The ULN for ALT has been defined as <30 U/L for men and boys and <19 U/L for women and girls. Persistently normal or abnormal may be defined as two ALT values below or above the ULN at unspecified intervals during a 6- to 12-month period. ALT levels fluctuate with CHB and require longitudinal monitoring to determine the trend. • The decision to stop any nucleos(t)ide analogue therapy must be weighed carefully. Biochemical relapse has been variously defined but includes ALT elevation to >2 times the ULN. A hepatitis flare has been defined as ALT elevation >5 times the ULN and severe hepatitis flare has been defined as ALT level >1000 U/L or ALT <1000 U/L plus a total bilirubin 3.5 mg/dL or an international normalized ratio 1.5. Viral relapse has been defined as HBV DNA >2000 IU/mL. Quantitative HBsAg at the end of treatment predicts HBsAg loss or relapse after stopping nucleos(t)ide analogues, but the levels predicting relapse are lower for Asian versus Caucasian people.

• Stopping nucleos(t)ide analogues before HBsAg loss should only be considered if HBsAg seroclearance is likely based on prediction with current biomarkers, especially HBsAg levels, at the time of stopping.
• People with hepatitis B should be educated about the importance of long-term monitoring to ensure adherence to monitoring and care. The benefits versus the disadvantages of stopping treatment should be also clearly explained.
• The ability to monitor everyone for safety after stopping therapy for resumption of HBV replication requires HBV DNA monitoring and recall policies. Both laboratory-based and POC DNA testing remain relatively costly and less available in low- and middle-income countries.
• Postpartum, women who have started nucleos(t)ide analogue prophylaxis to prevent vertical transmission should be strongly advised to continue treatment if indicated for their own health and especially if multiple subsequent pregnancies are anticipated. This would also avoid the risk of liver flare when treatment ends after each pregnancy and delivery.
• Monitoring for and managing relapse: HBV DNA concentrations typically rise rapidly before serum ALT concentrations. Treatment should be reinstated if concentrations rise to >4 log10 IU/mL before any rise in serum aminotransferases to circumvent the immune-mediated flare (32). The findings of the unpublished REEF-2 study provide strong support for this approach, which has now been incorporated into the clinical trials of new agents. Delayed resumption of therapy may have severe outcomes for these people.
• An array of immunosuppressive agents may induce HBV reactivation. These include cancer chemotherapy, checkpoint inhibitors, immunosuppressive therapy, bone marrow and stem cell treatment, anti-tumour necrosis factor and novel immunobiologics, including tyrosine kinase inhibitors, chimeric antigen receptor T-cell treatment and after treatment for comorbid hepatitis C. Since the composite risk can be difficult to determine, pre-emptive antiviral therapy is recommended