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      Research gaps in viral hepatitis

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          Abstract

          Introduction

          The World Health Organization has aimed for global elimination of both hepatitis B virus ( HBV) and hepatitis C virus ( HCV) by 2030. Treatments available to cure HCV and control HBV, as well as vaccination to prevent HBV infection, have certainly allowed for such bold goals, yet the final steps to usher in elimination require further evidence.

          Discussion

          We broadly discuss the needs for three major public health approaches. First, an effective vaccine exists for HBV and mass‐vaccination campaigns have resulted in decreases in hepatitis B surface antigen seroprevalence and overall rates of liver‐related morality. Still, HBV vaccination coverage is poor in certain regions of the world, while the reasons for such low coverage require further study. A prophylactic vaccine is probably needed to eliminate HCV, but is not being readily developed. Second, identifying HBV/ HCV infected individuals remains a priority to increase awareness of disease status, particularly for key populations. Research evaluating large‐scale implementation of novel, rapid and mobile point‐of‐care tests would be helpful to determine whether increased awareness is achievable in these settings. Third, antiviral therapy allows for strong HBV suppression and HCV cure, while its access depends on financial factors among many others. Although there is strong evidence to treat key populations and specific groups with progressed disease, as stated in current guidelines, the advantages of extending treatment eligibility to decrease onward spread of HBV/ HCV infection and prevent further burden of disease are lacking “real world” evidence. Novel anti‐ HBV treatments are being developed to target intrahepatocellular HBV replication, but are still in the early phases of clinical development. Each of the strategies mentioned above has specific implications for HIV infection.

          Conclusions

          There are certainly effective tools to combat the spread of viral hepatitis and treat infected individuals – yet how they are able to reach key populations, and the infrastructure required to do so, continue to represent the largest research gap when evaluating the progress towards elimination. Continuously adapted and informed research is required to establish the priorities in achieving elimination goals.

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          Most cited references51

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          Requirements for global elimination of hepatitis B: a modelling study.

          Despite the existence of effective prevention and treatment interventions, hepatitis B virus (HBV) infection continues to cause nearly 1 million deaths each year. WHO aspires to global control and elimination of HBV infection. We aimed to evaluate the potential impact of public health interventions against HBV, propose targets for reducing incidence and mortality, and identify the key developments required to achieve them.
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            HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma

            Background and Aims It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. We aimed to determine the impact of DAA-induced SVR on HCC risk. Methods We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1/1/1999 to 12/31/2015, including 35,871 (58%) interferon-only regimens, 4535 (7.2%) DAA+interferon regimens and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 6/15/2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs DAA+interferon vs Interferon-only) and HCC risk. Results We identified 3271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87) and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29, 95% CI 0.23–0.37), DAA+interferon (AHR 0.48, 95% CI 0.32–0.73) or interferon-only (AHR 0.32, 95% CI 0.28–0.37). Receipt of a DAA-only or DAA+interferon regimen was not associated with increased HCC risk compared to receipt of an interferon-only regimen. Conclusions DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared to treatment with interferon. Kaplan-Meier curves of survival free of HCC by cirrhosis and SVR status after DAA-only antiviral treatment: SVR is associated with a reduction in HCC risk both among patients with cirrhosis and those without cirrhosis.
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              Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts.

              (2016)
              Sustained virological response following interferon-based antiviral treatment of chronic hepatitis C is associated with decreased long-term risk of hepatocellular carcinoma (HCC) in advanced liver fibrosis. An unexpected high rate of HCC recurrence following antiviral treatment using direct-acting antiviral (DAA) has recently been reported.
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                Author and article information

                Contributors
                karine.lacombe2@aphp.fr
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                10 April 2018
                April 2018
                : 21
                : Suppl Suppl 2 , Towards global viral hepatitis elimination for all patients in all income settings, Guest Editors: Marina B Klein, Karine Lacombe ( doiID: 10.1111/jia2.2018.21.issue-S2 )
                : e25054
                Affiliations
                [ 1 ] INSERM UMR_S1136 Institut Pierre Louis d'Epidémiologie et de Santé Publique Paris France
                [ 2 ] Department of Infectious Diseases, Research and Prevention Public Health Service of Amsterdam Amsterdam Netherlands
                [ 3 ] Department of Infectious and Tropical Diseases Saint‐Antoine Hospital AP‐HP Paris France
                [ 4 ] Sorbonne Universités INSERM UPMC Univ Paris 06 Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136) Paris France
                Author notes
                [*] [* ] Corresponding author: Karine Lacombe, Service de Maladies Infectieuses, Hôpital Saint‐Antoine, 184 rue du Faubourg Saint‐Antoine, 75012 Paris, France. Tel: +33 1 49 28 24 38. ( karine.lacombe2@ 123456aphp.fr )
                Article
                JIA225054
                10.1002/jia2.25054
                5978714
                29633564
                05edae96-f885-4938-9ff6-90eb09e2a3fc
                © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 October 2017
                : 20 December 2017
                Page count
                Figures: 0, Tables: 0, Pages: 6, Words: 5822
                Categories
                Commentary
                Commentary
                Custom metadata
                2.0
                jia225054
                April 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.0 mode:remove_FC converted:31.05.2018

                Infectious disease & Microbiology
                hepatitis b virus,hepatitis c virus,public health,testing,antivirals,eradication

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