慢性肝病患者血、腹水内毒素水平的再评估
摘要
目的:采用动态浊度法对慢性肝病患者血、腹水中内毒素水平进行再评估。
方法:第一部分:入组30位健康志愿者、45位慢性乙肝患者、66位肝硬化患者以及42位原发性肝癌患者,利用鲎试剂定量动态浊度法对其外周血中内毒素水平进行测定。同时,记录下各位慢性肝病患者的血清生化指标(如总胆红素、白蛋白、凝血酶原时间及转氨酶)、合并存在的临床事件(上消化道出血、肝性脑病及肾功能不全)及肝硬化患者的病因(乙肝病毒性及非病毒性)和Child-Pugh分级。探讨各血清生化指标与血中内毒素水平之间有无相关性,并比较不同疾病、存在不同合并症以及肝硬化不同病因、严重程度的患者血中内毒素水平有无差异。第二部分:入组11例肝硬化腹水、5例肝癌腹水,利用鲎试剂定量动态浊度法对其腹水中内毒素水平进行测定。记录患者的腹水生化指标(如白蛋白、葡萄糖及乳酸脱氢酶)。探讨各腹水生化指标与腹水内毒素水平之间有无相关性,比较不同疾病腹水内毒素水平有无差异。
结果:第一部分:健康对照组、慢乙肝组、肝硬化组及原发性肝癌组血中内毒素中位数分别为0.018EU/ml、0.0928EU/ml、0.2132EU/ml及0.0792EU/ml,以0.1EU/ml为界值,内毒素阳性率分别为48.9%、62.1%、47.6%。经检验,健康对照组与慢性肝病各组内毒素水平差异显著(P＜0.001),慢性肝病各组之间的内毒素水平无显著差异,无并发症组与各并发症组之间无显著差异;肝硬化各病因组之间及各Child-Pugh级别之间无显著差异。血中内毒素水平与血清总胆红素、白蛋白、凝血酶原时间及转氨酶之间无明显相关性。第二部分:肝硬化无菌性腹水组与肝癌腹水组腹水中内毒素中位数分别为0.0104EU/ml与0.0208EU/ml,以0.1EU/ml为界值,内毒素阳性率分别为9.1%与0。经检验,差异无统计学意义。腹水中内毒素水平与腹水白蛋白、葡萄糖及乳酸脱氢酶之间无明显相关性。
结论:正常人外周血中不含内毒素或仅含痕量内毒素。慢性肝病患者存在不同程度的内毒素血症,其与肝病严重程度的关系尚需进一步研究,与血清生化指标之间无明显相关性。慢性肝病患者无菌性腹水中不含内毒素或仅含痕量内毒素,且与腹水生化指标之间无明显相关性。
Objective:To reevaluate the blood endotoxin concentration in patients with chronic liver diseases by means of dynamic turbidimetric analysis.
Methods:Part One:We enroll 30 healthy voluteers,45 patients with chronic hepatitis B(CHB),66 patients with cirrhosis and 42 patients with hepatocellular carcinoma(HCC),and determine the peripheral blood endotoxin level by means of dynamic turbidimetric analysis.At the same time,we record the patients' serum biochemical index(such as total bilibubin,albumin,prothrombin time and aminotransferase),complication(such as upper gastrointestinal bleeding,hepatic encephalopathy and hepatic renal syndrome) as well as cause(hepatitis B or non-hepatitis-B) and Child-Pugh stage of cirrhosis.Part Two:We enroll 11 patients with cirrhosis and 5 patients with HCC.Each of them has ascitis and its endotoxin level is determined by means of dynamic turbidimetric analysis.At the same time,we record the patients' ascitis biochemical index(such as albumin,glucose or lactate dehydrogenase).
