肝硬化患者腹水细菌移位的发生及短期随访结果

目的 探讨肝硬化患者非感染性腹水细菌移位(BT)的发生、转归及短期预后.方法 在细菌16S核糖体RNA(16S rRNA)基因保守区设计1对细菌通用引物.对87例肝硬化伴非感染性腹水患者的腹水和血清进行PCR扩增,检测细菌DNA作为BT的分子标志,细菌DNA阳性者通过核苷酸测序进一步鉴别细菌的种属.6个月后随访了解临床转归,对其中部分患者进行腹水细菌DNA复查.结果 87例肝硬化患者腹水细菌DNA阳性33例.血清细菌DNA阳性12例.腹水和血清中的细菌均以大肠埃希菌为主,同一患者腹水和血清的细菌鉴定结果一致且序列同源性达99%以上.6个月后患者腹水中细菌DNA的检测结果较入组时呈现动态变化.影响肝硬化患者预后的主要因素是肝功能Child-Pugh分级和BT.结论 非感染性腹水BT在肝硬化患者体内是一个动态过程,可能形成感染或被机体清除.肝功能Child-Pugh分级和BT的发生影响患者预后.     

聚合酶链反应检测肝硬化患者腹水中细菌DNA

目的:探讨PCR方法检测肝硬化患者腹水中细菌DNA的可行性.方法:在细菌16S rRNA基因保守区设计一对通用引物,对7种对照菌株、人基因组DNA、HBV DNA、37份肝硬化患者腹水进行聚合酶链反应扩增.结果:7种对照菌株均获得530 bp DNA片段.而与人基因组DNA、HBV DNA无交叉阳性反应,敏感性试验可检测出1pg的细菌DNA.37份腹水中有9份获得53bp DNA片段,阳性率24.3%(9/37),而腹水细菌培养阳性率为5.4%(2/37),两者比较差异有显著性意义(P＜0.05).结论:将通用引物通过PCR方法扩增细菌16S rRNA基因,具有高度敏感性、特异性,可应用于肝硬化患者腹水中细菌DNA的检测及细菌移位的研究.     

肝硬化患者腹水中细菌DNA的检测及临床意义

目的 利用PCR测序方法检测肝硬化患者腹水中的细菌DNA，探讨肝硬化患者发生细菌移位的高危因素及其后果。方法 在细菌16SrRNA基因保守区设计一对通用引物，对37份肝硬化患者腹水标本进行扩增，腹水中细菌DNA阳性者纯化后经核苷酸测序鉴别细菌种类；同时对患者的临床症状及实验室检查结果进行统计分析。结果 37份腹水标本中有9份获得530bp细菌DNA片段，占24．3％。测序共检测出4种细菌，其中大肠埃希菌6例，表皮葡萄球菌、溶血性链球菌、阴沟肠杆菌各1例；统计分析表明，腹水中细菌DNA阳性和阴性两组肝硬化患者在Child-Pugh积分（12．3±0．8，10．9±1．2）、上消化道出血的发生率（3例，1例）、血清TBil水平[（395．5±216．6）μmol／L，（192．7±206．3）μmol／L]、凝血酶原活动度[（31．3±9．7）％，（50．4±15．1）％]、腹水总蛋白浓度[（4．1±2．8）g／L，（7．9±5．2）g／L]、外周血WBC总数[（12．3±7．5）×10^9／L，（5．3±4．1）×10^9／L]等方面比较，差异有统计学意义（P〈0．05）。结论 PCR测序方法可应用于肝硬化患者腹水中细菌DNA的检测及细菌移位的研究；肝功能损害、腹水调理活性低下和上消化道出血是肝硬化患者发生细菌移位的高危因素和后果。     

