Histologic outcomes in hepatitis C–infected patients with varying degrees of virologic response to interferon-based treatments

Paul J. Pockros 1,*,‡, Fayez M. Hamzeh 2, Paul Martin 3, Ellen Lentz 2, Xiaolei Zhou 4, Sugantha Govindarajan 5, Anna S. Lok 6

DOI: 10.1002/hep.23809
Copyright © 2010 American Association for the Study of Liver Diseases

Author Information
1 Scripps Clinic, La Jolla, CA
2 Genentech, Inc., South San Francisco, CA
3 Miller School of Medicine, University of Miami, Miami, FL
4 RTI Health Solutions, Research Triangle Park, NC
5 University of Southern California–Keck School of Medicine and Liver Research Laboratory, Downey, CA
6 University of Michigan Medical Center, Ann Arbor, MI

Email: Paul J. Pockros (Pockros.Paul@scrippshealth.org)

*Correspondence: Paul J. Pockros, Division of Gastroenterology/Hepatology, Scripps Clinic, 10666, North Torrey Pines Road, La Jolla, CA 92037

†Potential conflict of interest: Nothing to report.
‡fax: 858-554-8065

Publication History
Article first published online: 23 JUL 2010
Accepted manuscript online: 16 JUN 2010 12:00AM EST
Manuscript Accepted: 7 JUN 2010
Manuscript Received: 25 JAN 2010

Funded by
Roche, Nutley, NJ

Abstract

Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon-based therapies can experience treatment-related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1-6) with baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80% of patients received peginterferon alfa-2a monotherapy or peginterferon alfa-2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon-based therapies, histologic benefits may be observed even in the absence of an SVR. (HEPATOLOGY 2010;)

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