Results:Part One:Peripheral blood endotoxin level in healthy volunteers, patients with CHB,cirrhosis and HCC is separately 0.018EU/ml,0.0928EU/ml, 0.2132EU/ml and 0.0792EU/ml.Setting up 0.1EU/ml as a limit,the positive rate is separately 48.9%,62.1%and 47.6%.The difference between the control group and CLD groups is significant(P＜0.001).Endotoxin levels between CLD subgroups have no significant difference.Neither do the level between complication subgroups, aetiological subgroups and Child-Pugh stage subgroups.Peripheral blood endotoxin level doesn't correlate with serum total bilirubin,albumin,prothrombin time or aminotransferase.Part Two:Ascitis endotoxin level in patients with cirrhosis and HCC is separately 0.0104EU/ml and 0.0208EU/ml.Setting up 0.1EU/ml as a limit, the positive rate is separately 9.1%and 0.The difference between cirrhosis group and HCC group is not significant.Ascitic endotoxin level doesn't correlate with ascitic albumin,glucose or lactate dehydrogenase.
Conclusion:Normal people have few endotoxin in their peripheral blood while patients with CLD have different degrees of endotoxemia.It remains a problem to study further that if peripheral blood endotoxin level is corelated to the severity of liver injury.Patients with CLD have few endotoxin in their ascitis.
方法:第一部分:入组30位健康志愿者、45位慢性乙肝患者、66位肝硬化患者以及42位原发性肝癌患者,利用鲎试剂定量动态浊度法对其外周血中内毒素水平进行测定。同时,记录下各位慢性肝病患者的血清生化指标(如总胆红素、白蛋白、凝血酶原时间及转氨酶)、合并存在的临床事件(上消化道出血、肝性脑病及肾功能不全)及肝硬化患者的病因(乙肝病毒性及非病毒性)和Child-Pugh分级。探讨各血清生化指标与血中内毒素水平之间有无相关性,并比较不同疾病、存在不同合并症以及肝硬化不同病因、严重程度的患者血中内毒素水平有无差异。第二部分:入组11例肝硬化腹水、5例肝癌腹水,利用鲎试剂定量动态浊度法对其腹水中内毒素水平进行测定。记录患者的腹水生化指标(如白蛋白、葡萄糖及乳酸脱氢酶)。探讨各腹水生化指标与腹水内毒素水平之间有无相关性,比较不同疾病腹水内毒素水平有无差异。
结果:第一部分:健康对照组、慢乙肝组、肝硬化组及原发性肝癌组血中内毒素中位数分别为0.018EU/ml、0.0928EU/ml、0.2132EU/ml及0.0792EU/ml,以0.1EU/ml为界值,内毒素阳性率分别为48.9%、62.1%、47.6%。经检验,健康对照组与慢性肝病各组内毒素水平差异显著(P＜0.001),慢性肝病各组之间的内毒素水平无显著差异,无并发症组与各并发症组之间无显著差异;肝硬化各病因组之间及各Child-Pugh级别之间无显著差异。血中内毒素水平与血清总胆红素、白蛋白、凝血酶原时间及转氨酶之间无明显相关性。第二部分:肝硬化无菌性腹水组与肝癌腹水组腹水中内毒素中位数分别为0.0104EU/ml与0.0208EU/ml,以0.1EU/ml为界值,内毒素阳性率分别为9.1%与0。经检验,差异无统计学意义。腹水中内毒素水平与腹水白蛋白、葡萄糖及乳酸脱氢酶之间无明显相关性。
结论:正常人外周血中不含内毒素或仅含痕量内毒素。慢性肝病患者存在不同程度的内毒素血症,其与肝病严重程度的关系尚需进一步研究,与血清生化指标之间无明显相关性。慢性肝病患者无菌性腹水中不含内毒素或仅含痕量内毒素,且与腹水生化指标之间无明显相关性。
Objective:To reevaluate the blood endotoxin concentration in patients with chronic liver diseases by means of dynamic turbidimetric analysis.
