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Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease

Published:January 14, 2005DOI:https://doi.org/10.1016/S1542-3565(04)00625-1
      Background & Aims: The aim of this study was to determine the diagnostic use of noninvasive markers of fibrosis in patients with chronic alcoholic liver disease. Methods: A total of 221 consecutive patients with an alcohol intake of >50 g/day (median, 100 g/day) and available liver biopsy examination and FibroTest FibroSure (FT) results were included prospectively. Fibrosis was assessed blindly on a 5-stage histologic scale similar to that of the METAVIR scoring system. Hyaluronic acid was measured and used as a standard serum marker of fibrosis. Results: Advanced fibrosis (F2–F4) was present at biopsy examination in 63% of patients. The mean FT value (SE) was F0 = .29 (.05); F1 = .29 (.03), F2 = .40 (.03), F3 = .53 (.04); and F4 = .88 (.02) (P < .05 between all groups, except between F0 and F1). As opposed to FT, there was no significant difference for hyaluronic acid between F2 and F1 and between F2 and F0. For F2–F4 vs. F0–F1, the FT area under the ROC curves (AUROC) = .84 (.03) and .79 (.03) for hyaluronic acid. For the diagnosis of F4, the AUROC was very high, .95 for FT and .93 for hyaluronic acid. The discordances of the 2 stages were attributed to biopsy failures in 26 cases and to FT failures in 13 cases. Conclusions: In heavy drinkers, FT is a simple and noninvasive quantitative estimate of liver fibrosis. The use of FT may decrease the need for liver biopsy examination.

      Abbreviations used in this paper:

      AT (ActiTest), AUROC (area under the receiver operating characteristic), FT (FibroTest FibroSure), GGT (γ-glutamyl-transpeptidase)
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      References

