Systematic review: cessation of long-term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen-negative chronic hepatitis B

BackgroundIt has been debated whether finite nucleos(t)ide analogue therapy is feasible in HBeAg-negative chronic hepatitis B. AimTo review this issue systematically. MethodsUsing text terms HBsAg and various nucleos(t)ide analogues, PubMed was searched between 1995 and 2014 to find studies on therapy >6months in adult HBeAg-negative chronic hepatitis B patients with off-therapy follow-up >6months. ResultsTwenty-two studies with a total of 1732 patients were identified and included. The median duration of therapy, consolidation therapy and off-therapy follow-up ranged from 6 months to 8years, 4 to 96weeks and 6 to 80months respectively. Patients were monitored with serum ALT and HBV DNA monthly in the first 1-3months and every 3-6months afterwards in most studies. The 1-year off-therapy virological relapse' (HBV DNA >2000IU/mL) and clinical relapse' (HBV DNA>2000IU/mL+ALT elevation) occurred in <70% and <50% of the patients, respectively, and <40% of the patients received re-treatment. These rates were higher in patients with shorter treatment, shorter consolidation therapy and those treated with less potent nucleos(t)ide analogues. Off-therapy severe flares were rare and hepatic decompensation was reported in only one patient with cirrhosis. Biochemical relapse reflecting enhanced immune-mediated hepatocyte killing may lead to a higher chance for off-therapy HBsAg seroclearance and be possibly desirable. ConclusionWith an appropriate stopping rule and a proper off-therapy monitoring plan, cessation of long-term nucleos(t)ide analogue therapy prior to HBsAg seroclearance in HBeAg-negative chronic hepatitis B is a feasible alternative to indefinite treatment.