抗病毒治疗对乙型肝炎病毒整合和肝细胞克隆扩增的影响

StephenW

抗病毒治疗对乙型肝炎病毒整合和肝细胞克隆扩增的影响
Ning Chow 1 , Danny Wong 1 2 , Ching-Lung Lai 1 2 , Lung-Yi Mak 1 2 , James Fung 1 2 , Hoi-Tang Ma 2 3 , Meng-Wai Lei 1 , Wai-Kay Seto 1 2 , Man-凤园 1 2
隶属关系
隶属关系

    1
    医学系。
    2
    肝脏研究国家重点实验室。
    3
    香港大学病理学系，玛丽医院，中国香港特别行政区。

    PMID: 35594553 DOI: 10.1093/cid/ciac383

抽象的

背景：本研究调查了核苷（酸）类似物（NUC）治疗对 HBV DNA 整合和肝细胞克隆扩增的影响，这两者都与慢性乙型肝炎的肝细胞癌（HCC）有关。

方法：纳入 28 名接受 NUC 的患者（11 名拉米夫定、7 名替比夫定、10 名恩替卡韦）。所有人都在基线和第 1 年进行了肝活检，7 人在第 10 年进行了第三次活检。通过反向 PCR 评估了 HBV DNA 整合和肝细胞克隆大小。

结果：所有患者在基线时均检测到 HBV 整合，中位整合频率为每个肝脏 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都与年龄和 HBV 病毒学参数无关。治疗一年后，所有患者仍可检测到 HBV 整合，每个肝脏的中位整合为 5.74×108（减少 0.22 log；P = .008），肝细胞克隆大小为 1.22×105（减少 0.40 log；P = .002)。在治疗的第 10 年仍可检测到 HBV 整合，每个肝脏的整合频率中位数为 4.84×107（从基线减少 0.93 log），肝细胞克隆大小为 2.55×104（从基线减少 1.02 log）。从基线到第 1 年到第 10 年，整合频率和肝细胞克隆大小均呈下降趋势（分别为 P = 0.066 和 0.018）。

结论：NUCs 降低了 HBV DNA 整合和肝细胞克隆扩增，表明除了直接病毒抑制之外还有另一种替代途径来降低 HCC 风险。我们的研究结果支持长期 NUC 治疗以预防 HCC 的观点。

关键词：乙型肝炎病毒；抗病毒治疗；肝细胞克隆扩增；病毒DNA整合。

StephenW

Effect of antiviral treatment on hepatitis B virus integration and hepatocyte clonal expansion
Ning Chow  1 , Danny Wong  1   2 , Ching-Lung Lai  1   2 , Lung-Yi Mak  1   2 , James Fung  1   2 , Hoi-Tang Ma  2   3 , Meng-Wai Lei  1 , Wai-Kay Seto  1   2 , Man-Fung Yuen  1   2
Affiliations
Affiliations

    1
    Department of Medicine.
    2
    State Key Laboratory of Liver Research.
    3
    Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.

    PMID: 35594553 DOI: 10.1093/cid/ciac383

Abstract

Background: This study investigated the effect of nucleos(t)ide analogues (NUC) treatment on HBV DNA integration and hepatocyte clonal expansion, both of which are implicated in hepatocellular carcinoma (HCC) in chronic hepatitis B.

Methods: Twenty-eight patients receiving NUCs (11 lamivudine, 7 telbivudine, 10 entecavir) were included. All had liver biopsies at baseline and year 1, and seven had a third biopsy at year 10. HBV DNA integration and hepatocyte clone size were assessed by inverse PCR.

Results: 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 one 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).

Conclusions: 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.

Keywords: Hepatitis B virus; anti-viral treatment; hepatocyte clonal expansion; viral DNA integration.