Nucleoside analogues improve the short-term and long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure

Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (ACLF) has an extremely poor prognosis. There is no standard approach for managing ACLF. Nucleos(t)ide analogue has been proven effective in suppressing viral replication, improving histology and biochemical, and decreasing the inflammatory response in patients with chronic hepatitis B. This study was designed to evaluate the short-term and long-term efficacy of nucleoside analogue treatment of patients with HBV-related ACLF. One hundred and six consecutive subjects were recruited from 2,308 patients with elevated alanine aminotransferase activity. Forty-two patients were treated with 0.5 mg entecavir (ETV) daily (ETV group); 30 patients received 100 mg lamivudine (LAM) daily (LAM group); 34 patients did not take any nucleos(t)ide analogues (non-NAs group). All eligible patients were given standard medical treatment. All the patients were followed up until death or until October 2010. The HBV DNA levels and the short-term and long-term efficacy of the drugs were evaluated. After 3 weeks of nucleoside analogue treatment and/or supportive therapy, HBV DNA levels were decreased when compared with the baseline level in the ETV group (7.04 +/- 1.58 log(10) IU/mL vs. 4.03 +/- 2.04 log(10) IU/mL, P = 0.001), the LAM group (7.25 +/- 0.89 log(10) IU/mL vs. 4.33 +/- 2.48 log(10) IU/mL, P = 0.01), and the non-NAs group (5.73 +/- 0.96 log(10) IU/mL vs. 4.21 +/- 1.47 log(10) IU/mL, P = 0.01). The ETV and LAM groups showed a similar accumulative mortality in the first 3 months of treatment (33.3% vs. 40%, chi(2) = 0.568, P = 0.374). The non-NAs group had a significantly high mortality, compared with the ETV group (64.7% vs. 33.3%, chi(2) = 7.163, P = 0.007), the LAM group (64.7% vs. 40%, chi(2) = 3.906, P = 0.042), and the nucleoside analogue group (ETV group + LAM group) (64.7% vs. 36.2%, chi(2) = 7.443, P = 0.006). All the 56 patients survived were followed up to October 2010. The median follow-up period was 7.3 months. Recurrence was observed in a total of 6 patients (10.72%), of whom 4 patients (33.33%) were from the non-NAs group, 2 (11.11%) from the LAM group after cessation LAM therapy by patients himself, and 0 from the ETV group (P = 0.003). Nucleoside analogue may improve the short-term and long-term prognosis of patients with HBV-related ACLF.