Abstract
A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P < 0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Marcellin P: Hepatitis C: the clinical spectrum of the disease. J. Hepatol 31(suppl 1):9–16, 1999
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, 1990
Di Bisceglie AM: Hepatitis C and hepatocellular carcinoma. Hepatology 26(suppl 1):34S–37S, 1997
Okuda K: Hepatocellular carcinoma. J Hepatol 32(suppl 1):225–237, 2000
Okuda K, Fujimoto I, Hanai A, Urano Y: Changing incidence of hepatocellular carcinoma in Japan. Cancer Res 47:4967–4972, 1987
Simonetti RG, Camma C, Fiorello F, Politi F, D'Amico G, Pagliaro L: Hepatocellular carcinoma. A worldwide problem and the major risk factors. Dig Dis Sci 36:962–972, 1991
El-Serag HB, Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340:745–750, 1999
Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M: Incidence of hepatocellular carcinoma in chronic hepatitis B and C: A prospective Study of 251 patients. Hepatology 21:650–655, 1995
Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, Arase Y, Fukuda M, Chayama K, Murashima N, Kumada H: Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: A prospective observation of 2215 patients. J Hepatol 28:930–938, 1998
Lindsay KL: Therapy of hepatitis C: Overview. Hepatology 26(suppl 1):71S–77S, 1997
Hoofnagle JH. Di Bisceglie AM: The treatment of chronic viral hepatitis. N Engl J Med 336:347–356, 1997
Davis GL: Current therapy for chronic hepatitis C. Gastroenterology 118:104–114, 2000
Shiratori S, Kato N, Yokosuka O, Imazeki F, Hashimoto E, Hayashi N, Nakamura A, Asada M, Kuroda H, Tanaka N, Arakawa Y, Omata M for the Tokyo-Chiba Hepatitis Research Group: Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Gastroenterology 113:558–566, 1997
Martinot-Peignoux M, Marcellin P, Ponteau M, Castelnau C, Boyer N, Pouliquin M, Degott C, Descombes I, Le Breton V, Milotova V, Benhamou JP, Erlinger S: Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotypes are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatology 22:1050–1056, 1995
Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Kobayashi M, Nakamura I, Murashima N, Kumada H, Kawanishi M: Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology 29:1124–1129, 1999
Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, Iijima A, Urushihara A, Kiyosawa K, Okuda M, Hino K, Okita K, and the Osaka Liver Disease Group: Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Hepatology 27:1394–1402, 1998
Imai Y, Kawata S, Tamura S, Yabuuchi I, Noda S, Inada M, Maeda Y, Shirai Y, Fukuzaki T, Kaji I, Ishikawa H, Matsuda Y, Nishikawa M, Seki K, Matsuzawa Y, for the Osaka Hepatocellular Carcinoma Prevention Group: Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Ann Intern Med 129:94–99, 1998
Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, Kuroki T, Nishiguchi S, Sata M, Yamada G, Fujiyama S, Yoshida H, Omata M: Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 132:517–524, 2000
Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T: Typing of hepatitis C virus by polymerase chain reaction with type-specific primers: Application to clinical surveys and tracing infectious sources. J Gen Virol 73:673–679, 1992
Tanaka T, Tsukiyama-Kohara K, Yamaguchi K, Yagi S, Tanaka S, Hasegawa A, Ohta Y, Hattori N, Kohara M: Significance of specific antibody assay for genotyping of hepatitis C virus. Hepatology 19:1347–1353, 1994
Simmonds P, Alberti A, Alter HJ, Bonino F, Bradly PW, Brechot C, Brouwer JT, Chan SW, Chayaman K, Chen DS: A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 19:1321–1324, 1994
Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Sheuer PJ: Classification of chronic hepatitis: Diagnosis, grading and staging. Hepatology 19:1513–1520, 1994
Kuwana K, Ichida T, Kamimura T, Okoshi S, Ogata N, Harada T, Endo K, Asakura H: Risk factors and the effect of interferon therapy in the development of hepatocellular carcinoma: A multivariate analysis in 343 patients. J Gastroenterol Hepatol 12:149–155, 1997
Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S: Randomized trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 346:1051–1055, 1995
Ohkoshi S, Tawaraya H, Kuwana K, Harada T, Watanabe M, Higuchi S, Kojima H, Kamimura T, Asakura H: A retrospectine study of hepatitis C virus carriers in a local endemic town in Japan. A possible presence of asymptomatic carriers. Dig Dis Sci 40:465–471, 1995.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takimoto, M., Ohkoshi, S., Ichida, T. et al. Interferon Inhibits Progression of Liver Fibrosis and Reduces the Risk of Hepatocarcinogenesis in Patients with Chronic Hepatitis C: A Retrospective Multicenter Analysis of 652 Patients. Dig Dis Sci 47, 170–176 (2002). https://doi.org/10.1023/A:1013244326874
Issue Date:
DOI: https://doi.org/10.1023/A:1013244326874