Analysis of clinical course and prognosis of culture-positive spontaneous bacterial peritonitis and neutrocytic ascites

The clinical significance and prognosis of culture-negative neutrocytic ascites in cirrhotic patients is a controversial topic. In the present study, the clinical and humoral presentation and the short-and long-term prognosis were analyzed in 36 patients with cirrhosis and culture-positive spontaneous bacterial peritonitis and in 28 patients with cirrhosis and ascitic fluid polymorphonuclear count greater than 250/mm³, a negative ascitic fluid culture, and without previous antibiotic therapy. On admission there were no significant differences between groups related to age, sex, alcoholism, fever, abdominal pain, serum albumin, serum urea, serum creatinine, Child-Pugh score, polymorphonuclear count, and total protein concentration in ascitic fluid. A greater frequency of positive blood culture was found in patients with spontaneous bacterial peritonitis (15/21 vs 2/18) (P<0.001). Mortality during the first episode was 36% in patients with spontaneous bacterial peritonitis and 46% in patients with culture-negative neutrocytic ascites (NS). Mortality during follow-up was high and survival probability at 12 months was 32% in spontaneous bacterial peritonitis and 31% in culture-negative neutrocytic ascites. The probability of recurrence at 12 months was 33% in spontaneous bacterial peritonitis and 34% in culture-negative neutrocytic ascites. Our results show that spontaneous bacterial peritonitis and culture-negative neutrocytic ascites are variants of the same disease with a high mortality and poor prognosis.     

Detection of bacterial DNA in serum and ascitic fluid of asymptomatic outpatients with cirrhosis and non‐neutrocytic ascites

Background and aims: Bacterial DNA (bactDNA) has been found in serum and ascitic fluid (AF) of 30–40% of hospitalized patients with cirrhosis and non‐neutrocytic ascites, but its prevalence in outpatients is unknown. The aim of this prospective study was to investigate the presence of bactDNA in AF and serum among cirrhotic outpatients with non‐neutrocytic ascites. Methods: Thirty‐one consecutive patients with cirrhosis and non‐neutrocytic ascites, who underwent therapeutic paracentesis in our outpatient clinic, were enrolled over a 13‐week period. Of these patients, 13 had a single paracentesis and 18 patients had several consecutive paracenteses (2–10) over the study period. Overall, 98 serum and non‐neutrocytic AF specimens were obtained and tested for the presence of bactDNA by polymerase chain reaction amplification of the 16S ribosomal RNA gene. Results: The main causes of cirrhosis were alcohol (53.5%) and hepatitis C (30%). The median MELD score was 16 and there were 54.8% Child–Pugh C patients. BactDNA was negative in all samples from 28 of the 31 patients, including 15 patients with several paracentesis. One patient had a single AF sample culture positive and bactDNA positive for Streptococcus mitis, whereas the simultaneous blood sample was negative. For each of the last two patients, DNA from Lactococcus lactis was detected in a single blood sample but not in the simultaneous AF sample. Conclusions: In contrast to that reported previously in hospitalized patients, bactDNA is rarely detected in serum and AF of outpatients with cirrhosis and non‐neutrocytic ascites.     

Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites

Background/Aims: Translocation of indigenous bacterial from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats.Methods: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria.Results: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice.Conclusions: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.     

NOD2 gene variants are a risk factor for culture‐positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis

