Sustained Virologic Response and Clinical Outcomes in Patients with Chronic Hepatitis C and Advanced Fibrosis

20 November 2007 | Volume 147 Issue 10 | Pages 677-684

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.

Editors' Notes Context Most studies of hepatitis C treatment report effects on surrogate measures, such as liver enzymes and viral load. Contribution The authors compared clinical outcomes in patients with chronic hepatitis C and advanced fibrosis who did and did not have sustained virologic response to treatment. They found that sustained virologic response decreased patients' hazard of liver failure. Caution Sustained virologic response also seemed to be associated with a reduction in liver cancer and liver-related death, but not enough events occurred in the sustained virologic response group to detect differences between groups in these other outcomes. Implication Sustained virologic response to chronic hepatitis C treatment is associated with a reduction in clinical events, mainly liver failure. —The Editors

 

Author and Article Information

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.

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).

Reproducible Research Statement: Study protocol, statistical code, and data set: Available to individuals by written request.

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.

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.

Dr. Heathcote: Toronto Western Hospital, University Health Network, 399 Bathurst Street, 6B Fell, Room 154, Toronto, Ontario M5T 2S8, Canada.

Drs. Wedemeyer and Manns: Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.

Dr. Reichen: Institute of Clinical Pharmacology, University of Bern, Institute of Clinical Pharmacology, Murtenstrasse 35, 3010 Bern, Switzerland.

Drs. Hofmann and Zeuzem: Internal Medicine I, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.

Author Contributions: Conception and design: B.J. Veldt, H. Wedemeyer, S.W. Schalm.

Analysis and interpretation of the data: B.J. Veldt, H. Wedemeyer, S. Zeuzem, B.E. Hansen, H.L.A. Janssen.

Drafting of the article: B.J. Veldt, H. Wedemeyer, S. Zeuzem, B.E. Hansen, H.L.A. Janssen.

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.

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.

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.

Statistical expertise: B.J. Veldt, B.E. Hansen, H.L.A. Janssen.

Obtaining of funding: B.J. Veldt, S.W. Schalm, H.L.A. Janssen.

Administrative, technical, or logistic support: H. Wedemeyer, W.P. Hofmann, S. Zeuzem, H.L.A. Janssen.

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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