Digestive Diseases and Sciences

, Volume 41, Supplement 12, pp 41S–48S | Cite as

Patterns of progression

Unpredictability and risk of decompensated cirrhosis
  • Nicolaos C. Tassopoulos


Hepatitis C virus (HCV) infection appears to have a slow but progressive evolution to chronic hepatitis and cirrhosis in a significant percentage of patients. Chronic hepatitis develops in 60–80% of patients. Worldwide prospective studies have shown that a further 20–30% of patients with chronic active hepatitis will develop cirrhosis regardless of the possible source of HCV infection. The percentage of cirrhotics is generally believed to increase progressively as the length of follow-up increases. In patients with chronic HCV, there also is high risk for the development of hepatocellular carcinoma. Factors influencing the rate of progression from chronic hepatitis to cirrhosis appear to include age at time of exposure, duration of infection, degree of liver damage at initial biopsy, immunological status, and possibly HCV genotype. The mean intervals between the time of initial infection and the diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma have been estimated to be 10, 20, and 30 years, respectively. The progression of disease is variable and is not always orderly and sequential. Patients can progress from chronic persistent hepatitis or chronic active hepatitis directly to hepatocellular carcinoma without first developing cirrhosis, especially those with genotype 1b. In addition, cirrhosis does not appear to lead to clinically apparent hepatic failure in all patients. Because of the variability in the clinical presentation and clinical progression of chronic HCV, long-term follow-up studies may be necessary to fully assess the sequelae of chronic HCV infection. Most patients with chronic HCV have abnormal liver histology but can present as otherwise healthy individuals. In contrast, patients with chronic HCV who have normal hepatic chemistries can have substantial hepatocellular damage. Consequently, treatment at diagnosis offers the greatest likelihood of eliminating the virus and preventing progression to more severe liver disease.

Key words

hepatitis C virus chronic hepatitis cirrhosis liver failure hepatocellular carcinoma 


