First Episode Of Spontaneous Bacterial Peritonitis Research Articles

A Validated Composite Score Demonstrates Potential Superiority to MELD-Based Systems in Predicting Short-Term Survival in Patients with Liver Cirrhosis and Spontaneous Bacterial Peritonitis-A Preliminary Study.

Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhosis patients with ascites, leading to high mortality rates if not promptly treated. However, specific prediction models for SBP are lacking. This study aimed to compare commonly used cirrhotic prediction models (CTP score, MELD, MELD-Na, iMELD, and MELD 3.0) for short-term mortality prediction and develop a novel model to improve mortality prediction. Patients with the first episode of SBP were included. Prognostic values for mortality were assessed using AUROC analysis. A novel prediction model was developed and validated. In total, 327 SBP patients were analyzed, with HBV infection as the main etiologies. MELD 3.0 demonstrated the highest AUROC among the traditional models. The novel model, incorporating HRS, exhibited superior predictive accuracy for in-hospital in all patients and 3-month mortality in HBV-cirrhosis, with AUROC values of 0.827 and 0.813 respectively, surpassing 0.8. MELD 3.0 score outperformed the CTP score and showed a non-significant improvement compared to other MELD-based scores, while the novel SBP model demonstrated impressive accuracy. Internal validation and an HBV-related cirrhosis subgroup sensitivity analysis supported these findings, highlighting the need for a specific prognostic model for SBP and the importance of preventing HRS development to improve SBP prognosis.

Predictive factors of recurrence in spontaneous bacterial peritonitis in Tunisian patients with cirrhosis.

Recurrent spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is associated with poor prognosis. To assess the prevalence and the risk factors for recurrence and to evaluate its impact on the prognosis. We conducted a retrospective study including patients with cirrhosis having a first episode of SBP. A recurrence of SBP was identified in 43.4% of the patients who survived after a first episode of SBP. The mean time to onset of the first SBP recurrence from the first episode was 32days. Recurrence factors were endoscopic hypertensive signs, a positive ascites culture, diarrhea and the MELD score. There was no impact on survival of recurrent SBP compared with the first SBP episode.

Bacteremia (Sepsis), Hepatorenal Syndrome, and Serum Creatinine Levels Rather than Types or Microbial Patterns Predicted the Short-Term Survival of Cirrhotic Patients Complicated with Spontaneous Bacterial Peritonitis

(1) Background: Spontaneous bacterial peritonitis (SBP) is a major and severe complication in cirrhosis patients with ascites. Over the years, advance in antibiotic treatment has led to changes in microbial patterns in some regions, including the emergence of extended-spectrum beta-lactamases resistant (ESBL)-producing bacteria and an increase in Gram-positive bacteria (GPC). In addition, three SBP types (classic SBP, culture-negative neutrophilic ascites (CNNA), and monomicrobial non-neutrocytic bacterascites (MNB)), may also have different prognoses. Therefore, the study aimed to investigate the microbial pattern and the predictors of short-term outcomes in patients with SBP. (2) Methods: Patients discharged with a diagnosis of the first episode of SBP between January 2006 and July 2017 were enrolled. Patients' clinical, demographic, hematological, and biochemical data were obtained at diagnosis, and the model for end-stage liver disease (MELD)-based scores were calculated accordingly. Patients were followed up until February 2018 or until death. (3) Results: A total of 327 patients were analyzed. The prevalence of classic SBP was nearly equivalent to CNNA. As for the microbial pattern, Gram-negative bacillus (GNB) remained more prevalent than GPC (75 vs. 25%), with E. coli being the most common bacterial species, followed by K. Pneumoniae and then Staphylococcus. The percentage of ESBL strain in culture-positive patients was 10.9%. By univariable and multivariable logistic regression survival analysis, there was no significant difference in predicting short-term mortality among the three SBP types, neither between GNB vs. GPC nor between ESBL- and non-ESBL-producing bacteria. Only bacteremia (sepsis), hepatorenal syndrome (HRS), and serum creatinine (Cr) were independent predictors of in-hospital and 3-month mortality, whereas HRS and Cr were independent predictors of 6-month mortality. (4) Conclusions: SBP types, Gram stain result, and ESBL strain did not affect survival. Only bacteremia (sepsis), HRS, and serum Cr independently predicted the short-term mortality in patients with SBP.

