- Irregular regeneration of hepatocytes
- Irregular regeneration score
- Hepatocellular carcinoma
- Chronic hepatitis C
We examined changes in the degree of irregular regeneration (IR) of hepatocytes and the F stage in patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) who received interferon (IFN) therapy. The IFN-treated group consisted of 148 C-viral CH and LC patients; the IFN-untreated (UT) group consisted of 42 patients. The liver biopsy specimens were examined histologically, followed by a separate scoring of the degree of IR of hepatocytes which was classified into the following 5 grades and scored (IR score): score 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe). The annual rates of the IR score were –0.593 in sustained virologic responders, –0.188 in sustained biochemical responders, 0.071 in nonresponders and 0.121 in UT patients. The annual rates of the F stage were –0.218 in sustained virologic responders, –0.061 in sustained biochemical responders, 0.123 in nonresponders and 0.157 in UT patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence was significantly higher in groups of IFN-treated patients without improvement of IR scores than in groups with improvement of IR scores. Multivariate analyses revealed that a lack of improvement in the IR score was a cardinal risk factor for the development of HCC in C-viral CH and LC patients. Our data suggest that IFN therapy leads to an improvement in the degree of IR of hepatocytes and thereby influences the development of HCC in patients with CH and LC.
Copyright © 2007 S. Karger AG, Basel
- Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshida K, Kakumu S, Iijima A, Urushihara A, Kiyosawa K, Okuda M, Hino K, Okita K: Risk factor for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology 1998;27:1394–1402.
- Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S: Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995;346:1051–1055.
- Tanaka K, Sata M, Uchimura Y, Suzuki H, Tanikawa K: Long-term evaluation of interferon therapy in hepatitis C virus-associated cirrhosis: does IFN prevent development of hepatocellular carcinoma? Oncol Rep 1998;5:205–208.
- 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.
- Matsumura H, Moriyama M, Goto I, Tanaka N, Ohkubo H, Arakawa Y: Natural course of progression of liver fibrosis in patients with chronic liver disease type C in Japan: a study of 527 patients at one establishment. J Viral Hepat 2000;7:268–275.
- 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.
- Serfaty L, Chazouilleres O, Poujol-Robert A, Morand-Joubert L, Dubois C, Chretien Y, Poupon RE, Petit JC, Poupon R: Risk factors for cirrhosis in patients with chronic hepatitis C virus infection: results of a case-control study. Hepatology 1997;26:776–779.
- Shiratori Y, Shiina S, Imamura M, Kato N, Kanai F, Okudaira T, Teratani T, Tohgo G, Toda N, Ohashi M, Omata M: Characteristic difference of hepatocellular carcinoma between hepatitis B- and C-viral infection in Japan. Hepatology 1995;22:1027–1033.
- 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: Histological improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000;132:517–524.
- 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 1995;21:650–655.
- Yano M, Kumada H, Kage M, Ikeda K, Shimamatsu K, Inoue O, Hashimoto E, Lefkowitch JH, Ludwig J, Okuda K: The long-term pathological evolution of chronic hepatitis C. Hepatology 1996;23:1334–1340.
- Desmet VJ, Gerber M, Hoofnagle J.H, Manns M, Scheuer PJ: Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520.
- Uchida T: Small hepatocellular carcinoma: its relationship to multistep hepatocarcinogenesis. Pathol Int 1995;45 :175–184.
- Uchida T: Pathology of hepatitis C. Intervirology 1994;37:126–132.
- Uchida T, Kronborg I, Peters RL: Acute hepatitis: morhpologic and functional correlations in human livers. Hum Pathol 1984;15:267–277.
- Ueno Y, Moriyama M, Uchida T, Arakawa, Y: Irregular regeneration of hepatocytes is an important factor of hepatocarcinogenesis of liver disease. Hepatology 2001;33:357–362.
- Shibata M, Morizane T, Uchida T, Yamagami T, Onozuko Y, Nakano M, Mitamura K, Ueno Y: Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in chronic hepatitis and cirrhosis with hepatitis-C-virus infection. Lancet 1998;351:1773–1777.
- Okamoto H., Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, et al: Typing of hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources. J Gen Virol 1992;73:673–679.
- Simmonds P, Alberti A, Alter J, et al: A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 1994;19:1321–1324.
Mitsuhiko Moriyama, MD, PhD
Division of Gastroenterology and Hepatology, Department of Medicine
Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku
Tokyo 173-8610 (Japan)
Tel. +81 3 3972 8111, Fax +81 3 3956 8496, E-Mail email@example.com
Received: January 24, 2006
Accepted after revision: February 21, 2006
Published online: December 22, 2006
Number of Print Pages : 12
Number of Figures : 5, Number of Tables : 8, Number of References : 19
Intervirology (International Journal of Basic and Medical Virology)
Vol. 50, No. 2, Year 2007 (Cover Date: February 2007)
Journal Editor: Liebert, U.G. (Leipzig)
ISSN: 0300–5526 (print), 1423–0100 (Online)
For additional information: http://www.karger.com/INT
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.