肝衰竭预后相关标志物的应用现状与展望

刘叶莹; 王婷; 窦爱华; 郑素军; 徐斌; 刘梅

doi:10.3969/j.issn.1001-5256.2019.05.046

肝衰竭预后相关标志物的应用现状与展望

DOI: 10.3969/j.issn.1001-5256.2019.05.046

首都医科大学附属北京佑安医院疑难肝病及人工肝中心

基金项目:

北京市医院管理局临床医学发展专项经费资助(XMLX201830)；北京卫生系统高技术人才培养项目基金(2015-3-104)；北京市教委科技计划面上项目(KM201610025021)；国家135科技重大专项“艾滋病和病毒性肝炎等重大传染病防治”(2017ZX10202203-006,2017ZX10302201-004,2018ZX10301407-005,2018ZX10302205-004)；

详细信息

中图分类号: R575.3
计量
- 文章访问数: 1003
- HTML全文浏览量: 22
- PDF下载量: 272
- 被引次数: 0
出版历程
- 收稿日期: 2018-11-05
- 出版日期: 2019-05-20

Current status and perspectives of prognostic markers for liver failure

Intractable Hepatic Diseases and Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University

Research funding:

摘要

摘要: 准确判断病情和预后对于提高肝衰竭患者的生存率和最优分配肝源具有重要意义。阐述了目前临床常用的预测肝衰竭预后相关标志物如ALT、AST、TBil、PT、PTA、国际标准化比值等应用现状,归纳了近年来新发现的相关标志物如炎性反应相关标志物、中性粒细胞明胶酶相关脂质运载蛋白、免疫反应相关标志物、角蛋白、肠道菌群、微小RNA、肝衰竭自身抗原抗体以及血液动力学紊乱等方面的研究进展,提出肝衰竭预后受多种因素影响,目前仍缺乏更敏感有效的标志物以及规范的预后评分系统。将新发现的标志物单独或与其他传统标志物联合应用,或将有助于提升肝衰竭预后判断的敏感性和特异性。
- 肝功能衰竭 /
- 预后 /
- 生物学标记 /
- 综述
Abstract: Accurate judgment of conditions and prognosis has important clinical significance in improving survival rate and optimal distribution of liver source in patients with liver failure. This article reviews the current application of prognostic markers for liver failure such as alanine aminotransferase, aspartate aminotransferase, total bilirubin, prothrombin time, prothrombin time activity, and international normalized ratio and summarizes the new markers discovered in recent years, such as inflammatory response-related markers, neutrophil gelatinase-associated lipocalin, immune response-related markers, keratin, intestinal flora, microRNAs, liver failure autoantigen and autoantibody, and hemodynamic disorder. It is pointed out that the prognosis of liver failure is affected by many factors and there is still a lack of more sensitive and effective markers and a standardized prognostic scoring system. The new markers used alone or in combination with traditional markers may help to improve the sensitivity and specificity of prognostic evaluation of liver failure.
- liver failure /
- prognosis /
- biological markers /
- review

HTML全文

参考文献(38)

[1] ZHANG DJ, ZHOU B, HOU JL. Research progress in prognostic models of acute-on-chronic liver failure[J]. J Clin Hepatol, 2018, 34 (6) :1351-1356. (in Chinese) 张东敬, 周彬, 侯金林.慢加急性肝衰竭预后模型的研究进展[J].临床肝胆病杂志, 2018, 34 (6) :1351-1356.

[2] YANG B, WU YK, CHEN ZC, et al. The dynamic changes of AST, ALT, TBil and PT and their relationship with prognosis of acute-on-chronic hepatitis B liver failure[J]. J Clin Hepatol, 2012, 28 (3) :205-208. (in Chinese) 杨波, 吴元凯, 陈忠诚, 等. ALT、AST、TBil及PT变化趋势与慢加急性乙型肝炎肝衰竭预后的关系[J].临床肝胆病杂志, 2012, 28 (3) :205-208.

[3] CAI XJ, SHEN Y, ZHU XH, et al. Evaluation of integrated model for end-stage liver disease model in predicting prognosis of acute-on-chronic liver failure and the choice of treatment[J/CD]. Chin J Exp Clin Infect Dis:Electronic Edition, 2018, 12 (5) :37-43. (in Chinese) 蔡晓娟, 沈毅, 朱晓红, 等.整合终末期肝病模型在慢加急性肝功能衰竭预后判断及治疗中的应用[J/CD].中华实验和临床感染病杂志:电子版, 2018, 12 (5) :37-43.