ASEPTIC: primary antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis—study protocol for an interventional randomised controlled trial

BackgroundBacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites.MethodsThe ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients’ health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events.DiscussionThis trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis.Trial registrationClinicalTrials.gov NCT043955365. Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central – Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).

Predictors of Short-Term Mortality Following First Episode of Spontaneous Bacterial Peritonitis in Hospitalized Cirrhotic Patients.

Background and aimsSpontaneous bacterial peritonitis (SBP) is an important cause of morbidity and mortality in patients with cirrhosis. This study aimed to identify the factors impacting morbidity and short-term mortality in a cohort of patients with cirrhosis following an index episode of SBP.MethodsIn a retrospective study of hospitalized cirrhotic cohort, 333 patient records were reviewed. Demographic, clinical, and laboratory, as well as radiological characteristics of the patient population were analyzed on day 1 of admission. The diagnosis of cirrhosis was based on the combination of laboratory, clinical, and radiological features. The diagnosis of SBP was established by abdominal paracentesis in the presence of cellular, biochemical, and microbiological features consistent with SBP. All independent variables were analyzed to generate a predictive model of mortality by using the Cox proportional hazards regression analysis (adjusted for age and gender).ResultsA total of 61 cirrhotic patients with ascites and a first episode of SBP were identified. The overall mortality among hospitalized patients was 19.7% and was associated with longer length of stay (12.6 vs. 7.6 days; p=0.01). Patient cohorts with multiple antibiotic resistant bacteria as a cause of SBP had a significantly higher mortality compared to those with other bacterial phenotypes (p=0.03). Multivariate analyses showed that a model for end-stage liver disease (MELD) score (hazard ratio [HR]=1.29; 95% CI: 1.10 to 1.92; p=0.023), Child-Turcotte-Pugh score (HR=1.23; 95% CI: 1.05 to 1.82; p=0.027), and acute kidney injury (HR=2.09; 95% CI: 1.41 to 3.47; p=0.01) were the predictors of mortality from SBP.ConclusionSBP predicts in-hospital mortality in cirrhotic patients. In addition to multiple antibiotic resistant bacteria, thresholds of both hepatic and renal injury independently predict adverse outcomes.

Bacterial infections in cirrhosis: a narrative review and key points for clinical practice

Bacterial infections are frequent complications of liver cirrhosis, accounting for severe clinical courses, and increased mortality. The reduction of the negative clinical impact of infections may be achieved by a combination of prophylactic measures to reduce the occurrence, early identification, and management. Spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia, cellulitis, and spontaneous bacteremia are frequent in cirrhosis. The choice of initial empirical antimicrobial therapy should be based on both site, severity, and origin of infection (community-acquired, nosocomial, or healthcare-associated) and on antibiotic resistance patterns. 3rd generation cephalosporins are generally indicated as empirical therapy in most community-acquired cases. However, for nosocomial and healthcare-associated infections, due to a high rate of multidrug-resistant (MDR) pathogens, a broader spectrum treatment is appropriate. In order to prevent antibiotic resistance emergence, microbiological cultures should be collected, and a de-escalation applied when antimicrobial susceptibility tests are available. Standard measures to prevent infections and the identification of carriers of MDR bacteria are essential strategies to prevent infections in cirrhosis. Antibiotic prophylaxis should be applied only to gastrointestinal bleeding, SBP recurrence prevention, and cirrhotics at high risk of a first episode of SBP.

Recurrence of spontaneous bacterial peritonitis in cirrhosis: novel predictors.

