中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 4
Apr.  2017

A risk factors analysis of acute-on-chronic liver failure complicated by spontaneous bacterial peritonitis

DOI: 10.3969/j.issn.1001-5256.2017.04.024
Research funding:

 

  • Received Date: 2016-11-16
  • Published Date: 2017-04-20
  • Objective To investigate the influencing factors for spontaneous bacterial peritonitis (SBP) in patients with acute-on-chronic liver failure (ACLF) , and to provide a reference for clinical diagnosis and prognosis evaluation.Methods A retrospective analysis was performed for the clinical data of 667 patients with ACLF who were hospitalized and treated in our hospital from January 2009 to December2014, and according to the presence or absence of SBP, they were divided into ACLF group (n=232) and ACLF-SBP group (n=435) .The general information, laboratory markers, and incidence of complications were compared between the two groups.The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups, and a logistic regression analysis was used to identify independent risk factors for ACLF complicated by SBP.Results The comparison of laboratory markers and comorbidities showed that there were significant differences between the two groups in albumin (Alb) (t=-4.110, P<0.001) , alanine aminotransferase (U=-6.653, P<0.001) , aspartate aminotransferase (t=-8.045, P<0.001) , blood sodium (t=-2.879, P=0.006) , prothrombin time activity (t=-2.140, P=0.037) , international normalized ratio (t=1.453, P=0.042) , hemoglobin (t=-3.446, P=0.001) , upper gastrointestinal bleeding (χ2=48.252, P=0.002) , hepatorenal syndrome (χ2=16.244, P=0.031) , and pulmonary infection (χ2=13.564, P<0.001) .The multivariate logistic regression analysis showed that there were significant differences in Alb (OR=1.119, 95% CI: 1.052 ~ 1.189) , platelet count (PLT) (OR=1.035, 95% CI: 0.755 ~ 1.084) , upper gastrointestinal bleeding (OR=1.117, 95% CI: 0.072 ~ 1.135) , and pulmonary infection (OR=2.275, 95% CI: 0.978 ~ 5.292) (P=0.002, 0.038, 0.022, and0.036) .Conclusion In the treatment of ACLF patients, risk factors including low Alb, low PLT, upper gastrointestinal bleeding, and pulmonary infection should be prevented, and early diagnosis and intervention of these risk factors helps to reduce the incidence of SBP.

     

  • 肝细胞癌(HCC)是我国最常见的恶性肿瘤之一。国家癌症中心最新数据显示,我国每年新发肝癌约37万人,约32.6万人死于肝癌,其中94.7%与慢性HBV感染有关[1-2]。早期发现、早期诊断和早期治疗是改善原发性肝癌预后的关键。然而目前尚缺乏原发性肝癌高敏感度和高特异度的诊断指标。自噬是细胞自我吞噬胞内长寿蛋白或受损细胞器并通过溶酶体途径进行的分解代谢过程,从而维持细胞稳态[3]。近年研究[4-7]显示自噬在HBV感染和HCC的发生发展起重要作用。但目前关于自噬相关蛋白在HBV相关HCC(HBV-HCC)患者血清中的表达及意义鲜有报道。本研究通过分析HBV-HCC、非HBV相关HCC(nonHBV-HCC)、慢性乙型肝炎(CHB)和健康对照者血清自噬相关蛋白7(ATG7)的表达水平,探讨ATG7对HBV-HCC的诊断价值。

    选取2018年6月—2020年12月于本院住院的HCC患者89例。HCC的诊断标准符合《原发性肝癌诊疗规范(2017年版)》[8]并经病理确认。排除标准如下:病理类型为肝内胆管癌或HCC-肝内胆管癌混合型者;已接受过肝移植术、局部消融、肝动脉化疗栓塞术、放化疗等抗肿瘤治疗者;继发性HCC患者;同时伴有其他肿瘤患者。CHB诊断符合《慢性乙型肝炎防治指南(2019年版)》[9]。根据血清是否检出HBsAg和/或HBV DNA分为HBV-HCC组及nonHBV-HCC组。选取同期50例CHB患者(CHB组)和20例健康体检者作为对照组(HC组)。

