When can we stop nucleoside analogues in patients with chronic hepatitis B?

Treatment with nucleoside analogue ( NA s) is now the most common treatment for chronic hepatitis B ( CHB ) and is recommended by all guidelines. Stopping NA s is a controversial issue in these patients, unless the clinical endpoints of HB eAg seroconversion or HB sAg seroclearance are achieved. While HB eAg seroconversion can occur in a significant number of patients, HB sAg seroclearance rates are low. HB sAg seroclearance is increasingly accepted as the ideal end of treatment, representing a functional cure. Treatment withdrawal leads to relapse in 50% of patients who achieve HB eAg seroconversion and complete at least 12 months of consolidation therapy. In HB eAg negative CHB , the Asian Pacific Association for the Study of the Liver ( APASL ) stopping rules show that although clinical relapse occurs in approximately 43% and virological relapse occurs in 70%, very few patients experience flare or decompensation. NA s treatment for >2 years was associated with a lower rate of relapse. Recently, stopping NA therapy was shown to be associated with HB sAg in 20%‐39% of HB eAg negative patients and more frequently in those with low quantitative HB sAg ( qHBsA g). However, the most optimal level is unclear. Quantitative HB sAg is becoming a useful tool to predict a sustained response or relapse before stopping therapy. In conclusion, stopping NA therapy is generally safe and can be an option in specific situations such as HB eAg seroconversion. However, it is associated with disease relapse. Thus, patient selection based on qHBsA g may help identify patients who are more likely to achieve HB sAg seroclearance or a sustained response.