Predictive Factors for Delayed Virologic Response of Adefovir Add-on Therapy in Lamivudine-resistant Chronic Hepatitis B

ABSTRACT

OBJECTIVE: Lamivudine (LAM) is the first nucleoside analog approved for chronic hepatitis B (CHB) patients, but acquired mutation of the reverse transcriptase of the virus during long-term therapy is limiting its use. Adeforvir dipivoxil (ADV) add-on therapy with ongoing LAM use has been a standard therapy for LAM resistance. The aim of this study was to explore the predictive factors associated with delayed virologic response at 12 months in patients who could not achieved initial virologic response (IVR) of add-on therapy. METHODS: One hundred and ninety three LAM-resistant CHB patients who had been on ADV add-on therapy with LAM and were not achieved IVR at 6 months were enrolled. They were classified into delayed viral response (DVR) group and non-DVR group, according to delayed viral response (VR) at 12 months of add-on therapy. Clinical factors predicting delayed VR at 12 months of add-on therapy were evaluated. RESULTS: DVR rate was 20.7% (n=40) at 12 months after the add-on treatment. Female (adjusted odds ratio, 3.463; P=0.002), lower hepatitis B virus (HBV) DNA at baseline ( or =7.0 log copies/mL; adjusted odds ratio, 0.369; P=0.012), and negative HBeAg at baseline (adjusted odds ratio, 0.332; P=0.034) were significant independent factors predicting DVR after 12 months of treatment. CONCLUSION: In LAM-resistant CHB patients with ADV add-on therapy, although there was no IVR after 6 months treatment, we could consider maintenance of treatment if patient is female, lower HBV DNA state, or HBeAg negative state at the time of starting add-on therapy.