Introduction 

Research has shown that high levels of hepatitis B surface antibody (HBsAb) at the end-of-treatment (EOT) were linked to lower risk of relapse after clinical cure of chronic hepatitis B (CHB). Also, baseline HBsAb independently predicted seroconversion of  hepatitis B surface antigen (HBsAg) and viremia recurrence in pegylated interferon (PEG-IFN)-administered CHB patients. Baseline HBsAg predicted functional cure for CHB, however, no standardized criteria for specific baseline levels are available in relapsed CHB, and HBsAb levels at the end of treatment are still under investigation.

Aim

To evaluate the optimal baseline HBsAg and EOT HBsAb levels which affect recurrence after a clinical cure for CHB.

Patient Profile 

Method

Study Design

• Multicenter, retrospective study 
• Follow-up was for 48 weeks after treatment cessation

Endpoint

Results 

Efficacy 

• At baseline, the level of HBsAg was significantly greater in the group with recurrence than in the group without recurrence (P = 0.038)
• At EOT, HBsAb levels were lower in the relapsed group than in the non-relapsed group (P = 0.014)
• Baseline serum HBsAg concentration ≥100 IU/mL was a risk factor for CHB recurrence (OR 3.74, P = 0.006) which indicated that these patients may be likelier to suffer a recurrence than patients with baseline HBsAg levels <100 IU/mL
• An EOT serum HBsAb concentration ≥500 mIU/mL was a protective factor for CHB recurrence (OR 0.08, P = 0.017) which indicated that these patients may be less likely to relapse than those with <500 mIU/mL
• During follow-up, the cumulative recurrence probabilities were low in HBsAg ≤100 IU/mL versus HBsAg >100 IU/mL group (Figure 1) 
• At EOT, the cumulative recurrence probabilities were lowest in patients with HBsAb ≥500 mIU/mL than in those with HBsAb <100 mIU/mL and 100 ≤ HBsAb <500 mIU/mL (Figure 1)
• The cumulative rates of EOT recurrence at 12, 24, 36, and 48 weeks were 9.7%, 14.7%, 18.4%, and 19.8%, respectively
• Clinical recurrence occurred most commonly at week 12 (48.15%)
• A nomogram was constructed which effectively predicted the risk probability of recurrence following clinical cure of CHB and it was suitable for application in a clinical setting (AUC 0.74; sensitivity 42%, specificity 93%)

Figure 1: Cumulative recurrence probability rate in CHB patient groups as per their HBsAg and HBsAb levels 

Safety   

Conclusion 

Patients who were functionally cured of CHB had a low incidence of recurrence among patients with baseline HBsAg levels <100 IU/mL and HBsAb levels >500 mIU/mL at the end of treatment.

Scientific Reports 2025; 15: 13873