The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA discontinuation in this setting and tried to identify factors affecting the probability of posttherapy remission. A literature search was performed in order to identify all published studies including patients who discontinued NAs in virological remission (VR) and were followed for ≥12 months thereafter. Twenty-five studies with 1716 patients were included. The pooled rates of durable VR remission were 51.4%, 39.3%, and 38.2% at 12, 24, and 36 months, respectively, after NA discontinuation, being relatively higher in initially hepatitis B e antigen (HBeAg)-positive patients (62.5%, 53.4%, 51.5%) than HBeAg-negative patients (43.7%, 31.3%, 30.1%) (P = 0.064). The weighted probability of durable biochemical remission was 65.4%, being numerically higher in HBeAg-positive than HBeAg-negative patients (76.2% versus 56.7%, P = 0.130). The weighted probability of hepatitis B surface antigen loss was 2.0%. The rates of durable VR did not significantly differ according to the VR definition (hepatitis B virus DNA <200, < 2000, < 20,000 IU/mL) or duration of on-therapy VR in HBeAg-positive patients, but they were significantly higher in studies with HBeAg-negative patients and on-therapy VR > 24 than ≤ 24 months (VR at 12 months off-NAs: 75.0% versus 35.6%, P = 0.005). The weighted probability of durable HBeAg seroconversion was 91.9% and 88.0% at 12 and 24 months, respectively, after NA discontinuation without being affected by the duration of on-therapy VR or consolidation therapy (>6 months in all studies).
Conclusion: Durable VR seems to be feasible in a substantial proportion of patients who discontinue long-term NA therapy; on-therapy VR > 24 months offers higher chances of off-NA VR in patients with HBeAg-negative chronic hepatitis B.
© 2016 by the American Association for the Study of Liver Diseases.