慢加急性乙型肝炎肝衰竭患者血清自噬相关蛋白水平及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2021.05.029

摘要/Abstract

摘要： 目的探讨慢加急性乙型肝炎肝衰竭(HBV-ACLF)患者血清p62、微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)和Beclin1水平变化及其临床意义。方法 2018年9月～2020年9月我院收治的HBV-ACLF患者60例和同期体检的健康人65例,计算终末期肝病模型评分(MELD),采用ELISA法测定血清p62、Beclin1和LC3-Ⅱ水平;应用受试者工作特征曲线(ROC)下面积(AUC)评估指标对HBV-ACLF患者预后的预测效能。结果 60例HBV-ACLF患者血清LC3-Ⅱ和Beclin1水平分别为(66.8±13.5)ng/mL和(11.7±3.6)ng/mL,均显著高于健康人【分别为(35.8±6.2)ng/mL和(8.2±2.9)ng/mL,P＜0.05】,而血清p62水平为(2.5±0.9)ng/mL,显著低于健康人【(4.5±1.6)ng/mL,P＜0.05】;在治疗观察90 d,本组HBV-ACLF患者死亡18例(30.0%);入院时死亡组血清LC3-Ⅱ、Beclin1和MELD评分为(76.25±12.1)ng/mL、(10.9±3.2)ng/mL和(20.1±3.3)分,均显著高于生存组【分别为(62.8±10.2)ng/mL、(13.4±3.5)ng/mL和(16.7±4.6)分,P＜0.05】,而血清p62水平为(1.7±0.6)ng/mL,显著低于生存组【(2.9±0.8)ng/mL,P＜0.05】;ROC曲线分析发现,以血清p62＜2.2 ng/mL、LC3-Ⅱ＞70.3 ng/mL和Beclin1＞12.6 ng/mL为截断点,预测HBV-ACLF患者预后不良的AUC分别为0.856、0.820和0.765,三者联合预测的AUC为0.910,与以MELD评分＞18.3 分为截断点的预测效能为0.917相差无几。结论应用血清p62、LC3-Ⅱ和Beclin1水平预测HBV-ACLF患者预后有一定的实用意义,值得进一步动态观察。

Abstract: Objective The aim of this study was to explore the clinical significance of serum p62, microtubule-associated protein 1 light chain 3-II (LC3-II) and Beclin1 in patients with hepatitis B virus infection-induced acute-on-chronic liver failure (HBV-ACLF). Methods Sixty patients with HBV-ACLF and 65 subjects who underwent physical examination in our hospital during the same period were recruited in this study between September 2018 and September 2020. The scores of model for end-stage liver disease (MELD) were calculated. Serum 62, Beclin1 and LC3-II levels were detected by ELISA. The predictive efficacy of serum p62, Beclin1 and LC3-II as well as MELD for prognosis of patients with HBV-ACLF was evaluated by area under the receiver operating characteristic curves (AUROC). Results At admission, serum LC3-Ⅱ and Beclin1 levels in patients with HBV-ACLF were (66.8±13.5)ng/mL and (11.7±3.6)ng/mL, both significantly higher than [(35.8±6.2)ng/mL and (8.2±2.9)ng/mL, respectively, P＜0.05], while serum p62 level was (2.5±0.9)ng/mL, significantly lower than [(4.5±1.6)ng/mL, P＜0.05] in the control; at day 90, 18 patients(30.0%)died; serum LC3-Ⅱ, Beclin1 levels and MELD score in dead patients at presentation were (76.25±12.1)ng/mL, (10.9±3.2)ng/mL and (20.1±3.3), all significantly higher than [(62.8±10.2)ng/mL,(13.4±3.5)ng/mL and (16.7±4.6), respectively, P＜0.05], while serum p62 level was (1.7±0.6)ng/mL, much lower than in the survivals; the ROC analysis showed that serum p62＜2.2 ng/mL, LC3-Ⅱ＞70.3 ng/mL and Beclin1＞12.6 ng/mL were set as the cut-off-value, the AUC were 0.856, 0.820 and 0.765 in predicting the poor prognosis of patients with HBV-ACLF, and the AUC of the three combination was 0.910, similar to 0.917 by MELD score when greater than 18.3 of it was set as the cut-off-value. Conclusion Serum p62, LC3-II and Beclin1 levels might be monitored and applied to predict the prognosis of patients with HBV-ACLF.

Key words: Acute-on-chronic liver failure, Microtubule-associated protein 1 light chain 3-II, p62, Beclin1, Prognosis, Diagnostic trial

黄霜湘, 姚朝光, 蓝婧, 欧琴, 覃冬林, 陈丽芬, 黄洁婕. 慢加急性乙型肝炎肝衰竭患者血清自噬相关蛋白水平及其临床意义探讨^*[J]. 实用肝脏病杂志, 2021, 24(5): 721-724.

Huang Shuangxiang, Yao Chaoguang, Lan Jing, et al. Clinical significance of serum autophagy-related proteins in patients with hepatitis B virus-induced acute on chronic liver failure[J]. Journal of Practical Hepatology, 2021, 24(5): 721-724.

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慢加急性乙型肝炎肝衰竭患者血清自噬相关蛋白水平及其临床意义探讨^*

Clinical significance of serum autophagy-related proteins in patients with hepatitis B virus-induced acute on chronic liver failure

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