Study on the predictive value of early alanine aminotransferase jump combined with hepatitis B surface antigen decline in chronic hepatitis B patients with nucleotide analogues sequential pegylated interferon therapy

Zeng Huang; Yang Haiqing; Li Yan; Peng Weihao; Zhang Jing; Ji Fang

doi:10.3760/j.issn.1673-4777.2025.07.012

Abstract：Objective To explore the predictive value of alanine aminotransferase(ALT)jump combined with hepatitis B surface antigen(HBsAg)decline for functional cure in chronic hepatitis B(CHB)patients treated with nucleotide analogues(NAs)sequential pegylated interferon(Peg-IFN)and establish a prediction model.Methods CHB patients who visited the Affiliated Hospital of Xuzhou Medical University from July 2019 to December 2022,were HBsAg positive for more than 6 months,hepatitis B virus(HBV)DNA≤3.3 log10IU/ml and received NAs antiviral therapy for at least 1 year,combined with Peg-IFN for 48 weeks,were retrospectively enrolled.The analysis was based on the baseline to 12 weeks alanine aminotransferase(ALT)jump(2-fold increase from baseline)and HBsAg decline(decrease from baseline).HBsAg response was defined as HBsAg＜3.2 and a decrease of＞1.0 log10IU/ml at 24 weeks.HBsAg＜2.0 log10IU/ml at 48 weeks was used as the efficacy evaluation index,and the predictive factors of HBsAg response were analyzed and a prediction model was constructed.The receiver operating characteristic curve was used to evaluate the model fitting effect.Results A total of 145 CHB patients treated with NAs followed by Peg-IFN were included in the study.Forty of 50 HBsAg responders at 24 weeks had HBsAg＜2.0 log10IU/ml at 48 weeks of treatment,with a positive predictive value(PPV)of 80.0％,and 19 of them(38.0％)achieved HBsAg loss.Multivariate Logistic regression analysis showed that baseline HBsAg(odds ratio=11.306,95％confidence interval:3.959-32.288,P＜0.001),baseline to week 12 ALT jump(odds ratio=3.435,95％confidence interval:1.107-10.659,P=0.033),and HBsAg decreased at 12 weeks(odds ratio=54.775,95％confidence interval:5.941-505.028,P＜0.001)were independent predictors of HBsAg response.The prediction model was established as follows:Logit P=2.425 × baseline HBsAg+4.003 × HBsAg decreased+1.234 × ALT flared-5.776(BHA model),its area under the curve was 0.843,the standard error was 0.037,95％confidence interval:0.769-0.916,according to the calculation formula of Jorden index,the cutoff value of P value was determined to be 0.51,and the sensitivity and specificity of its diagnosis were 86.70％and 67.30％.Conclusion Baseline HBsAg level,ALT jump combined with HBsAg decline at 12 weeks of treat-ment are associated with HBsAg response in CHB patients treated with NAs sequential Peg-IFN.The prediction model constructed by the above indicators can screen out patients who are likely to achieve functional cure at 48 weeks of combination therapy.