Dynamic decision analysis to determine optimal treatment duration in chronic hepatitis C

Abstract

Current guidelines for stopping treatment of chronic hepatitis C are based on hepatitis C ribonucleic acid measurements at 12 and 24 weeks. To explore an alternative approach for making individualized recommendations about treatment duration, based on simple alanine aminotransferase tests and on cost-per-cure. We analysed individual patient data from 13 randomized, controlled trials with interferon alone or combined with ribavirin. Using multiple logistic regression, we built a model that estimated the probability of sustained virological response for treatment durations of 24 and 48 weeks. Decisions to prolong treatment were based on an increase in probability of sustained virological response. If the increase was 10%, the cost-per-cure became decisive with a limit of 50,000. Noncirrhotics with genotype 2 or 3 did not benefit when treatment was continued beyond 24 weeks. Sustained virological response rates in cirrhotic patients increased by 14-47% if treatment was continued up to 48 weeks. In noncirrhotic genotype 1 or 4 patients who had elevated alanine aminotransferase levels at week 4, the probability of sustained virological response increased by <10% if treatment was continued up to 48 weeks; the cost-per-cure for these patients would exceed 50,000. The dynamics of alanine aminotransferase levels and cost-per-cure provides a useful alternative to determine the duration of therapy in chronic hepatitis C.