Gastroenterology
Volume 138, Issue 1 , Pages 136-146 , January 2010

Predicting Clinical and Histologic Outcomes Based on Standard Laboratory Tests in Advanced Chronic Hepatitis C

  • Marc G. Ghany

      Affiliations

    • Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
    • Corresponding Author InformationReprint requests Address requests for reprints to: Marc Ghany, MD, LDB, NIDDK, NIH, Bldg 10, Room 9B-16, 10 Center Drive, MSC 1800, Bethesda, Maryland 20892-1800. fax: (301) 402-0491
    • ,
  • Anna S.F. Lok

      Affiliations

    • Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan
    • ,
  • James E. Everhart

      Affiliations

    • Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
    • ,
  • Gregory T. Everson

      Affiliations

    • Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Denver, Colorado
    • ,
  • William M. Lee

      Affiliations

    • Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
    • ,
  • Teresa M. Curto

      Affiliations

    • New England Research Institutes, Watertown, Massachusetts
    • ,
  • Elizabeth C. Wright

      Affiliations

    • Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
    • ,
  • Anne M. Stoddard

      Affiliations

    • New England Research Institutes, Watertown, Massachusetts
    • ,
  • Richard K. Sterling

      Affiliations

    • Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, Virginia
    • ,
  • Adrian M. Di Bisceglie

      Affiliations

    • Division of Gastroenterology and Hepatology, St. Louis University School of Medicine, St. Louis, Missouri
    • ,
  • Herbert L. Bonkovsky

      Affiliations

    • Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut
    • Department of Molecular & Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, Connecticut
    • ,
  • Chihiro Morishima

      Affiliations

    • Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, Washington
    • ,
  • Timothy R. Morgan

      Affiliations

    • Division of Gastroenterology, University of California-Irvine, Irvine, California, and Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, California
    • ,
  • Jules L. Dienstag

      Affiliations

    • Gastrointestinal Unit (Medical Services), Massachusetts General Hospital and the Department of Medicine, Harvard Medical School, Boston, Massachusetts
    • ,
  • HALT-C Trial Group

Received 19 December 2008 ,Accepted 9 September 2009.

References 

  1. Williams R. Global challenges in liver disease. Hepatology. 2006;44:521–526
  2. Wise M, Bialek S, Finelli L, et al. Changing trends in hepatitis C-related mortality in the United States, 1995–2004. Hepatology. 2008;47:1128–1135
  3. Armstrong GL, Alter MJ, McQuillan GM, et al. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology. 2000;31:777–782
  4. Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002;36:S35–S46
  5. Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649
  6. Malinchoc M, Kamath PS, Gordon FD, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;31:864–871
  7. Yoo HY, Edwin D, Thuluvath PJ. Relationship of the Model for End-Stage Liver Disease (MELD) scale to hepatic encephalopathy, as defined by electroencephalography and neuropsychometric testing, and ascites. Am J Gastroenterol. 2003;98:1395–1399
  8. Huo TI, Lin HC, Wu JC, et al. Limitation of the Model for End-Stage Liver Disease for outcome prediction in patients with cirrhosis-related complications. Clin Transplant. 2006;20:188–194
  9. Lee WM, Dienstag JL, Lindsay KL, et al. Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. Control Clin Trials. 2004;25:472–492
  10. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699
  11. Di Bisceglie AM, Shiffman ML, Everson GT, et al. Prolonged therapy of advanced chronic hepatitis c with low-dose peginterferon. N Engl J Med. 2008;359:2429–2441
  12. Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan (IHIT Study Group. Inhibition of hepatocarcinogenesis by interferon therapy). Ann Intern Med. 1999;131:174–181
  13. Okanoue T, Itoh Y, Minami M, et al. Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in an advanced stage: a retrospective study in 1148 patients. J Hepatol. 1999;30:653–659Viral Hepatitis Therapy Study Group
  14. Lok AS, Seeff LB, Morgan TR, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology. 2009;136:138–148
  15. Fattovich G, Giustina G, Degos F, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112:463–472
  16. Serfaty L, Aumaitre H, Chazouilleres O, et al. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology. 1998;27:1435–1440
  17. Hu KQ, Tong MJ. The long-term outcomes of patients with compensated hepatitis C virus-related cirrhosis and history of parenteral exposure in the United States. Hepatology. 1999;29:1311–1316
  18. Benvegnu L, Gios M, Boccato S, et al. Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut. 2004;53:744–749
  19. Khan MH, Farrell GC, Byth K, et al. Which patients with hepatitis C develop liver complications?. Hepatology. 2000;31:513–520
  20. Sangiovanni A, Prati GM, Fasani P, et al. The natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients. Hepatology. 2006;43:1303–1310
  21. Sheth SG, Flamm SL, Gordon FD, et al. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 1998;93:44–48
  22. Bonacini M, Hadi G, Govindarajan S, et al. Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 1997;92:1302–1304
  23. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C (The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups). Lancet. 1997;349:825–832
  24. Bellentani S, Pozzato G, Saccoccio G, et al. Clinical course and risk factors of hepatitis C virus-related liver disease in the general population: report from the Dionysos study. Gut. 1999;44:874–980
  25. Ghany MG, Kleiner DE, Alter H, et al. Progression of fibrosis in chronic hepatitis C. Gastroenterology. 2003;124:97–104
  26. Ryder SD, Irving WL, Jones DA, et al. Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study. Gut. 2004;53:451–455
  27. Jonsson JR, Barrie HD, O'Rourke P, et al. Obesity and steatosis influence serum and hepatic inflammatory markers in chronic hepatitis C. Hepatology. 2008;48:80–87
  28. Moucari R, Asselah T, Cazals-Hatem D, et al. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134:416–423
  29. Fartoux L, Poujol-Robert A, Guechot J, et al. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut. 2005;54:1003–1008
  30. Conjeevaram HS, Kleiner DE, Everhart JE, et al. Race, insulin resistance and hepatic steatosis in chronic hepatitis C. Hepatology. 2007;45:80–87
  31. Leandro G, Mangia A, Hui J, et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology. 2006;130:1636–1642
  32. Fartoux L, Chazouilleres O, Wendum D, et al. Impact of steatosis on progression of fibrosis in patients with mild hepatitis C. Hepatology. 2005;41:82–87
  33. Everhart JE, Lok AS, Kim HY, et al. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology. 2009;137:549–557
  34. Hu KQ, Kyulo NL, Esrailian E, et al. Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States. J Hepatol. 2004;40:147–154
  35. Friedenberg F, Pungpapong S, Zaeri N, et al. The impact of diabetes and obesity on liver histology in patients with hepatitis C. Diabetes Obes Metab. 2003;5:150–155
  36. Younossi ZM, McCullough AJ, Ong JP, et al. Obesity and non-alcoholic fatty liver disease in chronic hepatitis C. J Clin Gastroenterol. 2004;38:705–709
  37. Ortiz V, Berenguer M, Rayon JM, et al. Contribution of obesity to hepatitis C-related fibrosis progression. Am J Gastroenterol. 2002;97:2408–2414
  38. Lo Iacono O, Venezia G, Petta S, et al. The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2007;25:1181–1191

