$96 Journal of Clinical Virology 2006, Vol 36 (suppl 2) Abstracts, 12th ISHVLD (b) partial biochemical response (ALT values mostly normal or occasionally elevated, but never >50 U/I). Results: In total, 116/177 (66%) of pts in the original study opted to participate in the LT study. Compared to the initial study population, pts participating in the kT study had slightly higher rates of response 6 months post-treatment (40% vs 36% combined biochemical and virological response). Of the 116 pts participating in the LT study, 69 (59%) had a biochemical response [44 (38%) complete response, 25 (22%) partial response]. 47 pts (41%) had a biochemical response and H BVDNA suppressed below 105cp/ml during the entire observation period. ALT and HBVDNA levels before, at the end of treatment and during the post-treatment pe- riod in patients with complete or partial biochemical responses are presented in the table. Table: ALT and HBVDNA levels in 69 patients with complete or partial long term ALT response ALT (U/I) HBV DNA (log cp/ml) med/mean (N) med/mean (N) Screening (-1 month) 77/98 (69) 6.8/6.9 (67) Baseline 62/92 (69) 7.3/7.3 (69) End of treatment 33/40 (67) 2.3/2.7 (67) 6 months post-treatment 18/20 (68) 3.2/3.5 (66) 9 months 19/20 (45) 3.8/3.9 (44) 12 months 18/21 (58) 3.9/4.0 (58) 24 months 18/21 (43) 3.6/3.9 (45) Conclusion: A finite 48-week course of PEGASYS is able to in- duce high rates of biochemical (59%) and virological (41%) response that are sustained 2 years after the end of treatment. Compared to pre-treatment levels, HBV DNA levels 1 and 2 years post-treatment were reduced in pts with sustained ALT responses by more than 3 log cp/ml. I-~-~ Anti-viral activity, histologic improvement and safety of entecavir in Japanese adult nucleoside-analogue naive patients with chronic hepatitis B infection: a phase 2 clinical trial K. Takaguchi 1 *, K. Kita 1, H. Ikeda 2, O. Yokosuka 3, M. Kawaguchi 4, K. Sakaguchi 5, T. Seriu 6, Y. Shiratori 5, M. Omata 7. Entecavir AI463-053 Study Group. 1Department of Internal Medicine, Kagawa Prefectural Central Hospital, Kagawa; 2Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Okayama; 3Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba; 4Department of Internal Medicine, Okayama Saiseikai General Hospital, 5Department of Internal Medicine 1, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama; 6Clinical Development, Bristol-Myers K.K., 7Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Background and Objectives: Entecavir (ETV) is a potent inhibitor of hepatitis B virus (HBV) with proven clinical efficacy. A randomized, double-blind, multi-center study was conducted in Japan (ETV-053) in adult patients with chronic hepatitis B infection (CHB) who had no prior history of nucleoside-analogue treatment. Methods: 66 patients with CHB were treated with daily oral doses of ETV 0.1 mg (32 patients), and 0.5 mg (34 patients) for 52 weeks. The primary endpoint was the proportions of patients who achieved at least a 2 log10 reduction in HBV DNA from baseline by PCR assay. Results: All patients achieved >~2 log10 reduction of HBV DNA at week 48. The mean reduction in HBV DNA from baseline was -4.49 and -4.84 log10 copies/mL for ETV 0.1 mg and 0.5 rag. High propor- tions of patients in both dose groups achieved ALT normalization at week 48: 96.4% and 93.8% for ETV 0.1 mg and 0.5 rag, respectively. 89% of patients had evaluable liver biopsies at baseline and at week 48; histologic improvement was observed in 72.4% and 80.0% for ETV 0.1 mg and 0.5rag. In addition, a significant improvement in liver fibrosis was observed in patients treated with ETV 0.5 rag. Genotype analysis showed that more than 90% of patients were infected with genotype C. Two patients showed an increase of HBV DNA of >~1 log10 from nadir, but in neither case were emerging mutations conferring resistance to entecavir detected. Overall, ETV was well tolerated and no patients discontinued study drug due to adverse events. Four patients experienced ALT flares, all were associated with at least a 2 log10 reduction in HBV DNA and resolved on continued ETV treatment. Conclusion: These results confirm the antiviral efficacy and safety of ETV in nucleoside-naive CHB Japanese patients. [-P_~ Sequential lamivudine and adefovir therapy maintains seroconversion rates in patients with HBeAg+ chronic hepatitis B S.G. Lira 1 ', M.O. Aung 2, B. Mak 3, D.S. Sutedja 3, Y.M. Lee4, Y.Y. Dan 3, D. Wai 5, E. Koay6. 