The combination of alanine aminotransferase and cytokines could predict the hepatitis B s antigen reduction in chronic hepatitis B patients in antiviral therapy

Background: & Aims: Hepatitis B s antigen (HBsAg) is an important reference for the amount of covalently closed circular DNA. Patients may benefit from low HBsAg levels. We evaluated changes in HBsAg and cytokines in chronic hepatitis B (CHB) patients with low HBsAg levels who underwent oral antiviral therapy. Methods: A total of 197 CHB patients with HBsAg < 3,000 IU/ml and HBV DNA ≤1,000 IU/ml after more than a year of antiviral therapy were divided into a nucleotide analogs (NAs) group and an entecavir (ETV) group. HBsAg levels were determined every 6 months until 42 months. The serum chemokine and cytokine levels at baseline and 6, 18, and 30 months among 54 hepatitis B e antigen (HBeAg)-positive patients were measured. Results: HBsAg loss (1.72%), HBsAg reduction below 100 IU/ml (13.79%) and HBsAg reduction ≥0.5 log10 (24.14%) occurred in the NAs group. The cumulative incidences of HBsAg reduction and the HBsAg change in the NAs group were better than those in the ETV group (P60 U/L during antiviral therapy (P<0.05). ALT change and IL4 level were identified as independent factors for HBsAg reduction (p=0.006; OR=30.491 [2.626-351.312], and p=0.027; OR=1.847 [1.071-3.186], respectively). Conclusions: NAs therapy had some advantages in promoting a reduction in HBsAg. In clinical practice, ALT, MDC, IL4, and IL23 may be biomarkers for predicting HBsAg reduction.