中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 7
Jul.  2016

Prognostic evaluation of primary biliary cirrhosis and its value in guiding therapeutic regimens

DOI: 10.3969/j.issn.1001-5256.2016.07.009
Research funding:

 

  • Received Date: 2016-05-03
  • Published Date: 2016-07-20
  • Prognostic evaluation of patients with primary biliary cirrhosis( PBC) and how to improve the prognosis have attracted much attention. Further therapeutic regimens for PBC patients with poor prognosis has become the direction of clinical and scientific studies. This article summarizes the association between baseline indices and prognosis and prognostic evaluation of patients undergoing ursodeoxycholic acid( UDCA) treatment,introduces the current status of UDCA combined with budesonide,fibrates,and obeticholic acid for patients with poor response to UDCA and the drugs being developed,and analyzes the influencing factors for prognosis and efficacy of UDCA. It is pointed out that prognosis and efficacy should be evaluated before and during UDCA treatment,and that therapeutic regimens should be adjusted in time to improve prognosis.

     

  • 全世界约有一半新诊断的肝细胞癌(hepatocellular cell carcinoma,HCC)病例发生在我国,其中HBV感染是主要危险因素,占全球HCC病例的50%~80%[1]。HBV通过多种机制在宿主细胞中持续存在,从而导致慢性HBV感染[2],并且诱导HCC发生[3]。超过80%的HCC在肝硬化基础上发展,这表明肝硬化在肝癌前环境中起着重要作用[4]。因此慢性HBV感染和肝硬化是肝癌发生的高风险因素。由于缺乏明显的症状和有效的筛查策略,80%的HCC患者被诊断时已为中晚期,其中仅有30%~40%患者符合当前有效治疗方案的条件[5],故在早期将慢性HBV感染、肝硬化与HCC区分诊断是延长患者生存期甚至根治HCC的关键。现急需一种检测方式能够在患有良性肝病的肝癌高危人群中早期筛查出HCC,从而降低病死率。影像学检查作为有效筛查方法被应用于临床,但是受限于设备以及检测人员。实验室检测则更能筛查大量人群,目前主要的早期实验室筛查方法为检测患者血清AFP,但单一指标检测的敏感度与特异度存在限制。考虑联合指标检测能够提高诊断效率,本文将探究AFP与GGT/AST联合检测在良性肝病和HCC区别诊断中发挥的作用,以期为临床诊断提供新的参考依据。

    选取2019年1月15日—6月15日于本院诊治的慢性乙型肝炎患者(CHB组)、乙型肝炎肝硬化患者(LC组)、HBV相关HCC患者(HCC组),另选取同期健康体检者作为对照(HC组)。纳入标准:(1)HCC组患者HBsAg为阳性且诊断完全符合《原发性肝癌诊疗规范(2017年版)》[6]; (2)HCC组、CHB组和LC组患者均为首次诊断,在接受治疗前收集生化指标; (3)临床资料完整。排除标准:(1)排除HCC之外的恶性肿瘤; (2)排除HBV以外的其他肝炎病毒感染; (3)排除患有严重糖尿病、甲状腺亢进以及心血管疾病等患者; (4)排除妊娠患者。研究对象均自愿参与本项研究。

    采集所有研究对象空腹6~8 h后的静脉血5 ml,以转速3500 r/min(离心半径=16 cm)离心5 min,分离血清后-80 ℃冷冻备用。采用Siemens公司ADVIACENTUAR XP全自动化学发光免疫分析仪及配套试剂盒检测血清AFP水平,参考区间为0~8.0 ng/ml。使用Siemens公司ADVIA2400全自动生化分析仪检测AST、ALT、GGT水平,参考区间分别为15~40、5~40、10~60 U/L。以上操作严格依据说明书进行,所有检测均在试剂盒说明书规定时间内完成,且严格遵守试验相关操作规程。

