Advances in the treatment of hepatitis C.

The health care burden caused by hepatitis C is projected to increase significantly in the next 20 years, on the basis of modeling estimates of cirrhosis, hepatic decompensation, and HCC likely to be seen in this population in the future. The number of cases of HCV-induced liver decompensation and mortality in the United States is projected to be approximately 4 times higher by the year 2018 than is currently seen, because of the aging of those presently infected. HCV also poses a significant quality-of-life decrement in the majority of individuals with chronic infection. Quality-of-life assessment in these patients has shown substantial reductions in both somatic and physical functioning compared with the general population, regardless of disease severity. The impact of chronic HCV on quality-of-life issues has been equated to that of non-insulin-dependent diabetes. Thus, HCV imparts a considerable toll on individual level of functioning and on overall health care resources. Hepatitis C evolves into a chronic infection in approximately 85% of individuals exposed to the virus, and progression to cirrhosis occurs in 20% to 30% of patients, with a disease duration up to 20 years. Hepatic decompensation will occur in approximately 20% and HCC in about 10% of those with HCV-related cirrhosis within 5 years of the determination of cirrhosis. End-stage liver disease caused by HCV is now the most common indication for liver transplantation in this country. Patients in whom liver decompensation develops should be considered for liver transplant evaluation, with referral to appropriate centers if these complications arise. Individuals with decompensated disease should not be treated with any of the current regimens available for HCV eradication, because these agents can accelerate hepatic dysfunction and will not mitigate the clinical outcome after the onset of decompensation. Available treatment options for HCV are rapidly changing, with INF as the standard and combination therapy with INF plus ribavirin rising to prominence as the optimal option. The need for abstinence from alcohol cannot be underestimated, given its documented synergistic effects on hepatotoxicity when combined with chronic HCV. Patients must be counseled in this regard and provided with the rationale for this recommendation. The benefits of therapy from a medical resource standpoint have recently been defined through analyses of cost-effectiveness. Bennett et al. used a mathematical model to estimate the cost-effectiveness of INF in the treatment of mild chronic HCV (no bridging fibrosis or cirrhosis). Therapy was found to be cost-saving for patients aged 20 to 35 years and was found to increase life expectancy by 3 and 1.5 years, respectively, at the spectrums of this age range. Kim et al. found the cost-effectiveness of a 12-month course of INF to compare favorably to other accepted medical interventions in the United States in patients younger than 60 years. Similar data for combination therapy has not yet been reported but would be expected to be comparable. Interferon monotherapy for 12 months is the current standard treatment recommendation for individuals with chronic HCV and elevated ALT levels. The explosive expansion of information now available to, and frequently quoted by, HCV patients seeking treatment will increasingly make this option less acceptable to a great many of this group. Combination therapy has emerged as the most efficacious option to date, both as initial treatment and for patients who relapse after standard INF. Unless data appear to the contrary, combination therapy should be considered first-line treatment in these groups. A suggested treatment algorithm for chronic HCV is outlined in Figure 2. Patients intolerant to ribavirin should be considered for continuation of INF to complete a 12-month course, dependent upon the assessment of HCV PCR status at week 12 of therapy. (ABSTRACT TRUNCATED)