1Dept of Gastroenterology and Hepatology, National University Hospital National University of Singapore, 21mmunovirology Group, Centre for Molecular Medicine, 3Dept of Gastroenterology and Hepatology, National University Hospital 4Medicine, 5Dept of Gastroenterology and Hepatology, National University of Singapore, eMolecular Diagnostic Lab, National University Hospital Singapore, Singapore Background and Objectives: Even with the advent of more nu- cleoside analogues, the optimal strategy for treatment of chronic hepatitis B is still being explored. Studies have focused on the efficacy of individual nucleosides or combinations, but little data is available on the strategy of sequential therapy. We examined the seroconversion rate, resistance and renal impairment in all patients with HBeAg+ chronic hepatitis B treated at a single centre. Methods: Data was collected prospectively on all chronic hep- atitis B patients prescribed nucleoside analogues lamivudine (LAM) and/or adefovir (ADV). Only patients who were HBeAg+ were se- lected for this analysis. Patients receiving nucleosides had hepatitis serology, LFTS, and HBV DNA and serum creatinine (only ADV) per- formed at baseline and 3-monthly. Nucleosides were discontinued 6 months after seroconversion in all patients. If viral breakthrough occurred, defined as >1 log rise in HBVDNA, testing for resistant mutants was performed. Kaplan-Meier (KM) analysis was performed and differences determined by log rank test. Patients with sero- reversion of HBeAg were excluded from the seroconversion analysis. Results: A total of 166 patients were followed for a mean of 28.15 too. 42 patients seroconverted during this time but 19% of pa- tients sero-reverted leaving the durability of seroconversion as 81%. The overall seroconversion rate was 35.46% based on KM analysis in the entire cohort based on first line therapy with LAM and ADV rescue upon development of resistance. When seroconversion KM curves of LAM and ADV were analysed, no difference was found, indicating that seroconversion rates were similar. LAM resistance oc- curred in 80% of patients over 42 months. ADV resistance occurred in 20.7% of pts over 20.2 months. An increased creatinine above normal was seen in 16.9% of patients which was similar in patients with and without cirrhosis. Poor virological response to ADV, defined as <2log reduction in HBVDNA at 6 months, was seen in 13.2% of ADV treated patients. There were no poor responders in LAM treated patients. Conclusion: Sequential therapy for HBeAg+ CHB appears to be a suitable option as seroconversion rates are maintained. However with a switch over to ADV, 13.2% of patients were poor responders, 16.9% of patients developed renal impairment, and 20.7% devel- oped resistance. IP• Combination of pegylated interferon and lamivudine for patients with chronic hepatitis B who have failed treatment previously S.S. Hissar*, M. Kumar, B.C. Sharma, S.K. Sarin. Gastroenterology, G.B. Pant Hospital, New Delhi, India Background and Objectives: Treatment with interferon or lamivu- dine or a combination is less effective in chronic hepatitis B (CHB) patients. Treatment of patients with failure to prior antiviral therapy is challenging. Our objective was to study the efficacy of pegylated interferon (peg-IFN) and lamivudine combination in CHB patients who have failed prior antiviral treatment. Methods: Twenty liver biopsy proven CHB patients with ALT levels >1.5. ULN, HBVDNA levels >141,000 copies/ml, and previous treatment failure with an adequate regimen were treated with a