Interleukin‐2 promotes pegylated interferon alpha for hepatitis B surface antigen loss: A retrospective pragmatic clinical study at the Fourth Affiliated Hospital of Zhejiang University Medical College

BACKGROUND AND AIMS: Interleukin‐2 (IL‐2) can be used as an adjuvant therapy when pegylated interferon alpha (Peg‐IFN‐α) does not effectively promote hepatitis B surface antigen (HBsAg) loss, but the relevant timing, kinetic patterns, and prognostic associations of this intervention are unclear. METHODS: A total of 115 patients with chronic hepatitis B (CHB) treated at our institution between October 2018 and March 2021 were included in this retrospective analysis. They were divided into two kinetic patterns by using K‐medoids cluster analysis. Profile and prognostic associations were statistically analyzed between the two patterns. RESULTS: After baseline standardization, before the intervention, the relative HBsAg level showed a continuously increasing trend, but after the intervention, it showed a continuously decreasing trend. Based on the relative change in the HBsAg level, two kinetic patterns, namely, a fluctuation platform pattern and a stepwise growth pattern, were identified by using K‐medoids cluster analysis for all 115 patients before IL‐2 intervention. Profile analysis showed that there were statistically significant differences between the two patterns before IL‐2 intervention (p < 0.05), but their profiles showed the same trend after 2 weeks of IL‐2 intervention. Prognostic association analysis showed that CD8+ T cells, alanine transaminase (ALT), age, natural killer (NK) cells, neutrophils, and course of treatment before IL‐2 intervention were the six main indicators affecting the relative decrease in the HBsAg level. CONCLUSION: For CHB patients who have received continuous Peg‐IFN‐α treatment, IL‐2 intervention should be given as early as possible when the HBsAg level has not decreased for four consecutive weeks or a fluctuation platform pattern is observed. After the intervention, a downward relative change in the HBsAg level can be maintained over 4 weeks. CD8+ T cells, ALT, NK cells, and neutrophils are baseline indicators closely related to the prognosis of this intervention.