中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

非肝硬化基础上慢加急性肝衰竭恢复期患者发生肝硬化的危险因素分析

李珊珊 徐曼曼 段钟平 陈煜

引用本文:
Citation:

非肝硬化基础上慢加急性肝衰竭恢复期患者发生肝硬化的危险因素分析

DOI: 10.3969/j.issn.1001-5256.2021.12.019
基金项目: 

中国肝炎防治基金会-天晴肝病研究基金资助课题 (TQGB20210013)

国家重点研发计划资助 (2017YFA0103000)

详细信息
    通信作者:

    陈煜,chybeyond1071@ccmu.edu.cn

    李珊珊和徐曼曼对本文贡献相同,为共同第一作者

  • 中图分类号: R575.2

Risk factors for liver cirrhosis in acute-on-chronic liver failure patients without liver cirrhosis in the convalescence stage

Research funding: 

Chinese Foundation for Hepatitis Prevention and Control-TianQing Liver Disease Research Fund Subject (TQGB20210013);

National Key R&D Program of China (2017YFA0103000)

  • 摘要:   目的  探讨影响非肝硬化基础上慢加急性肝衰竭(ACLF)恢复期患者发生肝细胞坏死后肝硬化的危险因素。  方法  回顾性收集2015年1月—2019年6月首都医科大学附属北京佑安医院收治的ACLF患者临床资料,纳入生存期大于48周和临床资料齐全的非肝硬化基础上ACLF患者57例,根据患者随访48周时是否有肝硬化表现,分为非肝硬化组和肝硬化组,比较两组间的临床指标、无创肝纤维化评分及预后评分,筛选能够独立影响患者进展为肝硬化的因素。正态分布的计量资料两组间比较采用t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U检验;计数资料两组间比较采用χ2检验或Fisher精确检验。采用logistic单因素及多因素分析48周内进展为肝硬化的危险因素,并通过经受试者工作特征曲线(ROC曲线)评估独立危险因素的预测效能。  结果  57例患者中有9例(15.8%)患者在随访4周内发生肝硬化,但随访48周肝硬化消失;在随访48周时,26例(45.6%)患者发生肝硬化,将患者分为非肝硬化组(n=31)和肝硬化组(n=26)。肝硬化组的ChE显著低于非肝硬化组[(2844.32±961.05)U/L vs (4137.59±1604.83)U/L,t=3.177, P=0.003],PLT显著低于非肝硬化组[(100.04±57.28)×109/L vs (138.84±56.46)×109/L,t=2.564, P=0.013],而肝纤维化评分(FIB-4)显著高于非肝硬化组[7.81 (3.92~11.36) vs 4.45 (2.14~7.80),Z=258.0,P=0.030],差异均有统计学意义。将上述指标纳入logistic单因素及多因素回归分析,结果显示低水平的ChE[OR(95%CI):1.001(1.000~1.002),P=0.010]和PLT[OR(95%CI):1.015(1.002~1.028),P=0.027]是非肝硬化基础上ACLF恢复期患者肝硬化发生的独立危险因素,经ROC曲线分析显示ChE、PLT联合预测非肝硬化基础上ACLF恢复期患者发生肝硬化的价值更高。  结论  低水平的ChE和PLT是影响非肝硬化基础上ACLF恢复期患者发生肝硬化的独立危险因素,ChE和PLT联合预测更有优势。

     

  • 图  1  回顾性动态观察57例非肝硬化基础上ACLF恢复期患者发生肝硬化情况

    图  2  预测非肝硬化基础上ACLF恢复期患者48周发生肝硬化的ROC曲线

    表  1  两组一般资料、实验室指标及相关评分比较

    项目 非肝硬化组(n=31) 肝硬化组(n=26) 统计值 P
    男[例(%)] 27(87.1) 22(84.6) 1.000
    年龄(岁) 39.61±10.65 43.50±10.60 t=-1.376 0.175
    并发症[例(%)]
      自发性腹膜炎 29(93.5) 23(88.5) 0.651
      腹水 17(54.8) 19(73.1) χ2=1.314 0.252
      肝性脑病 5(16.1) 1(3.8) 0.205
      急性肾损伤 3(9.7) 2(7.7) 1.000
      上消化道出血 1(3.2) 0 1.000
    ALT(U/L) 388.05(140.70~1330.53) 189.60(81.72~507.97) Z=497.0 0.080
    AST(U/L) 250.45(118.35~592.58) 197.40(98.92~406.53) Z=450.5 0.324
    ALP(U/L) 141.00(106.80~164.20) 138.30(120.00~160.70) Z=197.5 0.968
    GGT(U/L) 123.90(80.10~152.50) 79.30(56.00~146.70) Z=306.0 0.207
    Alb(g/L) 31.71±4.73 30.58±4.38 t=0.921 0.361
    TBil(μmol/L) 288.74±137.39 319.45±132.47 t=-0.857 0.395
    ChE(U/L) 4137.59±1604.83 2844.32±961.05 t=3.177 0.003
    INR 2.21 (1.90~2.84) 2.12 (1.73~2.45) Z=474.0 0.259
    Cr(μmol/L) 56.10(47.80~66.50) 63.50(52.25~71.75) Z=344.5 0.353
    Na(mmol/L) 136.95±4.17 136.15±3.27 t=0.818 0.417
    AFP(ng/ml) 86.42(32.79~185.45) 88.67(17.68~177.42) Z=353.0 0.435
    Hb(g/L) 133.00±19.50 123.50±20.85 t=1.752 0.086
    WBC(×109/L) 7.20(5.35~8.86) 6.44(4.90~9.30) Z=446.0 0.496
    PLT(×109/L) 138.84±56.46 100.04±57.28 t=2.564 0.013
    肝纤维化评分
      Sheth指数 0.65(0.49~1.05) 1.07(0.55~1.55) Z=295.0 0.121
      APRI指数 6.35(2.25~10.42) 4.93(2.96~9.04) Z=365.0 0.690
      FIB-4指数 4.45(2.14~7.80) 7.81(3.92~11.36) Z=258.0 0.030
    肝衰竭预后评分
      MELD-Na评分 21.33±3.75 20.49±4.42 t=0.754 0.455
      MELD评分 18.04(13.48~22.00) 16.67(14.16~22.76) Z=370.0 0.781
    下载: 导出CSV

