What question did this study set out to answer?

This research aims to compare the recurrence risk of HBsAg seroreversion after seroclearance in HBeAg-negative chronic hepatitis B patients receiving different Peg-IFNα therapies.

July 12, 2026Open Access

HBsAg seroreversion after pegylated interferon alpha induced HBsAg seroclearance in patients with chronic hepatitis B: a real-world cohort study

WZWei ZhangNanjing University of Chinese Medicine JCJia ChenZhejiang Chinese Medical University WSWenjin SunEzhou Central Hospital

Key Points

This research aims to compare the recurrence risk of HBsAg seroreversion after seroclearance in HBeAg-negative chronic hepatitis B patients receiving different Peg-IFNα therapies.
Conducted a retrospective cohort study involving 438 patients with chronic hepatitis B.
Participants were divided into training and validation cohorts to develop a predictive algorithm using Lasso-Cox regression.
Model performance was evaluated with calibration curves and time-dependent ROC analysis.
At 48 weeks, cumulative HBsAg seroreversion rates were 15.7% for combination therapy and 21.2% for monotherapy.
Significant predictors of seroreversion included baseline HBsAg level (HR = 1.507, P = 0.016) and end-of-treatment HBsAb level (HR = 0.973, P < 0.001).
The optimal cut-off for end-of-treatment HBsAb was determined to be 32.28 IU/L.

Abstract

The effect of different pegylated interferon alpha (Peg-IFNα) treatment strategies on the recurrence after Hepatitis B surface antigen (HBsAg) seroclearance has not yet been adequately elucidated. This real-world study was conducted to compare the risk of HBsAg seroreversion after HBsAg seroclearance in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB) receiving Peg-IFNα-2b combination therapy with nucleos(t)ide analogues (NAs) and Peg-IFNα-2b monotherapy, and further to identify predictors by developing a risk prediction model. Using a retrospective cohort design, 438 enrolled participants were partitioned to training and validation cohorts. The non-zero coefficient variables were identified via least absolute shrinkage and selection operator - Cox proportional hazards regression (Lasso-Cox), with subsequent multivariate Cox analysis establishing the predictive algorithm. Model performance underwent evaluation through calibration curves and time-dependent receiver operating characteristic (time-dependent ROC) analysis. The cumulative HBsAg seroreversion rates at 48 and 96 weeks were 15.7% and 18.9% in the combination group and 21.2% and 26.4% in the monotherapy group, respectively, with no statistically significant difference between groups.The final model incorporated two predictors: baseline HBsAg level (HR = 1.507, 95%CI: 1.081–2.101, P = 0.016), and end-of-treatment (EOT) hepatitis B surface antibody (HBsAb) level (HR = 0.973, 95%CI: 0.960–0.986, P < 0.001). The optimal cut-off value of HBsAb titer at EOT calculated by ROC curve was 32.28 IU/L. The calibration curves delineated favorable consistency for the nomogram model. Time-dependent ROC curves presented better discriminatory ability, with area under the curve (AUC) values of 0.781, 0.800, 0.820 and 0.827 at 12, 24, 48, and 96 weeks in the training set. The observed durability of HBsAg negativity was not significantly improved with Peg-IFNα combination therapy compared with monotherapy. Baseline HBsAg and EOT-HBsAb levels may support individualized recurrence risk stratification. Not applicable.

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