Methods:Part One:We enroll 30 healthy voluteers,45 patients with chronic hepatitis B(CHB),66 patients with cirrhosis and 42 patients with hepatocellular carcinoma(HCC),and determine the peripheral blood endotoxin level by means of dynamic turbidimetric analysis.At the same time,we record the patients' serum biochemical index(such as total bilibubin,albumin,prothrombin time and aminotransferase),complication(such as upper gastrointestinal bleeding,hepatic encephalopathy and hepatic renal syndrome) as well as cause(hepatitis B or non-hepatitis-B) and Child-Pugh stage of cirrhosis.Part Two:We enroll 11 patients with cirrhosis and 5 patients with HCC.Each of them has ascitis and its endotoxin level is determined by means of dynamic turbidimetric analysis.At the same time,we record the patients' ascitis biochemical index(such as albumin,glucose or lactate dehydrogenase).
Results:Part One:Peripheral blood endotoxin level in healthy volunteers, patients with CHB,cirrhosis and HCC is separately 0.018EU/ml,0.0928EU/ml, 0.2132EU/ml and 0.0792EU/ml.Setting up 0.1EU/ml as a limit,the positive rate is separately 48.9%,62.1%and 47.6%.The difference between the control group and CLD groups is significant(P＜0.001).Endotoxin levels between CLD subgroups have no significant difference.Neither do the level between complication subgroups, aetiological subgroups and Child-Pugh stage subgroups.Peripheral blood endotoxin level doesn't correlate with serum total bilirubin,albumin,prothrombin time or aminotransferase.Part Two:Ascitis endotoxin level in patients with cirrhosis and HCC is separately 0.0104EU/ml and 0.0208EU/ml.Setting up 0.1EU/ml as a limit, the positive rate is separately 9.1%and 0.The difference between cirrhosis group and HCC group is not significant.Ascitic endotoxin level doesn't correlate with ascitic albumin,glucose or lactate dehydrogenase.
Conclusion:Normal people have few endotoxin in their peripheral blood while patients with CLD have different degrees of endotoxemia.It remains a problem to study further that if peripheral blood endotoxin level is corelated to the severity of liver injury.Patients with CLD have few endotoxin in their ascitis.
引文
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2.Chan CC,Hwang S J,Lee FY,Wang SS,Chang FY,Li CP,Chu CJ,Lu RH,Lee SD.Prognostic value of plasma endotoxin levels in patients with cirrhosis.Scand J Gastroenterol.1997;32(9):942
3.Kaser A,Ludwiczek O,Waldenberger P,Jaschke W,Vogel W,Tilg H.Endotoxin and its binding proteins in chronic liver disease:the effect of transjugular intrahepatic portosystemic shunting.Liver.2002;22(5):380
4.徐沛演。肝炎肝硬化内毒素血症与临床及预后的关系.广东医学.2001;22(5):426
5.中华医学会感染病学分会与中华医学会肝病学分会.肝脏.2005年4月
6.中华医学会肝病学分会脂肪肝和酒精性肝病学组.肝脏.2006年01期
7.子吉耀.现代肝病诊断与治疗.复旦大学出版社.294
8.陈灏珠.实用内科学(第12版).人民卫生出版社.1993
9.Ryder SD,British Society of Gastroenterology.Guidelines for the diagnosis and treatment of hepatocellular carcinoma(HCC) in adults.Gut.2003;52 Suppl 3:ⅲ1.
