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

Treatment with nucleoside analogue (NAs) is now the most common treatment for chronic hepatitis B (CHB) and is recommended by all guidelines. Stopping NAs is a controversial issue in these patients, unless the clinical endpoints of HBeAg seroconversion or HBsAg seroclearance are achieved. While HBeAg seroconversion can occur in a significant number of patients, HBsAg seroclearance rates are low. HBsAg 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 HBeAg seroconversion and complete at least 12 months of consolidation therapy. In HBeAg 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. NAs treatment for >2 years was associated with a lower rate of relapse. Recently, stopping NA therapy was shown to be associated with HBsAg in 20%-39% of HBeAg negative patients and more frequently in those with low quantitative HBsAg (qHBsAg). However, the most optimal level is unclear. Quantitative HBsAg 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 HBeAg seroconversion. However, it is associated with disease relapse. Thus, patient selection based on qHBsAg may help identify patients who are more likely to achieve HBsAg seroclearance or a sustained response.