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The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa

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      Abstract

      BackgroundSimple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa.MethodsUsing liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets).ResultsOf 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4.ConclusionsThe GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa.

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      A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.

      Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score > or = 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.
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        An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.

         P Bedossa,  T Poynard (1996)
        Histological activity reflects the global assessment of basic necroinflammatory lesions and is a criterion of major importance in chronic hepatitis C. The aim of this study was to propose and test the accuracy of a simple algorithm that generates a single activity score based on basic pathological features. A panel of 10 pathologists reviewed 363 chronic hepatitis C liver biopsies and graded the activity of hepatitis according to their own experience (reference activity). Then, a consensual algorithm on the grading of activity was established by the 10 experts in a panel discussion. Finally, stepwise discriminant analysis was performed to define which basic features had been intuitively used in the reference activity (statistical activity). To test the accuracy of the algorithm, concordance between the activity defined by the algorithm and the reference activity was assessed. It was compared with concordance between the activity defined by the statistical model and the reference activity. The algorithm proposed by the panel for the grading of activity included piecemeal necrosis and lobular necrosis. Concordance between reference activity and activity defined by the algorithm was substantial (305 cases, 84%, kappa = .75). Discriminant analysis showed that piecemeal necrosis, lobular necrosis, and portal inflammation were independently used to grade the activity. Concordance between reference activity and activity defined by the statistical model was substantial (300 cases, 83%, kappa = .73), virtually identical to the concordance between reference activity and activity defined by algorithm. This study proposes a simple algorithm for the grading of activity in chronic hepatitis. Its accuracy is as high as that obtained using a statistical approach.
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          Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection.

           Mark Sulkowski,  ,  F Torriani (2006)
          Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of 3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients.
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            Author and article information

            Affiliations
            [1 ]Department of Hepatology, Imperial College London, St Mary's Hospital , London, UK
            [2 ]The Gambia Unit, Liver Unit, Medical Research Council , Fajara, The Gambia
            [3 ]Emerging Disease Epidemilogy Unit, Institut Pasteur , Paris, France
            [4 ]Department of Histopathology, Edward Francis Small Teaching Hospital , Banjul, The Gambia
            [5 ]Centre for Pathology, Imperial College London , London, UK
            [6 ]Ministry of Health and Social Welfare , Banjul, The Gambia
            [7 ]Department of infectious disease, Imperial College London, St Mary's Hospital , London, UK
            [8 ]Department of Hepatology and Gastroenterology, Principal Hospital , Dakar, Senegal
            [9 ]Université Paris Descartes, APHP, Groupe Hospitalier Cochin Port Royal, Institut Pasteur , Paris, France
            Author notes
            [Correspondence to ] Dr Maud Lemoine, Department of Hepatology, Imperial College London, St Mary's Hospital, London, W2 1NY, UK; m.lemoine@ 123456imperial.ac.uk

            ML and YS contributed equally.

            Journal
            Gut
            Gut
            gutjnl
            gut
            Gut
            BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
            0017-5749
            1468-3288
            August 2016
            24 June 2015
            : 65
            : 8
            : 1369-1376
            26109530
            4975834
            gutjnl-2015-309260
            10.1136/gutjnl-2015-309260
            Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

            This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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            Categories
            1506
            Hepatology
            Original article
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            Gastroenterology & Hepatology

            hepatitis b, fibrosis

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