The kinetics of HBsAg isoforms predicts response to Peg-IFN and BLV in patients with CHD

Introduction: CHD can be treated with either the entry inhibitor bulevirtide (BLV) or the immune modulator pegylated interferon alpha-2a (PEG-IFN). However, predicting treatment response remains uncertain. The composition of hepatitis B surface antigen (HBsAg), including large (L), middle (M), and small (S) forms, has been associated with HBsAg loss in hepatitis B virus (HBV) mono-infection and clinical outcomes were associated with higher MHBs% at baseline (BL) in HBV/HDV-coinfected patients.

Aim: This study aims to evaluate the HBsAg isoform composition before and during antiviral treatment in CHD

Methods: We analysed a retrospective European multicentre real-world cohort receiving either 180µg/week PEG-IFN (n=56) or 2mg/day BLV (n=50). Patients were divided into groups according to their treatment response after 12 months: I) Non-response (NR) II) Partial response (PR), III) Complete response (CR), VI) Functional cure of HBV with HBsAg loss. HBsAg composition, HDV RNA and HBV DNA were quantified in serum samples (if available) at time points BL, 6, 12, 18, and 24 months.

Results: At BL, all groups exhibited similar levels of HDV RNA, HBsAg, LHBs, and MHBs. The proportions of MHBs were lower in patients responding to treatment compared to NR (7.1%), those with>2 log IU/mL HDV RNA decrease (4.7%), undetectable HDV RNA (6.5%), or HBsAg loss (3.9%), regardless of treatment. HBV/HDV-coinfected patients showed higher proportions of HBsAg isoforms in comparison to HBV-monoinfections. During both BLV and PEG-IFN treatment, levels of LHBs and MHBs significantly decrease. In contrast, no decrease was detected in NR during BLV or PEG-IFN treatment. In addition, a BL-cutoff for LHBs or MHBs can predict response to treatment; individuals with BL-levels of<380ng /mL LHBs and<130ng/mL MHBs showed a higher likelihood of achieving CR. In both treatment groups, ∆LHBs and ∆MHBs initially increase during the first 6 months of treatment but significantly decrease afterwards ([Fig. 1]). In contrast, no significant decrease was found in patients with PR and NR.

Fig. 1  

Conclusion: HBsAg isoforms may serve as biomarkers for evaluating treatment response in CHD. Patients with a complete response to either BLV or PEG-IFN treatment exhibit significant changes in their HBsAg isoforms and composition. Baseline levels of LHBs and MHBs may help predict treatment response. The potential role of HBsAg isoforms in monitoring CHD treatment warrants further investigation.

 

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Artikel online veröffentlicht:
04. September 2025