456163.com (Y.W.); huazhou4456@ 123456163.com (H.Z.); xutianq@ 123456163.com (T.X.); xyxJ6300@ 123456sina.com (J.L.); guochengwang4456@ 123456163.com (G.W.); yongfengzhang666@ 123456163.com (Y.Z.); xiangchen322@ 123456163.com (X.C.); lin553210@ 123456163.com (Q.L.)
                [2 ]Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; yinanyao1130@ 123456163.com
                Author notes
                [†]

                These authors contributed equally to this work.

                Article
                Publisher ID: ijerph-13-01030
                DOI: 10.3390/ijerph13101030
                PMC ID: 5086769
                PubMed ID: 27775635
                SO-VID: 67304c66-cd47-4639-be18-0eaba1320d4b
                Copyright © © 2016 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 28 July 2016
                Date accepted : 13 October 2016
                Categories
                Subject: Article

                ScienceOpen disciplines: Public health
                Keywords: hepatitis c,genetic polymorphism,hla-dm gene,treatment outcome
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: hepatitis c, genetic polymorphism, hla-dm gene, treatment outcome

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