肝硬化患者腹水中细菌DNA与相关因素的关系

目的 探讨肝硬化患者腹水中细菌DNA与血浆内毒素、肠通透性、肠道菌群等因素的关系. 方法 选取失代偿期肝硬化伴腹水患者55例,于入院当日或次日抽取腹水行腹水中细菌DNA的提取及PCR扩增,同时行腹水常规、需氧菌及厌氧菌培养检查,于入院次日测定血浆内毒素、肠通透性并进行肠道菌群分析,同时测定血常规、肝肾功能、凝血功能等生物化学指标.30例健康成年人作为正常对照,行除腹水之外的上述检查. 结果 55例肝硬化患者腹水细菌培养均为阴性,其中19例(34.55%)患者腹水中检测到细菌DNA.与细菌DNA阴性组比较,细菌DNA阳性组患者的凝血酶原活动度明显降低(t=-3.184,P=0.002),而肝功能Child-Pugh评分(t=3.224,P=0.002)和腹水白细胞计数(t'=4.088,P=0.001)明显升高.与正常对照组比较,肝硬化患者血浆内毒素水平(t=13.705,P=0.000)、尿中乳果糖/甘露醇(L/M,t'=28.568,P=0.000)和肠道肠杆菌数量(t=2.912,P=0.005)明显升高,而肠道双歧杆菌数量明显减少(t=-3.669,P=0.000).与腹水中细菌DNA相关的指标为肠道肠杆菌数量(P=0.007)和凝血酶原活动度(P=0.011).结论 肝硬化患者发生腹水细菌移位的关键因素是肠腔细菌过度生长,并与肝病的严重程度相关.     

肝硬化细菌移位及其后果

随着人们对细菌移位（bacterial translocation，BT）后果研究的不断深入，BT的概念已从传统的有活性的肠道菌群通过肠道屏障到达肠系膜淋巴结和肠腔外其他器官或部位，延伸到细菌释放产物（如内毒素和细菌DNA）的移位。现就细菌移位过程中的多种机制，特别是肠内菌群和黏膜屏障功能的改变及免疫防御机制综述如下。     

肝硬化患者血清IL-6水平与腹水发生、内毒素血症及肠道细菌的关系

明确肝硬化患者血清IL．6水平与腹水发生、内毒素血症及肠道中大肠杆菌量的关系,并探讨其可能机制。方法：37例无感染征象的肝硬化患者纳入研究,18例健康者作为对照。分别以ELISA法、鲎试验及细菌培养法检测患者及对照者血清IL．6水平、血浆内毒素浓度及肠道太肠杆菌量。结果：肝硬化患者血清IL-6水平、血浆内毒素水平显著高于健康者。肝硬化伴腹水患者血清IL．6水平、粪太肠杆菌量均显著高于无腹水者,并发现血清IL-6水平与太肠杆菌量阃存在显著相关性。结论：肝硬化伴腹水患者血清IL-6水平显著升高,肠道中革兰阴性大肠杆菌的过度生长以及由此引起的细菌移位可能是导致此细胞因子高反应的重要因素,提示肝硬化患者血清IL-6水平可作为一个细菌移位的指标。     

肝硬化自发性细菌性腹膜炎患者粪便大肠杆菌毒力基因Colv和腹水细菌分布的相关性

目的了解肝硬化自发性细菌性腹膜炎(SBP)患者粪便大肠杆菌毒力基因Colv和腹水细菌分布的相关性。方法运用16S rRNA基因荧光定量多聚酶链反应检测65例肝硬化SBP患者腹水细菌DNA,并与其粪便大肠杆菌培养出毒力基因Colv的结果进行比较。结果 16S rRNA检测肝硬化SBP患者腹水标本的阳性率为64.6%,明显高于腹水细菌培养的4.6%(P0.01)。比对同一病例其粪便大肠杆菌毒力基因Colv和腹水标本中细菌16S rRNA阳性情况能达到70%,有一定的相关性。结论粪便大肠杆菌毒力基因Colv阳性与肝硬化SBP的发生有一定的相关性。     