        • Arteel G.
        • Marsano L.
        • Mendez C.
        • et al.
        Advances in alcoholic liver disease.
        Best Pract Res Clin Gastroenterol. 2003; 17: 625-647
        • Diehl A.M.
        Liver disease in alcohol abusers.
        Alcohol. 2002; 27: 7-11
        • Gordon H.
        Detection of alcoholic liver disease.
        World J Gastroenterol. 2001; 7: 297-302
        • Sussman S.
        • Dent C.W.
        • Skara S.
        • et al.
        Alcoholic liver disease (ALD).
        Subst Use Misuse. 2002; 37: 1887-1904
        • Chikritzhs T.N.
        • Jonas H.A.
        • Stockwell T.R.
        • et al.
        Mortality and life-years lost due to alcohol.
        Med J Aust. 2001; 174: 281-284
        • Menon K.V.
        • Gores G.J.
        • Shah V.H.
        Pathogenesis, diagnosis, and treatment of alcoholic liver disease.
        Mayo Clin Proc. 2001; 76: 1021-1029
        • Friedman S.L.
        • Maher J.J.
        • Bissell D.M.
        Mechanisms and therapy of hepatic fibrosis.
        Hepatology. 2000; 32: 1403-1408
        • McGill D.B.
        • Rakela J.
        • Zinsmeister A.R.
        • et al.
        A 21-year experience with major hemorrhage after percutaneous liver biopsy.
        Gastroenterology. 1990; 99: 1396-1400
        • Poynard T.
        • Ratziu V.
        • Bedossa P.
        Appropriateness of liver biopsy.
        Can J Gastroenterol. 2000; 14: 543-548
        • Cadranel J.F.
        • Rufat P.
        • Degos F.
        Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF).
        Hepatology. 2000; 32: 477-481
        • Poynard T.
        • Aubert A.
        • Bedossa P.
        • et al.
        A simple biological index for detection of alcoholic liver disease in drinkers.
        Gastroenterology. 1991; 100: 1397-1402
        • Oberti F.
        • Valsesia E.
        • Pilette C.
        • et al.
        Noninvasive diagnosis of hepatic fibrosis or cirrhosis.
        Gastroenterology. 1997; 113: 1609-1616
        • Naveau S.
        • Poynard T.
        • Benattar C.
        • et al.
        Alpha-2-macroglobulin and hepatic fibrosis. Diagnostic interest.
        Dig Dis Sci. 1994; 39: 2426-2432
        • Fabris C.
        • Falleti E.
        • Federico E.
        • et al.
        A comparison of four serum markers of fibrosis in the diagnosis of cirrhosis.
        Ann Clin Biochem. 1997; 34: 151-155
        • Tsutsumi M.
        • Takase S.
        • Urashima S.
        • et al.
        Serum markers for hepatic fibrosis in alcoholic liver disease.
        Alcohol Clin Exp Res. 1996; 20: 1512-1517
        • Robert A.
        • Chazouillères O.
        Prothrombin time in liver failure.
        Hepatology. 1996; 24: 1392-1394
        • Poynard T.
        • Imbert-Bismut F.
        • Ratziu V.
        Serum markers of liver fibrosis.
        Hepatology Rev. 2004; 1: 25-33
        • Imbert-Bismut F.
        • Ratziu V.
        • Pieroni L.
        • et al.
        Biochemical markers of liver fibrosis in patients with hepatitis C virus infection.
        Lancet. 2001; 357: 1069-1075
        • Poynard T.
        • Imbert-Bismut F.
        • Ratziu V.
        • et al.
        Biochemical markers of liver fibrosis in patients infected by hepatitis C virus: longitudinal validation in a randomized trial. The GERMED cyt-04 group.
        J Viral Hepat. 2002; 9: 128-133
        • Myers R.P.
        • Ratziu V.
        • Imbert-Bismut F.
        • et al.
        Biochemical markers of liver fibrosis.
        Am J Gastroenterol. 2002; 97: 2419-2425
        • Myers R.P.
        • Benhamou Y.
        • Imbert-Bismut F.
        • et al.
        Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus-coinfected patients.
        AIDS. 2003; 17: 1-5
        • Myers R.P.
        • de Torres M.
        • Imbert-Bismut F.
        • et al.
        Biochemical markers of fibrosis in patients with chronic hepatitis C.
        Dig Dis Sci. 2003; 48: 146-153
        • Poynard T.
        • McHutchison J.
        • Manns M.
        • et al.
        Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin.
        Hepatology. 2003; 38: 481-492
        • Halfon P.
        • Imbert-Bismut F.
        • Messous D.
        • et al.
        A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease.
        Comp Hepatol. 2002; 1: 3-7
        • Imbert-Bismut F.
        • Messous D.
        • Thibaut V.
        • et al.
        Intralaboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors.
        Clin Chem Lab Med. 2004; 42: 323-333
        • Munteanu M.
        • Messous D.
        • Thabut D.
        • et al.
        Intra-individual fasting versus postprandial variation of biochemical markers of liver fibrosis (Fibrotest) and activity (Actitest).
        Comp Hepatol. 2004; 3: 3
        • Poynard T.
        • Munteanu M.
        • Imbert-Bismut F.
        • et al.
        Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.
        Clin Chem. 2004; 50: 1344-1355
        • Myers R.P.
        • Tainturier M.H.
        • Ratziu V.
        • et al.
        Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B.
        J Hepatol. 2003; 39: 222-230
        • Rossi E.
        • Adams L.
        • Prins A.
        • et al.
        Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients.
        Clin Chem. 2003; 49: 450-454
      1. Poynard T, Imbert-Bismut F, Ratziu V, et al. Fibrotest even better than liver biopsy? Clin Chem 2003. Electronic letter. Available at: www.clinchem.org/cgi/eletters/49/3/450. Response: (21 March 2003). Accessed December 17, 2004.

