Virologic Response to Antiviral Therapy in Chronic Hepatitis B Patients With High Viral Load: A Real‐World Cohort Study

ABSTRACT Current guidelines for chronic hepatitis B (CHB) have progressively expanded antiviral treatment indications, with age > 30 years increasingly being incorporated as an important criterion. However, real‐world evidence regarding treatment outcomes in this expanded population remains limited. This study evaluated the 48‐week treatment response and its independent predictors in treatment‐naïve CHB patients aged > 30 years with a high baseline viral load. This retrospective study included 808 treatment‐naïve CHB patients aged > 30 years with baseline HBV DNA ≥ 2000 IU/mL who received first‐line nucleos(t)ide analogue (NA) monotherapy. Patients were classified into moderately high (MH; ≥ 2 × 10 3 to < 1 × 10 7 IU/mL) and extremely high (EH; ≥ 1 × 10 7 IU/mL) viral load groups. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for baseline imbalance. At week 48, the overall virological response (VR) rate was 90.0% (727/808). Among HBeAg‐positive patients at baseline, the HBeAg seroclearance and seroconversion rates were 14.0% (59/422) and 11.8% (50/422), respectively. Compared with the MH group, the EH group had significantly lower rates of VR (81.8% vs. 95.5%, p < 0.001), HBeAg seroclearance (9.4% vs. 22.6%, p < 0.001) and HBeAg seroconversion (7.2% vs. 20.5%, p < 0.001). Multivariable Cox regression analysis showed that ALT ≥ 5 × ULN was independently associated with a higher likelihood of VR, whereas HBeAg positivity and HBV DNA ≥ 1 × 10 7 IU/mL were independently associated with a lower likelihood of VR. These associations remained robust after PSM and IPTW adjustment. First‐line NA therapy achieved a favourable 48‐week VR in CHB patients aged > 30 years with a high viral load. However, HBeAg positivity and extremely high viral load were associated with suboptimal response, supporting intensified monitoring and individualised management.