Benefits of Treating Early
Histologic Stages of Chronic Hepatitis C
William G. Bennett, M.D., M.S.P.H. New England Medical Center, Boston, Mass. Journal: Liver Update, Vol. 10, No. 1, Winter 1996
Chronic hepatitis C is a slowly progressive disease with little effect on mortality over the initial 20 years. Interferon alfa-2b is the only therapy for chronic hepatitis C approved by the Food and Drug Administration. However, only a portion of eligible candidates for interferon (IFN) achieve a long-term viral negative response after a six month course. Although the probability of a long-term response is higher during the earlier stages of the disease, most of these patients will never progress to clinically significant liver disease. Because of the slowly progressive nature of the disease, poor pretreatment predictors of a long-term response, and the low probabiliby of a long-term viral-negative response, great interest has developed in the cost-effectiveness of administering interferon during the early histologic stages of the disease.
To estimate the benefits and costs of treating earlier stages of chronic hepatitis C, modeling methods were used to simulate the natural progression and costs of treating the various histologic stages of chronic hepatitis C with and without interferon treatment. Computer projections were made using a simulated patient cohort assuming: 1) a single six month course of IFN without retreatment; 2) sustained response (SR) defined as normal ALT for > 6 months after end of treatment; 3) SR would be permanent, i.e. retreatment unnecessary, if HCV-RNA remained negative; and 4) disease progression, based on published data. The likelyhood of SR occurring after IFN for different baseline histologies (Desment classification) was determined prospectively in 220 patients treated with IFN alfa-2b 3MU three times a week for six months. All biopsies were read by a single pathologist using the histologic activity index. SR occurred in 32.5% with mild chronic hepatitis (MCH), 29% with moderate chronic hepatitis (MoCH) without fibrosis, 10.6% with MoCH with fibrosis, and 8.6% with cirrhosis (CIR). Based on the literature, 86% would be anticipated to remain HCV-RNA negative.
Using lifetime projections, interferon increased life expectancy in all age groups. Life expectancy increase 0.1-8.1 years in patients with MCH and MoCH as compared to their untreated, age-matched counterparts. For comparison, screening 50 year olds for colorectal cancer should increase the average life expectancy by only one and a half months. It is important that this is the average gain for all treated patients, regardless of their response. If only those who achieve a long-term, viral-negative response are considered, a 20 year old with mild chronic hepatitis would gain 13 years. The discounted marginal cost per year of life gained for the treatment of mild chronic hepatitis ($215 at age 20) than for older patients ($44,319 at age 70). Cost-effectiveness was greater for the treatment of moderate chronic hepatitis (cost-saving at age 20, $2,946 at age 70).
There are two notable conclusions to this study: 1) a sustained response to IFN is dramatically higher in patients without fibrosis on liver biopsy and 2) a high SR to a single six month course of IFN in non-fibrotic patients increases life expectancy, may save medical costs, and is justified despite the slow progression of chronic hepatitis C.