Chronic hepatitis C: management of treatment failures

Forty percent to 50% of patients undergoing initial treatment of chronic hepatitis C with peginterferon plus ribavirin fail to achieve a sustained virologic response (SVR), thus prompting consideration of retreatment with alternative regimens. Patients may fail to respond to initial therapy secondary to an inadequate therapeutic regimen, host factors such as African American race, disease characteristics such as cirrhosis, or viral factors including genotype 1 and a high viral load. The decision to re-treat should be based on the presence of advanced fibrosis and the presence of clinical and virologic factors that predict the possibility of a successful outcome with further therapy. Retreatment of patients who were prior nonresponders to interferon monotherapy with interferon plus ribavirin results in overall SVR rates of 13%-15%, which can be increased to 16%-28% with the use of peginterferon plus ribavirin. Retreatment of patients who were prior nonresponders to interferon plus ribavirin with peginterferon plus ribavirin achieves overall SVR rates of 6%-15%; SVR rates are higher with favorable clinical or virologic factors. Prior relapsers to interferon plus ribavirin achieve SVR rates of 32%-50% after retreatment with peginterferon plus ribavirin. There is a limited experience with retreatment of patients who failed peginterferon plus ribavirin, but the use of interferon alfacon-1 plus ribavirin and higher doses of peginterferon and/or a longer duration of peginterferon plus ribavirin therapy are under study. Because therapy has improved in recent years, there are more patients who have been treated and failed initial therapy, highlighting the need for the development of more efficacious antiviral agents for the treatment of chronic hepatitis C.