肝硬化患者小肠细菌过度生长与肝功能及自发性腹膜炎的关系

据报道,肝硬化患者的肠道细菌明显上移,在小肠大量繁殖,引起小肠细菌过度生长（SIBO）,产生大量的代谢产物和毒素,可破坏黏膜屏障,损伤黏膜组织,形成肠道细菌移位、内毒素血症,造成肝硬化患者腹胀,并与自发性细菌性腹膜炎（SBP）密切相关。我们应用氢呼气试验（HBT）检测68例肝硬化患者,研究其SIBO的发生率及其与肝功能减退、腹水和SBP的关系。     

选择性肠道去污染对肝硬化自发性细菌性腹膜炎肠黏膜通透性的影响

目的观察肝硬化自发性细菌性腹膜炎（SBP）肠黏膜通透性和形态结构的变化及选择性肠道去污染对其通透性的影响。方法按诊断标准,将28例肝硬化SBP患者随机分为治疗组（15例）和对照组（13例）,在肝硬化腹水常规治疗和全身应用抗生素抗感染的基础上,治疗组加用诺氟沙星口服选择性肠道去污染（SDD）。采用酶联免疫吸附法（ELISA）测定治疗前后二胺氧化酶（DAO）、D-乳酸（D-Lac）和内毒素（ET）的水平;HE常规染色观察肠黏膜形态结构的变化。结果 常规治疗可降低DAO、D-Lac和ET水平（P〈0.05）,加用SDD可进一步减轻肠黏膜损伤,降低肠黏膜通透性,防止细菌移位。结论 SDD对肝硬化SBP肠黏膜屏障具有保护作用。     

肝炎肝硬化合并自发性细菌性腹膜炎患者TNF-α和IL-6检测的临床意义

目的探讨肝炎肝硬化（HC）合并自发性腹膜炎（SBP）患者血清和腹水中肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）水平变化及意义。方法用化学发光法检测82例肝炎HC合并腹水患者血清和腹水中TNF-α和IL-6水平,同时对患者进行腹水常规检查及细菌培养。对确诊SBP组进行抗感染等综合治疗,临床症状缓解后,复查血清和腹水中TNF-α与IL-6水平。结果肝炎HC合并SBP患者血清和腹水TNF-α和IL-6水平均高于无合并SBP组（P〈0.01）,腹水更敏感。经抗感染等综合治疗后,症状缓解后HC合并SBP患者血清和腹水TNF-α和IL-6水平均下降（P〈0.01）,死亡组初始TNF-α和IL-6水平高于存活组（P〈0.05）。结论血清和腹水TNF-α和IL-6水平检测对于SBP的早期诊断与治疗、判断与改善预后有一定意义。     

肝硬化伴院内感染自发性腹膜炎肾功能的变化与预后的关系

探讨肝硬化腹水患者院内感染自发性腹膜炎（SBP）后肾功能的变化及其与预后的关系。观察162例院内感染SBP患者肾功能的变化，分析肾功能损害（RI）的演变过程与死亡率的关系。结果显示有SBP的患者肾功能损害（SBP－RI）发生率明显高于无SBP患者肾功能损害发生率（P＜0．05），63例发生SBP－RI的患者中，进展型SBP－RI占36．51％，稳定型SBR－RI占33．33％，一过型SBP－RI占30．16％，进展型和稳定型SBP－RI死亡率（73．91％、42．86％）显著高于无SBP－RI者（16．16％），一过型SBP－RI（15．79％）不增加死亡率。引起SBP－RI的主要原因是感染，它的高死亡率与肾损害程度直接相关。     

血浆降钙素原测定在肝硬化伴自发性细菌性腹膜炎患者中的临床应用

目的　探讨血浆降钙素原 (procalcitonin ,PCT)对肝硬化伴自发性细菌性腹膜炎 (spontaneousbacterialperitonitis ,SBP)的诊断价值及与临床病程和预后的关系。方法　采用金标层析法测定 112例肝硬化腹水患者 (单纯腹水 5 1例 ,合并SBP 6 1例 )血浆PCT水平。结果　肝硬化腹水患者血浆PCT水平均显著高于正常 ,以 10ng/mL为阳性判断值时 ,SBP组阳性检出率显著高于无SBP组(P <0 0 0 1) ,且与培养是否阳性无关。最初三天血浆PCT水平变化与临床结局密切相关。结论　血浆PCT测定对肝硬化伴SBP的早期快速诊断及预后判断等有重要价值。     

