Pharmacoeconomics of Combination Therapy for HCV

John Wong, MD
Division of Clinical Decision Making
New England Medical Center
Tufts University School of Medicine
Boston, Massachusetts

Key Learning Objectives

At the end of the session the participants will be able to:
· understand the impact of hepatitis C and treatment on life expectancy and quality of life
· place the cost of therapy in the context of the lifetime cost of hepatitis C
· compare the cost-effectiveness of hepatitis C therapy to other well accepted medical interventions


Chronic hepatitis C affects 170 million people worldwide and more than 2.7 million in the US where it is the leading cause of death from chronic liver disease and accounts for 20% to 30% of all liver transplantation. It had led to a rising incidence of hepatocellular carcinoma in Japan and the United States. On an individual level, it results in impaired quality of life and indirect costs involving decreased productivity and lost days from work. The Centers for Disease Control and Prevention conservatively estimates US expenditures in excess of $600 million annually.

Sir William Osler once wrote that “Medicine is a science of uncertainty and an art of probability.” This saying certainly holds true for the treatment of hepatitis C. Some opponents to treatment suggest that hepatitis C is only slowly progressive, that treatment is only effective in a proportion of treated patients, that treatment is relatively expensive and that treatment has potential side-effects. Based on the prospective studies of transfusion associated non-A non-B hepatitis1 and extrapolating findings to 20 years following acute disease, 14% to 45% of patients should develop cirrhosis. Moreover, aside from excessive alcohol intake and male gender as risk factors, it is not possible to determine which patients will develop cirrhosis.2 Although not all patients develop cirrhosis, the implications of developing cirrhosis on length of life are substantial. Compared to normal individuals from the general population, 40 to 60 year olds with compensated cirrhosis would have their life expectancy shortened by 7 to 19 years.3

Combination therapy for 48 weeks (combining the US and international studies, n=1744) has an overall sustained viral negative response rate of 41% compared to 33% with 24 weeks of combination therapy and 16% with 48 weeks of interferon.4-5 Sustained response rates for 48 weeks of combination therapy reach as high as 67% in subgroups with favorable characteristics but exceed 20% even for traditionally difficult to treat subgroups (cirrhosis by liver biopsy or genotype 1). One approach to trying to select out those patients likely to progress to cirrhosis would be to perform repeated liver biopsies, but sustained response rates appear to decline with worsening Metavir fibrosis score and with advancing age, suggesting that delaying therapy may decrease the chance for a response.6 When compared to other common medical interventions, the projected life expectancy gains from 48 weeks of combination therapy for hepatitis C compare favorably. Based on stopping treatment for 24 week viral non-responders and on clinical trial data (actual drug usage with discontinuation or dose reduction for adverse events and estimates of health care resource utilization including office visits, laboratory tests and contraception), 48 weeks of combination therapy should cost ~$12,000 (US) which is comparable to the cost of one year of therapy for HIV infection. For comparison, lifetime treatment of 40 to 60 year-old patients with compensated cirrhosis should cost $34,000 to $53,000 (US). Increasing data suggest the sustained viral negativity is associated with transaminase normalization, histologic improvement, decreased risk for developing cirrhosis or decompensation and perhaps improved survival. Thus, the prevention of future expensive complications of hepatitis C should offset the cost of combination therapy, making it a cost-effective therapy when compared to other routinely accepted medical interventions.7 For example, when compared to coronary artery bypass surgery, combination therapy costs less and provides a higher gain in life expectancy.


Cirrhosis is likely to occur in ~28% of hepatitis C patients after 20 years, substantially decreasing life expectancy and increasing healthcare costs. Combination therapy for 48 weeks results in sustained response rates as high as 67% and should prevent the development of cirrhosis. Because the response rate worsens with increasing Metavir fibrosis score and advancing age, delaying treatment may not be an optimal strategy. Although combination therapy may be considered expensive, the cost of treatment should be substantially offset by future savings through the prevention of liver related complications.


1. Seeff LB. Natural history of hepatitis C. Hepatology 1997;26:21S-28S.

2. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997;349:825-32.

3. Wong JB, Bennett WG, Koff RS, Pauker SG. Pretreatment evaluation of chronic hepatitis C: risks, benefits and costs. JAMA 1998;280:2088-93.

4. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, et al. Randomised trial of interferon a2b plus ribavirin for 48 weeks or for 24 weeks versus interferon a2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Inventional Therapy Group. Lancet 1998;352:1426-32.

5. McHutchison JG, Gordon SC, Schiff ER, Schiff ER, Schiffman ML, Lee WM, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998;339:1485-92.

6. Wong JB, Koff RS. The risks and benefits of biopsy managed care of histologically mild chronic hepatitis c versus initial combination therapy. Hepatology 1999;30(pt 2):480A.

7. Wong JB, McHutchison JG, Poynard T, Ling MH, Albrecht J, Pauker SG. Cost-effectiveness of initial ribavirin/interferon alfa-2b for chronic hepatitis C. Gastroenterology 1999;116:A649.

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