Nonresponders to Previous Chronic Hepatitis C Treatment

The main strategy governing treatment of chronic hepatitis C is the prevention of future liver complications. There is good evidence that curing hepatitis C infection prevents progression of liver disease and allows histologic regression to occur. Therefore, the primary goal of medical treatment is to cure the viral infection. Combination therapy with peginterferon alfa and ribavirin is the current standard of care; there are no other medical therapies currently available. Those who failed to respond to an earlier version of antiviral therapy should strongly consider treatment with peginterferon/ribavirin if possible. Nearly half of patients who start peginterferon/ribavirin are unable to achieve a sustained disappearance of infection. If there were problems related to dosing or adherence the first time around, it is reasonable to consider re-treating with more aggressive support. Nonresponders to the current therapy who have early-stage liver disease can afford to wait until new antiviral agents come along in the next 5 to 10 years. However, physicians should encourage nonresponding patients with advanced fibrosis to consider experimental alternatives in the meantime, provided there is a logical rationale for the treatment proposed. Some re-treatment strategies still aim to cure the hepatitis C virus infection whereas others focus on limiting liver damage. The best candidates for the first strategy are patients who had temporary clearance of the virus during previous treatment and those with hepatitis C virus genotype 2 or 3 infection. Logical candidates for the second strategy are those who already have advanced fibrosis. It is preferable to pursue further attempts at treatment within the framework of a controlled trial. Studies with strong rationales include those investigating high-dose peginterferon/ribavirin, long-term peginterferon suppression, potential immune modulators, and potential inhibitors of liver fibrosis. The rationales are weaker for re-treatment with a second brand of peginterferon/ribavirin, daily standard interferon plus ribavirin, and ribavirin monotherapy.