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Fibrosis progression rates between chronic hepatitis B and C patients with elevated alanine aminotransferase levels

  • Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

We evaluated the annual rate of fibrosis progression in chronic hepatitis B and C patients with elevated alanine aminotransferase (ALT) levels.

Methods

Forty-nine chronic hepatitis B patients and 21 chronic hepatitis C patients, each of whom had undergone two or more liver biopsies at an interval of more than 1 year, were enrolled in this retrospective clinical research protocol. The annual rate of fibrosis progression was calculated by dividing the change in fibrosis stage between the first and second liver biopsies by the interval in years between them.

Results

The median interval in chronic hepatitis B and C was 3.4 (first and third quartiles, 1.8–4.7) and 3.2 (2.1–6.5) years, respectively. Overall, the mean fibrosis progression rate was 0.21 ± 0.31 (mean ± SD) fibrosis units (FU) per year in 49 patients with chronic hepatitis B, and 0.13 ± 0.18 FU/year in 21 patients with chronic hepatitis C. The ALT level was an independent variable correlating with fibrosis progression. In patients whose median ALT level was 70 IU/l or more, the mean fibrosis progression rate was 0.28 ± 0.32 FU/year in 36 patients with chronic hepatitis B, and 0.22 ± 0.23 FU/year in eight patients with chronic hepatitis C.

Conclusion

This paired-biopsy study of untreated chronic hepatitis B or C demonstrated that fibrosis progression occurred largely in patients with continuously elevated ALT levels even over a relatively short period, and that liver fibrosis might progress by one stage within an average of 4–5 years of follow-up in patients with elevated ALT of 70 IU/l or more.

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References

  1. Liaw YF, Tai DI, Chu CM, Chen TJ. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988;8:493–496.

    Article  PubMed  CAS  Google Scholar 

  2. Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 1988;61:1942–1956.

    Article  PubMed  CAS  Google Scholar 

  3. Fattovich G, Brollo L, Giustina G, Noventa F, Pontisso P, Alberti A, et al. Natural history and prognostic factors for chronic hepatitis type B. Gut 1991;32:294–298.

    Article  PubMed  CAS  Google Scholar 

  4. Lok AS, McMahon BJ; Practice Guideline Committee, American Association for the Study of Liver Diseases. Chronic hepatitis B. Hepatology 2001;34:1225–12241.

    Article  PubMed  CAS  Google Scholar 

  5. Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, et al. Interrelationship of blood transfusion non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 1990;12:671–675.

    Article  PubMed  CAS  Google Scholar 

  6. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995;332:1463–1466.

    Article  PubMed  CAS  Google Scholar 

  7. Yano M, Kumada H, Kage M, Ikeda K, Shimamatsu K, Inoue O, et al. The long-term pathological evolution of chronic hepatitis C. Hepatology 1996;23:1334–1340.

    Article  PubMed  CAS  Google Scholar 

  8. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata 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;31:174–181.

    Google Scholar 

  9. Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991;13:372–374.

    Article  PubMed  CAS  Google Scholar 

  10. Desmet VJ, Gerver M, Hoofnagle JH, Manns M, Sheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–15120.

    Article  PubMed  CAS  Google Scholar 

  11. French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994;24:15–20.

    Article  Google Scholar 

  12. Bedosa P, Poynard T, for the METAVIR Cooperative Study Group. An algorithm for grading of activity in chronic hepatitis C. Hepatology 1996;24:289–293.

    Article  Google Scholar 

  13. Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47–58.

    Article  PubMed  Google Scholar 

  14. Yu MW, Hsu FC, Sheen IS, Chu CM, Lin DY, Chen CJ, et al. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol 1997;145:1039–1047.

    PubMed  CAS  Google Scholar 

  15. Vogt M, Lang T, Frosner G, Klingler C, Sendl AF, Zeller A, et al. Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening. N Engl J Med 1999;341:866–870.

    Article  PubMed  CAS  Google Scholar 

  16. Kenny-Walsh E. Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. N Engl J Med 1999;340:1228–1233.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. Mathurin P, Moussalli J, Cadranel J-F, Thibault V, Charlotte F, Dumouchel P, et al. Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity. Hepatology 1998;27:868–872.