    表  2  预测非肝硬化基础上ACLF恢复期患者48周发生肝硬化的单因素和多因素分析

    变量 单因素分析 多因素分析
    OR(95%CI) P OR(95%CI) P
    ChE 1.001(1.000~1.002) 0.011 1.001(1.000~1.002) 0.010
    PLT 1.013(1.002~1.024) 0.020 1.015(1.002~1.028) 0.027
    FIB-4指数 0.933(0.847~1.027) 0.156
    下载: 导出CSV
  • [1] SHI Y, YANG Y, HU Y, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults[J]. Hepatology, 2015, 62(1): 232-242. DOI: 10.1002/hep.27795.
    [2] SARIN SK, CHOUDHURY A, SHARMA MK, et al. Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific association for the study of the liver (APASL): An update[J]. Hepatol Int, 2019, 13(4): 353-390. DOI: 10.1007/s12072-019-09946-3.
    [3] Liver Failure and ArtificiaI Liver Group, Chinese Society of Infeclious Diseases, Chinese MedicaI Association; Severe Liver Disease and Artificial Liver Group, Chinses Society of Hepatology, Chinese MedicaI Association. Guideline for diagnosis and treatment of liver failure (2018)[J]. J Clin Hepatol, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.

    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)[J]. 临床肝胆病杂志, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.
    [4] ZHANG MG, XING DW, HUANG XJ, et al. A study on correlation between ct grouping of liver cirrhosis and clinically hepatic functional reserve[J]. J Hepatobiliary Surg, 2009, 17(1): 40-42. DOI: 10.3969/j.issn.1006-4761.2009.01.016.

    张闽光, 邢东炜, 黄学菁, 等. 肝硬化CT类型与临床肝储备功能相关性研究[J]. 肝胆外科杂志, 2009, 17(1): 40-42. DOI: 10.3969/j.issn.1006-4761.2009.01.016.
    [5] ZHOU XS, QIU YW, SU TT, et al. Analysis of risk factors of cirrhosis after hepatitis necrosis in patients with chronic and acute liver failure[C]. The 10th National Conference on knotty and severe liver Diseasesm, 2019: 205-206.

    周学士, 邱源旺, 苏婷婷, 等. 慢加急性肝衰竭患者发生肝炎坏死后肝硬化的危险因素分析[C]. 第十届全国疑难及重症肝病大会, 2019: 205-206.
    [6] CUI SY, LIU L, ZHANG HX, et al. CT findings and clinical analysis of patients with acute on chronic liver failure due to hepatitis B cirrhosis[J]. J Hebei Med Univ, 2017, 38(7): 838-840. DOI: 10.3969/j.issn.1007-3205.2017.07.024.

    崔书彦, 刘莲, 张红霞, 等. 乙型肝炎、肝硬化所致慢加急性肝衰竭患者的CT表现与临床分析[J]. 河北医科大学学报, 2017, 38(7): 838-840. DOI: 10.3969/j.issn.1007-3205. 2017.07.024.
    [7] GUO HY, XU SC, LIAO M, et al. Liver stiffness for evaluating change of condition in patients with acute-on-chronic liver failure[J]. J Sun Yat-Sen Univ(Medical Sciences), 2019, 40(5): 723-730. DOI: 10.13471/j.cnki.j.sun.yat-sen. univ(med.sci).

    郭欢仪, 徐士丞, 廖梅, 等. 二维剪切波弹性成像肝硬度值评估慢加急性肝衰竭患者病情变化[J]. 中山大学学报(医学科学版), 2019, 40(5): 723-730. DOI: 10.13471/j.cnki.j.sun.yat-sen. univ(med.sci).
    [8] KONG J, XIANG XX. Value of serum cholinesterase in diagnosis/treatment and prognostic evaluation of liver diseases[J]. J Clin Hepatol, 2017, 33(9): 1806-1809. DOI: 10.3969/j.issn.1001-5256.2017.09.040.

