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      Effectiveness of sofosbuvir based direct-acting antiviral regimens for chronic hepatitis C virus genotype 6 patients: Real-world experience in Vietnam

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          Abstract

          Background

          Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice.

          Methods

          We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections.

          Results

          1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46–64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3–6.6 versus 6.3, 5.3–6.5 log10 IU/ml, p = <0.001, Mann Whitney U test). A sustained virological response (SVR), defined as an undetectable viral load measured between 12 and 24 weeks after completing treatment, and indicating cure, was seen in 97.3% (1711/1758) of patients. Treatment failure, defined as HCV viral load ≥15 IU/ml ≥12 weeks after completing treatment appeared to be more frequent in patients infected with genotype 6 virus (3.2%, 37/1148) than in those infected with genotype 1 (1.7%, 10/610), p = 0.050 chi-squared test). We found no evidence that patient’s age, gender, liver cirrhosis, diabetes, HBV or HIV coinfection, prior treatment failure with pegylated interferon therapy, body mass index (BMI), aspartate aminotransferase to platelet ratio index ( APRI), or fibrosis 4 (FIB-4) index were associated with treatment failure.

          Conclusions

          Our study suggests that patients with HCV genotype 6 infection in Vietnam may respond less well to treatment with sofosbuvir based DAAs than patients with genotype 1 infections. Further studies are needed to confirm this observation and to define whether it is driven by genotype-specific mutations.

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          Most cited references23

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          Sofosbuvir and ribavirin in HCV genotypes 2 and 3.

          In clinical trials, treatment with a combination of the nucleotide polymerase inhibitor sofosbuvir and the antiviral drug ribavirin was associated with high response rates among patients with hepatitis C virus (HCV) genotype 2 infection, with lower response rates among patients with HCV genotype 3 infection. We conducted a study involving patients with HCV genotype 2 or 3 infection, some of whom had undergone previous treatment with an interferon-based regimen. We randomly assigned 91 patients with HCV genotype 2 infection and 328 with HCV genotype 3 infection, in a 4:1 ratio, to receive sofosbuvir-ribavirin or placebo for 12 weeks. On the basis of emerging data from phase 3 trials indicating that patients with HCV genotype 3 infection had higher response rates when they were treated for 16 weeks, as compared with 12 weeks, the study was unblinded, treatment for all patients with genotype 3 infection was extended to 24 weeks, the placebo group was terminated, and the goals of the study were redefined to be descriptive and not include hypothesis testing. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 419 patients who were enrolled and treated, 21% had cirrhosis and 58% had received previous interferon-based treatment. The criterion for a sustained virologic response was met in 68 of 73 patients (93%; 95% confidence interval [CI], 85 to 98) with HCV genotype 2 infection who were treated for 12 weeks and in 213 of 250 patients (85%; 95% CI, 80 to 89) with HCV genotype 3 infection who were treated for 24 weeks. Among patients with HCV genotype 3 infection, response rates were 91% and 68% among those without and those with cirrhosis, respectively. The most common adverse events were headache, fatigue, and pruritus. Therapy with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of sustained virologic response. (Funded by Gilead Sciences; VALENCE ClinicalTrials.gov number, NCT01682720.).
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            Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

            Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.
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              A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt.

              The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. Data references were identified through indexed journals and non-indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. We estimated that 49.3-64.0 million adults in Asia, Australia and Egypt are anti-HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection. © 2011 John Wiley & Sons A/S.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Software
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draft
                Role: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: 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
                20 May 2020
                2020
                : 15
                : 5
                : e0233446
                Affiliations
                [1 ] The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
                [2 ] Oxford University Clinical Research Unit, Wellcome Trust Asia Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
                [3 ] Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
                Nihon University School of Medicine, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-6702-5355
                Article
                PONE-D-20-06277
                10.1371/journal.pone.0233446
                7239434
                32433676
                04d8fe67-aa34-43cc-bc91-c60287f4af73
                © 2020 Nguyen 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
                : 3 March 2020
                : 5 May 2020
                Page count
                Figures: 1, Tables: 3, Pages: 16
                Funding
                The author(s) received no specific funding for this work.
                Categories
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                Biology and Life Sciences
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                Custom metadata
                The data presented in the manuscript are extracted from the Hospital for Tropical Diseases, Ho Chi Minh City Vietnam and property of Hospital for Tropical Diseases, Ho Chi Minh City Vietnam. Institutional Review Board (IRB) of the Hospital for Tropical Diseases approved the access to fully anonymized dataset for analysis to the investigators and Oxford University Clinical research Unit (OUCRU). All data presented in the manuscript can be accessed through “OUCRU data sharing policy” and request for access to data can be sent to DAC@ 123456oucru.org .

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