AIM:To determine the efficacy of long-term lamivudinetreatment of a large number of Japanese patients withchronic hepatitis B.METHODS:In this retrospective,multi-center trial,318 Japanese patients with chronic hepatitis B received100 mg of lamivudine daily for up to 36(median 21)mo.Virological response was a decline to a serumHBV DNA level less than 3.7 log copies/mL.Virological breakthrough was defined as the reappearance of aserum HBV DNA level to more than 10-fold the minimumduring treatment.RESULTS:Lamivudine produced virological responsein 86.8% of the 318 patients at 6 mo,in 80.2% of252 patients at 12 mo,in 69.2% of 133 patients at 24mo,and in 53.6% of 28 patients at 36 mo.Forwardstepwise logistic regression analysis showed an HBV DNAlevel less than 6.8 log copies/mL(P<0.0001),HBeAgnegativity(P<0.0001),a platelet count of 100×10~9/L ormore(P=0.0162)at baseline,and a decline of the HBVDNA level of more than 3.2 log copies/mL as comparedwith the baseline level at 3 mo after the start oftreatment(P=0.0003)to be significantly associated withvirological response.Among patients with a virologicalresponse,virological breakthrough was seen in 5.3%of 19 patients who responded virologically at 1 mo,in20.7% of 203 patients at 3 mo,in 27.5% of 51 patientsat 6 mo,in 33.3% of 12 patients at 9 mo,and in 100%of 3 patients at≥15 mo.A virological breakthrough wasfound significantly more often in patients with delayedvirological response.CONCLUSION:Lamivudine treatment could suppressserum HBV DNA in most of the tested Japanese patients.Long-term efficacy might be seen in patients withoutHBeAg at baseline,in the absence of cirrhosis,and inpatients with a decline in HBV DNA level soon after thestart of treatment. AIM: To determine the efficacy of long-term lamivudinetreatment of a large number of Japanese patients with chronic hepatitis B. METHODS: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 ( median 21) mo.Virological response was a decline to a serum HBV DNA less than 3.7 log copies / mL. Virological breakthrough was defined as defined by the reappearance of aserum HBV DNA level to more than 10-fold the minimumduring treatment .RESULTS: Lamivudine produced virological responsein 86.8% of the 318 patients at 6 months in 80.2% of252 patients at 12 months in 69.2% of 133 patients at 24 months, and in 53.6% of 28 patients at 36 months. Forwardstepwise logistic regression analysis showed HBV DNAlevel less than than 6.8 log copies / mL (P <0.0001), HBeAgnegativity (P <0.0001), a platelet count of 100 × 10 -9 / L ormore (P = 0.0162) at baseline, and a decline of the HBVDNA level of more than 3.2 log copies / mL as comparedwith the baseline level at 3 mo after the st Art of treatment (P = 0.0003) to be significantly associated with viral response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded to virological at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5 % of 51 patientsat 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥ 15 mo. A virological breakthrough was significantly more often in patients with delayed virological response. CONCLUSION: Lamivudine treatment could suppressserum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBBeAg at baseline, in the absence of cirrhosis, and inpatients with a decline in HBV DNA level soon after the start of treatment.