Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review

Spontaneous bacterial(SBP) and spontaneous fungal peritonitis(SFP) can be a life-threatening infection in patients with liver cirrhosis(LC) and ascites. One of the possible mechanisms of developing SBP is bacterial translocation. Although the number of polymorphonuclear cells in the culture of ascitic fluid is diagnostic for SBP, secondary bacterial peritonitis is necessary to exclude. The severity of underlying liver dysfunction is predictive of developing SBP; moreover, renal impairment and infections caused by multidrug-resistant(MDR) organism are associated with a fatal prognosis of SBP. SBP is treated by antimicrobials, but initial empirical treatment may not succeed because of the presence of MDR organisms, particularly in nosocomial infections. Antibiotic prophylaxis is recommended for patients with LC at a high risk of developing SBP, gastrointestinal bleeding, or a previous episode of SBP, but the increase in the risk of developing an infection caused by MDR organisms is a serious concern globally. Less is known about SFP in patients with LC, but the severity of underlying liver dysfunction may increase the hospital mortality. SFP mortality has been reported to be higher than that of SBP partially because the difficulty of early differentiation between SFP and SBP induces delayed antifungal therapy for SFP.

Multivariate predictive model for asymptomatic spontaneous bacterial peritonitis in patients with liver cirrhosis

BACKGROUNDSpontaneous bacterial peritonitis (SBP) is a detrimental infection of the asciticfluid in liver cirrhosis patients, with high mortality and morbidity. Earlydiagnosis and timely antibiotic administration have successfully decreased themortality rate to 20%-25%. However, many patients cannot be diagnosed in theearly stages due to the absence of classical SBP symptoms. Early diagnosis ofasymptomatic SBP remains a great challenge in the clinic.AIMTo establish a multivariate predictive model for early diagnosis of asymptomaticSBP using positive microbial cultures from liver cirrhosis patients with ascites.METHODSA total of 98 asymptomatic SBP patients and 98 ascites liver cirrhosis patients withnegative microbial cultures were included in the case and control groups,respectively. Multiple linear stepwise regression analysis was performed toidentify potential indicators for asymptomatic SBP diagnosis. The diagnosticperformance of the model was estimated using the receiver operatingcharacteristic curve.RESULTSPatients in the case group were more likely to have advanced disease stages,cirrhosis related-complications, worsened hematology and ascites, and higher mortality. Based on multivariate analysis, the predictive model was as follows: y (P) = 0.018 + 0.312 × MELD (model of end-stage liver disease) + 0.263 × PMN(ascites polymorphonuclear) + 0.184 × N (blood neutrophil percentage) + 0.233 ×HCC (hepatocellular carcinoma) + 0.189 × renal dysfunction. The area under thecurve value of the established model was 0.872, revealing its high diagnosticpotential. The diagnostic sensitivity was 73.5% (72/98), the specificity was 86.7%(85/98), and the diagnostic efficacy was 80.1%.CONCLUSIONOur predictive model is based on the MELD score, polymorphonuclear cells,blood N, hepatocellular carcinoma, and renal dysfunction. This model mayimprove the early diagnosis of asymptomatic SBP.

Spontaneous bacterial peritonitis:A severe complication of liver cirrhosis

This report presents a survey of current knowledge concerning one of the relatively frequent and severe complications of liver cirrhosis and associated ascites-spontaneous bacterial peritonitis. Epidemiology,aetiology,pathogenesis,clinical manifestation,diagnosis and present possibilities of treatment are discussed.