Recurrence of spontaneous bacterial peritonitis (SBP) is still a matter of debate. We conducted this study to evaluate the probable factors that predict the recurrence of SBP in patients who recovered from the first episode of SBP and the long-term outcomes of SBP recurrence. One hundred twenty-four patients diagnosed with liver cirrhosis, SBP and did not receive secondary prophylaxis either with norfloxacin or other antibiotics were included in this prospective cohort pilot study. Clinical, biochemical and ascitic fluid analysis parameters were evaluated. Ascitic fluid interferon-γ-induced protein (IP-10), calprotectin, interleukin-6 and tumor necrosis factor-α were measured by ELISA. Of these, 76 patients survived with an in-hospital mortality rate of 38.7%. The survivors were classified into two groups according to recurrence and nonrecurrence of SBP and survival time, clinical parameters and cause of death were investigated. Thirty-one participants had one or more attacks of SBP, with a recurrence rate of 40.8% within one-year follow-up. Before discharge, multivariate analysis showed that ascitic IP-10 (≥1220 pg/ml), ascitic calprotectin (≥550 ng/ml), serum albumin (≤2.5 g/dl), nonuse of prophylactic β-blockers and use of proton-pump inhibitors (PPIs) were the independent variables in predicting recurrent SBP. Sepsis-related organ failure was the most common etiology of mortality in the recurrent SBP group within 3 and 6 months. Increased ascitic calprotectin and IP-10, hypoalbuminemia, nonuse of prophylactic β-blockers and use of PPI were independently associated with increased SBP recurrence rate. Sepsis-related organ failure was the most common etiology of mortality.

Factors that predict recurrent spontaneous bacterial peritonitis in cirrhotic patients.

The recurrence rate of spontaneous bacterial peritonitis (SBP) is increasing in cirrhotic patients. Antibiotic prophylaxis should be prescribed in all cirrhotic patients after the first episode of SBP. However, antibiotics promote the development of antibiotic-resistant bacteria. To identify the factors that predict the recurrence of SBP after the first episode in cirrhotic patients to optimise the stratification for secondary antibiotic prophylaxis. This retrospective study included 145 cirrhotic patients who had their first SBP episode during 2011-2015. The 86 patients who survived were divided into either the SBP recurrence or non-recurrence group according to patient SBP outcome during the 2-year follow-up. Demographical, clinical and laboratory parameters were recorded at SBP diagnosis and before hospital discharge. SBP recurrence rate, recurrence-free survival and in-hospital mortality were also analysed. The recurrence rate of SBP after the first episode was 69.8% (60/86), and the median recurrence-free survival time was 142days. The in-hospital mortality rate was 40.7% (59/145). The significant predictive factors for recurrence of SBP were serum potassium≥4mEq/L (HR: 1.89; P=.028), serum albumin≤2g/dL (HR: 2.5; P=.003) at diagnosis of SBP and platelet count before discharge≤100000/microliter (HR: 1.93; P=.029). SBP frequently recurs in cirrhotic patients. Serum potassium≥4mEq/L, serum albumin≤2g/dL at SBP diagnosis and platelet count≤100000/microliter before discharge were identified as factors that may predict the recurrence of SBP after the first episode.

Effect of acute kidney injury on long-term outcomes of spontaneous bacterial peritonitis in cirrhotic patients using the International Club of Ascites-acute kidney injury criteria.

This study aimed to investigate the effect of acute kidney injury (AKI) on long-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients using International Club of Ascites (ICA)-AKI criteria. A total of 157 cirrhotic patients with a first episode of SBP between 2007 and 2016 were analyzed. We investigated the long-term mortality with related risk factors of SBP in cirrhosis including the ICA-AKI criteria. The ICA-AKI stage at SBP diagnosis is evaluated by stages 0-3. Stage progression was defined as a progression of AKI to a higher stage. The ICA-AKI stage at the diagnosis of SBP was stage 0 in 91 (58%), stage 1 in 33 (21%), stage 2 in 19 (12%), and stage 3 in 14 patients (9%). Stage progression within 48h after SBP diagnosis was noted in 18 patients (12%). Multivariable analysis showed that the risk factors for overall survival were age ≥60years (hazard ratio [HR] 1.74, P=0.029), serum sodium ≤130mmol/L (HR 1.3, P=0.017), ICA-AKI stage 1 (HR 2.51, P=0.003), ICA-AKI stage 2 or 3 (HR 3.36, P<0.001), and stage progression at 48h after SBP diagnosis (HR 2.57, P=0.004). The differences in overall survival using the ICA-AKI in patients without AKI using the conventional criteria were significantly different (P=0.019). Acute kidney injury and its progression are significant risk factors for mortality in cirrhotic patients with SBP. The application of the ICA-AKI criteria is important and advantageous for early evaluation and intervention for a better prognosis in cirrhotic patients with SBP.