[4] MOREAU R, JALAN R, GINES P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis[J]. Gastroenterology, 2013, 144 (7) :1426-1437.

[5] LIU J, GAO CD, ZHANG LX, et al. Influence of neutrophillymphocyte ratio on prognosis of liver cancer:A meta-analysis[J]. J Clin Hepatol, 2017, 33 (7) :1305-1309. (in Chinese) 刘健, 高驰丹, 张立鑫, 等.中性粒细胞与淋巴细胞比值对肝癌预后影响的Meta分析[J].临床肝胆病杂志, 2017, 33 (7) :1305-1309.

[6] ZHANG L, CHEN W, SHENG YJ, et al. Value of Model for End-Stage Liver Disease score combined with neutrophillymphocyte ratio in predicting the short-term prognosis of patients with HBV-related acute-on-chronic liver failure[J]. J Clin Hepatol, 2018, 34 (3) :553-557. (in Chinese) 张丽, 陈文, 盛云健, 等. MELD评分联合中性粒细胞/淋巴细胞比值对HBV相关慢加急性肝衰竭短期预后的预测价值[J].临床肝胆病杂志, 2018, 34 (3) :553-557.

[7] SHIN JS, SUH KW, OH SY. Preoperative neutrophil to lymphocyte ratio predicts survival in patients with T1-2N0 colorectal cancer[J]. J Surg Oncol, 2015, 112 (6) :654-657.

[8] IETOMI K. A study on the role of granulocytes in carcinomabearing host———G/L ratio as a new host indicator[J]. Nihon Gan Chiryo Gakkai Shi, 1990, 25 (3) :662-671.

[9] ZHENG MH, SHI KQ, FAN YC, et al. A model to determine 3-month mortality risk in patients with acute-on-chronic hepatitis B liver failure[J]. Clin Gastroenterol Hepatol, 2011, 9 (4) :351-356. e3.

[10] MATLOUB AA, AGLAN HA, MOHAMED EL SOUDA SS, et al.Influence of bioactive sulphated polysaccharide-protein complexes on hepatocarcinogenesis, angiogenesis and immunomodulatory activities[J]. Asian Pac J Trop Med, 2016, 9 (12) :1200-1211.

[11] MOREAU R, JALAN R, GINES P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis[J]. Gastroenterology, 2013, 144 (7) :1426-1437. e9.

[12] LIU H, ZHANG H, WAN G, et al. Neutrophil-lymphocyte ratio:A novel predictor for short-term prognosis in acute-onchronic hepatitis B liver failure[J]. J Viral Hepat, 2014, 21 (7) :499-507.

[13] AROUCHA DC, CARMO RF, VASCONCELOS LR, et al. TNF-αand IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals[J]. J Med Virol, 2016, 88 (9) :1587-1595.

[14] YE Y, LIU J, LAI Q, et al. Decreases in activated CD8 (+) T cells in patients with severe hepatitis B are related to outcomes[J]. Dig Dis Sci, 2015, 60 (1) :136-145.

[15] ZHOU DS, LIU BF. Research progress of the relationship between cytokines and non-alcoholic fatty liver disease[J]. Acta Med Sinica, 2014, 27 (4) :128-131. (in Chinese) 周冬生, 刘博峰.细胞因子与非酒精性脂肪肝关系的研究进展[J].华夏医学, 2014, 27 (4) :128-131.

[16] LIN H, ZHENG WD. The diagnostic and prognostic value of AFP, AFU, TSGF and IL-8 in liver transplantation patients with liver cancer[J]. J Clin Exp Med, 2017, 16 (8) :52-56. (in Chinese) 林花, 郑卫东. AFP、AFU、TSGF及IL-8对肝癌患者诊断及肝移植术预后评估的价值研究[J].临床和实验医学杂志, 2017, 16 (8) :52-56.

[17] JOHNSON PJ, BERHANE S, KAGEBAYASHI C, et al. Assessment of liver function in patients with hepatocellular carcinoma:A new evidence-based approach-the ALBI grade[J]. J Clin Oncol, 2015, 33 (6) :550-558.

[18] HIRAOKA A, HORIIKE N, AKBAR SMF, et al. Soluble CD163in patients with liver diseases:Very high levels of soluble CD163 in patients with fulminant hepatic failure[J]. J Gastroenterol, 2005, 40 (1) :52-56.

[19] HIRAOKA A, HORIIKE N, AKBAR SM, et al. Soluble CD163 in patients with liver diseases:Very high levels of soluble CD163in patients with fulminant hepatic failure[J]. J Gastroenterol, 2005, 40 (1) :52-56.