Background: Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study. Methods: We determined common NOD2 variants by TaqMan polymerase chain reaction and analysed the ascitic fluid neutrophil count and bacterial culture results in 175 prospectively characterized hospitalized patients with decompensated cirrhosis who underwent diagnostic paracentesis in two German centres. Results: Ten patients presented with culture‐positive SBP, 19 with culture‐negative SBP and six had bacterascites. Minor allele frequencies for R702W, G908R and 1007fs in subjects with sterile non‐neutrocytic ascites were 3.2, 2.5 and 2.5% respectively. Patients with SBP [odds ratio (OR) 2.7; P=0.036], culture‐positive SBP (OR 6.0; P=0.012) and bacterascites (OR 6.0; P=0.050) were more often carriers of NOD2 variants than patients with sterile non‐neutrocytic ascites. The mutations 1007fs and G908R were associated with culture‐positive SBP (P≤0.005) and R702W with bacterascites (P=0.014). There was no significant association of NOD2 variants with culture‐negative SBP (OR 1.6; P=0.493). In logistic regression, previous SBP, a higher model for end‐stage liver disease (MELD) score and the presence of a NOD2 variant were independent predictors of ascitic fluid infection. The median survival was insignificantly shorter in patients with NOD2 variants (268 vs. 339 days; P=0.386). In patients without hepatocellular carcinoma at study entry (N=148), NOD2 was a predictor of survival after adjustment for the MELD score and age (hazard ratio 1.89; P=0.045). Conclusion: NOD2 variants increase the risk for culture‐positive SBP and bacterascites in cirrhosis and may affect survival.     

Norfloxacin and cisapride combination decreases the incidence of spontaneous bacterial peritonitis in cirrhotic ascites

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis with ascites, having high recurrence despite antibiotic prophylaxis. Small bowel dysmotility and bacterial overgrowth have been documented to be related to SBP. The purpose of the present paper was (i) to study whether addition of a prokinetic agent to norfloxacin ameliorates the development of SBP in high-risk patients; and (ii) to identify risk factors for SBP development. METHODS: A prospective, single blinded, randomized controlled trial was conducted in high-risk cirrhotic patients with ascites who had either recovered from an episode of SBP or who had low ascitic fluid protein. Norfloxacin 400 mg once daily (group I) or norfloxacin 400 mg once daily with cisapride 20 mg twice a day (group II) was given and occurrence of side-effects of therapy and mortality were recorded. RESULTS: Of the 94 patients, 48 (51%) were in group I, and 46 (49%) in group II. The actuarial probability of developing SBP at 12 month in group I was 56.8% and in group II, 21.7% (P = 0.026). Treatment failure was observed in five patients (10%) in group I and none in group II (P = 0.003). The actuarial probability of death at 18 months was 20.6% in group I and 6.2% in group II (P = 0.1). Low serum albumin, low ascitic fluid protein and alcoholic cirrhosis were related to development of SBP (P < 0.05). Additionally, low serum albumin (2.8 g/dL), gastrointestinal bleeding, alcoholic cirrhosis and low ascitic fluid protein were significantly associated with multiple occurrences of SBP. CONCLUSIONS: Prophylaxis with norfloxacin and cisapride significantly reduces the incidence of SBP in high-risk cirrhosis patients; low serum albumin, low ascitic fluid protein and alcoholic cirrhosis predispose to the development of SBP in high-risk cirrhosis patients; and low ascitic fluid protein should also be considered as a risk factor for the development of SBP requiring prophylaxis.     

应用多重PCR法鉴定蚊胃血血源的研揪

目的建立多重PCR法鉴定蚊胃血来源。方法依据常见蚊吸血对象(人、牛、猪和犬)的线粒体DNA细胞色素b序列的差异,设计种特异引物,建立多重PCR法,并应用该法检测现场按蚊标本。结果应用多重PCR法共检测249只按蚊,血源来自牛和猪的共91只和63只,未检出吸人血按蚊。立即处死并干燥保存的现场按蚊标本检测成功率最高,为92.50%。结论多重PCR法鉴定蚊胃血血源快速、灵敏,结果客观、可靠。     

Spontaneous bacterial peritonitis and culture negative neutrocytic ascites in patients with non-alcoholic liver cirrhosis