10.张嵗,陈礼明,张世兰,王海滨,肝硬化腹水患者血浆降钙素原和内毒素对肾功能的影响,中华肝脏病杂志.2003;11(12):758
11.Nádházi Z,Takáts A,Offenmüller K,Bert6k L.Plasma endotoxin level in healthy blood donors.Orv Hetil.1998;139(48):2889
12.Iwanaga S,Morita T,Harada T,Nakamura S,Niwa M,Takada K,Kimura T,Sakakibara S.Chromogenic substrates for horseshoe crab clotting enzyme.Its application for the assay of bacterial endotoxins.Haemostasis.1978;7(2-3):183
13.张蓉,叶维法.肝病患者276例血浆内毒素检测的临床意义.临床肝胆病杂志.1989;5(4):212
14.李筠,汪承柏.慢性肝病60例血浆内毒素与生化、病理和中医证型关系的研究.新消化病学杂志.1995;3(1):24
15.吴达军,刘俊.慢性乙型病毒性肝炎患者血浆内毒素、白介素-6和白介素-8水平的研究。临床消化病杂志.2007;19(5):309
16.Fukui H,Brauner B,Bode JC,Bode C.Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease:reevaluation with an improved chromogenic assay.J Hepatol.1991;12(2):162
17.韩德五主编.肝脏病理生理学.第一版.太原:山西高校联合出版社,1992,238
18.王淑霞,韩德五.内毒素血症在急性肝衰时肝内胆汁淤积形成中的作用.临床肝胆病杂志.1996;12(4):175
19.Violi F,Ferro D,Basili S,Saliola M,Quintarelli C,Alessandri C,Cordova C.Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis.Gastroenterology.1995;109(2):531
20.van der Poll T,Büller HR,ten Cate H,Wortel CH,Bauer KA,van Deventer SJ,Hack CE,Sauerwein HP,Rosenberg RD,ten Cate JW.Activation of coagulation after administration of tumor necrosis factor to normal subjects._N Engl J Med.1990;322(23):1622
21.赵龙凤,李红,韩德伍.内毒素血症在肝癌发生、发展中的作用.中国病理生理杂志.2001;17(10):995
22.Lin RS,Lee FY,Lee SD,Tsai YT,Lin HC,Lu RH,Hsu WC,Huang CC,Wang SS,Lo KJ.Endotoxemia in patients with chronic liver diseases:relationship to severity of liver diseases,presence of esophageal varices,and hyperdynamic circulation.J Hepatol.1995;22(2):165
23.张顺财.内毒素基础与临床.科学出版社.274
24.余叔侃,王心禾,黄华芳,等.重症肝炎中的内毒素血症.中华内科杂志.1983,22(3):156
25.Bigatello LM,Broitman SA,Fattori L,Di Paoli M,Pontello M,Bevilacqua G,Nespoli A.Endotoxemia,encephalopathy,and mortality in cirrhotic patients.Am J Gastroenterol.1987;82(1):11
26.邱梅 徐韶敏 张来 罗小华 郑晓瑛 肝硬化腹水患者腹水浓缩回输治疗前后血浆及腹水中内毒素变化 中西医结合肝病杂志.2007;17(4):237
27.贾淑云,杨成,孙斌,严海密,张质玉,高锦孝 肝硬化患者血浆及腹水中一氧化氮和内毒素的检测及其关系探讨 宁夏医学院学报.2006;28(1):39
28.苏英,杨宣,李新月肝硬化腹水患者内毒素、细胞因子水平的检测及临床意义临床肝胆病杂志.2006;22(3):202
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2.Chan CC,Hwang S J,Lee FY,Wang SS,Chang FY,Li CP,Chu CJ,Lu RH,Lee SD.Prognostic value of plasma endotoxin levels in patients with cirrhosis.Scand J Gastroenterol.1997;32(9):942
3.Kaser A,Ludwiczek O,Waldenberger P,Jaschke W,Vogel W,Tilg H.Endotoxin and its binding proteins in chronic liver disease:the effect of transjugular intrahepatic portosystemic shunting.Liver.2002;22(5):380
4.徐沛演。肝炎肝硬化内毒素血症与临床及预后的关系.广东医学.2001;22(5):426
5.中华医学会感染病学分会与中华医学会肝病学分会.肝脏.2005年4月
6.中华医学会肝病学分会脂肪肝和酒精性肝病学组.肝脏.2006年01期
7.子吉耀.现代肝病诊断与治疗.复旦大学出版社.294
8.陈灏珠.实用内科学(第12版).人民卫生出版社.1993
9.Ryder SD,British Society of Gastroenterology.Guidelines for the diagnosis and treatment of hepatocellular carcinoma(HCC) in adults.Gut.2003;52 Suppl 3:ⅲ1.
