自發(fā)性細(xì)菌性腹膜炎與可疑自發(fā)性細(xì)菌性腹膜炎臨床特點(diǎn)及其預(yù)測的生物學(xué)標(biāo)志物
發(fā)布時(shí)間：2019-01-27 08:32
【摘要】：研究背景:我國為慢性乙型病毒性肝炎大國,乙肝長期反復(fù)發(fā)作可導(dǎo)致肝臟炎癥浸潤,致肝臟纖維化的發(fā)生,隨著疾病的進(jìn)展可發(fā)展為肝硬化,甚至肝癌。腹水是肝硬化患者最常見的失代償臨床表現(xiàn),腹水產(chǎn)生的主要機(jī)制目前主要認(rèn)為:門靜脈高壓;及在一些血管活性物質(zhì)的作用下,致使小腸毛細(xì)血管壓力增大以及淋巴回流量增加,血漿膠體滲透壓降低,組織液回吸收的減少;肝功能損害嚴(yán)重時(shí),肝臟合成白蛋白功能減退造成低蛋白血癥;多數(shù)肝硬化腹水患者合并腎臟排水功能障礙導(dǎo)致水鈉潴留。肝硬化失代償期患者,腹水以及上消化道出血是重復(fù)再入院最常見原因。研究表明,腹水的產(chǎn)生嚴(yán)重影響肝硬化患者生活質(zhì)量,同時(shí)增加醫(yī)療的經(jīng)濟(jì)負(fù)擔(dān),其發(fā)生發(fā)展與肝硬化患者的預(yù)后不良有關(guān)。因此,對肝硬化腹水的規(guī)范管理,應(yīng)納入如肝硬化腹水入院患者接受診斷性腹腔穿刺術(shù)及時(shí)性;接受利尿劑治療時(shí)間;存在腹水感染高危因素,如食管靜脈曲張破裂出血,腹水低蛋白等的患者接受有效的抗生素預(yù)防等內(nèi)容作為管理指標(biāo),以便肝硬化失代償患者接受更好的醫(yī)療管理。目的在于改善患者癥狀和提高生活質(zhì)量,改善患者的長期預(yù)后。肝硬化常見感染為自發(fā)性細(xì)菌性腹膜炎,研究表明,肝硬化基礎(chǔ)上合并感染急性打擊時(shí),若未及時(shí)控制,會(huì)發(fā)展為慢加急性肝衰竭,致多個(gè)器官功能衰竭。因此在腹水管理中,對于腹水感染的預(yù)防,診斷和治療顯得至關(guān)重要。目前臨床上診斷自發(fā)性細(xì)菌性腹膜炎仍有局限性,隨著檢測技術(shù)的發(fā)展,利用外周血或腹水樣本檢測相關(guān)指標(biāo),或從基因組學(xué)或蛋白組學(xué)層面上尋找預(yù)測自發(fā)性細(xì)菌性腹膜炎生物學(xué)標(biāo)志尤為關(guān)鍵。研究目的:1.評估肝硬化腹水管理指標(biāo)對患者短期預(yù)后28天、90天存活的影響;2.比較入院接受診斷性腹腔穿刺術(shù)時(shí)間點(diǎn)(24小時(shí)內(nèi)、48小時(shí)內(nèi))對患者預(yù)后影響;3.比較入院接受腹腔穿刺術(shù)患者,自發(fā)性細(xì)菌性腹膜炎與可疑自發(fā)性細(xì)菌性腹膜炎臨床特點(diǎn);4.分析肝硬化腹水患者發(fā)生急性腎損傷危險(xiǎn)因素;5.檢測腹水中MPO-DNA、TREM-1以及PR3的水平,尋找預(yù)測自發(fā)性細(xì)菌性腹膜炎生物學(xué)標(biāo)志以及與短期死亡率的關(guān)系。研究方法:研究對象為2012年1月到2013年6月南方醫(yī)院肝病中心住院患者,利用電子數(shù)據(jù)采集系統(tǒng)(EDC)采集數(shù)據(jù)。入組標(biāo)準(zhǔn):1)肝硬化失代償患者;2)入院時(shí)近30天內(nèi)發(fā)生過急性失代償(腹水可合并肝性腦病、上消化道出血、明確部位感染)。排除標(biāo)準(zhǔn):1)年齡小于18歲或者大于80歲;2)入院時(shí)存在明確肝內(nèi)/肝腫瘤;3)合并嚴(yán)重的肝外疾病;4)腹水病因非肝硬化(結(jié)核性,癌性,布加氏綜合癥等)。收集硬化失代償患者腹水標(biāo)本,根據(jù)亞太肝病學(xué)會(huì)標(biāo)準(zhǔn)分為肝硬化失代償組和慢加急性肝衰竭組,用免疫酶聯(lián)吸附反應(yīng)檢測腹水中性粒細(xì)胞相關(guān)的蛋白酶,TREM-1、MPO-DNA、PR3的水平,分析其預(yù)測自發(fā)性細(xì)菌性腹膜炎的能力。統(tǒng)計(jì)方法學(xué)上,統(tǒng)計(jì)用SPSS20.0和Graph Pad Prism 6.02軟件進(jìn)行數(shù)據(jù)計(jì)算和統(tǒng)計(jì)學(xué)分析。計(jì)量資料采用均值±標(biāo)準(zhǔn)差或中位數(shù)或四分位間距(范圍)表示。正態(tài)分布資料采用獨(dú)立樣本T檢驗(yàn)、非正態(tài)分布采用非參數(shù)檢驗(yàn)比較組間差異;分類資料采用百分比表示,卡方檢驗(yàn)比較組間差異。生物學(xué)標(biāo)志診斷自發(fā)性細(xì)菌性腹膜炎的診斷價(jià)值用ROC曲線進(jìn)行判定。相關(guān)性分析采用非參數(shù)檢驗(yàn)Spearman分析,P0.05,說明存在相關(guān)性。急性腎損傷發(fā)生危險(xiǎn)因素分析采用將年齡、性別、中性粒細(xì)胞,肌酐等納入單因素分析,P0.1的因素,納入多因素分析。雙側(cè)P0.05為有統(tǒng)計(jì)學(xué)差異。研究結(jié)果:1.肝硬化患者腹水管理中,入院接受診斷性腹腔穿刺患者疾病嚴(yán)重程度高。入院48小時(shí)內(nèi)接受腹腔穿刺組相比48小時(shí)后接受腹腔穿刺組住院天數(shù)減低,可能降低90天的死亡率。2.自發(fā)性細(xì)菌性腹膜炎患者急性腎損傷發(fā)生率高、短期死亡率高;可疑自發(fā)性細(xì)菌性腹膜炎患者是一群急性腎損傷發(fā)生率較高,短期死亡率高的亞群。3.肝硬化腹水患者急性腎損傷發(fā)生獨(dú)立危險(xiǎn)因素為血清總膽紅素水平,自發(fā)性細(xì)菌性腹膜炎。自發(fā)性細(xì)菌性腹膜炎可加劇肝硬化急性失代償患者進(jìn)展到慢加急性肝衰竭,可疑自發(fā)性細(xì)菌性腹膜炎患者具有相似作用。4.腹水中TREM-1、蛋白酶3、MPO-DNA水平與疾病嚴(yán)重程度無關(guān)。TREM-1、蛋白酶3可作為預(yù)測肝硬化失代償患者自發(fā)性細(xì)菌性腹膜炎的生物學(xué)標(biāo)志;與短期死亡率有關(guān)。
[Abstract]:Background: Our country is a large country with chronic viral hepatitis B. The long-term recurrence of hepatitis B can lead to the infiltration of liver inflammation and the occurrence of liver fibrosis. With the development of the disease, it can be developed into liver cirrhosis and even liver cancer. Ascites are the most common decompensated clinical manifestations in the patients with liver cirrhosis. The main mechanism of the generation of ascitic fluid is: portal hypertension; and under the action of some vasoactive substances, the capillary pressure of the small intestine is increased and the flow of the lymph reflux is increased, and the osmotic pressure of the plasma colloid is reduced. The decrease of the absorption of the tissue fluid; when the liver function is