  1. 1.
    Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV: Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med 292:767–770, 1975Google Scholar
  2. 2.
    Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M: Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362, 1989Google Scholar
  3. 3.
    Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo QL, Kuo G: Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 321:1494–1500, 1989Google Scholar
  4. 4.
    Esteban JI, González A, Hernández JM, Viladomiu L, Sánchez C, López-Talavera JC, Lucea D, Martin-Vega C, Vidal X, Esteban R, Guardia J: Evaluation of antibodies to hepatitis C virus in a study of transfusion-associated hepatitis. N Engl J Med 323:1107–1112, 1990Google Scholar
  5. 5.
    Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Gerber MA, Sampliner RE, Meeks EL, Beach MJ for the Sentinel Counties: Chronic non-A, non-B hepatitis study team: The natural history of community-acquired hepatitis C in the United States. N Engl J Med 327:1899–1905, 1992Google Scholar
  6. 6.
    Aach RD, Stevens CE, Hollinger FB, Mosley JW, Peterson DA, Taylor PE, Johnson RG, Barbosa LH, Nemo GJ: Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays. N Engl J Med 325:1325–1329, 1991Google Scholar
  7. 7.
    Tremolada F, Casarin C, Tagger A, Ribero ML, Realdi G, Alberti A, Ruol A: Antibody to hepatitis C virus in post-transfusion hepatitis. Ann Intern Med 114:277–281, 1991Google Scholar
  8. 8.
    Alter HJ: Post transfusion hepatitis in the United States.In Viral Hepatitis and Liver Disease: Proceedings of the International Symposium on Viral Hepatitis and Liver Disease: Molecules Today, More Cures Tomorrow. K Nishioka, H Suzuki, S Mishiro, T Oda (eds). Tokyo, Springer-Verlag, 1994, pp 551–553Google Scholar
  9. 9.
    Koretz RL, Brezina M, Polito AJ, Quan S, Wilber J, Dinello R, Gitnick G: Non-A, non-B posttransfusion hepatitis: comparing C and non-C hepatitis. Hepatology 17:361–365, 1993Google Scholar
  10. 10.
    Tassopoulos NC, Hatzakis A, Delladetsima I, Koutelou MG, Todoulos A, Miriagou V: Role of hepatitis C virus in acute non-A, non-B hepatitis in Greece: A 5-year prospective study. Gastroenterology 102:969–972, 1992Google Scholar
  11. 11.
    Rodríguez M, Riestra S, San Román F, Pérez R, Suárez A, Sánchez JL, Rodrigo L: Prevalence of antibody to hepatitis C virus in prospectively followed acute non-A, non-B hepatitis, from different epidemiological categories. Liver 11:129–133, 1991Google Scholar
  12. 12.
    Nishioka K, Watanabe J, Furuta S, Tanaka E, Suzuki H, Iino S, Tsuji T, Yano M, Kuo G, Choo Q-L, Houghton M, Oda T: Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan. Liver 11:65–70, 1991Google Scholar
  13. 13.
    Alter HJ: Chronic consequences of non-A, non-B, hepatitis.In Current Perspectives in Hepatology: Festschrift for Hyman J. Zimmerman, MD. HJ Zimmerman, LB Seeff, JH Lewis (eds). New York, Plenum Medical Book Co., 1989, pp 83–97Google Scholar
  14. 14.
    Tassopoulos NC, Hatzakis A, Delladetsima I, Miriagou V, Koutelou M, Todoulos A, Giannikakis TH: Risk factors influencing the outcome of acute non-A, non-B hepatitis. J Hepatol 13(suppl 2):S75, 1991 (abstract)Google Scholar
  15. 15.
    Rakela J, Redeker AG: Chronic liver disease after acute non-A, non-B viral hepatitis. Gastroenterology 77:1200–1202, 1979Google Scholar
  16. 16.
    Iwarson S, Lindberg J, Lundin P: Progression of hepatitis non-A, non-B to chronic active hepatitis. A histologic follow-up of two cases. J Clin Pathol 32:351–355, 1979Google Scholar
  17. 17.
    Realdi G, Alberti A, Rugge M, Rigoli AM, Tremolada F, Schivazappa L, Ruol A: Long-term follow-up of acute and chronic non-A, non-B post-transfusion hepatitis: Evidence of progression to liver cirrhosis. Gut 23:270–275, 1982Google Scholar
  18. 18.
    Omata M, Iwama S, Sumida M, Ito Y, Okuda K: Clinicopathological study of acute non-A, non-B post-transfusion hepatitis: Histological features of liver biopsies in acute phase. Liver 1:201–208, 1981Google Scholar
  19. 19.
    Tremolada F, Casarin C, Bonetti P, Alberti A, Scaccabarozzi S, Tagger A, Realdi G: Risk factors of evolution to cirrhosis of chronic non-A, non-B post-transfusion hepatitis. Preliminary results of recombinantα-2a interferon therapy.In Viral Hepatitis C, D and E. T Shikata, RH Purcell, T Uchida (eds). Amsterdam, Elsevier, 1991, pp 197–200Google Scholar
  20. 20.
    Wejstål R, Hermodsson S, Norkrans G: Long-term follow-up of chronic hepatitis non-A, non-B—with special reference to hepatitis C. Liver 11:143–148, 1991Google Scholar
  21. 21.
    Bianchi L, DeGroote J, Desmet VJ, Gedigk P, Korb G, Popper H, Poulsen H, Scheuer PJ, Schmid M, Thaler H, Wepler W: Acute and chronic hepatitis revisited. Lancet 2:914–919, 1977Google Scholar
  22. 22.
    Mattsson L, Weiland O, Glaumann H: Chronic non-A, non-B hepatitis developed after transfusion, illicit self injections or sporadically. Outcome during long-term follow-up—a comparison. Liver 9:120–127, 1989Google Scholar
  23. 23.
    Delladetsima JK, Rassidakis G, Tassopoulos NC, Papatheodoridis GV, Smyrnoff T, Vafiadis I: Histopathology of chronic hepatitis C in relation to epidemiological factors. J Hepatol 24:27–32, 1996Google Scholar
  24. 24.
    Hopf U, Möller B, Küther D, Stemerowicz R, Lobeck H, Lüdtke-Handjery A, Walter E, Blum HE, Roggendorf M, Deinhardt F: Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV). J Hepatol 10:69–76, 1990Google Scholar
