Hepatitis - Treatment of the Relapse Patient

Relapse is defined as the reappearance of serum HCV RNA in a patient who had previously undetectable levels at the end of antiviral therapy. Occurrence of relapse following IEN mono therapy is more common than following combination IFN and ribavirin therapy.

While re-treatment of IFN-mono therapy relapse patients with a repeat course of similar therapy is ineffective, treatment with higher doses may improve sustained response rates. A large, multi center trial evaluated the use of high-dose consensus IFN (IFNalfa con-1) in patients who had relapse following a 24-week course of standard dose IFN-alfa-2b or IFN-alfa con-1. Subjects were randomized to receive 15 mcg of IFN alfa con-1 for either 24 or 48 weeks. The sustained viral response was 28% at 24 weeks and 58% at 48 weeks. Re-treatment at this higher dose was not associated with more significant side effects than treatment with the standard IFN regimen. Factors predictive of a sustained virologic response in this trial included low initial viral load, HCV genotype 2 or 3, and the absence of cirrhosis.

A second large study evaluated the use of combination IFN and ribavirin therapy in IFN mono therapy relapse patients. Patients were treated for a total of 6 months and randomized to receive standard-dose IFN-alfa-2b with or without ribavirin. A sustained virologic response was seen in 49% of patients treated with combination therapy and in only 8% of those treated with IFN mono therapy. Genotype other than type 1 and low pretreatment HCV-RNA levels were positive predictive factors of a sustained response in this trial. Twelve percent of subjects treated with ribavirin required a dose reduction or interruption secondary to anemia, whereas only 3% of those receiving IEN mono therapy required dose reduction.

As previously indicated, patients who relapse following IFN mono therapy may be effectively re-treated with either higher-dose IFN mono therapy or with combination IFN and ribavirin. But the increasing problem facing physicians today is how to approach the patient who relapses following combination therapy. At present, there are no large published studies to help answer this question. Several studies are ongoing with either pegylated interferon (peginterferon) alfa-2a or peginterferon alfa-2b in patients who relapsed following treatment with combination therapy of IFN plus ribavirin.