Article    Table of Contents                    Full Text of this article Free    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Marcellin, P.    Erlinger, S.    Related Articles in PubMed    PubMed Citation    PubMed

ARTICLE

Long-Term Histologic Improvement and Loss of Detectable Intrahepatic HCV RNA in Patients with Chronic Hepatitis C and Sustained Response to Interferon- Therapy

Patrick Marcellin, MD; Nathalie Boyer, MD; Anne Gervais, MD; Michele Martinot, BS; Michele Pouteau, MD; Corinne Castelnau, MD; Afef Kilani, MD; Jorge Areias, MD; Anne Auperin, MD; Jean Pierre Benhamou, MD; Claude Degott, MD; and Serge Erlinger, MD

15 November 1997 | Volume 127 Issue 10 | Pages 875-881

Background: Less than 20% of patients with chronic hepatitis C have a sustained response to interferon- therapy. The long-term benefit of interferon- with regard to hepatic viral clearance and histologic improvement remains unknown.

Objective: To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronic hepatitis C who have a sustained response to interferon- therapy.

Design: Prospective cohort study.

Setting: University hospital.

Patients: 80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon- therapy, and were followed for at least 12 months.

Measurements: Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment.

Results: The 80 patients had follow-up 1 to 7.6 years (mean ±SD, 4.0 ± 2.0 years) after interferon- treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon- treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested.

Conclusions: In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon- therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

Author and Article Information

From Hopital Beaujon, Clichy, France.
Acknowledgments: The authors thank Drs. C. Lemonnier and C. Langlois (Schering-Plough Corp.) for their support.
Grant Support: In part by a grant from the Association pour la Recherche contre le Cancer.
Requests for Reprints: Patrick Marcellin, MD, Service d'Hepatologie, Hopital Beaujon, 100 Boulevard du General Leclerc, 92118 Clichy, France.
Current Author Addresses: Drs. Marcellin, Boyer, Gervais, Pouteau, Castelnau, Kilani, Areias, Auperin, Benhamou, and Erlinger and Ms. Martinot: Service d'Hepatologie and Unite de Recherches de Physiopathologie Hepatique (INSERM U24), Hopital Beaujon, 100 Boulevard du General Leclerc, 92118 Clichy, France.

Related articles in Annals:

Articles
Estimates of the Cost-Effectiveness of a Single Course of Interferon-2b in Patients with Histologically Mild Chronic Hepatitis C
William G. Bennett, Yuji Inoue, J. Robert Beck, John B. Wong, Stephen G. Pauker, AND Gary L. Davis

Annals 1997 127: 855-865. [ABSTRACT][Full Text]  

Articles
Cost-Effectiveness of 6 and 12 Months of Interferon- Therapy for Chronic Hepatitis C
W. Ray Kim, John J. Poterucha, John E. Hermans, Terry M. Therneau, E. Rolland Dickson, Roger W. Evans, AND John B. Gross, Jr.

Annals 1997 127: 866-874. [ABSTRACT][Full Text]  

Editorials
Interferon- for Chronic Hepatitis C: Reducing the Uncertainties
Raymond S. Koff

Annals 1997 127: 918-920. [Full Text]  

This article has been cited by other articles:

				A. E. Duggan, J. M. Duggan, N. Assy, O. Embon, A. Evoli, S. Servidei, C. Ben Salem, H. Hmouda, K. Bouraoui, S. Leiner, et al. Peginterferon and Ribavirin for Hepatitis C N. Engl. J. Med., March 22, 2007; 356(12): 1269 - 1271. [Full Text] [PDF]

				J. D. Scott and D. R. Gretch Molecular Diagnostics of Hepatitis C Virus Infection: A Systematic Review JAMA, February 21, 2007; 297(7): 724 - 732. [Abstract] [Full Text] [PDF]

				Y. S. Khader, A. Dweek, A. Alkafajei, and A. Z. Rabi' Combination Therapy of Interferon and Ribavirin Versus Interferon Monotherapy in Treatment of Chronic Hepatitis C: A Meta-analysis of Clinical Trials Journal of Pharmacy Practice, October 1, 2006; 19(5): 265 - 274. [Abstract] [PDF]

				T. Wong and S. S. Lee Hepatitis C: a review for primary care physicians Can. Med. Assoc. J., February 28, 2006; 174(5): 649 - 659. [Abstract] [Full Text] [PDF]

				J. Paris, M. M. Pradhan, S. Allen, and W. M. Cassidy Cost of Hepatitis C Treatment in the Correctional Setting Journal of Correctional Health Care, April 1, 2005; 11(2): 199 - 212. [Abstract] [PDF]

				B J Veldt, G Saracco, N Boyer, C Camma, A Bellobuono, U Hopf, I Castillo, O Weiland, F Nevens, B E Hansen, et al. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy Gut, October 1, 2004; 53(10): 1504 - 1508. [Abstract] [Full Text] [PDF]

				S. J. Hadziyannis, H. Sette Jr., T. R. Morgan, V. Balan, M. Diago, P. Marcellin, G. Ramadori, H. Bodenheimer Jr., D. Bernstein, M. Rizzetto, et al. Peginterferon-{alpha}2a and Ribavirin Combination Therapy in Chronic Hepatitis C: A Randomized Study of Treatment Duration and Ribavirin Dose Ann Intern Med, March 2, 2004; 140(5): 346 - 355. [Abstract] [Full Text] [PDF]

				S. Zeuzem Heterogeneous Virologic Response Rates to Interferon-Based Therapy in Patients with Chronic Hepatitis C: Who Responds Less Well? Ann Intern Med, March 2, 2004; 140(5): 370 - 381. [Abstract] [Full Text] [PDF]

				D Dhumeaux, P Marcellin, and E Lerebours Treatment of hepatitis C. The 2002 French consensus Gut, December 1, 2003; 52(12): 1784 - 1787. [Full Text] [PDF]

				J. A. Salomon, M. C. Weinstein, J. K. Hammitt, and S. J. Goldie Cost-effectiveness of Treatment for Chronic Hepatitis C Infection in an Evolving Patient Population JAMA, July 9, 2003; 290(2): 228 - 237. [Abstract] [Full Text] [PDF]

				M. S. Sulkowski and D. L. Thomas Hepatitis C in the HIV-Infected Person Ann Intern Med, February 4, 2003; 138(3): 197 - 207. [Abstract] [Full Text] [PDF]

				T Bizollon, S N S Ahmed, S Radenne, M Chevallier, P Chevallier, P Parvaz, S Guichard, C Ducerf, J Baulieux, F Zoulim, et al. Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence Gut, February 1, 2003; 52(2): 283 - 287. [Abstract] [Full Text] [PDF]

				L. L Kjaergard, K. Krogsgaard, and C. Gluud Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials BMJ, November 17, 2001; 323(7322): 1151 - 1155. [Abstract] [Full Text] [PDF]

				J. M. Jacobson, L. Feinman, L. Liebes, N. Ostrow, V. Koslowski, A. Tobia, B. E. Cabana, D.-H. Lee, J. Spritzler, and A. M. Prince Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection Antimicrob. Agents Chemother., February 1, 2001; 45(2): 517 - 524. [Abstract] [Full Text]

				R. S. Koff Nonresponse to Interferon in Chronic Hepatitis C: Re-treatment Redux JAMA, January 10, 2001; 285(2): 212 - 214. [Full Text] [PDF]

				J. B. Wong and R. S. Koff Watchful Waiting with Periodic Liver Biopsy versus Immediate Empirical Therapy for Histologically Mild Chronic Hepatitis C: A Cost-Effectiveness Analysis Ann Intern Med, November 7, 2000; 133(9): 665 - 675. [Abstract] [Full Text] [PDF]

				N. Butkiewicz, N. Yao, W. Zhong, J. Wright-Minogue, P. Ingravallo, R. Zhang, J. Durkin, D. N. Standring, B. M. Baroudy, D. V. Sangar, et al. Virus-Specific Cofactor Requirement and Chimeric Hepatitis C Virus/GB Virus B Nonstructural Protein 3 J. Virol., May 1, 2000; 74(9): 4291 - 4301. [Abstract] [Full Text]