    Article  PubMed  CAS  Google Scholar 

  19. Sobesky R, Mathurin P, Charlott F, Moussalli J, Olivi M, Vidaud M, et al. Modeling the impact of interferon alpha treatment on liver fibrosis progression in chronic hepatitis C: a dynamic view. The MULTIVIRC Group. Gastroenterology 1999;116:378–386.

    Article  PubMed  CAS  Google Scholar 

  20. Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 1999;30:1054–1058.

    Article  PubMed  CAS  Google Scholar 

  21. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000;132:517–524.

    PubMed  CAS  Google Scholar 

  22. Fontaine H, Nalpas B, Poulet B, Carnot F, Zylberberg H, Brechot C, et al. Hepatitis activity index is a key factor in determining the natural history of chronic hepatitis C. Hum Pathol 2001;32:904–909.

    Article  PubMed  CAS  Google Scholar 

  23. Ghany MG, Kleiner DE, Alter H, Doo E, Khokar F, Promrat K, et al. Progression of fibrosis in chronic hepatitis C. Gastroenterology 2003;124:97–104.

    Article  PubMed  Google Scholar 

  24. Chu CM. Towards control of hepatitis B in the Asia-Pacific Region. Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 2000;15:E25–30.

    Article  PubMed  Google Scholar 

  25. Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47–58.

    Article  PubMed  Google Scholar 

  26. Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology 2006;43:S173–181.

    Article  PubMed  CAS  Google Scholar 

  27. Sugauchi F, Mizokami M, Orito E, Ohno T, Koto H, Suzuki S, et al. A novel variant genotype C of hepatitis B virus identified in isolates from Australian aborigines: complete genome sequence and phylogenetic relatedness. J Gen Virol 2001;82:883–892.

    PubMed  CAS  Google Scholar 

  28. Usuda S, Okamoto H, Iwanari H, Baba K, Tsuda F, Miyakawa Y, et al. Serological detection of hepatitis B virus genotypes by ELISA with monoclonal antibodies to type-specific epitopes in the pre S2-region product. J Virol Methods 1999;80:97–112.

    Article  PubMed  CAS  Google Scholar 

  29. Papatheodoridis GV, Petraki K, Cholongitas E, Kanta E, Ketikoglon I, Manesis EK. Impact of interferon-alpha therapy on liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B. J Viral Hepat 2005;12:199–206.

    Article  PubMed  CAS  Google Scholar 

  30. Forns X, Ampurdanes S, Sanchez-Tapias JM, Guilera M, Sans M, Sanchez-Fueyo A, et al. Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center. J Hepatol 2001;35:265–271.

    Article  PubMed  CAS  Google Scholar 

  31. Ohta T, Sakaguchi K, Fujiwara A, Fujioka S, Iwasaki Y, Makino Y, et al. Simple surrogate index of the fibrosis stage in chronic hepatitis C patients using platelet count and serum albumin level. Acta Med Okayama 2006;60:77–84.

    PubMed  Google Scholar 

  32. Taniguchi H, Iwasaki Y, Fujiwara A, Sakaguchi K, Moriya A, Yu PC, et al. Long-term monitoring of platelet count, as a noninvasive marker of hepatic fibrosis progression and/or regression in patients with chronic hepatitis C after interferon therapy. J Gastroenterol Hepatol 2006;21:281–287.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama, 700-8558, Japan

    Akiko Fujiwara, Kohsaku Sakaguchi, Shinichi Fujioka, Yoshiaki Iwasaki, Tomonori Senoh, Mamoru Nishimura, Masako Terao & Yasushi Shiratori

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  1. Akiko Fujiwara
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  2. Kohsaku Sakaguchi
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  3. Shinichi Fujioka
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  8. Yasushi Shiratori
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Fujiwara, A., Sakaguchi, K., Fujioka, S. et al. Fibrosis progression rates between chronic hepatitis B and C patients with elevated alanine aminotransferase levels. J Gastroenterol 43, 484–491 (2008). https://doi.org/10.1007/s00535-008-2183-8

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  • DOI: https://doi.org/10.1007/s00535-008-2183-8

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