Z Gastroenterol 2006; 44 - P174
DOI: 10.1055/s-2006-950771

48 weeks of adefovir mono therapy following 48 weeks of combination therapy with peginterferon alfa-2b and adefovir leads to additional biochemical and virological improvement

M Lütgehetmann 1, K Wursthorn 1, B Zöllner 2, P Buggisch 1, M Zankel 3, C Fischer 4, C Brosgart 5, J Petersen 2
  • 1Universitätsklinikum Hamburg-Eppendorf, I. Medizinische Klinik, Hamburg, Germany
  • 2Universitätsklinikum Hamburg-Eppendorf, Infektionsmedizin, Hamburg, Germany
  • 3Essex GmbH, München, Germany
  • 4Gilead Sciences, Martinsried, Germany
  • 5Gilead Sciences, Foster City, United States of America

Background and aim: Administration of 48 weeks of PEG-IFN alfa-2b and adefovir (ADV) combination therapy in chronically HBV infected patients resulted in a strong suppression of cccDNA, high rates of HBsAg seroconversion, and HBeAg seroconversion and loss, respectively (Wursthorn, EASL 2005). However, most HBV patients may need long-term antiviral therapy. The aim of the study is to determine virological and serological outcome including cccDNA in chronic Hepatitis B patients after 48 weeks of PEG-IFN alfa-2b and ADV therapy followed by 96 weeks of ADV mono therapy. Here we report on the interims analysis after 96 weeks of antiviral treatment.

Methods: 26 patients with chronic Hepatitis B were included in a single center open label pilot study. Patients received a 48 weeks course of 12kDa pegylated interferon alfa 2b 1.5µg/kg bw qw and ADV 10mg qd followed by 48 weeks of ADV 10mg qd. 25/26 patients were analysed at the time of abstract submission. Serum HBsAg was quantified as described previously (Werle-Lapostolle, Gastroenterology 2004).

Results: As reported previously (Wursthorn, EASL 2005) combination therapy led to reduction of intrahepatocellular cccDNA by -2.2 log accompanied by high numbers of HBsAg seroconversion (4/25 patients) and HBeAg seroconversion (5/13 HBeAg-positive patients). After another 48 weeks of ADV mono therapy (week 49–96) numbers of HBsAg and HBeAg seroconverters and levels of HBV-DNA suppression (median -4.9 log) remained stable. HBV-DNA in serum became undetectable in 14/25 patients (56%, LLoD 100 copies/ml, compared to 13/25 (52%) at week 48). HBsAg quantification revealed a continuous reduction from 33,4µg/ml at baseline over 7,6µg/ml at week 48 to 6,2µg/ml at week 96. This was paralleled by further reduction in serum ALT levels leading to normalisation in 24/25 (96%) patients after 96 weeks compared to 12/25 (48%) patients at week 48.

Conclusions: 48 weeks of ADV mono therapy following 48 weeks of combination therapy with PEG-IFN alfa-2b and ADV leads to substantial further biochemical and virological improvement. All patients are continuing in study on additional 48 weeks of ADV mono therapy followed by a third liver biopsy.