Abstract Medical records of 18 patients with spontaneous bacterial peritonitis (SBP) and 19 patients with culture negative neutrocytic ascites (CNNA) were reviewed. The diagnosis of SBP was based on a positive ascitic fluid culture, a polymorphonuclear cell count (PMN) greater than 250 cells/mm³ and the absence of an intra-abdominal source of infection. The diagnosis of CNNA was based on a PMN count greater than 250 cells/mm³, a negative ascitic fluid culture, the absence of an intra-abdominal source of infection and no antibiotic treatment in the preceding 30 days. All patients in both groups had liver cirrhosis, which was mainly (62.2%) due to HBV infection. A single strain, mostly 'a Gram-negative' bacillus, was recovered from the ascitic fluid culture in the vast majority of patients (83%) with SBP. There were no significant differences between the clinical data of both groups. However, the CNNA group had a significantly better Pugh score ( P value = 0.01) with a mean score of 9.42 ±2.24, compared to the SBP group (10.94 ±2.88). The only significant difference in the laboratory data was that the total bilirubin was higher in the SBP group ( P 0.01). Hospital mortality was significantly higher in the SBP patients compared to those with CNNA, 50 and 16%, respectively ( P 0.03). Recurrent ascitic fluid infection occurred in one of five patients who initially presented. In contrast no recurrence was documented in 12 patients with CNNA.
Spontaneous bacterial peritonitis is a serious complication of liver cirrhosis with significantly higher mortality than CNNA. A single organism, usually enteric, is the most common causative agent.     

肝硬化腹水患者并发自发性细菌性腹膜炎的危险因素分析

自发性细菌性腹膜炎(SBP)是肝硬化腹水患者一种常见且严重的并发症,发生率20%左右,院内病死率高达20%～40[1].认识SBP发生的危险因素,并及早预防其发生,对改善肝硬化腹水患者的预后至关重要.本研究对肝硬化腹水患者的临床和实验室资料进行分析,探讨肝硬化腹水患者发生SBP的危险因素.     

Association between acid suppressive therapy and spontaneous bacterial peritonitis in cirrhotic patients with ascites

Abstract

Objective. Proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) therapy may cause intestinal bacterial overgrowth and translocation. Therefore, acid suppressive therapy may increase the risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. Material and methods. A total of 176 cirrhotic patients with ascites who underwent diagnostic paracentesis between September 2004 and April 2009 were included in the analysis. Patients with gastrointestinal hemorrhage and/or antibiotic therapy within 2 weeks prior to hospital admission were excluded. SBP was defined as ≥250/mm³ polymorphonuclear white blood cells with or without a positive culture from the ascitic fluid. Eighty-three patients (mean age 56.1 years, 63 males) had SBP and 93 (mean age 54.7 years, 75 males) did not. Results. On the multivariate analysis, a Child–Pugh class C (OR = 2.890, 95% CI 1.443–5.786; p = 0.003), high MELD scores (≥20, OR = 3.540, 95% CI 1.155–10.849; p = 0.027), and PPI use (OR = 3.443, 95% CI 1.164–10.188; p = 0.025) were risk factors for SBP. H2RA was not associated with SBP. Conclusions. PPI use, as well as Child–Pugh class C and high MELD scores, was an independent risk factor for the development of SBP in cirrhotic patients with ascites. Further prospective studies are warranted to clarify this issue.     

Comparison of clinical characteristics and outcomes of spontaneous bacterial peritonitis and culture negative neutrocytic ascites

Objective: Ascitic fluid infections (AFI) in cirrhotic patients can be classified into two groups: spontaneous bacterial peritonitis (SBP) and culture-negative neutrocytic ascites (CNNA). The aim of this study was to compare the clinical characteristics and outcomes of the two groups of patients with AFI.

Methods: We retrospectively reviewed the medical records of cirrhotic patients with AFI. We evaluated demographic data, clinical presentations of AFI, laboratory findings, liver function, and mortality rates.

Results: Between January 2005 and December 2014, 533 patients with AFI were evaluated; 259 (48.6%) had SBP and 274 (51.4%) CNNA. Ascites neutrophil count (4410/mm³ versus 1046/mm³, p?<?.001) and the blood culture positive rate (38.1% versus 20.1%, p?<?.001) were higher in the SBP group, which also had a higher MELD score (24.29 versus 22.05, p?=?.004). Seven-day mortality was higher in the SBP group (9.4% versus 4.5%, p?=?.027) but there was no significant difference in 30-day (22.1% versus 17.5%) or 90-day mortality rate (36.1% versus 36.4%).