    收集研究对象性别和年龄,总蛋白(TP)、白蛋白(Alb)、TBil、DBil、ALT、AST、GGT和ALP等实验室指标。另收集HBV-HCC组患者的BCLC分期和肿瘤直径等病理资料。

    所有研究对象清晨空腹肘静脉采血,采血后1 h内送实验室,3000 r/min离心10 min分离血清,-80 ℃冰箱保存。ATG7检测前4 h室温下复溶。使用上海江莱生物技术有限公司人ATG7酶联免疫吸附测定试剂盒(批号:Aug 2020)进行检测,严格按试剂盒说明书操作,在加入终止液15 min内用PHOMO酶标仪(安图生物,合肥)在450 nm波长测定各孔光密度(OD值),用WPS表格以标准品的浓度为纵坐标,OD值为横坐标绘制标准曲线并取得多项式公式,根据多项式公式计算每个样本的ATG7浓度。

    本研究方案经由福建医科大学孟超肝胆医院伦理委员会审批,批号:科审2020-029-01。

    采用SPSS 22.0进行统计分析。非正态分布的计量资料以M(P25~P75)表示,多组间比较采用Kruskal-Wallis H检验,2组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ2检验;采用Spearman进行相关性分析。运用GraphPad Prism7.0绘制散点图,采用Medcalc18.11.3绘制受试者工作特征曲线(ROC曲线)并比较不同指标曲线下面积(AUC)。P<0.05为差异有统计学意义。

    HCC、CHB及HC 3组比较,男女比例差异无统计学意义,其余指标差异均有统计学意义(P值均<0.01)(表 1)。89例HCC患者中,67例(75.28%)血清HBsAg和/或HBV DNA阳性,纳入HBV-HCC组;剩余22例(24.72%)纳入nonHBV-HCC组,包括5例酒精性肝硬化,8例非酒精性脂肪肝,1例慢性丙型肝炎,2例肝硬化(病因未明),6例慢性肝炎(病因未明)。HBV-HCC组血清TBil水平及具有肝硬化背景病例数高于nonHBV-HCC组,而nonHBV-HCC组的血清AST水平和最大肿瘤直径高于HBV-HCC组,差异均有统计学意义(P值均<0.05),其余参数差异均无统计学意义(P值均>0.05)(表 2)。