Rifaximin for the prevention of spontaneous bacterial peritonitis

According to a review article by Biecker et al published in a previous issue of World Journal of Gastroenterology in March 2011, intestinal decontamination with norfloxacin remains the mainstay of primary prophylaxis of spontaneous bacterial peritonitis (SBP) at the expense of development of quinolone-resistant bacteria after long-term use. In our research, the administration of a 4-wk regimen with rifaximin 1200 mg/d reduced significantly the ascitic neutrophil count in cirrhotic patients with sterile ascites in line with a significant decrease in plasma endotoxin levels. Our observations concur with recent findings, showing a significantly reduced 5-year probability of SBP in cirrhotic patients taking rifaximin.     

Association between proton pump inhibitor use and spontaneous bacterial peritonitis in cirrhotic patients with ascites

BACKGROUND:

There are data suggesting a link between proton pump inhibitor (PPI) use and the development of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites; however, these data are controversial.

OBJECTIVE:

To assess whether the use of PPIs in cirrhotic patients with ascites is associated with an increased risk for SBP.

METHODS:

A retrospective case-control study (June 2004 to June 2010) was conducted at the Centre Hospitalier de l’Université de Montréal in Montreal, Quebec. Fifty-one cirrhotic patients admitted with paracentesis-proven SBP (≥250 neutrophils/mm³), occurring within seven days of hospital admission, met the inclusion criteria. These patients were matched 1:2 (for age, Child-Pugh class and year of admission) with 102 comparable cirrhotic patients with ascites who were admitted for conditions other than SBP.

RESULTS:

Patients with SBP had a significantly higher rate of pre-hospital PPI use (60.8%) compared with cirrhotic patients without SBP (42.2%; P=0.03). On multivariate analysis, PPI use was the only factor independently associated with SBP (OR 2.09 [95% CI 1.04 to 4.23]; P=0.04). Thirty-five (35%) patients in both groups had no documented indication for PPI use in their charts. Forty-five percent of the remaining cirrhotic patients with SBP had an inappropriate indication, as defined in the protocol, for PPI use compared with 25% of controls.

CONCLUSIONS:

Cirrhotic patients with SBP were twice as likely to have taken PPIs than patients without SBP. These findings reinforce the association between PPI use and SBP observed in other studies. A high percentage of cirrhotic patients were taking a PPI without any documented indication.     

Analysis of monocyte chemotactic protein-1 gene polymorphism in patients with spontaneous bacterial peritonitis

AIM: To investigate a genetic polymorphism of the monocyte chemotactic protein-1 ( MCP-1) gene in patients with spontaneous bacterial peritonitis (SBP).METHODS: MCP-1 genotyping was performed in 23 patients with SBP and 83 cirrhotic control patients with non-infected ascites.RESULTS: The frequency of carriers of the G-allele was lower in SBP patients but this difference did not reach statistical significance. However, in the subgroup of patients with alcoholic cirrhosis ( n = 80), carriersof the G-allele were significantly less frequent in SBPpatients(38.1%) than in cirrhotic controls (67.8%, P =0.021).CONCLUSION: In patients with alcoholic liver cirrhosis,the -2518 MCP-1 genotype AA is a risk factor for the development of SBP.     

