Early prediction of response during high-dose interferon induction therapy in difficult-to-treat chronic hepatitis C patients

Abstract number: 1733_1380

Gelderblom H.C., Zaaijer H.L., Weegink C.J., Dijkgraaf M.G.W., Jansen P.L.M., Beld M.G.H.M., Reesink H.W.

Background and Aims: The aims of our study were to determine (i) if early viral kinetics could predict treatment outcome in ``difficult-to-treat'' hepatitis C patients during high dose interferon induction treatment, (ii) if fast-responders (≥ 3 log drop in HCV RNA at week 4) could stop treatment at week 24.

Methods: We treated 100 hepatitis C patients (46 previous non-responders/relapsers (any genotype), 54 treatment-naïve genotype 1 and 4) with triple antiviral therapy: Amantadine hydrochloride and ribavirin, combined with 6 weeks interferon alfa2b induction (week 1–2: 18 MU/day, week 3–4: 9 MU/day, week 5–6: 6 MU/day), thereafter combined with weekly peginterferon alfa-2b, for 24 or 48 weeks. Fast-responders (≥3 log drop in HCV RNA at week 4) were randomised to 24 or 48 weeks. Patients with <3 log drop in HCV RNA at week 4 (slow-responders) were treated for 48 weeks. Patients with HCV RNA detectable by PCR at week 24 stopped treatment.

Results: 36 patients achieved SVR: 19 fast-responders after 24 weeks of treatment, 9 fast-responders and 8 slow-responders after 48 weeks of treatment. 64 patients became non-SVR (27 non-response, 9 breakthrough, 15 relapse, 13 dropout). Predictive values of early viral kinetics were different for treatment naïve patients and previous non-responders/relapsers. In treatment-naïve patients, PPV for SVR was 100% if HCV RNA was <5 IU/mL at week 1 or 2; PPV for non-SVR was 100% if HCV RNA was ≥ 615 IU/mL at week 12, or ≥ 5 IU/mL at week 16. In previous non-responders/relapsers PPV for non-SVR was 100% if HCV RNA was ≥ 615 IU/mL at week 4, or ≥ 5 IU/mL at week 8. Relapse rates among fast-responders treated for 24 or 48 weeks were 27% and 20%, respectively (P=ns). SVR in fast-responders treated for 24 or 48 weeks was independent of baseline HCV RNA ≥ or <800,000 IU/mL.

Conclusion: With high dose interferon induction therapy: (i) early viral kinetics can predict SVR and NR in treatment naïve patients and previous non-responders/relapsers, (ii) SVR is independent of baseline HCV RNA.