    本研究方案经由武汉大学人民医院临床研究伦理委员会审批,批号:WDRY2018-K047。

    采用SPSS 23.0软件、GraphPad Prism 6.0和MedCalc 18.2.1对数据进行统计分析。正态分布计量资料以x±s表示,多组间比较采用方差分析,进一步两两比较采用LSD-t检验。偏态分布计量资料以M(P25~P75)表示,多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Nemenyi检验。计数资料组间比较采用χ2检验。通过二元logistic回归分析,计算出预测变量,并绘制AFP、GGT/AST以及预测变量单独或联合检测的受试者工作特征曲线(ROC曲线),计算曲线下面积(AUC)及敏感度、特异度,采用Z检验对AUC进行比较。P<0.05为差异有统计学意义。

    共纳入研究对象352例,其中HC组86例,男42例,女44例,年龄23~82岁,平均(55.90±15.19)岁; CHB组68例,男38例,女30例,年龄22~77岁,平均(51.40±10.59)岁,HBV DNA阳性50例; LC组69例,男34例,女35例,年龄28~79岁,平均(53.49±11.35)岁,HBV DNA阳性36例,Child-Pugh A级25例,B级32例,C级12例; HCC组129例,男70例,女59例,年龄24~78岁,平均(54.60±11.17)岁,HBV DNA阳性50例,Child-Pugh A级79例,B级41例,C级9例,BCLC分期A期21例,B期31例,C期77例。4组研究对象年龄(F=1.455,P=0.227)与性别分布(χ2=1.346,P=0.718)差异均无统计学意义。

    HCC组与HC组、CHB组、LC组之间患者的AFP、GGT/AST、GGT比较差异均有统计学意义(P值均<0.05)(表 1)。

    表  1  各组AFP、GGT、AST及GGT/AST血清学水平比较
    组别 例数 AFP(ng/ml) GGT/AST GGT(U/L) AST(U/L)
    HC组 86 3.35(2.20~4.70) 0.98(0.71~1.36) 20.00(15.00~27.00) 21.00(18.00~24.00)
    CHB组 68 4.35(2.35~15.75) 0.82(0.46~1.25) 51.00(23.75~140.75)1) 61.00(34.25~125.00)1)
    LC组 69 8.60(2.70~54.20)1) 0.97(0.55~1.81) 69.00(27.00~113.00)1) 47.00(31.00~88.00)1)
    HCC组 129 157.10(9.90~6126.40)1)2)3) 2.00(1.19~3.11)1)2)3) 98.00(45.00~207.00)1)2)3) 46.00(29.00~88.00)1)2)
    H 124.018 70.202 126.282 135.987
    P <0.001 <0.001 <0.001 <0.001
    注:与HC组比较,1)P<0.05;与CHB组比较,2)P<0.05;与LC组比较,3)P<0.05。
    下载: 导出CSV 
    | 显示表格

    采用二元logistic回归分析得到不同组别之间两种指标的联合回归模型,然后进一步绘制其ROC曲线(图 1),计算AUC(表 2),结果显示,在HCC组与LC组、HCC组与HC组+CHB组+LC组、HCC组与CHB组+LC组中,AFP与GGT/AST联合诊断的AUC均显著高于AFP单独诊断的AUC(Z值分别为2.684、2.241、2.415,P值分别为0.007、0.025、0.016)。

    图  1  AFP与GGT/AST单独或联合检测诊断HCC的ROC曲线
    注:a,HCC组与CHB组; b,HCC组与LC组; c,HCC组与HC组+CHB组+LC组; d,HCC组与CHB组+LC组。
    表  2  AFP与GGT/AST单独或联合检测在辅助HCC诊断中的价值
    分组 标志物 AUC 95%CI 敏感度(%) 特异度(%) P
    HCC组vs CHB组 AFP 0.803 0.742~0.864 72.9 72.1 <0.05
    GGT/AST 0.789 0.717~0.861 67.4 83.8 <0.05
    联合 0.846 0.790~0.910 79.8 77.9 <0.05
    HCC组vs LC组 AFP 0.760 0.693~0.826 55.8 84.1 <0.05
    GGT/AST 0.727 0.650~0.803 90.7 46.4 <0.05
    联合 0.802 0.741~0.862 48.1 97.1 <0.05
    HCC组vs HC组+CHB组+LC组 AFP 0.835 0.791~0.879 86.0 68.2 <0.05
    GGT/AST 0.768 0.718~0.817 67.4 74.9 <0.05
    联合 0.843 0.802~0.885 73.6 78.5 <0.05
    HCC组vs CHB组+LC组 AFP 0.781 0.727~0.835 55.8 85.4 <0.05
    GGT/AST 0.758 0.700~0.815 67.4 77.5 <0.05
    联合 0.823 0.775~0.871 81.4 66.4 <0.05
    下载: 导出CSV 
    | 显示表格

