Predictors of low-level viremia in chronic hepatitis B and the efficacy of pegylated interferon-alpha: a real-world study.

BACKGROUND

Low-level viremia (LLV) is closely associated with the prognosis of patients with chronic hepatitis B (CHB), it can increase the incidence of cirrhosis and hepatocellular carcinoma. Our research aims to explore how to identify LLV early and implement effective therapeutic intervention.

METHODS

This retrospective study included 720 patients who were either treatment-naive or had not received treatment within the past 5 years. After 48 weeks follow-up, they were categorized into either the complete virological response (CVR) or LLV. Independent risk factors associated with LLV were screened by LASSO regression analysis and a prediction model incorporating these factors was developed. Furthermore, among patients who developed LLV, we compared the therapeutic efficacy of nucleos(t)ide analogue (NAs) monotherapy and pegylated interferon alpha (IFNα)-based combination therapy.

RESULTS

Firstly, four independent risk variables were found to be connected to the incidence of LLV, including age, baseline HBV DNA level, baseline HBsAg level, and baseline HBeAg status. The model showed AUCs of 0.861 (training) and 0.799 (validation), with good calibration. Secondly, between IFNα-based combination therapy and NAs monotherapy group, HBV DNA clearance rates showed no difference at week 24 but significant divergence at week 48 (p = 0.684 and p = 0.001). HBsAg decline rates (in patients with baseline HBsAg ≥ 1500 IU/mL) differed significantly at both 24/48 weeks (p < 0.001). Throughout the 48-week follow-up, the cumulative rates of HBV DNA clearance (p < 0.001), HBsAg loss (p < 0.001), HBeAg loss (p = 0.008), and HBeAg seroconversion (p = 0.001) were all significantly higher in the combination therapy group, though the cumulative HBsAg seroconversion rate was not (p = 0.535). Furthermore, stratified analysis confirmed the superior efficacy of IFNα-based combination therapy across key subgroups. It outperformed NAs monotherapy both in patients with HBsAg ≥ 1500 IU/mL (24w: p = 0.031; 48w: p = 0.002) and in those with HBV DNA < 500 IU/mL (24w: p = 0.01; 48w: p < 0.001).

CONCLUSION

Age, baseline HBV DNA level, HBsAg level, and HBeAg status were independently associated with the prevalence of LLV independently. Compared to NAs monotherapy, IFNα-based combination therapy in LLV patients demonstrated significantly higher rates of CVR, HBsAg decline, HBsAg loss/seroconversion, and HBeAg loss.