Integrated model for end-stage liver disease maybe superior to some other model for end-stage liver disease-based systems in addition to Child-Turcotte-Pugh and albumin-bilirubin scores in patients with hepatitis B virus-related liver cirrhosis and spontaneous bacterial peritonitis.

For mortality prediction of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis, no direct comparisons have been made among the eight models, Child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD), MELD-Na, integrated MELD (iMELD) score, MELD to sodium (MESO) index, modification of the MELD scoring system (Refit MELD), Refit MELD-Na and Albumin-Bilirubin (ALBI) score. Between January 2005 and July 2017, 314 patients who met the criteria for liver cirrhosis with the first episode of SBP were enrolled in this retrospective study. Clinical and laboratory data were obtained at diagnosis. Patients were followed up until February 2018 or death. Patients were predominantly middle-aged male. Hepatitis B virus (HBV) infection accounted for the majority of the etiologies (41.7%) with 33.6% of the patients received antivirals. The in-hospital mortality rate was 39.8%. The cumulative 3-month and 6-month mortality rates were 51.6 and 60.2%, respectively. For patients with HBV related, not hepatitis C virus or alcohol related, liver cirrhosis, iMELD had the highest area under receiver operating characteristic curve (AUC) and was significantly superior to MELD, MESO, and Refit MELD in addition to CTP and ALBI scores in predicting 3-month and 6-month mortality. For patients with HBV-related liver cirrhosis and SBP, iMELD had the highest AUC among these eight models and was significantly superior to MELD, MESO, and Refit MELD in addition to CTP and ALBI scores in predicting 3-month and 6-month mortalities.

Spontaneous bacterial peritonitis recurrence in patients with cirrhosis receiving secondary prophylaxis with norfloxacin.

Few studies carried out more than 20 years ago have evaluated spontaneous bacterial peritonitis (SBP) recurrence in patients receiving secondary antibiotic prophylaxis. These studies reported a 1-year recurrence rate of 20-26%. Changes in the bacteriology of SBP over the last few years might have negative effects on secondary prophylaxis. Our primary aim was to estimate the incidence of SBP recurrence in patients with cirrhosis receiving secondary prophylaxis with norfloxacin and to explore the factors associated with SBP recurrence. This was a retrospective cohort study of patients receiving norfloxacin for the secondary prophylaxis of SBP from 1 March 2003 to 31 March 2016. Follow-up was performed for 365 days after secondary prophylaxis was started. A competing risk analysis approach was used. A total of 115 patients were included. The prevalence of quinolone-resistant and multiresistant bacteria in the first episode of SBP among patients with culture-positive SBP was 70.96% [95% confidence interval (CI): 51.96-85.77%] and 12.90% (95% CI: 3.63-29.83%), respectively. The cumulative incidence of SBP recurrence was 28.53% (95% CI: 20.15-37.45%) after 365 days. Male patients showed an estimated subhazard ratio of SBP recurrence of 2.52 (95% CI: 1.07-5.91, P=0.034). No other risk factors for SBP recurrence were identified. The overall cumulative incidence of death after 365 days was 21.57% (95% CI: 14.14-30.04%), without significant differences among patients with or without SBP recurrence. Even though changes in the bacteriology of SBP occurred over time, its recurrence rate in patients receiving norfloxacin remains similar to what was reported in the initial studies.

The first episode of spontaneous bacterial peritonitis is a threat event in children with end-stage liver disease.

Studies on native liver survival (NLS) after the first episode of spontaneous bacterial peritonitis (SBP) are rare. Our objective was to evaluate NLS in children up to 1 year after SBP. A historical cohort study of 18 children followed after the first episode of SBP was conducted. NLS, in-hospital mortality, causes of death, and rate of multidrug-resistant organisms were reported. Biliary atresia was the most prevalent diagnosis (72.2%); all were Child-Pugh C, and the median age was 1.0 year. The probability of NLS was 77.8, 27.8, and 11.1% at 1, 3 and 6 months, respectively. At 9 months, no child had the native liver. In-hospital mortality was 38.9%, and the main causes of death were septic shock and acute-on-chronic liver failure. Escherichia coli was the predominant organism cultured. Multidrug-resistant organisms were not detected. The cumulative probability of NLS was 77.8% at 1 month, 27.8% at 3 months, and 11.1% at 6 months. At 9-month follow-up, none of children had their native liver. Ascites PMN count cell more than 1000 cells/mm, positive ascites culture, and prolonged international normalized ratio reached a significant value as predictive factors of NLS and were selected for multivariate analysis. We did not identify independent predictors of survival. Development of SBP was a late event in children and had a high effect on NLS.