				Y. Shiratori, F. Imazeki, M. Moriyama, M. Yano, Y. Arakawa, O. Yokosuka, T. Kuroki, S. Nishiguchi, M. Sata, G. Yamada, et al. Histologic Improvement of Fibrosis in Patients with Hepatitis C Who Have Sustained Response to Interferon Therapy Ann Intern Med, April 4, 2000; 132(7): 517 - 524. [Abstract] [Full Text] [PDF]

				The National Commission on Correctional Health Care and The Society of Correctional Physicians Joint Position Statement: The Management of Hepatitis C in Correctional Institutions Journal of Correctional Health Care, March 1, 2000; 7(1): 149 - 155. [PDF]

				K. S. Gutfreund and V. G. Bain Chronic viral hepatitis C: management update Can. Med. Assoc. J., March 1, 2000; 162(6): 827 - 833. [Abstract] [Full Text] [PDF]

				T. J. Liang, B. Rehermann, L. B. Seeff, and J. H. Hoofnagle Pathogenesis, Natural History, Treatment, and Prevention of Hepatitis C Ann Intern Med, February 15, 2000; 132(4): 296 - 305. [Abstract] [Full Text] [PDF]

				V. Baffis, I. Shrier, A. H. Sherker, and A. Szilagyi Use of Interferon for Prevention of Hepatocellular Carcinoma in Cirrhotic Patients with Hepatitis B or Hepatitis C Virus Infection Ann Intern Med, November 2, 1999; 131(9): 696 - 701. [Abstract] [Full Text] [PDF]

				M BONACINI, A G REDEKER;, and G H HAYDON Intrahepatic HCV levels in chronic HCV infection • Reply Gut, October 1, 1999; 45(4): 630a - 630. [Full Text]

				R. S. Koff Advances in the Treatment of Chronic Viral Hepatitis JAMA, August 11, 1999; 282(6): 511 - 512. [Full Text] [PDF]

				J.-M. Pawlotsky, G. Germanidis, P.-O. Frainais, M. Bouvier, A. Soulier, M. Pellerin, and D. Dhumeaux Evolution of the Hepatitis C Virus Second Envelope Protein Hypervariable Region in Chronically Infected Patients Receiving Alpha Interferon Therapy J. Virol., August 1, 1999; 73(8): 6490 - 6499. [Abstract] [Full Text]

				E. Ferrari, J. Wright-Minogue, J. W. S. Fang, B. M. Baroudy, J. Y. N. Lau, and Z. Hong Characterization of Soluble Hepatitis C Virus RNA-Dependent RNA Polymerase Expressed in Escherichia coli J. Virol., February 1, 1999; 73(2): 1649 - 1654. [Abstract] [Full Text]

				J. G. McHutchison, S. C. Gordon, E. R. Schiff, M. L. Shiffman, W. M. Lee, V. K. Rustgi, Z. D. Goodman, M.-H. Ling, S. Cort, J. K. Albrecht, et al. Interferon Alfa-2b Alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C N. Engl. J. Med., November 19, 1998; 339(21): 1485 - 1492. [Abstract] [Full Text] [PDF]

				G. L. Davis, R. Esteban-Mur, V. Rustgi, J. Hoefs, S. C. Gordon, C. Trepo, M. L. Shiffman, S. Zeuzem, A. Craxi, M.-H. Ling, et al. Interferon Alfa-2b Alone or in Combination with Ribavirin for the Treatment of Relapse of Chronic Hepatitis C N. Engl. J. Med., November 19, 1998; 339(21): 1493 - 1499. [Abstract] [Full Text] [PDF]

				S W SCHALM and S W SCHALM Adding ribavirin to interferon alpha -2b for chronic hepatitis C infection increased virological response and nausea • Commentary Gut, November 1, 1998; 43(5): 602 - 602. [Full Text] [PDF]

				M BERENGUER and T L WRIGHT Is the hepatocyte a Trojan horse for hepatitis C virus? Gut, April 1, 1998; 42(4): 456 - 458. [Full Text]

				INTERFERON-ALPHA FOR HEPATITIS C: IS IT WORTH IT? Journal Watch (General), December 12, 1997; 1997(1212): 1 - 1. [Full Text]