BACKGROUND: Pegylated interferon alpha2b (PEG-IFN-alpha(2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-alpha2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-alpha2b monotherapy. METHODS: Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-alpha2b with or without lamivudine. RESULTS: After 4 weeks of treatment, there was a median viral decline of 2.94 log10 copies/ml in those treated with PEG-IFN-alpha2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-alpha2b monotherapy group. Peak PEG-IFN-alpha2b levels were reached approximately one day after administration and subsequently declined exponentially, consistent with a viral load rebound near to baseline levels at the end of the dosing period in most patients receiving PEG-IFN-alpha2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-alpha2b administration, the mean maximal and mean antiviral effectiveness was 70% and 48% with a mean infected cell loss rate of 0.07 per day, while no significant biphasic decline was observed. CONCLUSIONS: PEG-IFN-alpha2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.
BACKGROUND: Pegylated interferon alpha2b (PEG-IFN-alpha(2b) is effective for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, although its mechanism of action remains unclear. HBeAg loss is achieved in 36% of patients after one year of PEG-IFN-alpha2b treatment and combination therapy with lamivudine is not superior to PEG-IFN-alpha2b monotherapy. METHODS: Early pharmacokinetics and viral kinetics were analysed in patients treated for 52 weeks with PEG-IFN-alpha2b with or without lamivudine. RESULTS: After 4 weeks of treatment, there was a median viral decline of 2.94 log10 copies/ml in those treated with PEG-IFN-alpha2b and lamivudine and only 0.45 log10 copies/ml in the PEG-IFN-alpha2b monotherapy group. Peak PEG-IFN-alpha2b levels were reached approximately one day after administration and subsequently declined exponentially, consistent with a viral load rebound near to baseline levels at the end of the dosing period in most patients receiving PEG-IFN-alpha2b monotherapy. Modelling of pharmacokinetics and viral kinetics data in this group revealed that viral load was minimal 3.6 days after PEG-IFN-alpha2b administration, the mean maximal and mean antiviral effectiveness was 70% and 48% with a mean infected cell loss rate of 0.07 per day, while no significant biphasic decline was observed. CONCLUSIONS:PEG-IFN-alpha2b induces a sustained response in a considerable number of patients despite limited direct antiviral activity during the first weeks of antiviral therapy.
Authors: T Jake Liang; Timothy M Block; Brian J McMahon; Marc G Ghany; Stephan Urban; Ju-Tao Guo; Stephen Locarnini; Fabien Zoulim; Kyong-Mi Chang; Anna S Lok Journal: Hepatology Date: 2015-10-27 Impact factor: 17.425