Outcomes of spontaneous bacterial peritonitis in liver transplant recipients with allograft failure.

Spontaneous bacterial peritonitis (SBP) carries appreciable morbidity and mortality in the pre-liver transplant (LT) setting. However, the occurrence of SBP and its consequences in the post-LT setting have not been well characterized. This is a retrospective study of SBP occurring in post-LT patients between January 2007 and December 2012. Outcomes were compared to a cohort of post-LT patients with allograft failure and ascites without SBP. The most common indication for liver transplantation in this cohort was hepatitis C. A total of 29 episodes of SBP in 21 patients were identified. Escherichia coli (19%) and Klebsiella pneumoniae (10%) were the most frequent pathogens identified. Six patients died during their first episode of SBP. Ten patients were eventually listed for liver re-transplantation (re-LT) after their first episode of SBP; 5 of these patients were transplanted and the other 5 died. Of the 5 who were transplanted, 2 died shortly after re-transplant, and 3 are still alive. The cause of death in the majority of patients was infection (83.3%). The median time from onset of ascites to death was 214days (range: 10-1085days) and from the first episode of SBP to death was 50.5days (range: 4-549days). In contrast, the median time from onset of ascites to death in patients with allograft failure and ascites without SBP was 331.5days (45-2400days). Allograft failure with ascites is a poor prognostic factor and these patients should be considered high risk for re-LT. SBP may accelerate the time to mortality.

Microbiology and resistance in first episodes of spontaneous bacterial peritonitis: implications for management and prognosis.

International guidelines for antibiotic treatment of spontaneous bacterial peritonitis (SBP) are based on studies conducted decades ago and do not reflect regional differences of bacterial epidemiology. We retrospectively analyzed epidemiology of agents, antibiotic resistance patterns, and survival in liver cirrhosis patients with their first episode of SBP during the years 2007-2013. Of the 311 patients included, 114 patients had a positive ascites culture, and 197 had an ascitic neutrophil count >250 μL. Gram-positive bacteria (47.8%) were more frequently found than Gram-negatives (44.9%), fungi in 7.2%. Enterobacter spp. (40.6%), Enterococcus spp. (26.1%), and Staphylcoccus spp. (13.8%) were the most frequently isolated agents. Third-generation cephalosporins covered 70.2% of non-nosocomial and 56.3% of nosocomial-acquired SBP cases.When SBP was diagnosed by a positive ascitic culture, survival was highly significantly reduced (mean: 13.9 ± 2.9 months; 95% confidence interval [CI]: 8.1-19.8) compared with culture-negative SBP patients (mean: 44.1 ± 5.4 months; 95% CI: 33.4-54.9; P = 0.000). Along with model of end-stage liver disease score and intensive care unit contact, a positive ascites culture remained an independent risk factor associated with poor survival (odds ratio: 1.49; 95% CI: 1.09-2.03) in multivariate analysis; piperacillin/tazobactam proved to be an adequate antibiotic for nosocomial and non-nosocomial SBP in 85.1% and 92.5%, respectively. SBP infection with Enterococcus spp. was associated with poor patient survival (P = 0.048). Third-generation cephalosporins have poor microbial coverage for treatment of SBP. Current guidelines need to adapt for the emerging number of Gram-positive infectious agents in SBP patients.

The Negative Prognostic Impact of a First Ever Episode of Spontaneous Bacterial Peritonitis in Cirrhosis and Ascites.