    HCC的发生通常伴有前期的慢性HBV感染和肝硬化,在慢性HBV感染以及患有肝硬化的高危人群中,利用有效的筛查方式早期发现HCC至关重要,是患者可能获得根治的关键[7]。本文纳入352例研究对象,基于相关纳排标准将其分为4组,统计分析结果发现HCC组与HC组、CHB组、LC组AFP和GGT/AST比较,差异均有统计学意义(P值均<0.05),此结果与以往研究结果[8]相符。

    AFP作为最早被发现的蛋白肿瘤标志物之一[9],其可反映肝功能情况,因此广泛用于实验室检查。综合全球多种指南,AFP在我国可作为良好的血清学指标[10],但其特异度低,易引起误判[11]。在CHB、LC患者中AFP水平也会升高,因此鉴别诊断HBV相关HCC患者时,AFP具有一定局限性,且部分HBV相关HCC患者的AFP水平并未达到筛查标准,因此容易漏查[12]

    GGT在哺乳动物组织中广泛分布,是一种质膜结合蛋白,血清中的GGT主要来源于肝胆系统[13]。已有研究[14]表明GGT通过诱导DNA损伤来促进肿瘤进展和不良预后,释放活性氧以激活与入侵相关的信号通路,与HCC发展关联密切。AST主要分布于肝细胞线粒体内,当肝脏严重病变坏死时,血清中AST水平会显著升高[15],作为肝功能检查常用生化指标,GGT与AST在临床中应用广泛[16]。本研究计算GGT/AST比值并发现其单独或联合AFP时在HBV相关HCC的诊断中具有一定价值,且该指标计算简单,不用另增检验项目,便于在HCC诊断过程中应用。

    本研究ROC曲线分析结果显示,在HCC组与LC组中,GGT/AST联合AFP后AUC明显提高,表明GGT/AST与AFP联合在鉴别HCC与LC时有良好的诊断效果; 在HCC组与HC组+CHB组+LC组以及CHB组+LC组分别区别诊断时,二者联合的AUC均明显高于AFP单独诊断的AUC,进一步说明GGT/AST联合AFP在鉴别HCC与良性肝病患者中有较好的诊断价值。

    综上所述,本研究表明GGT/AST联合AFP在HBV相关HCC的临床诊断中具有一定价值,提高了AFP的单独诊断效率。由于本研究样本量较小,因此相关研究结果仍需未来增加样本量予以验证。

