[Lamivudine in patients with chronic HBV infection and therapeutic difficulties]

The primary objective of this study was to determine the efficacy and safety of lamivudine (LAM) therapy in patients with chronic HBV infection and contraindications to IFN therapy, nonresponders to IFN and patients with advanced liver fibrosis.

In this open study, 38 patients (25 men and 13 women, age 19-68) with chronic hepatitis B virus infection (HBsAg, HBeAg and p-DNA HBV positive) were treated with LAM (150 mg daily) for 48 weeks. All were negative for HCV or HDV coinfection and had no decompensated liver disease. Fourteen patients (group I) were nonresponders to IFN therapy, 15 patients (group II) had different contraindications for IFN therapy (e.g. depression, low number of neutrophils and/or platelets), and 9 (group III) had advanced liver fibrosis (staging = 3 or 4 [Knodell]). In all cases ALT activity was at least 2 times ULN before the therapy. After discontinuation of therapy all patients were followed-up for another 36 weeks.

During first 8-12 weeks of therapy rapid inhibition of HBV replication (p-DNA negativization) was noticed in all cases. At the end of therapy seroconversion to anti-HBe was observed in 24 cases (63%): 9 patients (64%), 10 (67%) and 5 (55.5%) from groups I, II and III, respectively. In one case elimination of HBsAg and appearance of anti-HBs was observed. Sustained normalization of ALT activity was noticed in 22 patients (58%): 9 cases (64%) in group I, 8 (53%) in group II and 5 (55.5%) in III, respectively. During 24 weeks of follow-up in 4 cases (17%) reseroconversion to HBeAg with reapperance of p-DNA activity was observed. ALT activity in these cases was slightly elevated but without clinical signs of exacerbation. In no case serious side effects were observed.

The results indicate that monotherapy with lamivudine (150 mg daily) for 48 weeks induces sustained inhibition of viral replication and normalisation of transminases in majority of patients with chronic HBV infection who did not respond to IFN, had contraindications to IFN therapy, and in those who had advanced liver fibrosis. The absence of side effects during lamivudine therapy is of special importance especially in patients with advanced liver fibrosis.