Hu Qiankun, Zhang Xueyun, Cao Xiongyue, Tao Shuai, Chen Chong, Lu Mengxin, Zhao Conglin, Chen Liang, Li Qiang, Qi Xun, Huang Yuxian
Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Antiviral Res. 2025 Aug;240:106192. doi: 10.1016/j.antiviral.2025.106192. Epub 2025 May 20.
BACKGROUND & AIMS: The long-term clinical benefits of interferon (IFN)-based therapy compared to nucleos(t)ide analogue (NA) monotherapy in HBeAg-positive chronic hepatitis B (CHB) have not been well defined. This study aimed to evaluate the cumulative incidence of new-onset cirrhosis, serological responses, and hepatocellular carcinoma (HCC) development between these treatment strategies.
Two independent cohorts of non-cirrhotic, HBeAg-positive CHB patients were analyzed: a treatment-naïve cohort (n = 686) and an NA-experienced cohort (n = 531). Patients received either IFN-based therapy or NA monotherapy. Propensity score matching (PSM) was employed to minimize intergroup heterogeneity. The primary endpoint was the cumulative incidence of new-onset cirrhosis.
After PSM, the 10-year cumulative incidence of new-onset cirrhosis was significantly lower in the IFN-based therapy group compared to the NA monotherapy group in both the treatment-naïve (3.3 % vs 20.0 %, p = 0.005) and NA-experienced (4.9 % vs 20.9 %, p = 0.034) cohorts. IFN-based therapy also resulted in significantly higher serological response rates across both cohorts, including HBeAg loss (treatment-naïve: 84.7 % vs 55.6 %; NA-experienced: 60.4 % vs 43.6 %, both p < 0.001) and HBsAg loss (treatment-naïve: 14.3 % vs 5.7 %, p = 0.006; NA-experienced: 10.2 % vs 1.3 %, p < 0.001). Subgroup analysis showed that patients receiving IFN-based therapy who achieved HBeAg loss within 96 weeks had the greatest long-term benefits, with lower cirrhosis incidence and higher HBsAg loss rates. Although the incidence of HCC was lower in the IFN-based group, the difference did not reach statistical significance (both p > 0.05).
IFN-based therapy provides superior long-term benefits over NA monotherapy in reducing cirrhosis risk and enhancing serological responses in HBeAg-positive CHB patients.
在HBeAg阳性慢性乙型肝炎（CHB）患者中，与核苷（酸）类似物（NA）单药治疗相比，基于干扰素（IFN）的治疗的长期临床益处尚未明确界定。本研究旨在评估这些治疗策略之间新发肝硬化、血清学反应和肝细胞癌（HCC）发生的累积发生率。
分析了两组独立的非肝硬化、HBeAg阳性CHB患者队列：初治队列（n = 686）和经治NA队列（n = 531）。患者接受基于IFN的治疗或NA单药治疗。采用倾向评分匹配（PSM）以尽量减少组间异质性。主要终点是新发肝硬化的累积发生率。
PSM后，在初治队列（3.3% 对20.0%，p = 0.005）和经治NA队列（4.9% 对20.9%，p = 0.034）中，基于IFN的治疗组新发肝硬化的10年累积发生率均显著低于NA单药治疗组。基于IFN的治疗在两个队列中也导致显著更高的血清学反应率，包括HBeAg消失（初治：84.7% 对55.6%；经治NA：60.4% 对43.6%，均p < 0.001）和HBsAg消失（初治：14.3% 对5.7%，p = 0.006；经治NA：10.2% 对1.3%，p < 0.001）。亚组分析显示，在96周内实现HBeAg消失的接受基于IFN治疗的患者具有最大的长期益处，肝硬化发生率较低且HBsAg消失率较高。虽然基于IFN的治疗组中HCC的发生率较低，但差异未达到统计学意义（均p > 0.05）。
在降低HBeAg阳性CHB患者的肝硬化风险和增强血清学反应方面，基于IFN的治疗比NA单药治疗具有更好的长期益处。