 Conflicts of interest The authors disclose the following: financial relationships of the authors with Hoffmann-La Roche, Inc, are as follows: A. S. F. Lok is a consultant; G. T. Everson is a consultant, on the speaker's bureau, and receives research support; W. M. Lee receives research support; R. K. Sterling is consultant, on the speaker's bureau, and receives research support; A.M. Di Bisceglie is a consultant, on the speaker's bureau, and receives research support; H. L. Bonkovsky receives research support; and T. R. Morgan is a consultant, on the speaker's bureau, and receives research support. The remaining authors disclose no conflicts.

 In addition, many of the HALT-C Trial investigators have other associations with industry relating to the area of hepatitis C, and, to achieve the highest level of disclosure, we list these for you as well.

 A. S. F. Lok: Schering-Plough Corporation, consultant and receives research support; Vertex Pharmaceuticals, consultant; Idenix Pharmaceuticals, receives research support; Eisai Pharmaceuticals, receives research support. G. T. Everson: receives research support from Schering-Plough, Pharmasset, GlobeImmune, Source, Novartis/Human Genome Sciences, and GlaxoSmithKline and is a consultant and receives research support from Vertex Pharmaceuticals. W. M. Lee: receives research support from Aegerion, GlobeImmune, Orasure, Schering-Plough, Siemens Diagnostics, and Vertex Pharmaceuticals. A.M. Stoddard: equity interest in Johnson & Johnson, Procter & Gamble, Bristol-Myers Squibb, and Elan. R. K. Sterling: consultant and on the speaker's bureau for Schering-Plough; is on an advisory board for Vertex Pharmaceuticals; and is a consultant and receives research support from Wako Chemicals USA. A. M. Di Bisceglie: consultant, on the speaker's bureau, and receives research support from Idenix Pharmaceuticals; is a consultant for Schering-Plough, Novartis, Bristol-Myers Squibb, and Abbott; is a consultant and receives research support from Vertex Pharmaceuticals, Anadys, GlobeImmune, Pharmasset, Sci-Clone, Gilead Sciences, and Novartis. H. L. Bonkovsky: serves on a data monitoring and safety committee for Glaxo Smith Kline; served as a paid consultant for Boehringer-Ingelheim and Infacare Pharmaceuticals receives research support from Merck; consultant and receives research support from Novartis Pharmaceuticals; consultant and on speaker's bureau for Ovation, Inc; receives research support from Schering-Plough Corporation; receives research support from Vertex Pharmaceuticals. T. R. Morgan: is on the speaker's bureau and receives research support from Schering-Plough and is a consultant and receives research support from Vertex Pharmaceuticals. J. L. Dienstag: receives research support from Vertex Pharmaceuticals; serves on a Data Monitoring Committee for Schering-Plough Research Institute and Human Genome Sciences; and is on ad hoc hepatitis advisory board for Boehringer-Ingelheim.

 Funding Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below) and the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.

PII: S0016-5085(09)01599-6

doi: 10.1053/j.gastro.2009.09.007

Gastroenterology
Volume 138, Issue 1 , Pages 136-146 , January 2010

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