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20 November 2007

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

Authors: 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, PhDAuthor, Article, & Disclosure Information
Publication: Annals of Internal Medicine
Volume 147, Number 10
https://doi.org/10.7326/0003-4819-147-10-200711200-00003
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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.

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 147 • Number 10 • 20 November 2007
Pages: 677 - 684

History

Published online: 20 November 2007
Published in issue: 20 November 2007

Keywords

  1. Albumins
  2. Allergy and immunology
  3. Bile
  4. Biliary system
  5. Biochemistry
  6. Blood cells
  7. Body fluids
  8. Cell biology
  9. Cells
  10. Gastroenterology and hepatology
  11. Hepatitis C
  12. Hospital medicine
  13. Immune system proteins
  14. Immunology
  15. Infectious hepatitis
  16. Liver diseases
  17. Pathology and laboratory medicine
  18. Proteins
  19. Research and reporting methods
  20. Rheumatic conditions
  21. Rheumatology
  22. Statistical methods
  23. Survival analysis

Copyright

© 2007 American College of Physicians.

Authors

Affiliations

Bart J. Veldt, MD
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.
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E. Jenny Heathcote, MD
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.
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Heiner Wedemeyer, MD
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.
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Juerg Reichen, MD
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.
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W. Peter Hofmann, MD
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.
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Stefan Zeuzem, MD
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.
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Michael P. Manns, MD
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.
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Bettina E. Hansen, MSc
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.
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Solko W. Schalm, 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.
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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.
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Disclosures: 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.
Corresponding Author: 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:[email protected].
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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Bart J. Veldt, E. Jenny Heathcote, Heiner Wedemeyer, et al. Sustained Virologic Response and Clinical Outcomes in Patients with Chronic Hepatitis C and Advanced Fibrosis. Ann Intern Med.2007;147:677-684. [Epub 20 November 2007]. doi:10.7326/0003-4819-147-10-200711200-00003

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