M1895 Hepatitis B Patients Who are Lamivudine-Resistant, Adefovir Poor-Responders May Be Selected for Entecavir Monotherapy Based on Their Pre-Treatment Resistance Substitutions - A Four-Year Cohort Study

Abstract

Background: Entecavir is one of the treatment options for lamivudine-resistant hepatitis B patients though there is increased entecavir-resistance rate. The response of lamivudineresistant, adefovir poor-responders is unclear. Methods: We performed a four-year cohort study on the efficacy of entecavir 1mg/day on lamivudine-resistant patients. Enrolment criteria include: documented lamivudine resistannce mutations, HBV DNA ≥ 2x10(4)IU/ ml, ALT <1.3X upper limit of normal, and Child-Pugh score <7. Clinical outcomes, liver biochemistries, and HBVDNAweremonitored regularly every 16 weeks. Factors contributing to entecavir treatment failure were examined. Result: Fourteen Chinese patients who were lamivudine-resistant were recruited, twelve of whomwere poor-responders to adefovir rescue. Follow-up was complete at mean of 49 months. Mean HBV DNA fell from 1.03x10(7)IU/ml (baseline) to 1.35x10(2)IU/ml. The presence of rtM204V mutation (n=5) at baseline was found to be the major risk factor for entecavir failure. Compared with rtM204I (n=7) and rtA181V (n=2), rtM204V patients have high risk of virologic breakthrough requiring addon adefovir (4/5 patients), slower virologic responses, failure to reach undetectable HBV DNA levels (3/5 patients), high risk of entecavir-resistance (3/5 patients) and death (2/5 patients). All the other patients had undetectable HBV DNA by 18th month. Conclusion: Lamivudine-resistant, adefovir poor-responders can be selected for entecavir monotherapy, based on their pre-existing resistance substitutions (rtM204I and rtA181V). Those with rtM204V mutation had high risk of entecavir resistance and viral breakthrough, and could benefit from combination therapy from the start.