COST-EFFECTIVENESS OF COMBINED INTERFERON AND RIBAVIRIN VERSUS INTERFERON ALONE

Despite a remarkable recent expansion of knowledge of the consequences of chronic hepatitis C virus (HCV) infection and the short- and intermediate-term benefits of successful treatment, many uncertainties remain. These include gaps in information about the natural history of this liver disease when untreated, its effect on the health of affected individuals and the health care delivery system, the costs of the untreated disease, and the costs and long-term beneficial or potentially adverse consequences of treatment. It is now abundantly clear, however, that even in the absence of advanced disease, chronic hepatitis C reduces all measured domains of health-related quality of life as perceived by patients with this disease. 2 Furthermore, virologically successful treatment with interferon (IFN) improves health-related quality of life in these patients. It is now understood that it is not the HCV infection per se but rather the progression of chronic hepatitis C to cirrhosis and of cirrhosis to end-stage liver disease, with its life-threatening complications, or to hepatocellular carcinoma that are the major sources of morbidity in this disease. These sequelae are responsible for the high health care costs associated with chronic hepatitis C. As a consequence of progression to end-stage liver disease or hepatocellular carcinoma, a number of patients will die prematurely, and health care expenditures for these individuals will be high, despite their reduced life expectancy. Conversely, some patients will never progress to cirrhosis and its life-threatening complications. These individuals will use few health care resources. The burden of health care costs related to chronic hepatitis C are expected to increase over time, even in populations in which new infections are declining, unless progression to advanced disease can be interrupted by identifying infection early and initiating treatment programs before progression to advanced disease occurs. 4 Although histologic studies have suggested that rates of progression for HCV infection are continuous and linear, confirmation of true linearity has yet to be convincingly demonstrated, and some investigators have suggested that progression may be neither linear nor continuous. 3 Important factors influencing rates of progression are being identified. They include both host and viral factors, although host factors appear to be the key elements in disease progression. Effective methods to identify individual patients who are at risk for progression, however, remain to be established. The ability to identify these patients is important, because without such identification, it is necessary to treat virtually all patients to reduce the consequences of progression in that unknown proportion of patients who are destined to progress but cannot be identified prospectively. This strategy is further confounded by the inadequacy of all current treatment strategies for chronic hepatitis C. For most previously untreated patients, an initial course of treatment with IFN monotherapy or even with combination therapy (IFN plus ribavirin) is far from perfect. Sustained virologic responses are seen in only a minority of treated patients infected with HCV genotype 1, the predominant genotype in the United States and Europe. 13,15 Although this unhappy phenomenon is likely to remain unchanged for some time, it should also be recognized that in certain small subgroups, such as patients infected with HCV genotypes 2 or 3, in whom viral loads are low and liver histology is mild, response rates may exceed 50% to 75%. The low sustained virologic response rates reported for IFN monotherapy, coupled with awareness that progression is not invariable and that the costs of both pretreatment evaluation and treatment are high, have suggested the need for studies of the cost effectiveness of treatment. 12 Cost-effectiveness analysis measures the net cost of providing the service being studied and measures the outcomes obtained from the service. It calculates the cost for the effect of a service as a ratio: the cost per case identified or cost per life-year gained. Although improved response rates have been reported in patients treated with the combination of IFN and ribavirin, the cost of this treatment is higher than the cost of IFN monotherapy. 13,15 Hence, it is not surprising that the cost effectiveness of combination therapy compared with that for IFN alone has been an area of recent investigation.