Role of alpha-fetoprotein in prognostic evaluation of patients with liver failure
-
摘要: 我国是肝病大国,各种肝炎病毒、药物毒物及酒精等都会造成肝损伤,甚至肝衰竭。肝衰竭患者预后的关键在于肝自我修复及再生。甲胎蛋白(AFP)作为肿瘤标志物已在肝癌中得到深入研究,但其在肝衰竭患者肝再生中的研究尚有待深入。总结了AFP在肝再生中的基础研究以及在急性肝衰竭(ALF)和慢加急性肝衰竭(ACLF)中的临床研究,并归纳了本课题组前期研究结果——AFP是HBV相关ACLF后肝再生的重要预后指标及再生因子。经分析表明,继续深入研究AFP在各种肝衰竭中的预后作用以及肝再生中的发生机制,有助于进一步加深对AFP和肝再生的了解,为各种肝衰竭患者的临床诊治和预后评价提供新思路及方法。Abstract: China is a big country with liver diseases, and various hepatitis viruses, drug poisons, and alcohol can cause liver injury and even liver failure. The key to the prognosis of patients with liver failure is liver self-repair and regeneration. Alpha-fetoprotein (AFP) has been extensively studied as a tumor marker in liver cancer, but its role in liver regeneration in patients with liver failure awaits further studies. This article summarizes the basic research on AFP in liver regeneration and the clinical research on AFP in acute liver failure and acute-on-chronic liver failure (ACLF), as well as the previous research findings of our group that AFP is an important prognostic index and regeneration factor for liver regeneration after hepatitis B virus-related ACLF. The analysis shows that further studies on the role of AFP in the prognosis of various types of liver failure and the mechanism of liver regeneration will help deepen our understanding of AFP and liver regeneration, thereby providing new ideas and methods for the clinical diagnosis, treatment, and prognostic evaluation of patients with various types of liver failure.
-
Key words:
- Liver Failure /
- alpha-Fetoproteins /
- Liver Regeneration
-
[1] SAUZAY C, PETIT A, BOURGEOIS AM, et al. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma[J]. Clin Chim Acta, 2016, 463: 39-44. DOI: 10.1016/j.cca.2016.10.006. [2] GALLE PR, FOERSTER F, KUDO M, et al. Biology and significance of alpha-fetoprotein in hepatocellular carcinoma[J]. Liver Int, 2019, 39(12): 2214-2229. DOI: 10.1111/liv.14223. [3] BERGSTRAND CG, CZAR B. Demonstration of a new protein fraction in serum from the human fetus[J]. Scand J Clin Lab Invest, 1956, 8(2): 174. DOI: 10.3109/00365515609049266. [4] MIZEJEWSKI GJ. The alpha-fetoprotein third domain receptor binding fragment: In search of scavenger and associated receptor targets[J]. J Drug Target, 2015, 23(6): 538-551. DOI: 10.3109/1061186X.2015.1015538. [5] TERENTIEV AA, MOLDOGAZIEVA NT. Alpha-fetoprotein: A renaissance[J]. Tumour Biol, 2013, 34(4): 2075-2091. DOI: 10.1007/s13277-013-0904-y. [6] FORBES SJ, NEWSOME PN. Liver regeneration-mechanisms and models to clinical application[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(8): 473-485. DOI: 10.1038/nrgastro.2016.97. [7] SELL S. The hepatocyte: Heterogeneity and plasticity of liver cells[J]. Int J Biochem Cell Biol, 2003, 35(3): 267-271. DOI: 10.1016/s1357-2725(02)00182-6. [8] KUHLMANN WD, PESCHKE P. Hepatic progenitor cells, stem cells, and AFP expression in models of liver injury[J]. Int J Exp Pathol, 2006, 87(5): 343-359. DOI: 10.1111/j.1365-2613.2006.00485.x. [9] PETROPOULOS C, ANDREWS G, TAMAOKI T, et al. alpha-Fetoprotein and albumin mRNA levels in liver regeneration and carcinogenesis[J]. J Biol Chem, 1983, 258(8): 4901-4906. [10] NAKANO Y, NAKAO S, SUMIYOSHI H, et al. Identification of a novel alpha-fetoprotein-expressing