Viral blips during long-term treatment with standard or double dose lamivudine in HBe antigen negative chronic hepatitis B

AIM:To evaluate safety and effect on hepatitis B virus(HBV)suppression of a long-term treatment with lamivudine(LAM)at standard(100 mg/d)or double(200 mg/d)dose in chronic hepatitis B.METHODS:This was a case study with matched controls(1:3)in patients with chronic hepatitis B with anti-HBe antibodies.RESULTS:Twelve patients received LAM 200 mg/d and 35 LAM 100 mg/d,for a median of 28 mo.A primary response(PR;i.e.negative HBV-DNA with Amplicor assay)was achieved in 100% of LAM-200 patients and 83% of LAM-100 patients.A virological breakthrough occurred in 16.7 and 24.7%,respectively,of the PR-patients,with the appearance of typical LAM resistance mutations in all but one patient.Viremia blips(i.e.transient HBV-DNA below 80 IU/mL in patients who tested negative at Amplicor assay)were detected using a real time polymerase chain reaction(PCR)and occurred in seven out of nine patients with subsequent BT and in four out of 32 patients with end-of-study response(77.7% vs 12.5%;P = 0.001)at chi-square test).At the end of the study,51.4% of LAM-100 patients and 83.3% of LAM-200 patients had remained stably HBV-DNA negative.Double-dose LAM was well tolerated.CONCLUSION:Long-term treatment of anti-HBe positive chronic hepatitis B with double dose lamivudine causes a more profound and stable viral suppression ascompared to conventional treatment.