核苷(酸)类似物治疗慢性乙型肝炎患者血清HBV pgRNA变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2023.05.005

摘要/Abstract

摘要： 目的探讨接受核苷(酸)类似物(NAs)治疗的慢性乙型肝炎(CHB)患者血清乙型肝炎病毒前基因组RNA(HBV pgRNA)变化及其临床意义。方法 2019年9月～2021年9月我院收治的78例CHB初治患者,均接受NAs治疗。采用荧光定量PCR法检测血清HBV DNA和HBV pgRNA水平,采用ELISA法检测血清HBsAg水平。采用Cox回归分析影响抗病毒治疗CHB患者疗效的因素,应用受试者工作特征曲线(ROC)评价血清HBV pgRNA水平预测NAs治疗疗效的效能。结果经NAs抗病毒治疗48周,在78例CHB患者中66例(84.6%)获得完全应答;入组时,完全应答患者血清HBV DNA载量、HBsAg和HBV pgRNA水平分别为(6.0±0.7)lg IU/mL、(2.4±0.5)lg IU/mL和(3.0±0.9)lg copies/mL,显著低于未完全应答患者【分别为(7.1±1.3)lg IU/mL、(3.8±0.9)lg IU/mL和(6.8±0.4)lg copies/mL,P＜0.05);经Cox回归分析显示,入组时血清HBsAg(HR=1.432,95%CI:1.022～2.006)和HBV pgRNA(HR=1.237,95%CI:1.060～1.445)是影响抗病毒治疗疗效的因素(P＜0.05);经ROC分析显示,血清HBV pgRNA预测NAs治疗CHB患者完全应答的最佳截断点为4.8 lg copies/mL,其AUC值为0.825(95%CI:0.722～0.902),预测的灵敏度为89.4%,特异度为83.3%。结论对于初治的CHB患者,检测血清HBV pgRNA水平可能帮助预测NAs抗病毒治疗后的疗效,对制定治疗方案有很大的指导意义。

关键词: 慢性乙型肝炎, 核苷(酸)类似物, HBV前基因组RNA, 治疗, 应答

Abstract: Objective The aim of this study was to investigate serum hepatitis B virus pregenomic RNA (HBV pgRNA) level changes in patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogues (NAs) treatment. Methods 78 patients with CHB were recruited in our hospital between September 2019 and September 2021, and all were treated with NAs for 12 months. Serum HBV DNA and HBV pgRNA levels were detected by fluorescence quantitative PCR. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were observed. Serum HBsAg level was assayed by enzyme-linked immunosorbent assay. The factors influencing complete response (CR) to antiviral therapy were analyzed by Cox regression analysis, and the the predictive performance of serum HBV pgRNA for NAs treatment efficacy was evaluated by receiver operating characteristic (ROC) curves. Results At the end of 48 week observation of antiviral treatment, 66 patients with CHB obtained CR in our series; at presentation, serum HBV DNA loads, HBsAg levels and HBV pgRNA lads in patients with CR were (6.0±0.7)lg IU/mL, (2.4±0.5)lg IU/mL and (3.0±0.9)lg copies/mL, significantly lower than [(7.1±1.3)lg IU/mL, (3.8±0.9)lg IU/mL and (6.8±0.4)lg copies/mL, respectively, P＜0.05) in patients without CR; the Cox analysis showed that serum HBsAg levels (HR=1.432, 95%CI:1.022-2.006) and HBV pgRNA(HR=1.237, 95%CI:1.060-1.445) at admission were the factors influencing antiviral response (P＜0.05), and the ROC analysis demonstrated that the AUC was 0.825(95%CI:0.722-0.902), with the sensitivity of 89.4% and the specificity of 83.3% when serum HBV pgRNA loads equal to 4.8 lg copies/mL was set as the cut-off-value in predicting the antiviral response in patients with CHB. Conclusion The monitoring of serum HBV pgRNA loads has certain clinical predictive efficacy for antiviral therapy with NAs in patients with CHB, which needs further clinical investigation.

Key words: Hepatitis B, Nucleos(t)ide analogue, HBV pregenomic RNA, Therapy, Response

吴育龙, 庄见齐, 刘志成, 马侠槟. 核苷(酸)类似物治疗慢性乙型肝炎患者血清HBV pgRNA变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2023, 26(5): 622-625.

Wu Yulong, Zhuang Jianqi, Liu Zhicheng, et al. Changes of serum HBV pgRNA levels in patients with chronic hepatitis B receiving nucleos(t)ide analogues treatment[J]. Journal of Practical Hepatology, 2023, 26(5): 622-625.

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核苷(酸)类似物治疗慢性乙型肝炎患者血清HBV pgRNA变化及其临床意义探讨^*

Changes of serum HBV pgRNA levels in patients with chronic hepatitis B receiving nucleos(t)ide analogues treatment

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