Outcomes of Nucleos(t)ide Analogue Discontinuation in Noncirrhotic Patients With Chronic Hepatitis B: A Retrospective Study

Background Finite nucleos(t)ide analogue (NUC) therapy is an emerging treatment strategy in selected patients with chronic hepatitis B (CHB). We evaluated the feasibility, efficacy, and safety of NUC discontinuation in non-cirrhotic patients fulfilling the Asian Pacific Association for the Study of the Liver (APASL) stopping criteria. Methods We retrospectively analysed data from a tertiary gastroenterology clinic (January 2021-December 2024). Consecutive non-cirrhotic CHB patients meeting APASL criteria were included: hepatitis B e-antigen (HBeAg)-positive with stable HBeAg seroconversion and undetectable hepatitis B virus (HBV) DNA ≥12 months (preferably ≥3 years), or HBeAg-negative with ≥2 years of therapy and undetectable HBV DNA on three occasions, six months apart. Exclusion criteria were significant alcohol intake, viral coinfections, extrahepatic HBV disease, personal or family hepatocellular carcinoma (HCC) history, cirrhosis by imaging or elastography, or unwillingness to discontinue therapy. Patients were monitored for two years with clinical assessment, alanine aminotransferase (ALT), and HBV DNA. Retreatment was predefined upon virological or biochemical relapse. Results Twenty-nine patients were included (HBeAg-positive, 15; HBeAg-negative, 14). At three months, virological relapse occurred in 14/29 (48.3%) patients, more frequently in HBeAg-positive than in HBeAg-negative patients (10/15 (66.7%) vs 4/14 (28.6%); p = 0.047). No significant difference in virological relapse was observed between patients receiving tenofovir and those receiving entecavir (ETV) (5/15 (33.28%) vs 9/14 (64.28%); p = 0.09). All relapsed patients restarted the same NUC and achieved complete viral suppression within two years. Sustained off-therapy remission was observed in 15/29 (51.7%), more common in HBeAg-negative than HBeAg-positive patients (10/14 (71.4%) vs 5/15 (33.3%); p = 0.049). No flare, hepatic decompensation, antiviral non-response, or deaths occurred. Conclusions Finite NUC therapy was feasible and safe in non-cirrhotic CHB patients meeting APASL criteria. Sustained remission was maintained in half of the patients, supporting finite therapy with early monitoring and clear retreatment thresholds. However, larger multicentre studies are needed to validate these findings.