Conclusions: Patients in the SBP group had a higher MELD score, ascites neutrophil count, and positive blood culture rate. Although seven-day mortality rate was higher in the SBP group, the 30-day and 90-day mortality rates were similar in the two groups.     

Ascitic fluid infection in patients with hepatitis B virus-related liver cirrhosis: Culture-negative neutrocytic ascites versus spontaneous bacterial peritonitis

Background and Aim:  Ascitic fluid infection (AFI) consists of culture-negative neutrocytic ascites (CNNA) and spontaneous bacterial peritonitis (SBP). The present study compared the clinical characteristics and prognosis of CNNA and SBP in hepatitis B virus (HBV)-related cirrhotic patients.
Methods:  We analyzed 130 consecutive patients hospitalized due to the first episode of AFI between January 1998 and December 2007.
Results:  The mean age of the patients was 52.3 years (88 men, 42 women). Ninety-three patients (71.5%) had CNNA and 37 patients (28.5%) had SBP; 117 patients (90.0%) died after a median survival period of 6.4 months. Patients with CNNA and SBP survived for a median period of 6.9 months and 5.4 months, respectively ( P  = 0.417). Patients with SBP showed higher in-hospital mortality than those with CNNA (16.2 vs 4.3%; P  = 0.031). Binary logistic regression analysis showed that culture positivity of ascitic fluid (CNNA vs SBP) was the only independent predictor of in-hospital mortality ( P  = 0.042). In a Cox regression model for the 120 patients (92.3%) who survived the first episode of AFI, only the Child–Pugh score remained significant for survival ( P  = 0.007), whereas no association was observed for culture positivity of ascitic fluid (CNNA vs SBP) during the first episode of AFI ( P  = 0.752).
Conclusions:  Although in-hospital mortality was higher in patients with SBP than CNNA, the clinical course of the two groups was similar after the first episode of AFI. Thus, liver transplantation should be considered, irrespective of culture positivity of ascitic fluid.     

多重聚合酶链反应快速检测嗜水气单胞菌和爱德华菌

目的根据嗜水气单胞菌株和爱德华菌株16S rDNA基因的结构特点,设计合成了二对引物XZAH3、XZAH4和XZE7b、XZE8,建立了一种同时检测鉴别嗜水气单胞菌株和爱德华菌株的多重PCR技术。试验结果表明,用这两对引物对嗜水气单胞菌和爱德华菌株进行多重PCR,嗜水气单胞菌株只扩增出361bp一条带,而爱德华菌株只扩增出576bp一条带,而对其他鱼病病原的扩增不出现任何条带,结果均为阴性;敏感性测定结果表明,该多重PCR最低能检出10pg的嗜水气单胞菌株、爱德华菌株的DNA模板。     

终末期肝病模型对肝硬化腹水患者并发自发性腹膜炎的预测价值

MELD≤19分组、20～29分组和≥30分组分别为12.50%,52.38%和66.67%.MELD≤30分组与≤19分组的肝硬化腹水患者并发SBP比较,OR值为14(95%CI 5.41～36.20);20～29分组与≤19分组比较,OR值为7.7(95%CI 4.17～14.20).ROC曲线下面积(AUC)为0.774(95%CI 0.689～0.855).结论 MELD分值和肝硬化腹水患者SBP发病率线性正相关,高MELD分值提示发生SBP风险增加.     

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。     

β‐Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta‐analysis

Introduction: Bacterial infections have been hypothetized to be a trigger of variceal bleeding in cirrhotic patients and β‐blockers may have a protective effect by decreasing bacterial translocation, reducing portal pressure. The aim of our study was to evaluate the possible role of β‐blockers in preventing spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites. Materials and Methods: Extensive search of the literature including randomized controlled trial (RCT) and non‐RCT of primary and secondary prophylaxis for variceal bleeding in cirrhotics using β‐blockers were evaluated. We performed a meta‐analysis using the occurrence of SBP as endpoint in all the studies, using the random effect model. Results: Three RCT and three retrospective studies in which β‐blockers were evaluated against no treatment for the prevention of SBP in ascitic cirrhotics were included. There was a statistically significant difference of 12.1%, P<0.001 in favour of propranolol in preventing SBP, which was confirmed by sensitivity analysis evaluating only RCTs (7.8% difference). The effect was still present when haemodynamic responders were compared with non‐responders. Conclusions: This analysis suggests a role of β‐blockers in preventing SBP in ascitic cirrhotics, independent of haemodynamic response. Further formal RCTs are needed to confirm this finding.     

Bacterial translocation and clinical progression of HCV‐related cirrhosis in HIV‐infected patients

The aim of the study was to evaluate whether bacterial translocation (BT) predicts the clinical outcome in HIV/HCV‐coinfected patients with compensated cirrhosis. A cohort of 282 HIV/HCV‐coinfected patients with cirrhosis and no previous liver decompensation (LD) was recruited. Serum levels of the DNA sequences encoding the well‐conserved 16S rRNA subunit (16S rDNA), the lipopolysaccharide (LPS) and soluble CD14 (sCD14) at diagnosis of cirrhosis were measured. Primary endpoint was the emergence of the first LD and/or death of any cause. Secondary endpoints were LD, liver‐related death (LRD) and death of any cause. After a median (Q1‐Q3) follow‐up of 51 (27‐72) months, 67 patients (24%; 95% CI: 19‐29) developed their first LD or died during follow‐up. Baseline levels of 16S rDNA, LPS and sCD14 were not associated with the probability of developing the primary endpoint of the study. The mean (SD) survival time free of LD and/or death according to levels of 16S rDNA (<83, 83‐196, 197‐355, >355 [copies/μL]) was 78 (5), 72 (5), 81 (4) and 82 (4) months, respectively (P = .5). The corresponding figures for LPS (<0.1, 0.1‐0.6, 0.6‐1.5, > 1.5 [IU/mL]) were 76 (5), 71 (5), 77 (5) and 81 (4) months, respectively (P = .4). Baseline levels of BT serum markers were not associated with any of the secondary endpoints analysed in the study. Thus, BT does not seem to be a relevant predictor of clinical outcome in HIV/HCV‐coinfected patients with compensated cirrhosis.     

Recurrence of spontaneous bacterial peritonitis in cirrhotic patients non‐prophylactically treated with norfloxacin: serum albumin as an easy but reliable predictive factor

Background: Several large studies revealed that selective intestinal decontamination (SID) prevented recurrence of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. Nonetheless, there are no definitive patient selection parameters identifying who would benefit from SID. Aims: To investigate long‐term outcomes in cirrhosis patients with recurrence of SBP and to identify predictive factors for SBP recurrence. Methods: We retrospectively studied 146 cirrhosis patients diagnosed with a first episode of SBP from 2005 to 2006. Of these, 89 patients survived; the survivors were divided into two groups based on recurrence and non‐recurrence of SBP, and clinical parameters, survival time and cause of death were analysed. Results: The in‐hospital mortality was 39% (57/146). The SBP recurrence rate was 42.7% (38/89). The survival rate between patients with recurrent SBP and those without recurrence did not differ (P=0.092). Sepsis was the major cause of death in the recurrent SBP group, but not in the non‐recurrent group. Serum albumin level before discharge and β‐blocker use between the two groups differed significantly (P<0.0001). Using the cut‐off point for serum albumin level before discharge of 2.85 g/dl as a predictor for recurrence of SBP, the sensitivity was 70.2% and the specificity was 76.3%. Furthermore, long‐term survival of the group with high albumin before discharge was better than that of the corresponding group with low albumin (P=0.007). Conclusion: Spontaneous bacterial peritonitis was associated with high sepsis‐related mortality in cirrhotic patients. Serum albumin before discharge was a useful single parameter to predict the recurrence of SBP and long‐term survival.