    表  1  3组人口学和实验室特征比较
    参数 HCC组(n=89) CHB组(n=50) HC组(n=20) χ2 P
    年龄(岁) 56.0(48.0~66.5) 42.0(32.8~52.5) 37.5(30.0~48.8) 38.807 <0.001
    男性[例(%)] 77(86.52) 38(76.00) 13(65.00) 5.480 0.076
    TBil(μmol/L) 19.30(12.65~26.10) 19.55(12.78~29.28) 12.15(9.48~18.63) 10.478 0.005
    DBil(μmol/L) 7.60(4.70~10.85) 4.45(2.20~7.05) 5.30(4.15~6.35) 17.168 <0.001
    TP(g/L) 61.0(54.5~67.5) 66.5(60.8~73.3) 72.0(70.0~77.0) 34.168 <0.001
    Alb(g/L) 34.0(31.0~38.5) 37.5(34.0~41.0) 44.0(41.0~47.0) 42.516 <0.001
    ALT(U/L) 115.0(62.0~218.5) 87.5(26.5~206.8) 19.0(12.3~26.5) 37.212 <0.001
    AST(U/L) 149.0(54.0~286.0) 57.0(31.5~110.5) 17.0(14.3~20.0) 54.345 <0.001
    GGT(U/L) 52.0(34.0~110.5) 68.5(29.3~112.0) 17.0(14.3~24.5) 31.527 <0.001
    ALP(U/L) 81.0(60.5~103.0) 102.0(82.5~117.0) 66.5(52.8~88.3) 21.160 <0.001
    AFP(ng/mL) 37.90(5.00~712.32) 7.20(3.05~241.27) 2.85(2.18~4.48) 33.048 <0.001
    ATG7(ng/mL) 21.11(17.76~22.73) 19.21(16.65~20.82) 13.82(8.70~17.82) 33.134 <0.001
    下载: 导出CSV 
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    表  2  HBV-HCC组与nonHBV-HCC组生化和病理特征比较
    参数 HBV-HCC组(n=67) nonHBV-HCC组(n=22) 统计值 P
    年龄(岁) 55.0(46.0~ 65.0) 63.5(50.8~71.8) U=535.000 0.055
    男/女(例) 58/9 19/3 χ2=0.001 0.981
    TBil(μmol/L) 20.60(13.30~27.40) 16.00(11.15~21.48) U=524.500 0.043
    DBil(μmol/L) 7.70(4.80~10.90) 7.15(3.80~9.65) U=602.500 0.201
    TP(g/L) 61.0(50.0~67.0) 58.5(51.3~68.3) U=638.500 0.348
    Alb(g/L) 34.0(31.0~38.0) 33.0(30.3~39.0) U=709.500 0.793
    ALT(U/L) 95.0(54.0~198.0) 152.0(89.8~268.0) U=557.000 0.087
    AST(U/L) 136.0(37.0~240.0) 236.5(93.8~348.8) U=523.000 0.042
    GGT(U/L) 51.0(30.0~111.0) 58.0(35.0~113.3) U=658.000 0.452
    ALP(U/L) 76.0(60.0~99.0) 92.0(62.8~127.8) U=575.500 0.124
    AFP(ng/mL) 58.00(7.10~945.80) 18.28(2.48~405.33) U=536.500 0.057
    BCLC(A/B/C/D,例) 51/4/12/0 12/5/5/0 χ2=5.229 0.073
    最大肿瘤直径(cm) 3.95(2.50~7.70) 8.00(3.70~11.00) U=520.000 0.047
    肝硬化[例(%)] 55(82.09) 9(40.91) χ2=13.904 <0.001
    下载: 导出CSV 
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    HBV- HCC组、nonHBV-HCC组、CHB组和HC组血清ATG7水平分别为22.88(19.79~23.04)ng/mL、17.06(14.45~19.40)ng/mL、19.21(16.65~20.82)ng/mL和13.82(8.70~17.82)ng/mL,差异有统计学意义(χ2=65.144,P<0.001)。两两比较显示HBV-HCC组血清ATG7不仅高于CHB组(U=758.5,P<0.001)和HC组(U=94.0,P<0.001),也高于nonHBV-HCC组(U=142.0,P<0.001);而nonHBV-HCC组血清ATG7水平不仅低于HBV-HCC组,也低于CHB组(U=311.0,P=0.003),仅稍高于HC组(U=142.0,P=0.049)(图 1)。此外,在67例HBV-HCC患者中,有肝硬化背景和无肝硬化背景患者的血清ATG7水平分别为22.32 (19.79~22.99)ng/mL和20.89(19.40~23.37)ng/mL,差异无统计学意义(P>0.05)。

    图  1  4组血清ATG7表达水平比较

    Spearman相关性分析显示,血清ATG7表达水平和血清AFP水平呈正相关,但相关性较弱(r=0.354,95%CI:0.205~0.486,P<0.001)(图 2)。

    图  2  血清ATG7和AFP相关性分析

    ROC曲线分析显示,ATG7诊断HBV-HCC的AUC为0.818(95% CI:0.743~0.879),稍高于AFP(AUC=0.777,95%CI:0.698~0.843),但二者差异无统计学意义(Z=0.852,P=0.394)(图 3);ATG7诊断HBV-HCC的cut-off值为20.08 ng/mL,敏感度和特异度分别为71.64%和77.14%,均略高于AFP(68.66%和74.29%)。ATG7联合AFP的二元logistic回归预测概率的AUC为0.859 (95%CI:0.790~0.913),显著高于ATG7(Z=2.192,P=0.028)和AFP(Z=2.076,P=0.038)(图 3, 表 3)。