    孔剑, 向晓星. 血清胆碱酯酶在肝病诊疗及转归中的应用价值[J]. 临床肝胆病杂志, 2017, 33(9): 1806-1809. DOI: 10.3969/j.issn.1001-5256.2017.09.040.
    [9] LONG ZR, YANG LY. Clinical value of detection of serum cholinesterase in Child-Pugh classification of the patients with cirrhosis[J]. Lab Med Clin, 2009, 6(24): 2113-2114. DOI: 10.3969/j.issn.1672-9455.2009.24.018.

    龙峥嵘, 杨良勇. 血清胆碱酯酶活性测定对肝硬化Child-Pugh分级的临床价值[J]. 检验医学与临床, 2009, 6(24): 2113-2114. DOI: 10.3969/j.issn.1672-9455.2009.24.018.
    [10] LIU D, LI J, LU W, et al. Gamma-glutamyl transpeptidase to cholinesterase and platelet ratio in predicting significant liver fibrosis and cirrhosis of chronic hepatitis B[J]. Clin Microbiol Infect, 2019, 25(4): 514. e1-514. e8. DOI: 10.1016/j.cmi.2018.06.002.
    [11] WU D, RAO Q, CHEN W, et al. Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B[J]. Liver Int, 2018, 38(11): 1930-1939. DOI: 10.1111/liv.13756.
    [12] CHAUHAN A, ADAMS DH, WATSON SP, et al. Platelets: No longer bystanders in liver disease[J]. Hepatology, 2016, 64(5): 1774-1784. DOI: 10.1002/hep.28526.
    [13] VASINA EM, CAUWENBERGHS S, FEIJGE MA, et al. Microparticles from apoptotic platelets promote resident macrophage differentiation[J]. Cell Death Dis, 2011, 2(9): e211. DOI: 10.1038/cddis.2011.94.
    [14] DELEVE LD. Liver sinusoidal endothelial cells and liver regeneration[J]. J Clin Invest, 2013, 123(5): 1861-1866. DOI: 10.1172/JCI66025.
    [15] KODAMA T, TAKEHARA T, HIKITA H, et al. Thrombocytopenia exacerbates cholestasis-induced liver fibrosis in mice[J]. Gastroenterology, 2010, 138(7): 2487-2498, 2498. e1-7. DOI: 10.1053/j.gastro.2010.02.054.
    [16] HERNANDEZ-GEA V, FRIEDMAN SL. Platelets arrive at the scene of fibrosis……studies[J]. J Hepatol, 2011, 54(5): 1063-1065. DOI: 10.1016/j.jhep.2010.10.045.
    [17] WATANABE M, MURATA S, HASHIMOTO I, et al. Platelets contribute to the reduction of liver fibrosis in mice[J]. J Gastroenterol Hepatol, 2009, 24(1): 78-89. DOI: 10.1111/j.1440-1746.2008.05497.x.
    [18] TAKAHASHI K, MURATA S, FUKUNAGA K, et al. Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice[J]. World J Gastroenterol, 2013, 19(32): 5250-5260. DOI: 10.3748/wjg.v19.i32.5250.
    [19] WAI CT, GREENSON JK, FONTANA RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C[J]. Hepatology, 2003, 38(2): 518-526. DOI: 10.1053/jhep.2003.50346.
    [20] STERLING RK, LISSEN E, CLUMECK N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection[J]. Hepatology, 2006, 43(6): 1317-1325. DOI: 10.1002/hep.21178.
    [21] LEMOINE M, SHIMAKAWA Y, NAYAGAM S, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa[J]. Gut, 2016, 65(8): 1369-1376. DOI: 10.1136/gutjnl-2015-309260.
    [22] CHEN YP, HU XM, LIANG XE, et al. Stepwise application of fibrosis index based on four factors, red cell distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio for compensated hepatitis B fibrosis detection[J]. J Gastroenterol Hepatol, 2018, 33(1): 256-263. DOI: 10.1111/jgh.13811.
    [23] LI Q, LU C, LI W, et al. Globulin-platelet model predicts significant fibrosis and cirrhosis in CHB patients with high HBV DNA and mildly elevated alanine transaminase levels[J]. Clin Exp Med, 2018, 18(1): 71-78. DOI: 10.1007/s10238-017-0472-3.
    [24] OKAJIMA A, SUMIDA Y, TAKETANI H, et al. Liver stiffness measurement to platelet ratio index predicts the stage of liver fibrosis in non-alcoholic fatty liver disease[J]. Hepatol Res, 2017, 47(8): 721-730. DOI: 10.1111/hepr.12793.
    [25] BERGER A, RAVAIOLI F, FARCAU O, et al. Including ratio of platelets to liver stiffness improves accuracy of screening for esophageal varices that require treatment[J]. Clin Gastroenterol Hepatol, 2021, 19(4): 777-787. e17. DOI: 10.1016/j.cgh.2020.06.022.
  • 加载中
图(2) / 表(2)
计量
  • 文章访问数:  255
  • HTML全文浏览量:  48
  • PDF下载量:  40
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-04-25
  • 录用日期:  2021-05-21
  • 出版日期:  2021-12-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回