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      Differential prevalence and geographic distribution of hepatitis C virus genotypes in acute and chronic hepatitis C patients in Vietnam

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          Abstract

          Background

          The highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs).

          Methods

          We analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5’ UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS.

          Results

          355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], ( p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] ( p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] ( p = < 0.005).

          Conclusion

          HCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6.

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          Most cited references45

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          Clinical significance of hepatitis C virus genotypes.

          Nizar Zein (2000)
          On the basis of phylogenetic analysis of nucleotide sequences, multiple genotypes and subtypes of hepatitis C virus (HCV) have been identified. Characterization of these genetic groups is likely to facilitate and contribute to the development of an effective vaccine against infection with HCV. Differences among HCV genotypes in geographic distributions have provided investigators with an epidemiologic marker that can be used to trace the source of HCV infection in a given population. HCV genotype 1 may represent a more aggressive strain and one that is less likely to respond to interferon treatment than HCV genotype 2 or 3. However, these observations require confirmation before HCV genotyping can be used in clinical settings.
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            Epidemiology of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma

            Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent primary malignant tumors and accounts for about 90% of all primary liver cancers. Its distribution varies greatly according to geographic location and it is more common in middle and low- income countries than in developed ones especially in Eastern Asia and Sub Saharan Africa (70% of all new HCCs worldwide), with incidence rates of over 20 per 100,000 individuals. Explanation: The most important risk factors for HCC are Hepatitis B Virus (HBV) infection, Hepatitis C Virus (HCV) infection, excessive consumption of alcohol and exposition to aflatoxin B1. Its geographic variability and heterogeneity have been widely associated with the different distribution of HBV and HCV infections worldwide. Chronic HBV infection is one of the leading risk factors for HCC globally accounting for at least 50% cases of primary liver tumors worldwide. Generally, while HBV is the main causative agent in the high incidence HCC areas, HCV is the major etiological factor in low incidence HCC areas, like Western Europe and North America. Conclusion: HBV-induced HCC is a complex, stepwise process that includes integration of HBV DNA into host DNA at multiple or single sites. On the contrary, the cancerogenesis mechanism of HCV is not completely known and it still remains controversial as to whether HCV itself plays a direct role in the development of tumorigenic progression.
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              The changing epidemiology of hepatitis C virus infection in Europe.

              The epidemic of hepatitis C virus (HCV) infection in Europe is continuously evolving and epidemiological parameters (prevalence, incidence, disease transmission patterns and genotype distribution) have changed substantially during the last 15 years. Four main factors contribute to such changes: increased blood transfusion safety, improvement of healthcare conditions, continuous expansion of intravenous drug use and immigration to Europe from endemic areas. As a result, intravenous drug use has become the main risk factor for HCV transmission, prevalent infections have increased and genotype distribution has changed and diversified. Hence, prevalence data from studies conducted a decade ago may not be useful to estimate the current and future burden of HCV infection and additional epidemiological studies should be conducted, as well as new preventive strategies implemented to control the silent epidemic. This review summarizes recently published data on the epidemiology of HCV infection in Europe focusing on the factors currently shaping the epidemic.
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                Author and article information

                Contributors
                Role: InvestigationRole: MethodologyRole: Validation
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Visualization
                Role: Formal analysisRole: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: Investigation
                Role: Investigation
                Role: InvestigationRole: ResourcesRole: SoftwareRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: Funding acquisitionRole: Resources
                Role: ConceptualizationRole: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 March 2019
                2019
                : 14
                : 3
                : e0212734
                Affiliations
                [1 ] Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
                [2 ] The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
                [3 ] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom
                [4 ] Imperial College, London, United Kingdom
                [5 ] Roche Molecular Systems, Inc., Pleasanton, California, United States of America
                [6 ] Hawaii Center for AIDS, University of Hawaii at Manoa, Honolulu, HI, United States of America
                [7 ] Duke University School of Medicine, Durham, NC, United States of America
                Centers for Disease Control and Prevention, UNITED STATES
                Author notes

                Competing Interests: This study was partly funded by Roche molecular diagnostics, the employer of Gabrielle M. Heilek. Two authors, Karen Saylors and Nathan Wolfe (part of the group authorship) are affiliated to Metabiota. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

                ¶ Membership of VIZIONS consortium is provided in the acknowledgmenst

                Author information
                http://orcid.org/0000-0002-6702-5355
                Article
                PONE-D-18-28643
                10.1371/journal.pone.0212734
                6415813
                30865664
                b082c31f-b2cf-409c-b6c7-43f441da5098
                © 2019 Le Ngoc et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 October 2018
                : 10 February 2019
                Page count
                Figures: 3, Tables: 2, Pages: 20
                Funding
                Funded by: Roche Molecular System
                Award ID: RMS L15043
                Award Recipient :
                Funded by: Wellcome Trust (GB)
                Award Recipient :
                This work was supported by WT-VIZIONS (Wellcome Trust-Vietnamese Initiative on Zoonotic Infections) and by “Roche molecular diagnostics” under agreement no RMS L15043 with Oxford University, UK. Roche Molecular Systems, Inc. provided support in the form of salaries for author GMH but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.
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                All sequences from this suudy was submitted to GenBank (accession numbers for 5’UTR MH191406 - MH191721; core region MH191722 - MH192024 and, NS5B region MH192025 - MH192337).

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