    图  3  ATG7、AFP及二者联合检测的ROC曲线
    表  3  ATG7、AFP及其联合检测诊断HBV-HCC的性能
    项目 AUC cut-off值 敏感度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%)
    AFP 0.777 12.20 ng/mL 68.66 74.29 71.9 71.2
    ATG7 0.818 20.08 ng/mL 71.64 77.14 75.0 74.0
    ATG7+AFP 0.859 0.56 74.63 88.57 86.2 78.5
    下载: 导出CSV 
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    本研究通过ELISA技术检测HCC患者血清ATG7表达水平,结果显示HBV-HCC患者血清ATG7显著升高,血清ATG7是诊断HBV-HCC的良好标志物,ATG7与AFP联合诊断可显著提高HBV-HCC的诊断效率。

    ATG7作为一种泛素样修饰物激活酶,通过激活ATG8和ATG12调节自噬体的延伸,是自噬体形成过程的关键蛋白之一[10]。近年研究[11-12]提示ATG7及自噬在HBV-HCC发生发展中发挥重要作用。首先,HBV感染或HBV病毒蛋白的表达可诱导ATG7表达及自噬反应。本研究中CHB组血清ATG7显著高于健康对照组,印证了自噬与HBV感染有关。其次,多项研究[13-14]显示包括ATG7在内的多种自噬相关蛋白在HCC组织表达显著提高。近年的分子细胞学试验进一步揭示多种分子可通过ATG7调节自噬促进HCC发生发展[15-17]。研究[15]显示长链非编码RNA HOX转录反义RNA(HOTAIR)可通过上调ATG7表达激活自噬促进HCC细胞系增殖。癌性锚蛋白重复序列可直接与胞质中的ATG7蛋白相互作用诱导自噬从而促进HCC细胞进展[16]。肿瘤坏死因子α诱导蛋白8(TNFAIP8)则通过与ATG3-ATG7复合物相互作用调节自噬促进HCC细胞增殖[17]。相反,靶向敲减ATG7可抑制自噬,从而促进细胞凋亡、延缓细胞周期及抑制HCC细胞增殖[13]。上述研究结果表明ATG7与HBV-HCC密切相关。本研究数据显示HBV-HCC患者血清ATG7显著高于CHB和健康对照组,进一步证实了自噬与HBV-HCC的相关性,提示血清ATG7是一种潜在HBV-HCC标志物。而且HBV-HCC患者血清ATG7也显著高于nonHBV-HCC,提示不同病因的HCC发病机制不同,其血清标志物也可不同。

    虽然AFP已在临床应用数十年,但诊断敏感度不高。最近的一项系统综述[18]显示,AFP诊断HCC的合并敏感度仅为63.9%。与此相符,本研究中AFP诊断HBV-HCC的敏感度、特异度和AUC分别为68.66%、74.29%和0.777。虽然ATG7的敏感度与AFP相仿,但其特异度较高,总体诊断性能较好。此外,ATG7和AFP相关性较弱,提示二者联合检测可有效提高诊断性能。早前有学者[19]提出应用logistic回归分析有助于提高多指标联合诊断效率。本研究结果显示ATG7联合AFP的二元logistic回归预测模型对HBV-HCC的整体诊断性能较好,AUC及诊断敏感度和特异度均显著高于ATG7及AFP。

    总之,本研究显示ATG7是HBV-HCC的良好标志物,与AFP有较好的互补性,二者联合检测可显著提高HBV-HCC的诊断效率。然而本研究为单中心横断面研究,纳入研究病例有限,因此其诊断性能仍有待进一步扩大样本的多中心临床验证。

