接受抗病毒治疗的慢性乙型肝炎患者中残留的HBV DNA和pgRNA病

StephenW

Residual HBV DNA and pgRNA viraemia is associated with hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy
Lung-Yi Mak  1   2 , Qi Huang  3 , Danny Ka-Ho Wong  1   2 , Luisa Stamm  3 , Ka-Shing Cheung  1   4 , Kwan-Lung Ko  1 , Ran Yan  3 , Lea Ouyang  3 , James Fung  1   2 , Wai-Kay Seto  1   2   4 , Man-Fung Yuen  5   6
Affiliations

    PMID: 33772643 DOI: 10.1007/s00535-021-01780-5

Abstract

Background: We aimed to assess whether residual hepatitis B virus (HBV) viraemia is associated with HCC development.

Methods: This is a case-control study of 104 patients [52 HCC and 52 non-HCC (matched with age, gender, cirrhosis and treatment duration)] on ≥ 3 years entecavir (ETV) with unquantifiable HBV DNA by Cobas Taqman assay v2.0 (Roche Diagnostics; lower limit of quantification [LLOQ] 20 IU/mL). Serial sera within 1, 1-2, and > 2 years prior to HCC diagnosis or last follow-up (LFU) were measured for HBV DNA and pre-genomic (pg) RNA using a highly sensitive semi-quantitative PCR assay with lower limit of detection of 10 IU/mL and LLOQ of 51.5 IU/mL, respectively.

Results: Among the 104 patients (80.8% male, median age 61.2 years old, 38.5% cirrhosis, median duration of ETV 45.5 months), 38.5% and 9.6% HCC patients had undetectable serum DNA and pgRNA, respectively, compared to 65.4% and 36.5% in non-HCC patients; P = 0.005 & 0.001, respectively, at the time of HCC diagnosis/LFU. Detectable HBV DNA and pgRNA were associated with a higher 2-year risk of HCC development (HR 2.79, 95% CI 1.424-5.468 & HR 4.544, 95% CI 1.07-19.289, respectively). No significant differences were observed for qHBsAg levels between HCC and non-HCC patients.

Conclusions: More than 50% CHB patients on ETV with HBV DNA < LLOQ by standard assay had persistent viraemia as determined by a more sensitive assay. Detectable HBV DNA or pgRNA by more sensitive assays was associated with HCC development. More potent viral suppression is required to further reduce the risk of HCC.

Keywords: Entecavir; HBV; Liver cancer; Viraemia.

StephenW

接受抗病毒治疗的慢性乙型肝炎患者中残留的HBV DNA和pgRNA病毒血症与肝细胞癌相关
麦龙怡1 2，齐煌3，黄家豪1 2，路易莎·斯塔姆3，张家诚1 4，关龙1，冉艳3，欧亚莉亚3，冯德祥1 2，围-濑户凯1 2 4，袁文峰5 6
隶属关系

    PMID：33772643 DOI：10.1007 / s00535-021-01780-5

抽象的

背景：我们旨在评估残留的乙型肝炎病毒（HBV）病毒血症是否与肝癌的发展有关。

方法：这是一项病例对照研究，采用Cobas Taqman分析法v2对≥3年的恩替卡韦（ETV）不可量化的HBV DNA进行了104例患者[52例HCC和52例非HCC（与年龄，性别，肝硬化和治疗持续时间匹配）]。 .0（Roche Diagnostics；定量下限[LLOQ] 20 IU / mL）。使用具有下限的高灵敏度半定量PCR分析法，对HCC诊断或最后一次随访（LFU）之前的1、1-2和> 2年内的连续血清中的HBV DNA和基因组前（pg）RNA进行了测量分别检测10 IU / mL和LLOQ 51.5 IU / mL。

结果：在104例患者中（男性80.8％，中位年龄61.2岁，肝硬化38.5％，ETV中位持续时间45.5个月），分别有38.5％和9.6％的HCC患者血清DNA和pgRNA检出率分别为65.4％和pgRNA。非HCC患者中36.5％；在进行HCC诊断/ LFU时，P分别为0.005和0.001。可检测的HBV DNA和pgRNA与2年HCC发生风险较高相关（分别为HR 2.79、95％CI 1.424-5.468和HR 4.544、95％CI 1.07-19.289）。在HCC和非HCC患者之间，qHBsAg水平没有观察到显着差异。

结论：通过标准检测，超过50％的ETV上HBV DNA <LLOQ的CHB患者具有持续的病毒血症，这是通过更敏感的检测确定的。通过更灵敏的检测方法检测到的HBV DNA或pgRNA与HCC的发展有关。需要更有效的病毒抑制以进一步降低HCC的风险。

关键字：恩替卡韦；乙肝病毒;肝癌;病毒血症。