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      Systematic review with meta‐analysis: direct comparisons of biomarkers for the diagnosis of fibrosis in chronic hepatitis C and B

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          Summary

          Background

          Blood tests and transient elastography ( TE), proposed as alternatives to biopsy for identifying advanced fibrosis ( METAVIR‐stage‐F2 or greater) or cirrhosis, have never been compared using an intention to diagnose approach, with direct comparisons only, and Bayesian approach.

          Aim

          To permit more appropriate comparisons.

          Methods

          From an overview of articles (2002–2014), we selected studies that directly compared the diagnostic accuracy of FibroTest, aspartate aminotransferase–platelet ratio index ( APRI), FIB4 or TE, with biopsy as a reference, in patients with chronic hepatitis C ( CHC) or B ( CHB). Investigators abstracted and checked study details and quality by using pre‐defined criteria. Bayesian method in intention to diagnose was the primary outcome.

          Results

          Of 1321 articles identified, 71 studies including 77 groups according to aetiology (All‐ CB) were eligible: 37 Only‐C, 28 Only‐B and 12 Mixed‐C‐B. There were 185 direct comparisons between the area under the ROC curves ( AUROCs), 99 for the diagnosis of advanced fibrosis and 86 for cirrhosis. In All‐ CB, Bayesian analyses revealed significant AUROCs differences in identifying advanced fibrosis in favour of FibroTest vs. TE [credibility interval: 0.06(0.02–0.09)], FibroTest vs. APRI [0.05 (0.03–0.07)] and for identifying cirrhosis TE vs. APRI [0.07 (0.02–0.13)] and FIB4 vs. APRI [0.04(0.02–0.05)]. No differences were observed between TE and FibroTest, for identifying cirrhosis in All‐ CB, and in sub‐groups (Only‐C, Only‐B, Mixed‐ CB) for both cirrhosis and fibrosis.

          Conclusions

          In CHC and CHB, APRI had lower performances than FIB‐4, TE and FibroTest. TE had lower performance than FibroTest for identifying advanced fibrosis in All‐ CB, without significant difference for identifying cirrhosis in all groups.

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          Most cited references31

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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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            Sifting the evidence-what's wrong with significance tests?

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              Exceeding the limits of liver histology markers.

              Alternatives to liver biopsy for staging liver disease caused by hepatitis C virus (HCV) have not appeared accurate enough for widespread clinical use. We characterized the magnitude of the impact of error in the "gold standard" on the observed diagnostic accuracy of surrogate markers. We calculated the area under the receiver operating characteristic curve (AUROC) for a surrogate marker against the gold standard (biopsy) for a range of possible performances of each test (biopsy and marker) against truth and a gradient of clinically significant disease prevalence. In the 'best' scenario where liver biopsy accuracy is highest (sensitivity and specificity of biopsy are 90%) and the prevalence of significant disease 40%, the calculated AUROC would be 0.90 for a perfect marker (99% actual accuracy) which is within the range of what has already been observed. With lower biopsy sensitivity and specificity, AUROC determinations > 0.90 could not be achieved even for a marker that perfectly measured disease. We demonstrate that error in the liver biopsy result itself makes it impossible to distinguish a perfect surrogate from ones that are now judged by some as clinically unacceptable. An alternative gold standard is needed to assess the accuracy of tests used to stage HCV-related liver disease.
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                Author and article information

                Journal
                Aliment Pharmacol Ther
                Aliment. Pharmacol. Ther
                10.1111/(ISSN)1365-2036
                APT
                Alimentary Pharmacology & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                0269-2813
                1365-2036
                30 October 2015
                January 2016
                : 43
                : 1 ( doiID: 10.1111/apt.2016.43.issue-1 )
                : 16-29
                Affiliations
                [ 1 ]BioPredictive ParisFrance
                [ 2 ]Capionis ParisFrance
                [ 3 ] Hepatology DepartmentAssistance Publique‐Hôpitaux de Paris Hôpital Pitié‐Salpêtrière ParisFrance
                [ 4 ] INSERM & Université Pierre et Marie Curie ‐ Univ Paris 06UMR_S 938 Centre de Recherche Saint‐Antoine & Institute of Cardiometabolism and Nutrition (ICAN) ParisFrance
                Author notes
                [*] [* ] Correspondence to:

                Dr T. Poynard, 47‐83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.

                E‐mail: tpoynard@ 123456teaser.fr

                Article
                APT13446
                10.1111/apt.13446
                4737301
                26516104
                8cacd74a-9667-414e-a8dd-4edbe726ef40
                © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 27 June 2015
                : 05 August 2015
                : 02 September 2015
                : 28 September 2015
                : 05 October 2015
                Page count
                Pages: 14
                Funding
                Funded by: Association pour la Recherche sur Maladies Virales et Hépatiques (ARMHV)
                Funded by: BioPredictive
                Funded by: APHP
                Categories
                Systematic Review with Meta‐analysis
                Systematic Reviews with Meta‐analyses
                Custom metadata
                2.0
                apt13446
                January 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.5 mode:remove_FC converted:28.01.2016

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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