Diagnosis, treatment and prevention of spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis (SBP) is a frequent complication in cirrhotic patients with ascites. Diagnosis of SBP is established by a polymorphonuclear cell count in ascitic fluid > or =250 cells/mm(3). The organism responsible for the infection is isolated in 60-70% of the cases. The remaining cases are considered to have a variant of SBP (culture-negative SBP) and are treated in the same way as those with a positive culture. The SBP resolution rate ranges between 70 and 90%, and hospital survival between 50 and 70%. An early diagnosis and the use of a more adequate antibiotic therapy are the most probable reasons for the improvement in prognosis for SBP in recent decades. Despite the resolution of the infection, SBP may trigger severe complications such as renal impairment, gastrointestinal bleeding and accentuation of hepatic insufficiency which are responsible for the associated mortality. Patients recovering from an episode of SBP should be considered as potential candidates for liver transplantation.     

Increasing frequency of Gram-positive bacteria in spontaneous bacterial peritonitis.

AIM: To evaluate the characteristics and possible recent changes of the microbial causes of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. METHODS: We retrospectively evaluated 42 cirrhotic patients with positive ascitic fluid culture and without evidence of secondary peritonitis who were admitted consecutively to our Department between 1998 and 2002. RESULTS: Twenty (48%) of 42 patients with positive ascitic fluid culture were diagnosed during 1998-1999 (period A) and the remaining 22 (52%) patients during 2000-2002 (period B). Gram-negative bacteria were the cause of SBP in 15 (75%) of the 20 patients during period A and in only nine (41%) of the 22 patients during period B (P=0.026). SBP patients with Gram-positive bacteria compared with those with Gram-negative bacteria were less frequently in Child class C (P=0.058) and had significantly higher ascitic fluid protein (P=0.014) and albumin concentrations (P=0.009) and lower ascitic fluid neutrophil count (P=0.008). Resistance to quinolones was detected significantly more frequently in the isolated Gram-positive than Gram-negative bacteria (P<0.001). CONCLUSION: Culture-positive SBP in cirrhotic patients are caused more frequently by Gram-positive bacteria during the recent years, which are, in their vast majority, resistant to quinolones.     

Spontaneous bacterial peritonitis from Salmonella: an unusual bacterium with unusual presentation

Spontaneous bacterial peritonitis (SBP) is a common cause of morbidity and mortality in patients with advanced cirrhosis and portal hypertension. While gram-negative rods and Enterococcus species are the common offending organisms, Salmonella has also been recognized as a rare and atypical offending organism. Atypical features of Salmonella SBP include both its occurrence in cirrhotic patients with immunosuppressive state and its lack of typical neutroascitic response. Diagnosis is often delayed as it requires confirmation from ascitic fluid culture. We report a case of Salmonella SBP occurring in a patient with decompensated cryptogenic cirrhosis with concurrent low-grade non-Hodgkin lymphoma and prior treatment with rituximab. Physicians should be aware of the atypical presentation, especially in cirrhotic patients who are immunosuppressed.     

Usefulness of urine strip test in the rapid diagnosis of spontaneous bacterial peritonitis.

PURPOSE: Rapid and accurate diagnosis of spontaneous bacterial peritonitis (SBP) is mandatory for timely treatment in cirrhotic patients. The purpose of this study was to assess the usefulness of two different reagent strips, the UriSCAN and the Multistix10SG, for the rapid bedside diagnosis of SBP. METHODS: A total of 75 paracenteses in 53 cirrhotic patients with ascites were performed. All ascitic fluid was analyzed with the two reagent strips, and compared with the manual cell count with differential and ascitic fluid culture. SBP was defined as an ascitic polymorphonuclear cell count > or =250/mm3. RESULTS: SBP was diagnosed in 18 of the 75 samples. If we considered the positive UriSCAN result of 2 or more, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. When we considered the positive UriSCAN result of 3, the sensitivity, specificity, PPV, and NPV were 67%, 100%, 100%, and 89%, respectively. When we considered the positive Multistix10SG result of 3, the sensitivity, specificity, PPV, and NPV were 50%, 100%, 100%, and 87%, respectively. CONCLUSION: Urine reagent strip might be useful for rapid and accurate diagnosis of SBP in cirrhotic patients with ascites.