Download PDF
Semin Liver Dis 2000; Volume 20(Number 01): 0047-0056
DOI: 10.1055/s-2000-9258
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4663

Fibrosis in Patients with Chronic Hepatitis C: Detection and Significance

Thierry Poynard1 , Vlad Ratziu1 , Yves Benmanov1 , Vincent Di Martino1 , Pierre Bedossa2 , Pierre Opolon1
  • 1Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Paris
  • 2Service d'Anatomie Pathologique, Hôpital de Bicètre, Paris, France
Further Information

Publication History

Publication Date:
31 December 2000 (online)

    Permissions and Reprints

ABSTRACT

Estimates of the extent of hepatic fibrosis and the rate of fibrosis progression represent important surrogate end points for evaluation of the vulnerability of an individual patient and for assessment of the impact of treatment on natural history in chronic hepatitis C. Using the median fibrosis progression rate, the median expected time to cirrhosis in untreated patients is around 30 years. However, one third of patients have an expected median time to cirrhosis of less than 20 years and one third will only progress to cirrhosis in more than 50 years, if ever. Factors independently associated with fibrosis progression are duration of infection, age, male gender, consumption of alcohol, human immunodeficiency virus co-infection, and low CD4 count. Evaluation of fibrosis progression is useful to decide treatment. Among patients with sustained viral response, fibrosis regresses. Evaluation of fibrosis progression has permitted validation of the concept of suppressive therapy. Among patients without viral clearance, interferon alone or in combination with ribavirin significantly reduces fibrosis progression rate in comparison with progression before treatment and to control groups. There is a major need for noninvasive markers of liver fibrosis. None are clearly useful today for the diagnosis of early stages of fibrosis.

KEYWORD

fibrosis - HCV - ribavirin - liver biopsy

REFERENCES

  • 1 WHO. Hepatitis C: global prevalence.  Wkly Epidemiol Rec . 1997;  72 341-344
    PubMedGoogle Scholar
  • 2 Seeff L B, Buskell-Bales Z, Wright E C. Long-term mortality after transfusion-associated non-A non-B hepatitis.  N Engl J Med . 1992;  327 1906-1911
    CrossrefPubMedGoogle Scholar
  • 3 Tong M J, el-Farra N S, Reikes A R, Co R L. Clinical outcomes after transfusion-associated hepatitis C.  N Engl J Med . 1995;  332 1463-1466
    CrossrefPubMedGoogle Scholar
  • 4 Darby S C, Ewart D W, Giangrande P LF. Mortality from liver cancer and liver disease in haemophilic men and boys given blood products contaminated with hepatitis C.  Lancet . 1997;  350 1425-1431
    CrossrefPubMedGoogle Scholar
  • 5 El-Serag H B, Mason A. Rising incidence of hepatocellular carcinoma in the United States.  N Engl J Med . 1999;  34 745-750
    PubMedGoogle Scholar
  • 6 Taylor-Robinson S D, Foster G R, Arora S, Hargreaves S, Thomas H C. Increase in primary liver cancer in the UK, 1979-94 [letter].  Lancet . 1997;  350 1142-1143
    PubMedGoogle Scholar
  • 7 Deuffic S, Poynard T, Buffat L, Valleron A-J. Trends in primary liver cancer [letter].  Lancet . 1998;  351 214-215
    PubMedGoogle Scholar
  • 8 Deuffic S, Buffat L, Poynard T, Valleron A J. Modeling the hepatitis C virus epidemic in France.  Hepatology . 1999;  29 1596-1601
    CrossrefPubMedGoogle Scholar
  • 9 Poynard T, Bedossa P, Opolon P, for the OBSVIRC, METAVIR, CLINIVIR and DOSVIRC groups. Natural history of liver fibrosis progression in patients with chronic hepatitis C.  Lancet . 1997;  349 825-832
    CrossrefPubMedGoogle Scholar
  • 10 Sobesky R, Mathurin P, Charlotte F. Modeling the impact of interferon alfa treatment on liver fibrosis progression in chronic hepatitis C: a dynamic view.  Gastroenterology . 1999;  116 378-386
    PubMedGoogle Scholar
  • 11 Perrillo R P. The role of liver biopsy in hepatitis C.  Hepatology . 1997;  26 57S-61S
    CrossrefPubMedGoogle Scholar
  • 12 Consensus Statement. EASL International Consensus Conference on Hepatitis C.  J Hepatol . 1999;  30 956-961
    CrossrefPubMedGoogle Scholar
  • 13 Poynard T, Lebrec D. The inconvenience of investigations used in hepatology: patients' and hepatologists' opinions.  Liver . 1982;  2 369-375
    PubMedGoogle Scholar
  • 13a Scheuer P J. Classification of chronic viral hepatitis: a need for reassessment.  J Hepatol . 1991;  13 372-374
    CrossrefPubMedGoogle Scholar
  • 14 Ludwig J. The nomenclature of chronic active hepatitis: an obituary.  Gastroenterology . 1993;  105 274-278
    PubMedGoogle Scholar
  • 15 Desmet V J, Gerber M, Hoofnagle J H, Manns M, Scheuer P J. Classification of chronic hepatitis: diagnosis, grading and staging.  Hepatology . 1994;  19 1513-1519
    CrossrefPubMedGoogle Scholar
  • 16 Bedossa P, Poynard T, the METAVIR Cooperative Group. Inter- and intra-observer variation in the assessment of liver biopsy of chronic hepatitis C.  Hepatology . 1994;  20 1:15-20
    PubMedGoogle Scholar
  • 17 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
    PubMedGoogle Scholar
  • 18 Knodell K G, Ishak K G, Black W C. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis.  Hepatology . 1981;  1 431-435
    CrossrefPubMedGoogle Scholar
  • 19 Wong V S, Wight D G, Palmer C R, Alexander G J. Fibrosis and other histological features in chronic hepatitis C virus infection: a statistical model.  J Clin Pathol . 1996;  49 465-469
    PubMedGoogle Scholar
  • 20 Poynard T, Bedossa P. Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. METAVIR and CLINIVIR Cooperative Study Groups.  J Viral Hepatol . 1997;  4 199-208
    CrossrefPubMedGoogle Scholar
  • 21 Paradis V, Mathurin P, Laurent A. Histological features predictive of liver fibrosis in chronic hepatitis C infection.  J Clin Pathol . 1996;  49 998-1004
    PubMedGoogle Scholar
  • 22 Yano M, Kumada H, Kage M. The long term pathological evolution of chronic hepatitis C.  Hepatology . 1996;  23 1334-1340
    CrossrefPubMedGoogle Scholar
  • 23 Datz C, Cramp M, Haas T. The natural course of hepatitis C virus infection 18 years after an epidemic outbreak of non-A, non-B hepatitis in a plasmapheresis centre.  Gut . 1999;  44 563-567
    CrossrefPubMedGoogle Scholar
  • 24 Poynard T, McHutchison J, Davis G, Esteban-Mur R, Goodman Z, Bedossa P, Albrecht J, and the FIBROVIRC Project Group. Impact of interferon alfa-2b and ribavirin on the liver fibrosis progression in patients with chronic hepatitis C.  Hepatology . 1998;  28 497A
    PubMedGoogle Scholar
  • 25 Wiley T E, McCarthy M, Breidi L, McCarthy M, Layden T J. Impact of alcohol on the histological and clinical progression of hepatitis C infection.  Hepatology . 1998;  28 805-809
    CrossrefPubMedGoogle Scholar
  • 26 Benhamou Y, Bochet M, Di Martino V. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group.  Hepatology . 1999;  30 1054-1058
    CrossrefPubMedGoogle Scholar
  • 27 von Frerichs. Uber den diabetes Berlin: Hirschwald 1884
  • 28 Schupfer F. De la possibilité de faire ``intra vitam'' un diagnostic précis des maladies du foie et de la rate.  Semin Méd . 1907;  27 229-230
    PubMedGoogle Scholar
  • 29 Huard P. La ponction biopsie du foie et son utilité dans le diagnostic des affections hépatiques.  Ann Anat Path . 1935;  12 1118-1124
    PubMedGoogle Scholar
  • 30 Theodossi A, Spiegelhalter D, Portmann B, Eddleston A L, Williams R. The value of clinical, biochemical, ultrasound and liver biopsy data in assessing patients with liver disease.  Liver . 1983;  3 315-326
    PubMedGoogle Scholar
  • 31 Soloway R D, Baggenstoss A H, Schoenfield L J, Summerskill W H. Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy.  Am J Dig Dis . 1971;  16 1082-1086
    PubMedGoogle Scholar
  • 32 Theodossi A, Skene A M, Portmann B. Observer variation in assessment of liver biopsies including analysis by kappa statistics.  Gastroenterology . 1980;  79 232-241
    PubMedGoogle Scholar
  • 33 Pagliaro L, Rinaldi F, Craxi A. Percutaneous blind biopsy versus laparoscopy with guided biopsy in diagnosis of cirrhosis. A prospective, randomized trial.  Dig Dis Sci . 1983;  28 39-43
    CrossrefPubMedGoogle Scholar
  • 34 Colombo M, Del Ninno E, de Franchis R. Ultrasound-assisted percutaneous liver biopsy: superiority of the Tru-Cut over the Menghini needle for diagnosis of cirrhosis.  Gastroenterology . 1998;  95 487-489
    PubMedGoogle Scholar
  • 35 Papini E, Pacella C M, Rossi Z. A randomized trial of ultrasound-guided anterior subcostal liver biopsy versus the conventional Menghini technique.  J Hepatol . 1991;  13 291-297
    PubMedGoogle Scholar
  • 36 Lindor K D, Bru C, Jorgensen R A. The role of ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy.  Hepatology . 1996;  23 1079-1083
    CrossrefPubMedGoogle Scholar
  • 37 Maharaj B, Maharaj R J, Leary W P. Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver.  Lancet . 1986;  1 523-525
    PubMedGoogle Scholar
  • 38 Crawford A R, Lin X Z, Crawford J M. The normal adult human liver biopsy: a quantitative reference standard.  Hepatology . 1998;  28 323-331
    CrossrefPubMedGoogle Scholar
  • 39 Urena M A, Ruiz-Delgado F C, Gonzalez E M. Assessing risk of the use of livers with macro and microsteatosis in a liver transplant program.  Transplant Proc . 1998;  30 3288-3291
    CrossrefPubMedGoogle Scholar
  • 40 Gayral F, Potier M, Salmon R, Labayle D, Larrieu H. Vascular complications of needle biopsy of the liver.  J Chir (Paris) . 1979;  116 261-264
    PubMedGoogle Scholar
  • 41 Lebrec D, Goldfarb G, Degott C, Rueff B, Benhamou J P. Transvenous liver biopsy: an experience based on 1000 hepatic tissue samplings with this procedure.  Gastroenterology . 1982;  83 338-340
    PubMedGoogle Scholar
  • 42 Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies.  J Hepatol . 1986;  2 165-173
    CrossrefPubMedGoogle Scholar
  • 43 McGill D B, Rakela J, Zinsmeister A R, Ott B J. A 21-year experience with major hemorrhage after percutaneous liver biopsy.  Gastroenterology . 1990;  99 1396-1400
    PubMedGoogle Scholar
  • 44 Maharaj B, Bhoora I G. Complications associated with percutaneous needle biopsy of the liver when one, two or three specimens are taken.  Postgrad Med J . 1992;  68 964-967
    PubMedGoogle Scholar
  • 45 Van Thiel H D, Gavaler J S, Wright H, Tzakis A. Liver biopsy. Its safety and complications as seen at a liver transplant center.  Transplantation . 1993;  55 1087-1090
    PubMedGoogle Scholar
  • 46 Janes C H, Lindor K D. Outcome of patients hospitalized for complications after outpatient liver biopsy.  Ann Intern Med . 1993;  118 96-98
    CrossrefPubMedGoogle Scholar
  • 47 Gilmore I T, Burroughs A, Murray-Lyon I M, Williams R, Jenkins D, Hopkins A. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London.  Gut . 1995;  36 437-441
    CrossrefPubMedGoogle Scholar
  • 48 Vivas S, Palacio M A, Rodriguez M, Lomo J, Cadenas F, Giganto F, Rodrigo L. Ambulatory liver biopsy: complications and evolution in 264 cases.  Rev Esp Enferm Dig . 1998;  90 175-182
    PubMedGoogle Scholar
  • 49 Teare J P, Sherman D, Greenfield S M. Comparison of serum procollagen III peptide concentrations and PGA index for assessment of hepatic fibrosis.  Lancet . 1993;  342 895-898
    CrossrefPubMedGoogle Scholar
  • 50 Oberti F, Valsesia E, Pilette C. Noninvasive diagnosis of hepatic fibrosis or cirrhosis.  Gastroenterology . 1997;  113 1609-1616
    CrossrefPubMedGoogle Scholar
  • 51 Bonacini M, Hadi G, Govindarajan S, Lindsay K L. 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
    PubMedGoogle Scholar
  • 52 Gaiani S, Gramantieri L, Venturoli N. What is the criterion for differentiating chronic hepatitis from compensated cirrhosis?.  <~>A prospective study comparing ultrasonography and percutaneous liver biopsy. J Hepatol . 1997;  27 979-985
    CrossrefPubMedGoogle Scholar
  • 53 Aube C, Oberti F, Korali N. Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis.  J Hepatol . 1999;  30 472-478
    CrossrefPubMedGoogle Scholar
  • 54 Mathurin P, Moussalli J, Cadranel J F. Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity.  Hepatology . 1998;  27 868-872
    CrossrefPubMedGoogle Scholar
  • 55 Shiffman M L, Hofmann C M, Contos M J, Luketic V A, Sanyal A J, Sterling R K, Ferreira-Gonzalez A, Mills A S, Garret C. A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia.  Gastroenterology . 1999;  117 1164-1172
    CrossrefPubMedGoogle Scholar
  • 56 Poynard T, Leroy V, Cohard M. Meta-analysis of interferon randomized trials in the treatment of viral hepatitis: Effects of dose and duration.  Hepatology . 1996;  24 778-789
    PubMedGoogle Scholar
  • 57 Camma C, Giunta M, Linea C, Pagliaro L. The effect of interferon in chronic hepatitis C: a quantitative evaluation of histology by meta-analysis.  J Hepatol . 1997;  26 1187-1199
    CrossrefPubMedGoogle Scholar
  • 58 Capra F, Casaril M, Gabrielli G B. Dolci Alpha-interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers.  J Hepatol . 1993;  18 112-118
    CrossrefPubMedGoogle Scholar
  • 59 Fukuda Y, Nakano I, Katano Y. Assessment and treatment of liver disease in Japanese haemophilia patients.  Haemophilia . 1998;  4 595-600
    CrossrefPubMedGoogle Scholar
  • 60 Kaplanski G, Farnarier C, Payan M J, Bongrand P, Durand J M. Increased levels of soluble adhesion molecules in the serum of patients with hepatitis C. Correlation with cytokine concentrations and liver inflammation and fibrosis.  Dig Dis Sci . 1997;  42 2277-2284
    CrossrefPubMedGoogle Scholar
  • 61 Kasahara A, Hayashi N, Mochizuki K. Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum markers of fibrosis in patients with chronic hepatitis C. Relationship to interferon response.  J Hepatol . 1997;  26 574-583
    CrossrefPubMedGoogle Scholar
  • 62 Mazzoran L, Tamaro G, Mangiarotti M A. Effects of interferon therapy on fibrosis serum markers in HCV-positive chronic liver disease.  Eur J Gastroenterol Hepatol . 1998;  10 125-131
    PubMedGoogle Scholar
  • 63 Napoli J, Bishop G A, McGuinness P H, Painter D M, McCaughan G W. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines.  Hepatology . 1996;  24 759-765
    PubMedGoogle Scholar
  • 64 Verbaan H, Bondeson L, Eriksson S. Non-invasive assessment of inflammatory activity and fibrosis (grade and stage) in chronic hepatitis C infection.  Scand J Gastroenterol . 1997;  32 494-499
    PubMedGoogle Scholar
  • 65 Wong V S, Hughes V, Trull A, Wight D G, Petrik J, Alexander G J. Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C virus infection.  J Viral Hepatol . 1998;  5 187-192
    CrossrefPubMedGoogle Scholar
  • 66 Yamada M, Fukuda Y, Koyama Y. Serum hyaluronic acid reflects the effect of interferon treatment on hepatic fibrosis in patients with chronic hepatitis C.  J Gastroenterol Hepatol . 1996;  11 646-651
    PubMedGoogle Scholar
  • 67 Yamada M, Fukuda Y, Nakano I, Katano Y, Takamatsu J, Hayakawa T. Serum hyaluronan as a marker of liver fibrosis in hemophiliacs with hepatitis C virus-associated chronic liver disease.  Acta Haematol . 1998;  99 212-216
    CrossrefPubMedGoogle Scholar