乙型肝炎病毒相关慢加急性肝衰竭患者血清miRNA差异表达谱及其预后预测价值

摘要/Abstract

摘要： 目的探讨乙型肝炎病毒相关慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者血清微小RNA(miRNA)差异表达谱及其对预后的预测价值。方法选取2018年5月至2019年5月在广州医科大学附属市八医院住院的HBV感染患者55例,其中HBV-ACLF组30例、慢性乙型肝炎(chronic hepatitis B,CHB)组20例,另设立健康对照(health control,HC)组25例,分析3组患者miRNA表达差异情况,及HBV-ACLF患者好转组与未愈组miRNA表达差异情况。结果 75例研究对象中,男59例,女16例,年龄(39.7±9.1)岁;HBV-ACLF组好转 17例,未愈13例。3组性别、年龄、肌酐水平及白细胞计数差异无统计学意义(P>0.05);HBV-ACLF组与CHB组、HC组比较,具有较低的红细胞计数、血红蛋白水平、血小板计数及较高ALT、AST水平,且miRNA-144-3P、miRNA-205-5p、miRNA-96-5p、miRNA451a表达上调,差异均有统计学意义(均P<0.05)。HBV-ACLF好转组与未愈组比较,miRNA-205-5p、miRNA-96-5p均为上调表达,差异有统计学意义(P<0.05)。结论与CHB患者及健康人群相比,HBV-ACLF患者miRNA表达谱存在差异;miRNA 205-5p及miRNA 96-5p高表达可能预示着HBV-ACLF 患者预后良好。

关键词: 乙型肝炎病毒, 慢加急性肝衰竭, 微小RNA, 预测

Abstract: Objective To investigate the prognostic value of serum miRNA in hepatitis B virus-related chronic and acute liver failure (HBV-ACLF), and to guide clinical diagnosis and treatment.Methods Patients with hepatitis B virus infection admitted to our hospital from May 2018 to May 2019 were enrolled. All the patients were divided into HBV-ACLF group and chronic hepatitis B (CHB) group, a health control (HC) group was also established. The differential expression of miRNA among the 3 groups were analyzed.Results A total of 75 patients (59 males and 16 females) were included, with an average age of 39.7±9.1 years. There were 30 patients in HBV-ACLF group (17 cases were improved and 13 cases were not cured), 20 cases in CHB group and 25 cases in HC group. There was no significant difference in sex, age, creatinine level and white blood cell count among the 3 groups (P>0.05). Compared with cases in CHB group and HC group, patients in HBV-ACLF group had lower erythrocyte count, hemoglobin level and platelet count (P<0.001), higher levels of alanine aminotransferase, aspartate aminotransferase (P<0.001). The expression levels of miRNA-144-3P, miRNA-205-5p, miRNA-96-5p and miRNA451a were significantly up-regulated in HBV-ACLF group (P<0.05). In HBV-ACLF group, the expression levels of miRNA-205-5p and miRNA-96-5p in patients with condition improved were up-regulated, the difference was statistically significant (P<0.05).Conclusion The miRNA expression profiles in patients with HBV-ACLF is significantly different from that in CHB patients and healthy people. High expression of miRNA 205-5p and miRNA 96-5p in patients with HBV-ACLF may indicate a good prognosis.

Key words: Hepatitis B virus, Acute-on-chronic liver failure, MicroRNA, Prognosis

谢志伟, 陆霭琪, 杨可立, 陈彬彬, 关玉娟, 肖光明, 李剑萍. 乙型肝炎病毒相关慢加急性肝衰竭患者血清miRNA差异表达谱及其预后预测价值[J]. 肝脏, 2022, 27(8): 853-857.

XIE Zhi-wei, LU Ai-qi, YANG Ke-li, CHEN Bin-bin, GUAN Yu-juan, XIAO Guang-ming, LI Jian-ping. Differential expression and prognostic value of serum miRNA in patients with hepatitis B virus-related acute-on-chronic liver failure[J]. Chinese Hepatolgy, 2022, 27(8): 853-857.