cell population induced by the Jagged1/Notch2 signal in murine fibrotic liver[J]. Hepatol Commun, 2017, 1(3): 215-229. DOI: 10.1002/hep4.1026. [11] DEZSÖ K, NAGY P, PAKU S. Human liver regeneration following massive hepatic necrosis: Two distinct patterns[J]. J Gastroenterol Hepatol, 2020, 35(1): 124-134. DOI: 10.1111/jgh.14721. [12] JIN DK, VACHER J, FEUERMAN MH. alpha-Fetoprotein gene sequences mediating Afr2 regulation during liver regeneration[J]. Proc Natl Acad Sci U S A, 1998, 95(15): 8767-8772. DOI: 10.1073/pnas.95.15.8767. [13] WENG MZ, ZHUANG PY, HEI ZY, et al. ZBTB20 is involved in liver regeneration after partial hepatectomy in mouse[J]. Hepatobiliary Pancreat Dis Int, 2014, 13(1): 48-54. DOI: 10.1016/s1499-3872(14)60006-0. [14] ZHANG H, SHI JH, JIANG H, et al. ZBTB20 regulates EGFR expression and hepatocyte proliferation in mouse liver regeneration[J]. Cell Death Dis, 2018, 9(5): 462. DOI: 10.1038/s41419-018-0514-0. [15] RODGERS SK, HORROW MM. Acute (fulminant) liver failure: A clinical and imaging review[J]. Abdom Radiol (NY), 2021, 46(7): 3117-3127. DOI: 10.1007/s00261-021-02973-5. [16] CHAYANUPATKUL M, SCHIANO TD. Acute liver failure secondary to drug-induced liver injury[J]. Clin Liver Dis, 2020, 24(1): 75-87. DOI: 10.1016/j.cld.2019.09.005. [17] GREK A, ARASI L. Acute liver failure[J]. AACN Adv Crit Care, 2016, 27(4): 420-429. DOI: 10.4037/aacnacc2016324. [18] KARVOUNTZIS GG, REDEKER AG. Relation of alpha-fetoprotein in acute hepatitis to severity and prognosis[J]. Ann Intern Med, 1974, 80(2): 156-160. DOI: 10.7326/0003-4819-80-2-156. [19] MURRAY-LYON IM, ORR AH, GAZZARD B, et al. Prognostic value of serum alpha-fetoprotein in fulminant hepatic failure including patients treated by charcoal haemoperfusion[J]. Gut, 1976, 17(8): 576-580. DOI: 10.1136/gut.17.8.576. [20] BLOOMER JR, WALDMANN TA, MCINTIRE KR, et al. Serum alpha-fetoprotein in patients with massive hepatic necrosis[J]. Gastroenterology, 1977, 72(3): 479-492. DOI: 10.1016/S0016-5085(77)80260-6 [21] SEO SI, KIM SS, CHOI BY, et al. Clinical significance of elevated serum alpha-fetoprotein (AFP) level in acute viral hepatitis A (AHA)[J]. Hepatogastroenterology, 2013, 60(127): 1592-1596. [22] CARRARO P, BURIGHEL D, de SILVESTRO G, et al. Early prognostic biochemical indicators of fulminant hepatic failure[J]. Int J Clin Lab Res, 1998, 28(3): 196-199. DOI: 10.1007/s005990050044. [23] SINGH S, HYNAN LS, RULE JA, et al. Changes in alpha-foetoprotein and Gc-globulin in relation to outcomes in non-acetaminophen acute liver failure[J]. Liver Int, 2019, 39(12): 2368-2373. DOI: 10.1111/liv.14216. [24] CHURCH RJ, KULLAK-UBLICK GA, AUBRECHT J, et al. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort[J]. Hepatology, 2019, 69(2): 760-773. DOI: 10.1002/hep.29802. [25] SCHMIDT LE, DALHOFF K. Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury[J]. Hepatology, 2005, 41(1): 26-31. DOI: 10.1002/hep.20511. [26] SAKURAI T, MARUSAWA H, SATOMURA S, et al. Lens culinaris agglutinin-A-reactive alpha-fetoprotein as a marker for liver atrophy in fulminant hepatic failure[J]. Hepatol Res, 2003, 26(2): 98-105. DOI: 10.1016/s1386-6346(03)00013-5. [27] SCHIØDT FV, OSTAPOWICZ G, MURRAY N, et al. Alpha-fetoprotein and prognosis in acute liver failure[J]. Liver Transpl, 2006, 12(12): 1776-1781. DOI: 10.1002/lt.20886. [28] DU WB, PAN XP, LI LJ. Prognostic models for acute liver failure[J]. Hepatobiliary Pancreat Dis Int, 2010, 9(2): 122-128. [29] KAKISAKA K, KATAOKA K, ONODERA M, et al. Alpha-fetoprotein: A biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure[J]. Hepatol Res, 2015, 45(10): e12-e20. DOI: 10.1111/hepr.12448. [30] LI JN, HAN C, WANG XP, et al. Current research on liver regeneration: Pathogenesis and serum markers[J]. J Clin Hepatol, 2020, 36(8): 1896-1899. DOI: 10.3969/j.issn.1001-5256.2020.08.048.李嘉妮, 韩川, 王孝平, 等. 肝再生的发生机制及血清标志物的研究现状[J]. 临床肝胆病杂志, 2020, 36(8): 1896-1899. DOI: 10.3969/j.issn.1001-5256.2020.08.048. [31] TAKETA K. Alpha-fetoprotein: Reevaluation in hepatology[J]. Hepatology, 1990, 12(6): 1420-1432. DOI: 10.1002/hep.1840120625. [32] YANG SS, CHENG KS, LAI YC, et al. Decreasing serum alpha- fetoprotein levels in predicting poor prognosis of acute hepatic failure in patients with chronic hepatitis B[J]. J Gastroenterol, 2002, 37(8): 626-632. DOI: 10.1007/s005350200099. [33] TAKIKAWA Y, SUZUKI K. Is AFP a new reliable marker of liver regeneration in acute hepatic failure?[J]. J Gastroenterol, 2002, 37(8): 681-682. DOI: 10.1007/s005350200111. [34] ZHAO J, LI L, LI XH, et al. Value of a new predictive model in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure[J]. Chin Critical Care Med, 2020, 32(8): 988-993. DOI: 10.3760/cma.j.cn121430-20200102-00075.赵洁, 李力, 李秀惠, 等. 乙型肝炎病毒相关慢加急性肝衰竭患者短期预后模型的建立及预测价值研究[J]. 中华危重病急救医学, 2020, 32(8): 988-993. DOI: 10.3760/cma.j.cn121430-20200102-00075. [35] ZHENG M, GAO CM, ZHAO JF. The value of serum proalbumin combined with AFP in predicting the prognosis of HBV-ACLF[J]. Anhui Med J, 2019, 40(5): 514-516. DOI: 10.3969/j.issn.1000-0399.2019.05.011.郑敏, 高春明, 赵久法. 血清前清蛋白联合甲胎蛋白预测乙肝相关慢加急性肝衰竭预后的价值[J]. 安徽医学, 2019, 40(5): 514-516. DOI: 10.3969/j.issn.1000-0399.2019.05.011. [36] XIE Z, VIOLETTA L, CHEN E, et al. A prognostic model for hepatitis B acute-on-chronic liver failure patients treated using a plasma exchange-centered liver support system[J]. J Clin Apher, 2020, 35(2): 94-103. DOI: 10.1002/jca.21762. [37] ZHAO P, ZHAI YF, ZHANG HH. Application of serum alpha fetoprotein and prothrombin time activity in predicting prognosis of patients with acute-on-chronic liver failure[J]. J Prac Hepatol, 2017, 20(2): 230-231. DOI: 10.3969/j.issn.1672-5069.2017.02.027.赵萍, 翟玉峰, 张怀宏. 血清甲胎蛋白和凝血酶原活动度水平对慢加急性肝衰竭患者预后的预测价值研究[J]. 实用肝脏病杂志, 2017, 20(2): 230-231. DOI: 10.3969/j.issn.1672-5069.2017.02.027. [38] HUANG GQ, XIE YY, ZHU PW, et al. Stratified alpha-fetoprotein pattern accurately predicts mortality in patients with acute-on-chronic hepatitis B liver failure[J]. Expert Rev Gastroenterol Hepatol, 2018, 12(3): 295-302. DOI: 10.1080/17474124.2018.1424540. [39] WANG X, SHEN C, YANG J, et al. Alpha-fetoprotein as a predictive marker for patients with hepatitis B-related acute-on-chronic liver failure[J]. Can J Gastroenterol Hepatol, 2018, 2018: 1232785. DOI: 10.1155/2018/1232785. [40] WANG X, SUN M, YANG X, et al. Value of liver regeneration in predicting short-term prognosis for patients with hepatitis B-related acute-on-chronic liver failure[J]. Biomed Res Int, 2020, 2020: 5062873. DOI: 10.1155/2020/5062873.
本文二维码
计量
- 文章访问数: 890
- HTML全文浏览量: 330
- PDF下载量: 104
- 被引次数: 0