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Sustained Virologic Response and Clinical Outcomes in Patients with Chronic Hepatitis C and Advanced Fibrosis
- Bart J. Veldt, MD;
- E. Jenny Heathcote, MD;
- Heiner Wedemeyer, MD;
- Juerg Reichen, MD;
- W. Peter Hofmann, MD;
- Stefan Zeuzem, MD;
- Michael P. Manns, MD;
- Bettina E. Hansen, MSc;
- Solko W. Schalm, MD, PhD; and
- Harry L.A. Janssen, MD, PhD
- From Erasmus MC University Medical Center, Rotterdam, the Netherlands; Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Medizinische Hochschule Hannover, Hannover, Germany; Institute of Clinical Pharmacology, University of Bern, Bern, Switzerland; and Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Abstract
Background: Clinical outcomes of chronic hepatitis C infection in patients with advanced fibrosis include liver failure, hepatocellular carcinoma, and death.
Objective: To investigate whether sustained virologic response to treatment for hepatitis C is associated with improved clinical outcomes.
Design: Retrospective cohort study.
Setting: 5 hepatology units of tertiary care centers in Europe and Canada caring for patients with chronic hepatitis C treated between 1990 and 2003.
Patients: Consecutively treated patients with chronic hepatitis C who had biopsy-proven advanced fibrosis or cirrhosis (Ishak score, 4 to 6).
Measurements: Sustained virologic response, defined as absence of detectable hepatitis C virus RNA at 24 weeks after the end of treatment, and clinical outcomes, defined as death (liver-related or non–liver-related), liver failure, and hepatocellular carcinoma.
Results: Of 479 patients, 29.6% had sustained virologic response and 70.3% did not. Median follow-up was 2.1 years (interquartile range, 0.8 to 4.9 years). Four patients with and 83 without sustained virologic response had at least 1 outcome event. Sustained virologic response was associated with a statistically significant reduction in the hazard of events (adjusted hazard ratio, 0.21 [95% CI, 0.07 to 0.58]; P = 0.003). The effect was largely attributable to a reduction in liver failure, which developed in no patients with and 42 patients without sustained virologic response (5-year occurrence, 0% vs. 13.3% [CI, 8.4% to 18.2%]; unadjusted hazard ratio, 0.03 [CI, 0.00 to 0.91]).
Limitations: Because few events occurred in the sustained virologic response group, the study had limited ability to detect differences between groups in individual outcomes. In addition, the study was retrospective; selection and survival biases may therefore influence estimates of effect.
Conclusion: Sustained virologic response to treatment is associated with improved clinical outcomes, mainly prevention of liver failure, in patients with chronic hepatitis C and advanced fibrosis.
Article and Author Information
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Potential Financial Conflicts of Interest: Consultancies: E.J. Heathcote (Hoffmann-La Roche, Schering-Canada), S. Zeuzem (Schering-Plough, Roche, Human Genome Sciences, Novartis), H. Wedemeyer (Roche, Schering-Plough). Honoraria: E.J. Heathcote (Schering-Plough, Hoffmann-La Roche), S. Zeuzem (Schering-Plough, Roche, Human Genome Sciences, Novartis), H. Wedemeyer (Roche, Schering-Plough), H.L.A. Janssen (Schering-Plough, Roche). Grants received: B.J. Veldt (Netherlands Organisation for Health Research and Development), E.J. Heathcote (Hoffmann-La Roche, Schering-Plough), S. Zeuzem (Roche, Novartis), H.L.A. Janssen (Schering-Plough, Roche), H. Wedemeyer (Roche, Schering-Plough).
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Reproducible Research Statement:Study protocol, statistical code, and data set: Available to individuals by written request.
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Requests for Single Reprints: Harry L.A. Janssen, MD, PhD, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Room Ca 326a, PO Box 2040, 3000 CA Rotterdam, the Netherlands; e-mail, mailto:h.janssen{at}erasmusmc.nl.
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Current Author Addresses: Drs. Veldt, Hansen, Schalm, and Janssen: Department of Gastroenterology & Hepatology and Epidemiology & Biostatistics, Erasmus MC University Medical Center, Room Ca 326a, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
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Dr. Heathcote: Toronto Western Hospital, University Health Network, 399 Bathurst Street, 6B Fell, Room 154, Toronto, Ontario M5T 2S8, Canada.
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Drs. Wedemeyer and Manns: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
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Dr. Reichen: Institute of Clinical Pharmacology, University of Bern, Institute of Clinical Pharmacology, Murtenstrasse 35, 3010 Bern, Switzerland.
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Drs. Hofmann and Zeuzem: Internal Medicine I, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
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Author Contributions: Conception and design: B.J. Veldt, H. Wedemeyer, S.W. Schalm.
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Analysis and interpretation of the data: B.J. Veldt, H. Wedemeyer, S. Zeuzem, B.E. Hansen, H.L.A. Janssen.
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Drafting of the article: B.J. Veldt, H. Wedemeyer, S. Zeuzem, B.E. Hansen, H.L.A. Janssen.
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Critical revision of the article for important intellectual content: B.J. Veldt, E.J. Heathcote, H. Wedemeyer, J. Reichen, W.P. Hofmann, S. Zeuzem, M.P. Manns, B.E. Hansen, S.W. Schalm, H.L.A. Janssen.
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Final approval of the article: B.J. Veldt, H. Wedemeyer, J. Reichen, W.P. Hofmann, S. Zeuzem, M.P. Manns, B.E. Hansen, S.W. Schalm, H.L.A. Janssen.
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Provision of study materials or patients: B.J. Veldt, E.J. Heathcote, H. Wedemeyer, W.P. Hofmann, S. Zeuzem, M.P. Manns, H.L.A. Janssen.
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Statistical expertise: B.J. Veldt, B.E. Hansen, H.L.A. Janssen.
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Obtaining of funding: B.J. Veldt, S.W. Schalm, H.L.A. Janssen.
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Administrative, technical, or logistic support: H. Wedemeyer, W.P. Hofmann, S. Zeuzem, H.L.A. Janssen.
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Collection and assembly of data: B.J. Veldt, E.J. Heathcote, H. Wedemeyer, J. Reichen, W.P. Hofmann, S. Zeuzem, H.L.A. Janssen
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