  • [1]BEUERS U,GERSHWIN ME,GISH RG,et al.Changing nomenclature for PBC:from‘cirrhosis’to‘cholangitis’[J].Gut,2015,64(11):1671-1672.
    [2]SHAPIRO JM,SMITH H,SCHAFFNER F.Serum bilirubin:a prognostic factor in primary biliary cirrhosis[J].Gut,1979,20(2):137-140.
    [3]ROLL J,BOYER JL,BARRY D,et al.The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis[J].N Engl J Med,1983,308(1):1-7.
    [4]CHRISTENSEN E,NEUBERGER J,CROWE J,et al.Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis.Final results of an international trial[J].Gastroenterology,1985,89(5):1084-1091.
    [5]DICKSON ER,GRAMBSCH PM,FLEMING TR,et al.Prognosis in primary biliary cirrhosis:model for decision making[J].Hepatology 1989,10(1):1-7.
    [6]PRINCE M,CHETWYND A,NEWMAN W,et al.Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis:follow-up for up to 28 years[J].Gastroenterology,2002,123(4):1044-1051.
    [7]HEATHCOTE EJ.Management of primary biliary cirrhosis.The American Association for the Study of Liver Diseases practice guidelines[J].Hepatology,2000,31(4):1005-1013.
    [8]ANGULO P,LINDOR KD,THERNEAU TM,et al.Utilization of the Mayo risk score in patients with primary biliary cirrhosis receiving ursodeoxycholic acid[J].Liver,1999,19(2):115-121.
    [9]CORPECHOT C,ABENAVOLI L,RABAHI N,et al.Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis[J].Hepatology,2008,48(3):871-877.
    [10]CHAN AW,CHAN RC,WONG GL,et al.New simple prognostic score for primary biliary cirrhosis:albumin-bilirubin score[J].JGastroenterol Hepatol,2015,30(9):1391-1396.
    [11]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.
    [12]KUMAGI T,GUINDI M,FISCHER SE,et al.Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis[J].Am J Gastroenterol,2010,105(10):2186-2194.
    [13]CORPECHOT C,CHAZOUILLRES O,POUPON R.Early primary biliary cirrhosis:biochemical response to treatment and prediction of long-term outcome[J].J Hepatol,2011,55(6):1361-1367.
    [14]AZEMOTO N,ABE M,MURATA Y,et al.Early biochemical response to ursodeoxycholic acid predicts symptom development in patients with asymptomatic primary biliary cirrhosis[J].J Gastroenterol,2009,44(6):630-634.
    [15]LAMMERS WJ,van BUUREN HR,HIRSCHFIELD GM,et al.Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis:an international follow-up study[J].Gastroenterology,2014,147(6):1338-1349.
    [16]PARS A,CABALLERA L,RODS J.Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid[J].Gastroenterology,2006,130(3):715-720.
    [17]KUIPER EM,HANSEN BE,de VRIES RA,et al.Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid[J].Gastroenterology,2009,136(4):1281-1287.
    [18]FLOREANI A,CAZZAGON N,MARTINES D,et al.Performance and utility of transient elastography and noninvasive markers of liver fibrosis in primary biliary cirrhosis[J].Dig Liver Dis,2011,43(11):887-892.
    [19]CORPECHOT C,CARRAT F,POUJOL-ROBERT A,et al.Noninvasive elastography-based assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis[J].Hepatology,2012,56(1):198-208.
    [20]DUAN WJ,ZHANG FK,OU XJ,et al.The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid[J].Chin J Hepatol,2011,19(2):118-120.(in Chinese)段维佳,张福奎,欧晓娟,等.原发性胆汁性肝硬化患者对熊去氧胆酸应答欠佳的影响因素分析[J].中华肝脏病杂志,2011,19(2):118-120.
    [21]CARBONE M,SHARP SJ,FLACK S,et al.The UK-PBC risk scores:derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis[J].Hepatology,2016,63(3):930-950.
    [22]LAMMERSWJ,HIRSCHFIELD GM,CORPECHOT C,et al.Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy[J].Gastroenterology,2015,149(7):1804-1812.