        • Halfon P.
        • Bourliere M.
        • Deydier R.
        • et al.
        Independent prospective multicentre validation of biochemical markers (FibroTest-ActiTest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C (abstr).
        Hepatology. 2003; 38: 188A
        • Callewaert N.
        • Van Vlierberghe H.
        • Van Hecke A.
        • et al.
        Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics.
        Nat Med. 2004; 10: 1-6
        • Borroni G.
        • Cazzaniga M.
        • Ceriani R.
        • et al.
        Comparison of usefulness and accuracy of simple noninvasive models as predictors of cirrhosis in chronic hepatitis (abstr).
        J Hepatol. 2004; 40: 137
        • Naveau S.
        • Giraud V.
        • Borotto E.
        • et al.
        Excess weight risk factor for alcoholic liver disease.
        Hepatology. 1997; 25: 108-111
        • Poynard T.
        • Naveau S.
        • Doffoel M.
        • et al.
        Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using matched and simulated controls.
        J Hepatol. 1999; 30: 1130-1137
        • Bedossa P.
        • Poynard T.
        An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.
        Hepatology. 1996; 24: 289-293
        • Bedossa P.
        • Poynard T.
        • Naveau S.
        • et al.
        Observer variation in assessment of liver biopsies of alcoholic patients.
        Alcohol Clin Exp Res. 1988; 12: 173-178
        • Poynard T.
        • Mathurin P.
        • Lai C.L.
        • et al.
        A comparison of fibrosis progression in chronic liver diseases.
        J Hepatol. 2003; 38: 257-265
        • Hintze J.L.
        NCSS 2003 User Guide.
        Number Cruncher Statistical Systems 2003 software NCSS. Kaysville, UT2003
        • Hanley J.A.
        • McNeil B.J.
        A method of comparing the areas under receiver operating characteristic curves derived from the same cases.
        Radiology. 1983; 148: 839-843
        • Poynard T.
        • Imbert-Bismut F.
        • Munteanu M.
        • et al.
        Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.
        Comp Hepatol. 2004; 3: 8
        • Poynard T.
        • Abella A.
        • Pignon J.P.
        • et al.
        Apolipoprotein AI and alcoholic liver disease.
        Hepatology. 1986; 6: 1391-1395
        • Bedossa P.
        • Poynard T.
        • Abella A.
        • et al.
        Apolipoprotein AI is a serum and tissue marker of liver fibrosis in alcoholic patients.
        Alcohol Clin Exp Res. 1989; 13: 829-833
        • Poynard T.
        • Bedossa P.
        • Mathurin P.
        • et al.
        Apolipoprotein A1 and hepatic fibrosis.
        J Hepatol. 1995; 22: 107-110
        • Paradis V.
        • Laurent A.
        • Mathurin P.
        • et al.
        Role of liver extracellular matrix in transcriptional and post-transcriptional regulation of apolipoprotein A-I by hepatocytes.
        Cell Mol Biol. 1996; 42: 525-534
        • Paradis V.
        • Mathurin P.
        • Ratziu V.
        • et al.
        Binding of apolipoprotein A-I and acetaldehyde-modified apolipoprotein A-I to liver extracellular matrix.
        Hepatology. 1996; 23: 1232-1238
        • Mathurin P.
        • Vidaud D.
        • Vidaud M.
        • et al.
        Quantification of apolipoprotein A-I and B messenger RNA in heavy drinkers according to liver disease.
        Hepatology. 1996; 23: 44-51
        • Aube C.
        • Oberti F.
        • Korali N.
        • et al.
        Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis.
        J Hepatol. 1999; 30: 472-478
        • Tsutsumi M.
        • Urashima S.
        • Takase S.
        • et al.
        Characteristics of serum hyaluronate concentrations in patients with alcoholic liver disease.
        Alcohol Clin Exp Res. 1997; 21: 1716-1721
        • Stickel F.
        • Hoehn B.
        • Schuppan D.
        • et al.
        Review article.
        Aliment Pharmacol Ther. 2003; 18: 357-373
        • Labayle D.
        • Chaput J.C.
        • Albuisson F.
        • et al.
        Analyse histologique comparative des biopsies du lobe droit et du lobe gauche dans les lésions alcooliques du foie.
        Gastroenterol Clin Biol. 1979; 3: 235-240
        • Bedossa P.
        • Dargère D.
        • Paradis V.
        Sampling variability of liver fibrosis in chronic hepatitis C.
        Hepatology. 2003; 38: 1449-1457
        • Bravo A.A.
        • Sheth S.G.
        • Chopra S.
        Liver biopsy.
        N Engl J Med. 2001; 344: 495-500