serious, the hypoproteinemia is caused by the decrease of the function of the synthesis of albumin in the liver; and the combined renal drainage dysfunction in the majority of the liver cirrhosis ascites patients leads to the retention of the sodium. The most common cause of repeated readmission in patients with decompensation of liver cirrhosis, ascites, and upper gastrointestinal bleeding. The research shows that the generation of ascites has a serious effect on the quality of life of the patients with liver cirrhosis, and the economic burden of the medical treatment is increased, and the development of the ascites is related to the poor prognosis of the patients with liver cirrhosis. Therefore, the management of the specification of the liver cirrhosis ascites shall be included in the timeliness of the diagnosis of the diagnosis of the ascites due to the ascites due to the cirrhosis of the liver, the time for the treatment of the diuretics, and the high risk factors of the ascites infection, such as the bleeding of the esophageal varices, Patients with ascitic low protein and the like receive effective antibiotic prevention and other contents as the management index, so that the patients with decompensation of liver cirrhosis receive better medical management. The aim is to improve the patient's symptoms and improve the quality of life and to improve the long-term prognosis of the patient. The common infection of liver cirrhosis is spontaneous bacterial peritonitis. Therefore, in the management of ascites, it is very important to prevent, diagnose and treat the ascitic infection. The present clinical diagnosis of spontaneous bacterial peritonitis is still limited, with the development of the detection technology, the correlation index is detected by using the peripheral blood or the ascites sample, or the biological marker for predicting the spontaneous bacterial peritonitis is particularly critical from the aspect of the genomics or proteomics. Study objective: 1. To evaluate the effect of the management index of the liver cirrhosis ascites on the survival of the short-term prognosis of the patients for 28 days and 90 days. The patient's prognosis was compared with the time point (within 24 hours, within 48 hours) of the diagnostic abdominal puncture (24 hours, within 48 hours). The clinical characteristics of the spontaneous bacterial peritonitis and the suspected spontaneous bacterial peritonitis were compared and the clinical characteristics of the spontaneous bacterial peritonitis and the suspected spontaneous bacterial peritonitis were compared. The risk factors of acute kidney injury in patients with liver cirrhosis ascites were analyzed. The levels of MPO-DNA, TREM-1 and PR3 in the ascites were detected, and the relationship between the biological markers of spontaneous bacterial peritonitis and the short-term mortality was found. Methods: The subjects were hospitalized patients from January 2012 to June 2013, and the data were collected by the electronic data acquisition system (EDC). in group standard: 1) decompensated patients with liver cirrhosis; 2) acute decompensation (ascites may be combined with hepatic encephalopathy, upper gastrointestinal bleeding, clear site infection) within approximately 30 days of admission. Exclusion criteria: 1) age is less than 18 years or greater than 80 years; 2) there is clear hepatic/ liver tumor in admission; 3) serious extrahepatic disease; 4) ascites due to non-liver cirrhosis (tuberculosis, cancer, Budd's syndrome, etc.). collecting and hardening the ascites specimen of the decompensated patient, and dividing the ascites sample into the liver cirrhosis decompensation group and the slow-plus acute liver failure group according to the standard of the Asia-Pacific liver disease, and detecting the levels of the protease, the TREM-1, the MPO-DNA and the PR3 related to the ascites neutrophils by using an immune enzyme-linked adsorption reaction, Analysis of its ability to predict spontaneous bacterial peritonitis. In the statistical methodology, the data and statistical analysis were carried out using the SPSS10.0 and Graph Pad Prism 6.02 software. The measurement data is represented by mean, standard deviation or median or quartile spacing (range). The normal distribution data is tested by independent samples T, and the non-normal distribution adopts the non-unitary test to compare the difference among the groups; the classification data is expressed as a percentage, and the card-side test compares the differences among the groups. The diagnostic value of the biological marker for the diagnosis of spontaneous bacterial peritonitis is determined by the ROC curve. The correlation analysis was analyzed by non-invasive test Spearman, P <0.05, and there was a correlation. The risk factors of acute kidney injury were analyzed by the factors including age, sex, neutral granulocyte and muscle tone in single factor analysis, and the factor of P0.1 was included in multi-factor analysis. There was a statistical difference between the two sides, P0.05. Study Results: 1. In the management of ascites in the patients with liver cirrhosis, the severity of the disease was high in the patients with the diagnostic abdominal puncture. The number of days in which the abdominal puncture group was received within 48 hours of admission to the abdominal puncture group was reduced and the death rate of 90 days was likely to be reduced. The incidence of acute renal injury in patients with spontaneous bacterial peritonitis is high and the short-term mortality is high; the patients with suspected spontaneous bacterial peritonitis are a group of sub-groups with high incidence of acute kidney injury and high short-term mortality. The independent risk factors of acute kidney injury in the patients with liver cirrhosis ascites were serum total bilirubin level and spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis can increase the progress of patients with acute decompensation of liver cirrhosis to slow and acute hepatic failure, and the patients with suspected spontaneous bacterial peritonitis have similar effects. The levels of TREM-1, MMP-3 and MPO-DNA in ascites were not related to the severity of the disease. TREM-1 and Protease 3 can be used as a biological marker for predicting spontaneous bacterial peritonitis in patients with decompensation of liver cirrhosis and related to short-term mortality.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R572.2;R575.2
本文編號(hào)：2416098
[Abstract]:Background: Our country is a large country with chronic viral hepatitis B. The long-term recurrence of hepatitis B can lead to the infiltration of liver inflammation and the occurrence of liver fibrosis. With the development of the disease, it can be developed into liver cirrhosis and even liver cancer. Ascites are the most common decompensated clinical manifestations in the patients with liver cirrhosis. The main mechanism of the generation of ascitic fluid is: portal hypertension; and under the action of some vasoactive substances, the capillary pressure of the small intestine is increased and the flow of the lymph reflux is increased, and the osmotic pressure of the plasma colloid is reduced. The decrease of the absorption of the tissue fluid; when the liver function is serious, the hypoproteinemia is caused by the decrease of the function of the synthesis of albumin in the liver; and the combined renal drainage dysfunction in the majority of the liver cirrhosis ascites patients leads to the retention of the sodium. The most common cause of repeated readmission in patients with decompensation of liver cirrhosis, ascites, and upper gastrointestinal bleeding. The research shows that the generation of ascites has a serious effect on the quality of life of the patients with liver cirrhosis, and the economic burden of the medical treatment is increased, and the development of the ascites is related to the poor prognosis of the patients with liver cirrhosis. Therefore, the management of the specification of the liver cirrhosis ascites shall be included in the timeliness of the diagnosis of the diagnosis of the ascites due to the ascites due to the cirrhosis of the liver, the time for the treatment of the diuretics, and the high risk factors of the ascites infection, such as the bleeding of the esophageal varices, Patients with ascitic low protein and the like receive effective antibiotic prevention and other contents as the management index, so that the patients with decompensation of liver cirrhosis receive better medical management. The aim is to improve the patient's symptoms and improve the quality of life and to improve the long-term prognosis of the patient. The common infection of liver cirrhosis is spontaneous bacterial peritonitis. Therefore, in the management of ascites, it is very important to prevent, diagnose and treat the ascitic infection. The present clinical diagnosis of spontaneous bacterial peritonitis is still limited, with the development of the detection technology, the correlation index is detected by using the peripheral blood or the ascites sample, or the biological marker for predicting the spontaneous bacterial peritonitis is particularly critical from the aspect of the genomics or proteomics. Study objective: 1. To evaluate the effect of the management index of the liver cirrhosis ascites on the survival of the short-term prognosis of the patients for 28 days and 90 days. The patient's prognosis was compared with the time point (within 24 hours, within 48 hours) of the diagnostic abdominal puncture (24 hours, within 48 hours). The clinical characteristics of the spontaneous bacterial peritonitis and the suspected spontaneous bacterial peritonitis were compared and the clinical characteristics of the spontaneous bacterial peritonitis and the suspected spontaneous bacterial peritonitis were compared. The risk factors of acute kidney injury in patients with liver cirrhosis ascites were analyzed. The levels of MPO-DNA, TREM-1 and PR3 in the ascites were detected, and the relationship between the biological markers of spontaneous bacterial peritonitis and the short-term mortality was found. Methods: The subjects were hospitalized patients from January 2012 to June 2013, and the data were collected by the electronic data acquisition system (EDC). in group standard: 1) decompensated patients with liver cirrhosis; 2) acute decompensation (ascites may be combined with hepatic encephalopathy, upper gastrointestinal bleeding, clear site infection) within approximately 30 days of admission. Exclusion criteria: 1) age is less than 18 years or greater than 80 years; 2) there is clear hepatic/ liver tumor in admission; 3) serious extrahepatic disease; 4) ascites due to non-liver cirrhosis (tuberculosis, cancer, Budd's syndrome, etc.). collecting and hardening the ascites specimen of the decompensated patient, and dividing the ascites sample into the liver cirrhosis decompensation group and the slow-plus acute liver failure group according to the standard of the Asia-Pacific liver disease, and detecting the levels of the protease, the TREM-1, the MPO-DNA and the PR3 related to the ascites neutrophils by using an immune enzyme-linked adsorption reaction, Analysis of its ability to predict spontaneous bacterial peritonitis. In the statistical methodology, the data and statistical analysis were carried out using the SPSS10.0 and Graph Pad Prism 6.02 software. The measurement data is represented by mean, standard deviation or median or quartile spacing (range). The normal distribution data is tested by independent samples T, and the non-normal distribution adopts the non-unitary test to compare the difference among the groups; the classification data is expressed as a percentage, and the card-side test compares the differences among the groups. The diagnostic value of the biological marker for the diagnosis of spontaneous bacterial peritonitis is determined by the ROC curve. The correlation analysis was analyzed by non-invasive test Spearman, P <0.05, and there was a correlation. The risk factors of acute kidney injury were analyzed by the factors including age, sex, neutral granulocyte and muscle tone in single factor analysis, and the factor of P0.1 was included in multi-factor analysis. There was a statistical difference between the two sides, P0.05. Study Results: 1. In the management of ascites in the patients with liver cirrhosis, the severity of the disease was high in the patients with the diagnostic abdominal puncture. The number of days in which the abdominal puncture group was received within 48 hours of admission to the abdominal puncture group was reduced and the death rate of 90 days was likely to be reduced. The incidence of acute renal injury in patients with spontaneous bacterial peritonitis is high and the short-term mortality is high; the patients with suspected spontaneous bacterial peritonitis are a group of sub-groups with high incidence of acute kidney injury and high short-term mortality. The independent risk factors of acute kidney injury in the patients with liver cirrhosis ascites were serum total bilirubin level and spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis can increase the progress of patients with acute decompensation of liver cirrhosis to slow and acute hepatic failure, and the patients with suspected spontaneous bacterial peritonitis have similar effects. The levels of TREM-1, MMP-3 and MPO-DNA in ascites were not related to the severity of the disease. TREM-1 and Protease 3 can be used as a biological marker for predicting spontaneous bacterial peritonitis in patients with decompensation of liver cirrhosis and related to short-term mortality.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R572.2;R575.2
【參考文獻(xiàn)】
相關(guān)期刊論文 前3條
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2 Chinmaya Kumar Bal;Ripu Daman;Vikram Bhatia;;Predictors of fifty days in-hospital mortality in decompensated cirrhosis patients with spontaneous bacterial peritonitis[J];World Journal of Hepatology;2016年12期
3 José Manuel Benítez;Valle García-Sánchez;;Faecal calprotectin: Management in inflammatory bowel disease[J];World Journal of Gastrointestinal Pathophysiology;2015年04期
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