    [23]Chinese Society of Hepatology,Chinese Medical Association;Chinese Society of Gastroenterology,Chinese Medical Association;Chinese Society of Infectious Diseases,Chinese Medical Association.Consensus on the diagnosis and management of primary biliary cirrhosis(cholangitis)(2015)[J].J Clin Hepatol,2015,31(12):1980-1988.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会感染病学分会.原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015)[J].临床肝胆病杂志,2015,31(12):1980-1988.
    [24]LEUSCHNER M,MAIER KP,SCHLICHTING J,et al.Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis:results of a prospective double-blind trial[J].Gastroenterology,1999,117(4):918-925.
    [25]ANGULO P,JORGENSEN RA,KEACH JC,et al.Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid[J].Hepatology,2000,31(2):318-323.
    [26]RAUTIAINEN H,KRKKINEN P,KARVONEN AL,et al.Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis:a three-year randomized trial[J].Hepatology,2005,41(4):747-752.
    [27]RABAHI N,CHRTIEN Y,GAOUAR F,et al.Triple therapy with ursodeoxycholic acid,budesonide and mycophenolate mofetil in patients with features of severe primary biliary cirrhosis not responding to ursodeoxycholic acid alone[J].Gastroenterol Clin Biol,2010,34(4-5):283-287.
    [28]RAUTIAINEN H,KARVONEN AL,KARKKAINEN P,et al.6year follow up of liver histology after budesonide to UDCA combination therapy in PBC compared with UDCA monoterapy[J].J Hepatol,2011,54(Suppl):s517.
    [29]RAUTIAINEN H,FRKKILM,NEUVONEN M,et al.Pharmacokinetics and bone effects of budesonide in primary biliary cirrhosis[J].Aliment Pharmacol Ther,2006,24(11-12):1545-1552.
    [30]NEVENS F,ANDREONE P,MAZZELLA G,et al.The first primary biliary cirrhosis(PBC)phase 3 trial in two decades---an international study of the FXR agonist obeticholic acid[J].J Hepatol,2014,60:s525.
    [31]HIRSCHFIELD GM,MASON A,LUKETIC V,et al.Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid[J].Gastroenterology,2015,148(4):751-761.
    [32]IWASAKI S,OHIRA H,NISHIGUCHI S,et al.The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis:a prospective,multicenter study[J].Hepatol Res,2008,38(6):557-564.
    [33]KANDA T,YOKOSUKA O,IMAZEKI F,et al.Bezafibrate treatment:a new medical approach for PBC patients?[J].J Gastroenterol,2003,38(6):573-578.
    [34]ITAKURA J,IZUMI N,NISHIMURA Y,et al.Prospective randomized crossover trial of combination therapy with bezafibrate and UDCA for primary biliary cirrhosis[J].Hepatol Res,2004,29(4):216-222.
    [35]LEVY C,PETER JA,NELSON DR,et al.Pilot study:fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid[J].Aliment Pharmacol Ther,2011,33(2):235-242.
    [36]LENS S,LEOZ M,NAZAL L,et al.Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid[J].Liver Int,2014,34(2):197-203.
    [37]CORPECHOT C.Primary biliary cirrhosis beyond ursodeoxycholic acid[J].Semin Liver Dis,2016,36(1):15-26.
    [38]SUN LM,WANG YP,LIU YM,et al.Differential characteristics ofA-MA-M2 autoantibody in primary biliary cirrhosis and non-PBC patients[J].Chin J Hepatol,2015,23(5):343-349.(in Chinese)孙丽梅,王一鹏,刘燕敏,等.抗线粒体抗体M2亚型在非原发性胆汁性肝硬化患者中的特点[J].中华肝脏病杂志,2015,23(5):343-349.
    [39]de LEMOS AS,FOUREAU DM,JACOBS C,et al.Drug-induced liver injury with autoimmune features[J].Semin Liver Dis,2014,34(2):194-204.
    [40]LIU YM,LIAO HY,YAN HP,et al.A clinical study of bilirubin rise in short-term in patients with primary biliary cirrhosis[J].Chin J Hepatol,2012,20(8):632-633.(in Chinese)刘燕敏,廖慧钰,闫惠平,等.原发性胆汁性肝硬化患者胆红素短期内上升临床分析[J].中华肝脏病杂志,2012,20(8):632-633.
    [41]European Association for the Study of the Liver.EASL clinical practice guidelines:management of cholestatic liver diseases[J].JHepatol,2009,51(2):237-267.
