TY  - JOUR
T1  - Baseline Liver Fibrosis Severity Predicts Superior HBeAg Clearance and Fibrosis Reversal following Peg-IFNα plus Nucleos(t)ide Analog Therapy in HBeAg-positive Chronic Hepatitis B Patients 
AU  - Zhang, Yaqin
AU  - Chen, Fengxin
AU  - Wang, Shuojie
AU  - Wei, Xin
AU  - Wang, Shiyu
AU  - Yao, Linmei
AU  - Gao, Zixuan
AU  - Deng, Wen
AU  - Li, Minghui
JF  - Journal of Clinical and Translational Hepatology
VL  - 
IS  - 000
SN  - 2310-8819
SP  - 
EP  - 
Y1  - 2026-07-09
DO  - 10.14218/JCTH.2026.00093
UR  - https://www.xiahepublishing.com/2310-8819/JCTH-2026-00093
AB  - Background and Aims 
The impact of baseline liver fibrosis severity on the effectiveness of pegylated interferon (Peg-IFN) combined with nucleos(t)ide analogs (NAs) in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) has not been fully clarified. This study aimed to investigate whether the effectiveness of this combination therapy differed according to the severity of baseline liver fibrosis.
Methods
A total of 172 HBeAg-positive CHB patients receiving Peg-IFN plus NAs were stratified according to non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) into three groups: no significant fibrosis (n = 75), significant fibrosis (n = 70), and advanced fibrosis/cirrhosis (n = 27). The primary outcome was the HBeAg clearance rate at 24 months of treatment. Secondary outcomes included the hepatitis B surface antigen (HBsAg) clearance rate, the rate of HBsAg level decline > 1.0 log10, virological response, and improvement in non-invasive fibrosis indices.
Results
At 24 months, HBsAg clearance and complete virological response rates were comparable across the three groups. Cumulative HBeAg clearance rates differed significantly (log-rank P = 0.027): 16.00%, 30.00%, and 40.74% in the three groups, respectively, with Group 3 higher than Groups 1 and 2. Multivariate analysis identified a significantly higher likelihood of HBeAg clearance in Group 3 versus Group 1 (adjusted odds ratio = 6.373, 95% confidence interval: 1.288–31.531, P = 0.023). Additionally, analysis of liver fibrosis outcomes showed that patients with more severe baseline fibrosis had a higher proportion of improvement in non-invasive fibrosis indices, with 95.00% in Group 3, while 42.98% of the overall cohort achieved fibrosis improvement.
Conclusions
Baseline fibrosis severity is associated with higher HBeAg clearance and greater improvement in non-invasive fibrosis indices during Peg-IFN plus NAs therapy in HBeAg-positive CHB.