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Estimates of the Cost-Effectiveness of a Single Course of Interferon-α2b in Patients with Histologically Mild Chronic Hepatitis C

William G. Bennett, MD; Yuji Inoue, MD; J. Robert Beck, MD; John B. Wong, MD; Stephen G. Pauker, MD; and Gary L. Davis, MD
[+] Article, Author, and Disclosure Information

For author affiliations and current author addresses, see end of text. From the University of Florida College of Medicine, Gainesville, Florida; Baylor College of Medicine, Houston, Texas; Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan; and New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts. Acknowledgments: The authors acknowledge the contributions of their panel of expert hepatologists (Norman Gitlin, MD, Emory University, Atlanta, Georgia; Karen L. Lindsay, MD, University of Southern California, Los Angeles, California; Dr. Patrick Marcellin and Dr. Castelnau, Hopital Beaujon, Clichy, France; Leonard B. Seeff, MD, Veterans Administration Medical Center, Washington, D.C.; and Eugene R. Schiff, MD, University of Miami, Miami, Florida); the hepatopathologist who reviewed the liver slides for the pooled analysis (Dr. Michele Chevallier, Lyon, France); the principal investigators who represented all of the investigators who allowed us access to their study databases (Drs. Mario Rizzetto and Giorgio Saracco, Torino, Italy; Dr. Thierry Poynard, Paris, France; Dr. J.M. Metreau, Cretiel, France; Karen Lindsay, MD, University of Southern California, Los Angeles, California; and Gary L. Davis, MD, University of Florida, Gainesville, Florida); Haku Ishida, MD, Baylor College of Medicine, Houston, Texas, for statistical assistance; Janice Albrecht, PhD, Schering-Plough Research Institute, Kenilworth, New Jersey, for facilitating access to study databases and histologic material; and Bill Treolar, Clinical Resource Management, Shands Hospital at the University of Florida, Miami, Florida, for assistance with cost data. Grant Support: In part by Schering-Plough Corp. Requests for Reprints: Gary L. Davis, MD, PO Box 100214, University of Florida, Gainesville, FL 32610-0214. Current Author Addresses: Dr. Bennett: Internal Medicine Associates, 104 Doctors Park, Starkville, MS 39759.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;127(10):855-865. doi:10.7326/0003-4819-127-10-199711150-00001
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Background: Chronic hepatitis C is a major cause of illness and death in the United States. Interferon-α2b can induce clinical, biochemical, and virologic remission in some patients with chronic hepatitis C, but the long-term cost-effectiveness of this treatment, particularly in patients with histologically mild disease, is unknown.

Objective: To estimate the cost-effectiveness of interferon-α2b in mild chronic hepatitis C.

Design: Meta-analysis of five prospective trials and cost-effectiveness analysis. Projection of the clinical and economic outcomes expected from loss of hepatitis C virus was done by using a Markov simulation. The potential effect of uncertainty in the model assumptions was tested by using sensitivity analyses.

Data Sources: Search of the MEDLINE database, opinions of expert panels, hospital cost data, and adjusted physician charges.

Patients: Hypothetical cohorts with histologically mild chronic hepatitis C.

Intervention: The model assumed a single 6-month course of recombinant interferon-α2b.

Measurements: Life expectancy, quality-adjusted life expectancy, costs, and marginal cost-effectiveness ratios from a managed care perspective.

Results: In 27% of patients with mild chronic hepatitis C treated with interferon-α2b for 6 months, serum alanine aminotransferase levels permanently returned to normal and viral status remained negative. The model estimated that interferon-α2b treatment in this population should increase life expectancy by 3.1 years if given at 20 years of age, by 1.5 years at 35 years of age, and by 22 days at 70 years of age; discounted marginal cost-effectiveness ratios are $500, $1900, and $62 000 per year of life gained, respectively. Varying the long-term response rates and progression rates for mild and moderate chronic hepatitis to near zero in sensitivity analyses substantially affected the results: Ratios ranged from $31 000 for a 20-year-old patient to $640 000 for a 70-year-old patient.

Conclusions: On the basis of estimations in this mathematical model of the natural history of chronic hepatitis C, treating mild chronic hepatitis with interferon-α2b should prolong life expectancy at a reasonable marginal cost per year of life gained, particularly in younger patients.


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Figure 1.
Schematic of the Markov model with health states and annual probabilities (expressed as percentages) of disease progression.

The annual probability for liver transplantation from any liver failure state is 3.1%. The two health states for both variceal bleeding and hepatic encephalopathy refer to the rates of progression for the first and subsequent years. HCC = hepatocellular carcinoma; HCV = hepatitis C virus.

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Figure 2.
The effect of discounting on the marginal cost-effectiveness ratio.arrow

The y-axis values that exceed zero represent an excess cost of interferon-α2b; values less than zero represent a net cost savings from interferon-α2b. The x-axis represents the probability of a sustained viral-negative response to treatment with the 27% base-case value for patients with histologically mild chronic hepatitis C ( ).

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Figure 3.
The effect of age at the time of interferon-α2b treatment for histologically mild chronic hepatitis C on the estimated gain in life expectancy.
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Figure 4.
The effect of age at the time of interferon-α2b treatment for histologically mild chronic hepatitis C on the discounted marginal cost-effectiveness ratio.
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