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    [6]Wu YiChen, Yao HongYu, Wang KaiLi, Jiang QiYu, Liu Chang, Xing HanQian, Liu SuXia, You ShaoLi, Zhao Jun. Effect of plasma exchange on bioactivity of peripheral blood CD34+ cells in patients with acute-on-chronic (subacute) liver failure[J]. Journal of Clinical Hepatology, 2018, 34(11): 2383-2387. doi: 10.3969/j.issn.1001-5256.2018.11.023
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    [8]Zhou Jian, Wan Hong, Yang ZhengMao, Wang ZhaoXun. Clinical effect of plasma perfusion combined with plasma exchange in treatment of patients with acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2017, 33(4): 715-718. doi: 10.3969/j.issn.1001-5256.2017.04.023
    [9]Hou HuanRong, Shang Jia, Kang Yi, Li YuKui, Ceng YanLi, Ding GangQiang, Mao ZhongShan, Xiao ErHui. Clinical effect of plasma exchange combined with hemofiltration in patients with subacute liver failure induced by antitubercular agents[J]. Journal of Clinical Hepatology, 2016, 32(2): 342-346. doi: 10.3969/j.issn.1001-5256.2016.02.030
    [10]Zhang LiangJie, Chen HuiJuan, Zhao ShouSong. Effects of artificial liver plasma exchange on cytokines in patients with liver failure[J]. Journal of Clinical Hepatology, 2015, 31(4): 578-581. doi: 10.3969/j.issn.1001-5256.2015.04.024
    [11]Wu ShaoHong, Gan JianHe, Huang XiaoPing, Lin Hua, Lu NianFang, Wu JiangQuan, Zheng RuiQiang. Clinical effect of albumin dialysis combined with plasma perfusion in treatment of liver failure[J]. Journal of Clinical Hepatology, 2014, 30(5): 434-437. doi: 10.3969/j.issn.1001-5256.2014.05.013
    [12]Liu XiaoHui, Guo HaiQing, Zhang Jing, Duan ZhongPing. Progress in technology and clinical application of non- bioartificial liver support system[J]. Journal of Clinical Hepatology, 2013, 29(9): 661-665. doi: 10.3969/j.issn.1001-5256.2013.09.007
    [13]You ShaoLi, Liu HongLing, Rong YiHui, Zhu Bing, Zang Hong, Liu WanShu, Wan ZhiHong, Mao PanYong, Xin ShaoJie. Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV- related acute- on- chronic liver failure[J]. Journal of Clinical Hepatology, 2013, 29(9): 685-688. doi: 10.3969/j.issn.1001-5256.2013.09.013
    [14]Hu QiJiang, Jiang YingAn. Evaluation of the therapeutic efficacy of lamivudine combined with plasma exchange for treating acute-on-chronic hepatitis B liver failure [J]. Journal of Clinical Hepatology, 2013, 29(2): 107-109.
    [15]Zhou Jian, Wan Hong. Relationship between changes in serum cytokine levels after artificial liver therapy and clinical prognosis in patients with liver failure[J]. Journal of Clinical Hepatology, 2013, 29(7): 535-537. doi: 1001-5256 (2013) 07-0535-03
    [16]Zhang AiMin, You ShaoLi, Wan ZhiHong, Rong YiHui, Zhu Bing, Zang Hong, Xin ShaoJie. Combination therapy of plasma perfusion, plasma exchange, and entecavir in patients with hepatitis B acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2012, 28(10): 744-747.
    [17]Zhang WenHua, Jia WenLing, Zhou ZiYing, Tang HaiTao, Wang FengMei. Investigation on the method and safety of the non-heparinized plasma exchange therapy in treating patients with hepatic failure[J]. Journal of Clinical Hepatology, 2012, 28(1): 50-52.
    [18]Liao JinMao, Li ZhuoRi, Hu XiaoXuan. The therapeutic effect of plasma exchange therapy in patients with severe hepatitis[J]. Journal of Clinical Hepatology, 2012, 28(4): 302-304.
    [19]Liu ZhiHong, Jiang JianNing, Luo GuangHan, Wu JiZhou, Deng YiMing, Su MingHua, Wu JianLin, Zhang Lu. The value of MELD score for evaluation of plasma exchange in patients with liver failure[J]. Journal of Clinical Hepatology, 2010, 26(6): 615-617.
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