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      Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis

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          Abstract

          Sustained virological response is durable in patients treated for hepatitis C virus. Recurrence rates are generally low but increase in patient populations with risk factors for reinfection. The evidence supports the notion that risk of recurrence is driven by reinfection.

          Abstract

          Background.  Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or reinfection, reverses the beneficial effects of SVR.

          Methods.  A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected “low-risk” patients; (2) Mono-HCV infected “high-risk” patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR.

          Results.  In the 43 studies of HCV mono-infected “low-risk” patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71–3.35; I 2 = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%–1.69%). For the 14 studies of HCV monoinfected “high-risk” patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07–33.46; I 2 = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%–15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00–123.49; I 2 = 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%–48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse.

          Conclusions.  SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.

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          Most cited references64

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          Meta-analysis in clinical trials

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            Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

            The Lancet, 385(9963), 117-171
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              Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence.

              In efforts to inform public health decision makers, the Global Burden of Diseases, Injuries, and Risk Factors 2010 (GBD2010) Study aims to estimate the burden of disease using available parameters. This study was conducted to collect and analyze available prevalence data to be used for estimating the hepatitis C virus (HCV) burden of disease. In this systematic review, antibody to HCV (anti-HCV) seroprevalence data from 232 articles were pooled to estimate age-specific seroprevalence curves in 1990 and 2005, and to produce age-standardized prevalence estimates for each of 21 GBD regions using a model-based meta-analysis. This review finds that globally the prevalence and number of people with anti-HCV has increased from 2.3% (95% uncertainty interval [UI]: 2.1%-2.5%) to 2.8% (95% UI: 2.6%-3.1%) and >122 million to >185 million between 1990 and 2005. Central and East Asia and North Africa/Middle East are estimated to have high prevalence (>3.5%); South and Southeast Asia, sub-Saharan Africa, Andean, Central, and Southern Latin America, Caribbean, Oceania, Australasia, and Central, Eastern, and Western Europe have moderate prevalence (1.5%-3.5%); whereas Asia Pacific, Tropical Latin America, and North America have low prevalence (<1.5%). The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival for those who already have evidence of liver disease. Copyright © 2012 American Association for the Study of Liver Diseases.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                15 March 2016
                19 January 2016
                19 January 2016
                : 62
                : 6
                : 683-694
                Affiliations
                [1 ]Division of Medicine, Imperial College London
                [2 ]Pharmacology and Therapeutics, Liverpool University
                [3 ]Research Institute of Primary Care and Health Sciences, Keele University , Staffordshire, United Kingdom
                Author notes
                Correspondence: B. Simmons, St Mary's Campus, Imperial College London, Norfolk Place, London W2 1PG, UK ( bryony.simmons13@ 123456alumni.imperial.ac.uk ).
                Article
                civ948
                10.1093/cid/civ948
                4772843
                26787172
                60f33d51-a904-44c5-af25-ee75263e3945
                © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@ 123456oup.com .

                History
                : 30 July 2015
                : 30 October 2015
                Funding
                Funded by: UNITAID
                Funded by: Biomedical Research Centre of Imperial College
                Funded by: Medical Research Council (MRC) STOP hepatitis C virus (HCV) consortium
                Categories
                Articles and Commentaries
                Editor's choice

                Infectious disease & Microbiology
                hepatitis c,sustained virologic response,recurrence,relapse,reinfection

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