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PWE-143 Sequential Oral Anti-Viral Therapy Following Pegylated-Interferon-Alpha Failure Significantly Increases Hbsag Decline
  1. U S Gill1,
  2. L Payaniandy2,
  3. J Schulz2,
  4. D Payaniandy2,
  5. V Ross3,
  6. Y Kallis2,
  7. P Kooner2,
  8. R Marley2,
  9. G R Foster1,
  10. P T Kennedy1
  1. 1The Liver Unit, Blizard Institute, Barts and The London SMD, QMUL
  2. 2Hepatology
  3. 3Pharmacy, Barts Health NHS Trust, London, UK

Abstract

Introduction Tenofovir and Entecavir are potent oral antivirals (OAV’s) and leading agents in the treatment of Chronic Hepatitis B (CHB). Despite this, they have limited ability to reduce HBsAg, thus indefinite or life-long therapy is mandated as these drugs rarely achieve immunological control. Pegylated-Interferon-Alpha (PEG-IFNα) is associated with better rates of HBsAg decline, but only a minority of patients achieve sustained immune control. New strategies to reduce HBsAg and achieve immune control, including combination PEG-IFNα & OAV are under investigation at present. Here we report data on treatment response in a cohort receiving sequential OAV therapy following PEG-IFNα failure.

Methods 55 patients (male = 41), median age 31 (range 18–55) were treated with PEG-IFNα over the course of the study. 13 patients remain on therapy and 5 patients discontinued due to poor response or intolerance. 37 patients, HBeAg positive (n = 29), completed 48 weeks PEG-IFNα and were included in the analysis. 23/37 patients (HBeAg positive = 18), following treatment with PEG-IFNα were considered non-responders and treated with sequential OAV therapy. Treatment response in this cohort was compared with 60 patients, (male = 54), median age 45 (range 21–70) receiving OAV monotherapy over a 12-month period. Serum ALT, HBV DNA and HBsAg were quantified at baseline and longitudinally in both cohorts.

Results In the sequential therapy group, baseline median ALT was 60 IU/L (range 31–194) and median HBV DNA 5.15 logIU/ml compared with 43 IU/L and 3.43 logIU/ml respectively for the OAV monotherapy group. ALT normalisation and reduction in HBV DNA to undetectable levels was similar in both groups over follow-up (p- = n.s). Following 12-months of OAV monotherapy the decline in HBsAg in this group overall was 0.06 logIU/ml compared to baseline (p = n.s). In patients receiving sequential OAV therapy there was a significant decline in HBsAg over follow-up compared to baseline (0.65 log IU/ml, p = 0.0001). In addition 4/18 HBeAg positive patients seroconverted on sequential therapy and 1 patient cleared HBsAg.

Conclusion Sequential OAV therapy following treatment failure with PEG-IFNα is associated with greater reductions of HBsAg than PEG-IFNα alone or OAV monotherapy. This suggests PEG-IFNα may prime the immune response, even in the context of treatment failure, leading to better responses with sequential OAV therapy. Further studies are needed to confirm this finding and determine whether a similar priming effect is observed with shorter courses of PEG-IFNα in line with current PEG-IFNα stopping rules.

Disclosure of Interest None Declared.

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