Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
State Key Laboratory of Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
Clin Infect Dis. 2023 Feb 8;76(3):e801-e809. doi: 10.1093/cid/ciac383.
This study investigated the effect of nucleos(t)ide analogue (NUC) treatment on hepatitis B virus (HBV) DNA integration and hepatocyte clonal expansion, both of which are implicated in hepatocellular carcinoma (HCC) in chronic hepatitis B.
Twenty-eight patients receiving NUCs (11 lamivudine, 7 telbivudine, 10 entecavir) were included. All had liver biopsies at baseline and year 1, and 7 had a third biopsy at year 10. HBV DNA integration and hepatocyte clone size were assessed by inverse polymerase chain reaction.
All patients had detectable HBV integration at baseline, with a median integration frequency of 1.01 × 109 per liver and hepatocyte clone size of 2.41 × 105. Neither integration frequency nor hepatocyte clone size correlated with age and HBV virologic parameters. After 1 year of treatment, HBV integration was still detectable in all patients, with a median of 5.74 × 108 integration per liver (0.22 log reduction; P = .008) and hepatocyte clone size of 1.22 × 105 (0.40 log reduction; P = .002). HBV integration remained detectable at year 10 of treatment, with a median integration frequency of 4.84 × 107 integration per liver (0.93 log reduction from baseline) and hepatocyte clone size of 2.55 × 104 (1.02 log reduction from baseline). From baseline through year 1 to year 10, there was a decreasing trend in both integration frequency and hepatocyte clone size (P = .066 and.018, respectively).
NUCs reduced both HBV DNA integration and hepatocyte clonal expansion, suggesting another alternative pathway besides direct viral suppression to reduce HCC risk. Our findings supported the notion for a long-term NUC treatment to prevent HCC.
本研究旨在探讨核苷（酸）类似物（NUC）治疗对乙型肝炎病毒（HBV）DNA 整合和肝细胞克隆扩增的影响，这两者均与慢性乙型肝炎相关肝细胞癌（HCC）有关。
纳入 28 例接受 NUC 治疗的患者（拉米夫定 11 例、替比夫定 7 例、恩替卡韦 10 例）。所有患者均在基线和第 1 年进行了肝活检，其中 7 例在第 10 年进行了第三次肝活检。通过反转聚合酶链反应评估 HBV DNA 整合和肝细胞克隆大小。
所有患者基线时均检测到 HBV 整合，中位整合频率为每肝 1.01×109，肝细胞克隆大小为 2.41×105。整合频率和肝细胞克隆大小均与年龄和 HBV 病毒学参数无关。治疗 1 年后，所有患者仍可检测到 HBV 整合，中位整合频率为每肝 5.74×108（降低 0.22 对数；P=0.008），肝细胞克隆大小为 1.22×105（降低 0.40 对数；P=0.002）。治疗 10 年后仍可检测到 HBV 整合，中位整合频率为每肝 4.84×107（与基线相比降低 0.93 对数），肝细胞克隆大小为 2.55×104（与基线相比降低 1.02 对数）。从基线到第 1 年至第 10 年，整合频率和肝细胞克隆大小均呈下降趋势（P=0.066 和 0.018）。
NUC 降低了 HBV DNA 整合和肝细胞克隆扩增，提示除直接抑制病毒外，还有另一种降低 HCC 风险的替代途径。我们的发现支持长期 NUC 治疗以预防 HCC 的观点。
