Discontinuation of nucleos(t)ide analogue therapy in chronic hepatitis B
Nucleos(t)ide analogue (NA) therapy discontinuation should occur only after specialist consultation and when close monitoring after stopping is guaranteed. [1]
NA therapy should not be discontinued in patients with cirrhosis due to risk of hepatic decompensation and acute hepatitis flares. [2]
HBeAg-positive chronic hepatitis B discontinuation criteria
In HBeAg-positive patients without advanced liver disease, NA therapy can be stopped 12 months after confirmed HBeAg/anti-HBe seroconversion and undetectable HBV DNA if close monitoring is guaranteed after stopping therapy. [1]
This discontinuation criterion is listed as a low-level evidence, weak recommendation (LoE 2, weak recommendation) in the EASL guidance. [1]
NA therapy discontinuation after HBeAg/anti-HBe seroconversion is specifically framed around NA-induced and/or persistent risk of relapse, so close post-discontinuation monitoring is emphasized. [1]
HBeAg-negative chronic hepatitis B discontinuation criteria
In selected HBeAg-negative patients without advanced liver disease, NA therapy can be discontinued before HBsAg loss if HBV DNA has been undetectable for at least 3–4 years, HBsAg level is low, and close monitoring is guaranteed after stopping therapy. [1]
This discontinuation approach is listed as a low-to-moderate level evidence, weak recommendation (LoE 1–2, weak recommendation) in the EASL guidance. [1]
Additional biomarkers can be used to improve selection prior to stopping, including HBcrAg and HBV RNA, but the primary time-based and low-HBsAg criteria remain the core requirements. [1]
Patient selection factors for stopping decisions
Stopping decisions should incorporate HBsAg levels, HBeAg status, comorbidities, duration of HBV DNA suppression, stage of liver fibrosis, and patient preferences and understanding. [1]
These factors are explicitly included as determinants of appropriateness and safety for NA discontinuation. [1]
HBsAg loss as an indication for stopping
NA therapy should be stopped after confirmed HBsAg loss with or without anti-HBs seroconversion in the absence of coexisting risk factors. [1]
This HBsAg-loss stopping rule is listed as a low-level evidence, strong recommendation (LoE 2, strong recommendation) in the EASL guidance. [1]
Monitoring requirements after stopping
After NA discontinuation, monitoring should include close assessment during the early post-stopping interval, followed by less frequent monitoring intervals thereafter. [1]
Monitoring intensity after stopping should be adjusted based on fibrosis stage and other clinical factors because post-discontinuation relapse risk is not uniform across patients. [1]
Special populations and exclusion from discontinuation
Patients with cirrhosis should receive lifelong NA therapy and should not discontinue antivirals because of the risk of reactivation and acute hepatitis flare. [2]
This exclusion is stated as a strong recommendation in the WHO chronic hepatitis B guidance. [2]
Patients with advanced liver disease should not be included among those considered for HBeAg-positive or HBeAg-negative stopping criteria described for non-cirrhotic individuals. [1]
Evidence notes on off-therapy outcomes
In HBeAg-positive patients, the probability of sustained off-therapy virological remission decreases over longer follow-up intervals after discontinuation despite initial remission in a substantial proportion of patients. [1]
In HBeAg-negative patients, the discontinuation strategy is therefore constrained to selected patients with long-term HBV DNA suppression and low HBsAg and requires guaranteed monitoring. [1]
Practical stopping rules by HBeAg status
HBeAg-positive, non-cirrhotic: stop NA 12 months after confirmed HBeAg/anti-HBe seroconversion plus undetectable HBV DNA with guaranteed close monitoring. [1]
HBeAg-negative, selected non-cirrhotic: stop NA when HBV DNA is undetectable for at least 3–4 years plus low HBsAg plus guaranteed close monitoring. [1]
Cirrhosis: do not stop NA therapy. [2]
Stopping after confirmed HBsAg loss remains an accepted stopping rule. [1]