Introduction Patients persistently infected with genotype 3 HCV are more likely to have a sustained viral response (SVR) to interferon and ribavirin therapy than patients infected with genotype 1. However many patients with advanced fibrosis infected with genotype 3 HCV relapse following therapy. The mechanisms underlying relapse are not known.

Aim To examine the speed of relapse and compare quasispecies prior to and immediately following relapse.

Method 30 chronically infected patients with advanced fibrosis (fibrosis score >F3/6) were treated for 24–48 weeks with Peg IFN α 2a and ribavirin. Plasma samples were taken pre-treatment, during treatment and weekly post treatment. The HCV quasispecies in the pre-treatment sample and the first HCV-RNA positive post-treatment samples of the relapsed patients were assessed.

Results All of the patients responded with loss of virus on treatment. 18 had a sustained viral response and 12 patients relapsed post-treatment. All of the patients that relapsed did so within 4–6 weeks of treatment cessation.

HCV-RNA was extracted from the pre- and post samples of relapsed patients. 10–15 clones from both samples were successfully prepared and sequenced over the E2 region, including the HVR1, 2 and 3 regions and the PKR-eIF2α region in five patients. Construction of phylogenetic trees showed that in two patients the quasispecies that emerged post-treatment were similar to those seen pre-treatment but in three patients a dramatic shift in populations occurred.

Conclusion Relapse post therapy is very rapid and two distinct patterns of relapse were seen. These data suggest that there may be different mechanisms of relapse following treatment withdrawal in patients with genotype 3 HCV.