LAUSR

HBeAg loss during nucleos(t)ide analogue (Nuc) therapy is significantly higher in patients with hepatitis flare (ALT ≥ 5‐times upper limited of normal). It is not clear whether ALT level higher above the hepatitis flare leads to greater HBeAg loss rate nor its durability. This study aimed to investigate the impact of pretherapy ALT level on HBeAg loss in each year of Nuc treatment. Entecavir or Tenofovir treated HBeAg‐positive chronic hepatitis B (CHB) patients were recruited consecutively. Patients with prior treatment history that experienced HBeAg seroconversion and reversion were excluded. Pretherapy age, gender, cirrhosis, genotype, ALT, HBsAg and HBV DNA levels were analysed. The hazard function was calculated for the probability of HBeAg loss in each year. Of the 290 patients, the 3‐year cumulative HBeAg loss rate was 58.1%, higher in patients with hepatitis flare than those without (67.6% vs. 39.6%, P < 0.001). The HBeAg loss rate in the first year correlated positively with higher ALT levels at a stepwise fashion. The hazard function in patients with hepatitis flare was 0.74 at half year, then dropped to 0.33 by the first year and was lower thereafter to a rate closer to that of the patients without hepatitis flare. In conclusion, the impact of pretherapy ALT levels on HBeAg loss rate was not long‐lasting and was effective mainly in the first year of Nuc therapy. Strategies such as adding an immune‐modulating agent may help enhance HBeAg loss rate after the first year of Nuc therapy for those who remained HBeAg positive.