Long‐Term Dynamic Changes of Alanine Aminotransferase Levels Are Associated With Liver‐Related Events in Nucleos(t)ide Analogue‐Treated Chronic Hepatitis B Patients in China

ABSTRACT Background The role of alanine aminotransferase (ALT) dynamics during nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) is unclear. We aimed to evaluate the correlation between ALT dynamics and liver‐related events (LRE), and explore the optimal threshold of ALT during NA treatment. Methods We enrolled 18,129 NA‐treated patients, comprising 3104 patients from the Search‐B study (NCT02167503) and 15,025 patients from a real‐world cohort in Hong Kong. Latent‐class mixed model (LCMM) was adopted to identify trajectory patterns of ALT during treatment. ALT value at the 95 th percentile of the trajectory group with the lowest LRE risk was obtained as the optimal threshold. Results During a median follow‐up of 53.3 months, 1164 patients developed LRE with a 7‐year cumulative incidence of 9.9%. In the Search‐B cohort, LCMM recognised 3 trajectory groups with progressively increasing ALT levels, which were positively associated with LRE risk. Subsequently, the optimal thresholds for ALT were obtained as 23 U/L for men and 16 U/L for women. The 7‐year cumulative incidence of LRE was 5.5% for ALT ≤ 23 or 16 U/L, significantly lower than that for ALT > 23 or 16 U/L but ≤ 40 U/L (10.8%; aHR = 2.0, p < 0.001), and ALT > 40 U/L (15.1%; aHR = 3.4, p < 0.001). Similarly, in the Hong Kong cohort, ALT > 23 or 16 U/L but < 40 U/L and ALT > 40 U/L also increased the LRE risk, with aHRs of 2.0 ( p = 0.003) and 6.1 ( p < 0.001), respectively. Conclusion On‐treatment ALT levels were significantly correlated with the prognosis of CHB. ALT ≤ 23 U/L for men and ≤ 16 U/L for women were identified as the optimal thresholds during NA treatment, suggesting that CHB patients should strive for a lower ALT level beyond the traditional normal range.