  25. 25.
    Titó L, Sánchez JM, Costa J, Jové J, Vilella A, Bruguera M, Rodés J: Long-term follow-up of chronic NANB (C) hepatitis. J Hepatol 11(suppl 2):S61, 1990 (abstract)Google Scholar
  26. 26.
    Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, Furuta S, Akahane Y, Nishioka K, Purcell RH, Alter HJ: Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: Analysis by detection of antibody to hepatitis C virus. Hepatology 12:671–675, 1990Google Scholar
  27. 27.
    Tong MJ, El-Farra NS, Reikes AR, Co RL: Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 332:1463–1466, 1995Google Scholar
  28. 28.
    Di Bisceglie AM, Goodman ZD, Ishak KG, Hoofnagle JH, Melpolder JJ, Alter HJ: Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis. Hepatology 14:969–974, 1991Google Scholar
  29. 29.
    Koretz RL, Abbey H, Coleman E, Gitnick G: Non-A, non-B posttransfusion hepatitis. Looking back in the second decade. Ann Intern Med 119:110–115, 1993Google Scholar
  30. 30.
    Patel A, Sherlock S, Dusheiko G, Scheuer P, Ellis LA, Ashrafzadeh P: Clinical course and histological correlations in post-transfusion hepatitis C: The Royal Free Hospital experience. Eur J Gastroenterol Hepatol 3:491–495, 1991Google Scholar
  31. 31.
    Takahashi M, Yamada G, Miyamoto R, Doi T, Endo H, Tsuji T: Natural course of chronic hepatitis C. Am J Gastroenterol 88:240–243, 1993Google Scholar
  32. 32.
    Martin P, Di Bisceglie AM, Kassianides C, Lisker-Melman M, Hoofnagle JH: Rapidly progressive non-A, non-B hepatitis in patients with human immunodeficiency virus infection. Gastroenterology 97:1559–1561, 1989Google Scholar
  33. 33.
    Bernard B, Lunel F, Valla D, Perrin M, Le Charpentier Y, Opolen P: Factors involved in the prognosis of chronic non-A, non-B hepatitis: Comparison between 38 immunodeficient and 34 non-immunodeficient patients.In Viral Hepatitis C, D and E. T Shikata, RH Purcell, T Uchida (eds). Amsterdam, Elsevier, 1991, pp 123–127Google Scholar
  34. 34.
    Eyster ME, Diamondstone LS, Lien J-M, Ehmann WC, Quan S, Goedert JJ for the Multicenter Hemophilia Cohort Study: Natural history of hepatitis C virus infection in multitransfused hemophiliacs: Effect of coinfection with human immunodeficiency virus. J AIDS 6:602–610, 1993Google Scholar
  35. 35.
    Simmonds P, Alberti A, Alter HJ, Bonino F, Bradley DW, Brechot C, Brouwer JT, Chan S-W, Chayama K, Chen D-S, Choo Q-L, Colombo M, Cuypers HTM, Date T, Dusheiko GM, Esteban JI, Fay O, Hadziyannis SJ, Han J, Hatzakis A, Holmes EC, Hotta H, Houghton M, Irvine B, Kohara M, Kolberg JA, Kuo G, Lau JYN, Lelie PN, Maertens G, McOmish F, Miyamura T, Mizokami M, Nomoto A, Prince AM, Reesink HW, Rice C, Roggendorf M, Schalm SW, Shikata T, Shimotohno K, Stuyver L, Trepo C, Weiner A, Yap PL, Urdea MS: A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 19:1321–1324, 1994Google Scholar
  36. 36.
    Silini E, Bono F, Cividini A, Cerino A, Bruno S, Rossi S, Belloni G, Brugnetti B, Civardi E, Salvaneschi L, Mondelli MU: Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities. Hepatology 21:285–290, 1995Google Scholar
  37. 37.
    Hay CRM, Preston FE, Triger DR, Underwood JCE: Progressive liver disease in haemophilia: An understated problem? Lancet 1:1495–1498, 1985Google Scholar
  38. 38.
    Aledort LM, Levine PH, Hilgartner M, Blatt P, Spero JA, Goldberg JD, Bianchi L, Desmet V, Scheuer P, Popper H, Berk PD: A study of liver biopsies and liver disease among hemophiliacs. Blood 66:367–372, 1985Google Scholar
  39. 39.
    Resnick RH, Stone K, Antonioli D: Primary hepatocellular carcinoma following non-A, non-B posttransfusion hepatitis. Dig Dis Sci 28:908–911, 1983Google Scholar
  40. 40.
    Gilliam JH, Geisinger KR, Richter JE: Primary hepatocellular carcinoma after chronic non-A, non-B post-transfusion hepatitis. Ann Intern Med 101:794–795, 1984Google Scholar
  41. 41.
    Kiyosawa K, Akahane Y, Nagata A, Furuta S: Hepatocellular carcinoma after non-A, non-B posttransfusion hepatitis. Am J Gastroenterol 79:777–781, 1984Google Scholar
  42. 42.
    Caporaso N, Romano M, Marmo R, de Sio I, Morisco F, Minerva A, Coltorti M: Hepatitis C virus infection is an additive risk factor for development of hepatocellular carcinoma in patients with cirrhosis. J Hepatol 12:367–371, 1991Google Scholar
  43. 43.
    Colombo M, Kuo G, Choo QL, Donato MF, Del Ninno E, Tommasini MA, Dioguardi N, Houghton M: Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet 2:1006–1008, 1989Google Scholar
  44. 44.
    Ruiz J, Sangro B, Cuende JI, Beloqui O, Riezu-Boj JI, Herrero JI, Prieto J: Hepatitis B and C viral infections in patients with hepatocellular carcinoma. Hepatology 16:637–641, 1992Google Scholar
  45. 45.
    Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H, Kawashima T: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328:1797–1801, 1993Google Scholar
  46. 46.
    DeMitri MS, Poussin K, Baccarini P, Pontisso P, D'Errico A, Simon N, Grigioni W, Alberti A, Beaugrand M, Pisi E, Bréchot C, Paterlini P: HCV-associated liver cancer without cirrhosis. Lancet 345:413–415, 1995Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Nicolaos C. Tassopoulos
    • 1
  1. 1.Liver Unit, First Department of MedicineWestern Attica General HospitalAthensGreece

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