A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia

doi:10.1016/S0016-5085(99)70402-6

Gastroenterology

Volume 117, Issue 5, November 1999, Pages 1164-1172

https://doi.org/10.1016/S0016-5085(99)70402-6 Get rights and content

Abstract

Background & Aims: At least half of patients with chronic hepatitis C virus (HCV) fail to respond to interferon or interferon/ribavirin therapy. Histological improvement is observed in some nonresponders. We conducted a randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in this subset of nonresponders. Methods: Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months. Results: Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0 ± 15.6), log HCV-RNA titer (5.85 ± 0.15 copies/mL), histology score (9.5 ± 0.2), and percentage with cirrhosis (25%). After 6 months of treatment, significant reductions (P < 0.05) in serum ALT level (62.6 ± 9.6), log HCV-RNA titer (4.79 ± 0.13 copies/mL), and hepatic inflammation (4.0 ± 0.2) were observed. These improvements were maintained in the patients randomized to continue interferon. Stopping treatment was associated with an increase in serum ALT, log HCV-RNA, and hepatic inflammation back to baseline. After 30 months of treatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients had histological improvement (P < 0.03). Discontinuation of interferon was associated with an increase in mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30% of patients (P < 0.01). Conclusions: These data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic.

GASTROENTEROLOGY 1999;117:1164-1172

Section snippets

Patient population

Entry criteria included the following: (1) well-documented chronic hepatitis C, defined by a history of increased serum alanine aminotransferase (ALT) levels above normal limits for at least 6 months, presence of anti-HCV in serum by second-generation enzyme-linked immunosorbent assay, HCV RNA in serum by quantitative polymerase chain reaction assay, and histological evidence of chronic hepatitis; (2) prior treatment with interferon alfa-2b (Intron-A; Schering-Plough, Kenilworth, NJ), 5 million

Characteristics of study population

A total of 167 nonresponders to interferon therapy were evaluated for inclusion to the study. Of the 65 patients who met entry criteria, 53 agreed to participate. No significant differences in mean age, sex, race, or mean values for serum ALT level, HCV-RNA titer, or Knodell score existed between patients enrolled to the study and the 12 patients who chose not to participate (data not shown).

All 53 patients enrolled to the study were virological nonresponders and therefore remained HCV RNA

Discussion

The primary goal of therapy in a patient with chronic HCV is to achieve a sustained virological response, complete resolution of chronic hepatitis, and a return to normal liver histology. To achieve this goal depends on viral characteristics (genotype and titer) and the specific therapy used.1, 2, 3, 4, 11, 24 Recent studies have clearly shown that the combination of interferon plus ribavirin is superior to interferon alone at achieving this primary goal, regardless of HCV genotype and titer

Acknowledgements

The authors thank M. Lou Usry, R.N., and the nursing staff of the Clinical Research Center for assistance in patient care and Chis Gennings, Ph.D. (Department of Biostatistics, Medical College of Virginia Commonwealth University), for assistance with statistical analysis.

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Background and aims. The histologic hallmarks of chronic HCV include inflammation and fibrosis. The impact of interferon therapy on liver histology was evaluated.
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^☆: Address requests for reprints to: Mitchell L. Shiffman, M.D., Hepatology Section, Medical College of Virginia Commonwealth University, Box 980341, Richmond, Virginia 23298. e-mail: [email protected]; fax: (804) 828-4945.

^☆☆: Supported in part by National Institutes of Health Clinical Research Center Grant MO1-R00065 to the Medical College of Virginia Commonwealth University and a grant-in-aid from Schering-Oncology Biotech (Kenilworth, NJ).

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Liver, Pancreas, and Biliary TractA randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia☆,☆☆

Abstract

Section snippets

Patient population

Characteristics of study population

Discussion

Acknowledgements

Lancet

Lancet

Hepatology

Hepatology

Gastroenterology

Hepatology

Hepatology

Hepatology

Lancet

J Hepatol

Hepatology

Mol Diag

Hepatology

Hepatology

J Hepatol

J Hepatol

J Hepatol

Hum Pathol

Hepatology

Lancet

Lancet

J Hepatol

Interferon alfa-2b monotherapy versus interferon alfa 2b plus ribavirin as initial treatment for chronic hepatitis C: results of a US multi-center randomized controlled trial

N Engl J Med

Liver, Pancreas, and Biliary Tract
A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia☆,☆☆