Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B

Abstract

Purpose The 2 reported trials investigated the effectiveness of treatment with peginterferon alfa-2a in Asian patients with chronic hepatitis B (CHB). Methods Patients with HBeAg-positive (n = 708) or HBeAg-negative (n = 332) CHB were enrolled in 2 randomized, double blind, placebo-controlled studies.Patients received peginterferon alfa-2a 180 lg once weekly, peginterferon plus lamivudine 100 mg per day, or lamivudine alone for 48 weeks. Patients were followed up at 6 and 12 months posttreatment. Results Peginterferon alfa-2a provided significantly higher rates of HBeAg seroconversion (31%) in HBeAgpositive patients than did lamivudine (19%, P = 0.005) 6 months posttreatment, irrespective of genotype. Of these, 83% achieving seroconversion during treatment or early posttreatment sustained their response at 12 months posttreatment. In patients who seroconverted, 69% maintained HBV DNA suppression at \10,000 copies/ml and alanine aminotrasferase (ALT) normalization. In HBeAg-negative patients, peginterferon produced a significantly higher combined response of HBV DNA at \20,000 copies/ml and ALT normalization (45%) than lamivudine (31%, P = 0.032), irrespective of genotype. Almost 80% of these patients sustained their response at 12 months posttreatment. Conclusions In conclusion, a finite course of peginterferon alfa-2a provides significant and sustained treatment benefit in Asian CHB patients, who have traditionally been regarded as difficult to treat.

Reviews for APASL guidelines: immunomodulator therapy of chronic hepatitis B

“…In that phase III trial, 61% of the patients were Asian. The combined response, defined as ALT normalization and HBV DNA \20,000 copies/ml at 6 months after the end of 48 weeks Peg IFN-a-2a therapy, was 45% in Asian patients, which was similar to the 36% in overall patients [43]. Of the Asian patients with a normal ALT at 6 months post-treatment with Peg IFN-a-2a (n = 58) who participated in the long-term follow-up, 78% maintained a normal ALT at 12 months post-treatment [43].…”

“…In a subsequent phase III trial involving 814 patients ([85% Asian), a 48-week course of Peg IFN-a-2a monotherapy 180 lg once weekly achieved ALT normalization in 41%, HBeAg seroconversion in 32%, HBV DNA level \10 5 copies/ml in 32%, HBV DNA \400 copies/ml in 14%, and HBsAg seroconversion in 3% of the patients assessed 24 weeks after treatment was stopped [42]. Recent analyses of only Asian patients in that phase III trial found a similar HBeAg seroconversion rate of 31% [43]. In a study of Peg IFN-a-2b involving mainly Caucasian patients (79%), a 52-week course (100 lg once weekly for 32 weeks followed by 50 lg weekly for 20 weeks) gave a 26-week sustained HBeAg seroconversion in 29% of patients and HBsAg clearance in 7% of patients [44].…”

“…The long-term follow-up post-Peg IFN-a-2a therapy showed delayed HBeAg seroconversion in 14% of the initial non-responders and durability of HBeAg seroconversion in 86% of initial responders at 1 year after the end of treatment [45]. Among Asian patients who achieved a sustained HBeAg seroconversion at 12 months post-treatment, 69% had HBV DNA levels \10,000 copies/ml and 38% had HBV DNA levels \400 copies/ ml [43].…”

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

“…PegIFN-a therapy results in HBeAg seroconversion rates of up to 32% and 48%, respectively, when assessed at weeks 24 and 48 post-treatment [43][44][45][46] and sustained after cessation of therapy in the majority (80-90%) of HBeAgpositive patients [47]. Baseline HBV and ALT levels are predictive factors for HBeAg seroconversion [47].…”

“…Baseline HBV and ALT levels are predictive factors for HBeAg seroconversion [47]. On treatment, HBeAg level of \10 Paul Ehrlich Institute Unit/ ml at week 24 and HBsAg level of \1500 IU/ml at week 12 of PegIFN therapy are also reported to favor HBeAg seroconversion [48].…”