[20] ARIZA X, ANGELI P, BARRETO R, et al. O74 urinary neutrophil gelatinase-associated lipocalin (NGAL) is a strong predictor of short-term outcome in patients with acute decompensation of cirrhosis. Relationship with acute-on-chronic liver failure (ACLF) [J]. J Hepatol, 2014, 60 (1) :s30-s31.

[21] ARIZA X, GRAUPERA I, COLL M, et al. Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis[J]. J Hepatol, 2016, 65 (1) :57-65.

[22] MEIROW Y, BANIYASH M. Immune biomarkers for chronic inflammation related complications in non-cancerous and cancerous diseases[J]. Cancer Immunol Immunother, 2017, 66 (1) :1-13.

[23] WANG K, WU ZB, YE YN, et al. Plasma interleukin-10:A likely predictive marker for hepatitis B virus-related acute-on-chronic liver failure[J]. Hepat Mon, 2014, 14 (7) :e19370.

[24] ZHOU J, ZHU L, CAO HJ, et al. Differential expression profile of long non-coding RNA in hepatic tissue between drug-induced liver and immune liver injury[J]. Chin J Pathophysiol, 2015, 31 (2) :313-318. (in Chinese) 周军, 朱灵, 曹海军, 等.药物性肝损伤与免疫性肝损伤肝组织中lncRNA表达谱的差异分析[J].中国病理生理杂志, 2015, 31 (2) :313-318.

[25] MOOKERJEE RP. Prognosis and biomarkers in acute-onchronic liver failure[J]. Semin Liver Dis, 2016, 36 (2) :127-132.

[26] WU F, YU CH, ZHANG HH, et al. Effect of mitochondrial cytochrome c on hepatocyte apoptosis in non-alcoholic fatty liver disease in rabbits[J]. Chin J Comp Med, 2016, 26 (4) :7-13. (in Chinese) 吴方, 余陈欢, 张欢欢, 等.线粒体-细胞色素C途径在兔非酒精性脂肪肝肝细胞凋亡中的作用[J].中国比较医学杂志, 2016, 26 (4) :7-13.

[27] CAO Z, LI F, XIANG X, et al. Circulating cell death biomarker:Good candidates of prognostic indicator for patients with hepatitis B virus related acute-on-chronic liver failure[J].Sci Rep, 2015, 5 (1) :14240.

[28] JOKA D, WAHL K, MOELLER S, et al. Prospective biopsycontrolled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis[J]. Hepatology, 2012, 55 (2) :455-464.

[29] BECHMANN LP, JOCHUM C, KOCABAYOGLU P, et al. Cytokeratin 18-based modification of the MELD score improves prediction of spontaneous survival after acute liver injury[J]. J Hepatol, 2010, 53 (4) :593-595.

[30] ANTOINE DJ, JENKINS RE, DEAR JW, et al. Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity[J]. J Hepatol, 2012, 56 (5) :1070-1079.

[31] POSSAMAI LA, MCPHAIL MJ, QUAGLIA A, et al. Character and temporal evolution of apoptosis in acetaminophen-induced acute liver failure[J]. Crit Care Med, 2013, 41 (11) :2543-2550.

[32] CARVALHO NR, TASSI CC, DOBRASCHINSKI F, et al. Reversal of bioenergetics dysfunction by diphenyl diselenide is critical to protection against the acetaminophen-induced acute liver failure[J]. Life Sci, 2017, 180:42-50.

[33] KU NO, STRNAD P, BANTEL H, et al. Keratins:Biomarkers and modulators of apoptotic and necrotic cell death in the liver[J]. Hepatology, 2016, 64 (3) :966-976.

[34] CHEN Y, GUO J, QIAN G, et al. Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality[J].J Gastroenterol Hepatol, 2015, 30 (9) :1429-1437.

[35] CALIN GA, CROCE CM. MicroRNA-Cancer connection:The beginning of a new tale[J]. Cancer Res, 2006, 66 (15) :7390-7394.

[36] OLIVEIRA KG, MALTA FM, NASTRI AC, et al. Increased hepatic expression of miRNA-122 in patients infected with HCV genotype 3[J]. Med Microbiol Immunol, 2016, 205 (2) :111-117.

[37] LAWRIE CH, GAL S, DUNLOP HM, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma[J]. Br J Haematol, 2010, 141 (5) :672-675.

[38] GARG H, KUMAR A, GARG V, et al. Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure[J]. J Gastroenterol Hepatol, 2013, 28 (8) :1361-1367.

施引文献

资源附件(0)

访问统计