  • [1]LI C, LIU HL, ZANG H, et al.Expression of myeloid-derived suppressor cells in peripheral blood in patients with HBV-related acute-on-chronic liver failure[J].Infect Dis Info, 2013, 26 (6) :343-347. (in Chinese) 李晨, 刘鸿凌, 臧红, 等.外周血髓源性抑制细胞在HBV相关慢加急性肝衰竭患者中表达的研究[J].传染病信息, 2013, 26 (6) :343-347.
    [2]ZHANG L, BAI H, LI XC, et al.Early diagnosis and prognosis prevision for patients of spontaneous bacterial peritonitis[J].J China Med Univ, 2008, 37 (1) :109-111. (in Chinese) 张琳, 白菡, 李向春, 等.自发性细菌性腹膜炎患者的临床早期诊断及预后判定[J].中国医科大学学报, 2008, 37 (1) :109-111.
    [3] WEI CX, GONG HY.Advances in the diagnosis of spontaneous bacterial peritonitis[J].Med Inf, 2013, 26 (1) :317-318. (in Chinese) 魏超霞, 龚环宇.自发性细菌性腹膜炎的诊断进展[J].医学信息, 2013, 26 (1) :317-318.
    [4]Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association;Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association.Diagnostic and treatment guidelines for liver failure (2012 version) [J].J Pract Hepatol, 2013, 16 (3) :210-216. (in Chinese) 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 (2012年版) [J].实用肝脏病杂志, 2013, 16 (3) :210-216.
    [5]WIEST R, KRAG A, GERBES A.Spontaneous bacterial peritonitis:recent guidelines and beyond[J].Gut, 2012, 61 (2) :297-310.
    [6]NU'EZ MARTNEZ, MERINO RODRGUEZ B, DAZ SNCHEZ A, et al.Optimization of ascitic fluid culture in spontaneous bacterial peritonitis[J].Gastroenterol Hepatol, 2011, 34 (5) :315-321.
    [7]ZHU Y, ZHANG HY, ZHANG CJ, et al.Diagnostic criteria for spontaneous bacterial peritonitis in patients with chronic liver failure[J].J Third Milit Med Univ, 2011, 33 (21) :2227-2229. (in Chinese) 朱研, 张辉艳, 张长江, 等.慢性肝衰竭并发自发性细菌性腹膜炎诊断标准探讨[J].第三军医大学学报, 2011, 33 (21) :2227-2229.
    [8]LIU FF, WU JY, ZHANG HY, et al.Clinical characteristics of patients with hepatitis B-induced acute-on-chronic liver failure and the effects of plasma exchanges on their prognosis[J].J Pract Hepatol, 2016, 19 (2) :188-191. (in Chinese) 刘菲菲, 吴吉圆, 张海月, 等.慢加急性乙型肝炎肝衰竭临床特征及血浆置换治疗对其预后的影响[J].实用肝脏病杂志, 2016, 19 (2) :188-191.
    [9]ZOU ZS, CHEN JM, XIN SJ, et al.Single factor study of prognosis from 520 cases with chronic severe hepatitis[J].Chin J Exp Clin Virol, 2002, 16 (3) :246-248. (in Chinese) 邹正升, 陈菊梅, 辛绍杰, 等.影响慢性重型肝炎预后的单因素研究-附520例临床分析[J].中华实验和临床病毒学杂志, 2002, 16 (3) :246-248.
    [10]PENG XG, YAO JJ, YU WL, et al.Meta analysis on prognostic factors of patients with severe hepatitis B[J/CD].Chin J Exp Clin Infect Dis:Electronic Edition, 2011, 5 (1) :14-19. (in Chinese) 彭新国, 姚津剑, 于伟玲, 等.重型乙型肝炎预后荟萃分析[J/CD].中华实验和临床感染病杂志:电子版, 2011, 5 (1) :14-19.
    [11]LUO L, YUAN CL, LAI N, et al.Severe hepatitis:prognostic factors and nursing interventions[J].World Chin J Dig, 2011, 19 (19) :2068-2071. (in Chinese) 罗玲, 袁春兰, 赖宁, 等.重型肝炎预后因素分析与护理对策[J].世界华人消化杂志, 2011, 19 (19) :2068-2071.
    [12]CAO L, WANG CH, ZHAN GQ.The relationship between serum sodium and disease severity of patients with HBV elated acute-on-chronic liver failure[J].J Hubei Univ Med, 2015, 34 (4) :357-360. (in Chinese) 曹玲, 王崇慧, 占国清.HBV相关慢加急性肝衰竭患者血清钠与病情严重程度的关系[J].湖北医药学院学报, 2015, 34 (4) :357-360.
    [13]GAO HB, PAN C, LIN MH, et al.Analysis of prognostic factors for patients with hepatitis B viurs-related liver failure and construction of a prognostic assessment model[J].Chin J Infect Dis, 2013, 31 (6) :347-352. (in Chinese) 高海兵, 潘晨, 林明华, 等.乙型肝炎病毒相关肝功能衰竭预后因素分析及预后评估模型的构建[J].中华传染病杂志, 2013, 31 (6) :347-352.
    [14]CRDENAS A, SOLE, RODRGUEZ E, et al.Hyponatremia influences the outcome of patients with acute-on-chronic liver failure:an analysis of the CANONIC study[J]Crit Care, 2014, 18 (6) :700
    [15]JIANG CZ, YAN XZ.Research advances in acute-on-chronic liver failure[J].J Clin Hepatol, 2015, 31 (9) :1501-1503. (in Chinese) 蒋承志, 严喜章.慢加急性肝衰竭的研究进展[J].临床肝胆病杂志, 2015, 31 (9) :1501-1503.
    [16]WLODZIMIROW KA, ESLAMI S, ABU-HANNA A, et al.A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality[J].Liver Int, 2013, 33 (1) :40-52.
    [17]GUO LW, DING AK, LIU W, et al.Analysis on prognostic factors in 253 cases of acute-on-chronic liver failure caused by hepatitis B virus[J].J Pathog Biol, 2014, 9 (3) :275-278. (in Chinese) 郭利伟, 丁艾昆, 刘伟, 等.253例乙型肝炎病毒引起的慢加急性肝衰竭预后影响因素分析[J].中国病原生物学杂志, 2014, 9 (3) :275-278.
    [18]YIN PB, ZENG QL, LI JJ, et al.The dynamic changes of TBIL、WBC、HGB、PT、PTA、INR of HBV-associated acute-on-chronic liver failure[J].Henan Med Res, 2016, 25 (3) :403-405. (in Chinese) 尹朋博, 曾庆磊, 李晶晶, 等.乙肝相关性慢加急性肝衰竭的TBil、WBC、HGB、PT、PTA、INR变化趋势分析[J].河南医学研究, 2016, 25 (3) :403-405.
    [19]CHEN MS, GAN QR, JIANG XY, et al.Clinical analysis of pulmonary infection in patients with hepatitis B virus-related acuteon-chronic liver failure[J].Chin J Infect Dis, 2015, 33 (4) :193-197. (in Chinese) 陈明胜, 甘巧蓉, 江晓燕, 等.乙型肝炎病毒相关慢加急性肝功能衰竭患者合并肺部感染的临床分析[J].中华传染病杂志, 2015, 33 (4) :193-197.
    [20]HONG L, YE ZY, SUN QF, et al.Relationship between complications and prognosis of acute-on-chronic hepatitis B liver failure[J].Chin J Microecol, 2011, 23 (9) :829-831. (in Chinese) 洪亮, 叶志勇, 孙庆丰, 等.慢加急性乙型肝炎肝衰竭并发症与预后的关系研究[J].中国微生态学杂志, 2011, 23 (9) :829-831.
    [21]TANG WL, ZHAO GD, DONG ZX, et al.Prognostic risk factors and prognosis model for liver failure[J].Infect Dis Info, 2011, 24 (3) :159-162. (in Chinese) 汤伟亮, 赵钢德, 董志霞, 等.肝衰竭预后危险因素及预后模型建立的研究[J].传染病信息, 2011, 24 (3) :159-162.
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