参考文献

[1] 刘添皇. 慢性重型肝炎病原学特征、病变基础、年龄、性别、抗病毒治疗与病死率相关性的分析. 临床医药实践B版. 2010. 19(1): 11-12.
[2] Fischer J, Silva TE, Soares E, et al. From stable disease to acute-on-chronic liver failure: circulating cytokines are related to prognosis in different stages of cirrhosis. Cytokine. 2017. 91: 162-169.
[3] DU X, SHI Y, YANG Y, et al. DAMP molecular IL-33 augments monocytic inflammatory storm in hepatitis B-precipitated acute-on-chronic liver failure. Liver Int, 2018,38(2):229-238.
[4] Singh AK, Rooge SB, Varshney A, et al. Global microRNA expression profiling in the liver biopsies of hepatitis B virus-infected patients suggests specific microRNA signatures for viral persistence and hepatocellular injury. Hepatology, 2018,67(5):1695-1709.
[5] 任雪维, 张吉才. 肝细胞肝癌患者血浆miR-29a水平的变化及其临床意义. 现代检验医学杂志,2017,32(2):33-35,40
[6] Ji F, Yang B, Peng X, et al. Circulating microRNAs in hepatitis B virus-infected patients. J Viral Hepat, 2011,18(7):e242-251.
[7] Van Der Ree MH, Jansen L, Kruize Z, et al. Plasma microRNA levels are associated with hepatitis B e antigen status and treatment response in chronic hepatitis B patients. J Infect Dis, 2017,215(9):1421-1429.
[8] Sharma AD, Narsin N, Händel EM, et al. MicroRNA-221 regulates FAS-induced fulminant liver failure. Hepatology, 2011,53(5):1651-1661.
[9] Wen Y, Peng SF, Fu L, et al. Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure. Hepatobiliary Pancreat Dis Int, 2018,17(2):126-132.
[10] 吴炳, 张涵斌, 柯淑慧, 等. miR-200a在乙型肝炎病毒相关慢加急性肝衰竭患者血清中的表达及其与预后的关系. 中国老年学杂志,2020,40(14):2990-2993.
[11] 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版). 国际流行病学传染病学杂志,2018,45(6):379-387.
[12] Clària J, Stauber RE, Coenraad MJ, et al. Systemic inflammation in decompensated cirrhosis: characterization and role in acute-on-chronic liver failure. Hepatology, 2016,64(4):1249-1264.
[13] 黄允, 李艳, 彭锐, 等. HBV感染致肝损伤患者CRP,hsCRP和SAA临床价值的探讨. 现代检验医学杂志,2017,32(2):49-52.
[14] Lippi G, Targher G, Montagnana M, et al. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med, 2009,133(4):628-632.
[15] 许姗姗, 韦新焕, 林伟, 等. 慢加急性肝衰竭患者血小板计数及其动态变化的临床意义. 临床肝胆病杂志,2018,34(4):810-813.
[16] Riazalhosseini B, Mohamed R, Apalasamy YD, et al. Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B. Rev Soc Bras Med Trop, 2017,50(2):161-166.
[17] Zhou Shao-jun, Liu Fu-yao, Zhang An-hong, et al. MicroRNA-199b-5p attenuates TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Br J Cancer, 2017,117(2):233-244.
[18] Tseng CW, Huang HC, Shih AC, et al. Revealing the anti-tumor effect of artificial miRNA p-27-5p on human breast carcinoma cell line T-47D. Int J Mol Sci, 2012,13(5):6352-6369.
[19] Chen X, Chen Y, Dai L, et al. MiR-96-5p alleviates inflammatory responses by targeting NAMPT and regulating the NF-κB pathway in neonatal sepsis. Biosci Rep, 2020,40(7):BSR20201267.
[20] An G, Liang S, Sheng C, et al. Upregulation of microRNA-205 suppresses vascular endothelial growth factor expression-mediated PI3K/Akt signaling transduction in human keloid fibroblasts. Exp Biol Med (Maywood), 2017,242(3):275-285.
[21] Wu W, Yan H, Zhao H, et al. Characteristics of systemic inflammation in hepatitis B-precipitated ACLF: differentiate it from No-ACLF. Liver Int, 2018,38(2):248-257.
[22] Bernal W, Jalan R, Quaglia A, et al. Acute-on-chronic liver failure. Lancet, 2015,386(10003):1576-1587.
[23] Wasmuth HE, Kunz D, Yagmur E, et al. Patients with acute on chronic liver failure display "sepsis-like" immune paralysis. J Hepatol, 2005,42(2):195-201.