The prognostic impact of the first ever episode of spontaneous bacterial peritonitis (SBP) on patient outcomes is not well described. Our aim was to compare the clinical outcomes of cirrhotic patients with ascites, and with or without a first episode of SBP. Consecutive patients with cirrhosis and ascites were prospectively enrolled. Demographics, liver and renal function, and hemodynamics were documented at baseline, at resolution of SBP, and thereafter at 4 monthly intervals for 12 months. Complications of cirrhosis and survival were noted. Twenty-nine cirrhotic patients with a first ever episode of SBP (group A) and 123 control patients slightly younger but similar in gender who never had SBP (group B) were enrolled. At SBP diagnosis, group A had worse liver and renal function (Model of End-Stage Liver Disease : 21.1±10.6 vs. 14.4±5.0), lower serum sodium concentrations, and a more hyperdynamic circulation compared with group B (all P<0.001). SBP resolution resulted in improvement in all measures to baseline levels. During follow-up, group A required more frequent hospital admissions than group B (58% vs. 43%), developed more cirrhotic complications, including further SBP (31% vs. 3%*), hyponatremia (12% vs. 0.8%*), acute kidney injury (50% vs. 23%*), hepatorenal syndrome type 1 (46% vs. 7%*), liver transplantation (62% vs. 30%*), and had a worse overall 1-year survival (38% vs. 70%*) (*P<0.05). A first SBP episode is commonly followed by multiple complications, and overall worse prognosis. Consideration should be given to assess cirrhotic patients for liver transplant after the first episode of SBP.

Infection spontanée du liquide d’ascite au cours de la cirrhose

Spontaneous bacterial peritonitis (SBP) is a severe complication occurring in patients with cirrhosis, and is associated with high mortality. Liver transplantation should be considered after a first episode of SBP. Gram-negative bacilli are the major cause of SBP, however there is an increasing trend of Gram-positive cocci related SBP. Management includes empirical antibiotic treatment and albumin infusion. The choice of antibiotics depends on the site of acquisition (community-acquired vs nosocomial or health-care associated infection) and local resistance profile, due to the emergence of drug-resistant bacteria. Secondary prophylaxis is recommended after resolution of SBP and reduces recurrence and mortality. Primary prophylaxis in patients with low protein ascites (<15 g/L) should be restricted to patients with severe cirrhosis awaiting for liver transplantation.

The burden of extended-spectrum β-lactamase-producing Enterobacteriaceae in patients with cirrhosis.

Patients with cirrhosis have high susceptibility to bacterial infections [1]; 24 % of patients admitted to the hospital for an acute decompensation of cirrhosis have bacterial infection [2]. The most common infection is spontaneous bacterial peritonitis (SBP) [1, 2]. It is well known that SBP is caused by Gram-negative bacteria such as Escherichia coli or Klebsiella pneumoniae originating from the intestinal lumen [3]. The translocation of intestinal bacteria is a crucial step in the process leading to SBP [1, 4]. Little is known about underlying mechanisms that explain bacterial translocation [4]. During the last 30 years the mortality of SBP has decreased from 70 to 30 % [3]. This was the result of large use of a strategy which includes high index of suspicion leading to diagnosis paracentesis, diagnosis of SBP based on neutrophil count C250/mL in the ascitic fluid and subsequent rapid initiation (before results of culture) of wide spectrum, non-nephrotoxic antibiotics (e.g., third generation cephalosporins) against Enterobacteriaceae (E. coli, K. pneumonia) which are the most common causes of SBP [3]. In the late 1990s mortality of SBP was further decreased to 10 % with the combined use of empiric antibiotics and the intravenous administration of human albumin [5]. This beneficial effect was related to a significant decrease in the development of kidney failure (known as hepatorenal syndrome, HRS) [5]. Today, SBP remains the most common trigger of infection-induced acute-onchronic liver failure (ACLF) [2]. ACLF whichever its trigger, is characterized by the failure(s) of organs (including kidney, cerebral, liver, coagulation, circulation and lungs) and high risk of death depending on the number of failing organs [2]. Due to the severity of SBP, efforts have been made to prevent this complication. In patients who survive an episode of SBP long-term prophylaxis with the fluoroquinolone norfloxacin significantly decreases the risk of recurrent SBP [3]. The impact on survival is unknown. In patients with low ascitic fluid protein levels (\1.5 g/dL) but without a prior episode of SBP the efficacy of primary prophylaxis using a fuoroquinolone is still unclear. One trial has shown that norfloxacin significantly decreased the risk for developing a first episode of SBP [6], a finding that was not confirmed in another trial with ciprofloxacin [7]. Recently, an increasing number of cases of SBP due to extended spectrum b-lactamase (ESBL)-producing E. coli, K. pneumonia have been reported in Asia [8–11] and Europe [12–16]. Some risk factors for SBP caused by ESBL-producing bacteria Enterobacteriaceae have been identified including the in-hospital acquisition of infection [10–15], long-term norfloxacin prophylaxis [13], use of blactams within the last 3 months [13], and infection by multiresistant bacteria in the last 6 months [13]. ESBLproducing strains are resistant not only to third-generation cephalosporins, amoxicillin-clavulanic acid but also to quinolones and trimethoprim-sulfamethoxazole [13]. R. Moreau (&) Inserm UMR_S 1149, Centre de Recherche sur l’Inflammation (CRI), Inserm et Universite Paris-Diderot, Paris 7 – Site Bichat, 16 Rue Henri Huchard, 75890 Paris Cedex 18, France e-mail: Richard.moreau@inserm.fr

