Wang Lilin, Lu Junfeng, Liu Dan, Ren Shan, Chen Xinyue, Hu Zhongjie, Zheng Sujun
The First Department of Liver Disease Center, Beijing You'an Hospital, Capital Medical University, Beijing, China.
Front Med (Lausanne). 2025 Aug 22;12:1642961. doi: 10.3389/fmed.2025.1642961. eCollection 2025.
Low-level viremia (LLV) is associated with the progression of liver fibrosis and a high risk of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). The present study aimed to compare the efficacy between nucleos(t)ide analogs (NAs) therapy and combination therapy of NAs and pegylated interferon-α (pegIFN-α) in entecavir (ETV)-treated CHB patients with LLV.
This was a retrospective cohort study. ETV-treated CHB patients with LLV were included and divided into the NA group and the NA+IFN group. The NA group comprised patients switching to tenofovir alafenamide fumarate, whereas the NA+IFN group comprised those adding on pegIFN-α additionally. We compared changes in HBV markers and complete virological response (CVR) between the two groups.
A total of 127 patients were enrolled, including 51 in NA+IFN group and 76 in NA group. In the NA+IFN group, the decline in HBsAg level from baseline (△ HBsAg) was significantly greater (-0.17 logIU/mL vs. -0.06 logIU/mL, = 0.011) at week 24, and HBsAg clearance rate and △ HBsAg were significantly higher (8.9% vs. 0%, = 0.017; -0.27 logIU/mL vs. -0.11 logIU/mL, = 0.023) at week 48. The 48-week CVR rate in the NA+IFN group was 66.7% (34/51), which was comparable to 68.4% (52/76) in the NA group ( = 0.836).
In ETV-treated patients with LLV, receiving NAs plus pegIFN-α tends to increase the effect of HBsAg clearance.
低水平病毒血症（LLV）与慢性乙型肝炎（CHB）患者肝纤维化进展及肝细胞癌高风险相关。本研究旨在比较核苷（酸）类似物（NAs）疗法与NAs联合聚乙二醇化干扰素-α（pegIFN-α）疗法对恩替卡韦（ETV）治疗的LLV CHB患者的疗效。
这是一项回顾性队列研究。纳入ETV治疗的LLV CHB患者，分为NA组和NA+IFN组。NA组患者换用富马酸替诺福韦酯，而NA+IFN组患者额外加用pegIFN-α。我们比较了两组之间乙肝病毒标志物变化及完全病毒学应答（CVR）情况。
共纳入127例患者，其中NA+IFN组51例，NA组76例。在NA+IFN组，第24周时HBsAg水平从基线的下降幅度（△HBsAg）显著更大（-0.17 logIU/mL对-0.06 logIU/mL，P = 0.011），第48周时HBsAg清除率及△HBsAg显著更高（8.9%对0%，P = 0.017；-0.27 logIU/mL对-0.11 logIU/mL，P = 0.023）。NA+IFN组48周CVR率为66.7%（34/51），与NA组的68.4%（52/76）相当（P = 0.836）。
在ETV治疗的LLV患者中，接受NAs联合pegIFN-α治疗往往可提高HBsAg清除效果。
