Issn Print: 0954-691X
Publication Date: 2001/12/01
Durability of HBeAg seroconversion in chronic hepatitis B patients after lamivudine, α-interferon or lamivudine–α-interferon combination therapy.
Excerpt
Interferon-alpha (IFN) induced HBeAg seroconversion is durable in 80–90% of chronic hepatitis B patients. Preliminary reports on the durability of HBeAg seroconversion following lamivudine therapy are contradictory. We investigated the durability of response following IFN, lamivudine or IFN–lamivudine combination therapy in a meta-analysis of individual patient data. 24 Centers included patients, treated in randomized controlled trials or cohort studies, with an HBeAg seroconversion (HBeAg negative, anti-HBe positive, HBV DNA negative) at the end of lamivudine therapy (> 24 weeks) within 12 months after start of IFN (> 16 weeks) or combination therapy. All patients were HBV DNA and HBeAg positive before start of therapy. Relapse was defined as reappearance of serum HBeAg or HBV DNA. Follow-up data till the last observation or the time of relapse were collected. The cumulative relapse rate for the total study population was calculated by Kaplan–Meier method, followed by Cox regression multivariate analysis. 130 Responders were included: 59 after lamivudine, 50 after IFN and 21 after combination therapy. Median (range) follow-up from HBeAg seroconversion till last observation or relapse was 82 weeks. Groups were comparable regarding sex, age and pre-treatment HBV DNA and ALT levels; the percentage Asians in the lamivudine group was significantly higher. The cumulative HBeAg relapse rate at 2 years was 55% for lamivudine 21%, 28% for IFN, and 25% for combination therapy (P = 0.01). At 2 years, HBV DNA relapsed in 60% of the lamivudine treated patients, 28% of the IFN, and 25% of the combination therapy group (P = 0.002). Multivariate analysis identified pre-treatment HBV DNA and therapy as 2 independent predictive factors of post-treatment relapse; race, baseline ALT, center and type of study were not correlated to the outcome. According to Cox regression analysis stratified for center and correcting for race and HBV DNA; the relative HBeAg relapse risk of lamivudine versus combination therapy and of IFN versus combination therapy were 7.7 and 1.2, respectively.
Conclusions Relapse after HBeAg seroconversion was independent of race and pre-treatment ALT. The durability of lamivudine induced HBeAg seroconversion is significantly lower compared to that after IFN or combination therapy.
AB van Nunen, BE Hansen, DJ Suh, HF Löhr, H Fontiane, L Chemello, BC Song, HLA Janssen, J Heathcote, RA de Man, SW Schalm. University Hospital Rotterdam; University of Ulsan, Seoul; Joh Gutenberg Universität, Mainz; University of Padova, Italy; Hopitaux de Paris, France; Toronto Western Hospital, Canada.
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