CD4+ T-Cell Function and the Risk for Developing Spontaneous Bacterial Peritonitis in Patients With Cirrhosis

Spontaneous bacterial peritonitis (SBP) is common in cirrhotic patients and has high associated mortality. SBP is preventable with antibiotic prophylaxis. The aim of this study was to identify patients at high risk to develop SBP based on their peripheral blood CD4 T-cell function. Fifty-seven patients with cirrhosis and ascites were followed for the development of SBP. All patients had CD4 assay performed through phytohemagglutinin stimulation of peripheral blood, which was quantified by measuring adenosine triphosphate (ATP) release by luciferin/luciferase assay. A receiver operating characteristic curve was used to evaluate the CD4 assay as a predictor of SBP. A time to SBP or death analysis was performed and Kaplan-Meier plots were used to assess the association between CD4 ATP concentration and hazard of SBP or mortality. The median follow-up time was 7.3 (4.8, 13) months. Patients who developed a first episode of SBP had a lower median CD4 ATP concentration compared to patients without SBP (120 vs. 239 ng/mL; P<0.001). The best independent predictor of SBP was peripheral CD4 function and an ATP level of ≤201 ng/mL provides 83% sensitivity and 71% specificity for future prediction of SBP. Patients with ATP concentration ≤201 ng/mL had a 4.7 times greater hazard of developing SBP than those with ATP level >201 ng/mL (P<0.001). Patients with SBP had 7.9 times higher hazard of mortality then those without SBP (P=0.008). The risk of developing SBP was significantly increased in patients with cirrhosis and ascites who had depressed CD4 T-cell function.

Spontaneous Bacterial Peritonitis in Patients with Hepatitis B Virus-Related Liver Cirrhosis: Community-Acquired versus Nosocomial

PurposeSpontaneous bacterial peritonitis (SBP) frequently develops in patients with liver cirrhosis; however, there is little data to suggest whether the acquisition site of infection influences the prognosis. This study compared the bacteriology, clinical characteristics and treatment outcomes of community-acquired SBP (CA-SBP) and nosocomial SBP (N-SBP).Materials and MethodsThe medical records of 130 patients with hepatitis B virus (HBV)-related liver cirrhosis, who had experienced a first episode of SBP between January 1999 and December 2008, were reviewed.ResultsThe study population included 111 (85.4%) patients with CA-SBP and 19 (14.6%) patients with N-SBP. Baseline and microbiological characteristics as well as clinical course, including in-hospital mortality, did not differ between patients with CA-SBP and those with N-SBP (all p>0.05). The median survival time was 6.5 months, and 117 (90.0%) patients died during the follow-up period. Patients with CA-SBP and N-SBP survived for median periods of 6.6 and 6.2 months, respectively, without significant difference (p=0.569). Time to recurrence did not differ between patients with CA-SBP and N-SBP (4.7 vs. 3.6 months, p=0.925).ConclusionThe acquisition site of infection did not affect clinical outcomes for patients with HBV-related liver cirrhosis who had experienced their first episode of SBP. Third-generation cephalosporins may be effective in empirically treating these patients, regardless of the acquisition site of the infection.

Diagnosis and therapy of ascites in liver cirrhosis

Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm(3) and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis.