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自发性细菌性腹膜炎与可疑自发性细菌性腹膜炎临床特点及其预测的生物学标志物

发布时间:2019-01-27 08:32
【摘要】:研究背景:我国为慢性乙型病毒性肝炎大国,乙肝长期反复发作可导致肝脏炎症浸润,致肝脏纤维化的发生,随着疾病的进展可发展为肝硬化,甚至肝癌。腹水是肝硬化患者最常见的失代偿临床表现,腹水产生的主要机制目前主要认为:门静脉高压;及在一些血管活性物质的作用下,致使小肠毛细血管压力增大以及淋巴回流量增加,血浆胶体渗透压降低,组织液回吸收的减少;肝功能损害严重时,肝脏合成白蛋白功能减退造成低蛋白血症;多数肝硬化腹水患者合并肾脏排水功能障碍导致水钠潴留。肝硬化失代偿期患者,腹水以及上消化道出血是重复再入院最常见原因。研究表明,腹水的产生严重影响肝硬化患者生活质量,同时增加医疗的经济负担,其发生发展与肝硬化患者的预后不良有关。因此,对肝硬化腹水的规范管理,应纳入如肝硬化腹水入院患者接受诊断性腹腔穿刺术及时性;接受利尿剂治疗时间;存在腹水感染高危因素,如食管静脉曲张破裂出血,腹水低蛋白等的患者接受有效的抗生素预防等内容作为管理指标,以便肝硬化失代偿患者接受更好的医疗管理。目的在于改善患者症状和提高生活质量,改善患者的长期预后。肝硬化常见感染为自发性细菌性腹膜炎,研究表明,肝硬化基础上合并感染急性打击时,若未及时控制,会发展为慢加急性肝衰竭,致多个器官功能衰竭。因此在腹水管理中,对于腹水感染的预防,诊断和治疗显得至关重要。目前临床上诊断自发性细菌性腹膜炎仍有局限性,随着检测技术的发展,利用外周血或腹水样本检测相关指标,或从基因组学或蛋白组学层面上寻找预测自发性细菌性腹膜炎生物学标志尤为关键。研究目的:1.评估肝硬化腹水管理指标对患者短期预后28天、90天存活的影响;2.比较入院接受诊断性腹腔穿刺术时间点(24小时内、48小时内)对患者预后影响;3.比较入院接受腹腔穿刺术患者,自发性细菌性腹膜炎与可疑自发性细菌性腹膜炎临床特点;4.分析肝硬化腹水患者发生急性肾损伤危险因素;5.检测腹水中MPO-DNA、TREM-1以及PR3的水平,寻找预测自发性细菌性腹膜炎生物学标志以及与短期死亡率的关系。研究方法:研究对象为2012年1月到2013年6月南方医院肝病中心住院患者,利用电子数据采集系统(EDC)采集数据。入组标准:1)肝硬化失代偿患者;2)入院时近30天内发生过急性失代偿(腹水可合并肝性脑病、上消化道出血、明确部位感染)。排除标准:1)年龄小于18岁或者大于80岁;2)入院时存在明确肝内/肝肿瘤;3)合并严重的肝外疾病;4)腹水病因非肝硬化(结核性,癌性,布加氏综合症等)。收集硬化失代偿患者腹水标本,根据亚太肝病学会标准分为肝硬化失代偿组和慢加急性肝衰竭组,用免疫酶联吸附反应检测腹水中性粒细胞相关的蛋白酶,TREM-1、MPO-DNA、PR3的水平,分析其预测自发性细菌性腹膜炎的能力。统计方法学上,统计用SPSS20.0和Graph Pad Prism 6.02软件进行数据计算和统计学分析。计量资料采用均值±标准差或中位数或四分位间距(范围)表示。正态分布资料采用独立样本T检验、非正态分布采用非参数检验比较组间差异;分类资料采用百分比表示,卡方检验比较组间差异。生物学标志诊断自发性细菌性腹膜炎的诊断价值用ROC曲线进行判定。相关性分析采用非参数检验Spearman分析,P0.05,说明存在相关性。急性肾损伤发生危险因素分析采用将年龄、性别、中性粒细胞,肌酐等纳入单因素分析,P0.1的因素,纳入多因素分析。双侧P0.05为有统计学差异。研究结果:1.肝硬化患者腹水管理中,入院接受诊断性腹腔穿刺患者疾病严重程度高。入院48小时内接受腹腔穿刺组相比48小时后接受腹腔穿刺组住院天数减低,可能降低90天的死亡率。2.自发性细菌性腹膜炎患者急性肾损伤发生率高、短期死亡率高;可疑自发性细菌性腹膜炎患者是一群急性肾损伤发生率较高,短期死亡率高的亚群。3.肝硬化腹水患者急性肾损伤发生独立危险因素为血清总胆红素水平,自发性细菌性腹膜炎。自发性细菌性腹膜炎可加剧肝硬化急性失代偿患者进展到慢加急性肝衰竭,可疑自发性细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水平与疾病严重程度无关。TREM-1、蛋白酶3可作为预测肝硬化失代偿患者自发性细菌性腹膜炎的生物学标志;与短期死亡率有关。
[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.
【学位授予单位】:南方医科大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R572.2;R575.2

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相关期刊论文 前3条

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