10.张嵗,陈礼明,张世兰,王海滨,肝硬化腹水患者血浆降钙素原和内毒素对肾功能的影响,中华肝脏病杂志.2003;11(12):758
11.Nádházi Z,Takáts A,Offenmüller K,Bert6k L.Plasma endotoxin level in healthy blood donors.Orv Hetil.1998;139(48):2889
12.Iwanaga S,Morita T,Harada T,Nakamura S,Niwa M,Takada K,Kimura T,Sakakibara S.Chromogenic substrates for horseshoe crab clotting enzyme.Its application for the assay of bacterial endotoxins.Haemostasis.1978;7(2-3):183
13.张蓉,叶维法.肝病患者276例血浆内毒素检测的临床意义.临床肝胆病杂志.1989;5(4):212
14.李筠,汪承柏.慢性肝病60例血浆内毒素与生化、病理和中医证型关系的研究.新消化病学杂志.1995;3(1):24
15.吴达军,刘俊.慢性乙型病毒性肝炎患者血浆内毒素、白介素-6和白介素-8水平的研究。临床消化病杂志.2007;19(5):309
16.Fukui H,Brauner B,Bode JC,Bode C.Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease:reevaluation with an improved chromogenic assay.J Hepatol.1991;12(2):162
17.韩德五主编.肝脏病理生理学.第一版.太原:山西高校联合出版社,1992,238
18.王淑霞,韩德五.内毒素血症在急性肝衰时肝内胆汁淤积形成中的作用.临床肝胆病杂志.1996;12(4):175
19.Violi F,Ferro D,Basili S,Saliola M,Quintarelli C,Alessandri C,Cordova C.Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis.Gastroenterology.1995;109(2):531
20.van der Poll T,Büller HR,ten Cate H,Wortel CH,Bauer KA,van Deventer SJ,Hack CE,Sauerwein HP,Rosenberg RD,ten Cate JW.Activation of coagulation after administration of tumor necrosis factor to normal subjects._N Engl J Med.1990;322(23):1622
21.赵龙凤,李红,韩德伍.内毒素血症在肝癌发生、发展中的作用.中国病理生理杂志.2001;17(10):995
22.Lin RS,Lee FY,Lee SD,Tsai YT,Lin HC,Lu RH,Hsu WC,Huang CC,Wang SS,Lo KJ.Endotoxemia in patients with chronic liver diseases:relationship to severity of liver diseases,presence of esophageal varices,and hyperdynamic circulation.J Hepatol.1995;22(2):165
23.张顺财.内毒素基础与临床.科学出版社.274
24.余叔侃,王心禾,黄华芳,等.重症肝炎中的内毒素血症.中华内科杂志.1983,22(3):156
25.Bigatello LM,Broitman SA,Fattori L,Di Paoli M,Pontello M,Bevilacqua G,Nespoli A.Endotoxemia,encephalopathy,and mortality in cirrhotic patients.Am J Gastroenterol.1987;82(1):11
26.邱梅 徐韶敏 张来 罗小华 郑晓瑛 肝硬化腹水患者腹水浓缩回输治疗前后血浆及腹水中内毒素变化 中西医结合肝病杂志.2007;17(4):237
27.贾淑云,杨成,孙斌,严海密,张质玉,高锦孝 肝硬化患者血浆及腹水中一氧化氮和内毒素的检测及其关系探讨 宁夏医学院学报.2006;28(1):39
28.苏英,杨宣,李新月肝硬化腹水患者内毒素、细胞因子水平的检测及临床意义临床肝胆病杂志.2006;22(3):202
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