Predictors of fifty days in-hospital mortality in decompensated cirrhosis patients with spontaneous bacterial peritonitis

AIM: To determine the predictors of 50 d in-hospital mortality in decompensated cirrhosis patients with spontaneous bacterial peritonitis(SBP).METHODS: Two hundred and eighteen patients admitted to an intensive care unit in a tertiary care hospital between June 2013 and June 2014 with the diagnosis of SBP(during hospitalization) and cirrhosis were retrospectively analysed. SBP was diagnosed by abdominal paracentesis in the presence of polymorphonuclear cell count ≥ 250 cells/mm3 in the peritoneal fluid. Student's t test, multivariate logistic regression, cox proportional hazard ratio(HR), receiver operating characteristics(ROC) curves and Kaplan-Meier survival analysis were utilized for statistical analysis. Predictive abilities of several variables identified by multivariate analysis were compared using the area under ROC curve. P < 0.05 were considered statistical significant. RESULTS: The 50 d in-hospital mortality rate attributable to SBP is 43.11%(n = 94). Median survival duration for those who died was 9 d. In univariate analysis acute kidney injury(AKI), hepatic encephalopathy, septic shock, serum bilirubin, international normalized ratio, aspartate transaminase, and model for end-stage liver disease- sodium(MELD-Na) were significantly associated with in- hospital mortality in patients with SBP(P ≤ 0.001). Multivariate coxproportional regression analysis showed AKI(HR = 2.16, 95%CI: 1.36-3.42, P = 0.001) septic shock(HR = 1.73, 95%CI: 1.05-2.83, P = 0.029) MELD-Na(HR = 1.06, 95%CI: 1.02-1.09, P ≤ 0.001) was significantly associated with 50 d in-hospital mortality. The prognostic accuracy for AKI, MELD-Na and septic shock was 77%, 74% and 71% respectively associated with 50 d inhospital mortality in SBP patients.CONCLUSION: AKI, MELD-Na and septic shock were predictors of 50 d in-hospital mortality in decompensated cirrhosis patients with SBP.

Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver

Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.

Predictors of Spontaneous Bacterial Peritonitis (SBP) in Liver Cirrhosis: Current Knowledge and Future Frontiers

Spontaneous bacterial peritonitis (SBP) in patients with cirrhotic liver disease is a serious complication that contributes to the high morbidity and mortality rate seen in this population. Currently, there is a lack of consensus amongst the research community on the clinical predictors of SBP as well as the risks and benefits of prophylactic antibiotic therapy in these patients. Pharmacological gastric acid suppression (namely with PPIs and H2RAs) are frequently prescribed for these patients, many times without a clear indication, and may contribute to gut bacterial overflow and SBP development. However, this remains controversial as there are conflicting findings in SBP prevalence between PPI/H2RA-users and non-users. In addition, studies show recent antibiotic use, whether for SBP prophylaxis or for another infectious process, appear to be associated with higher rates of SBP and drug-resistant organisms. Other researchers have also explored the link between zinc, platelet indices (MPV), and macrophage inflammatory protein-1 β (MIP-1β) levels in liver cirrhosis, all of which appear to be promising markers for classifying SBP risk and diagnosis. This literature review was limited by the number and quality of studies available as most are retrospective in nature. Thus, more ongoing, prospective studies and trials are needed to judge the true value of the findings in the studies reviewed in hopes that they can guide appropriate prevention, diagnosis, and management of SBP.

Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis(SBP) is the most common infection in end-stage liver disease patients.SBP is defined as an ascitic fluid infection with a polymorphonuclear leucocyte count ≥ 250/mm^3 without an evident intra-abdominal surgically treatable source.Several mechanisms contribute to SBP occurrence,including translocation of gut bacteria and their products,reduced intestinal motility provoking bacterial overgrowth,alteration of the gut's barrier function and local immune responses.Historically,Gram-negative enteric bacteria have been the main causative agents of SBP,thereby guiding the empirical therapeutic choice.However,over the last decade,a worryingly increasing prevalence of Gram-positive and multi-drug resistant(MDR) SBP has been seen.Recently,the microbiological spectrum of SBP seems to have changed in Europe due to a high prevalence of Gram-positive bacteria(48%-62%).The overall proportion of MDR bacteria is up to 22%-73% of cases.Consequently,empirical therapy based on thirdgeneration cephalosporins or amoxicillin/clavulanic acid,can no longer be considered the standard of care,as these drugs are associated with poor outcomes.Theaim of this review is to describe,with an epidemiological focus,the evidence behind this rise in Gram-positive and MDR SBP from 2000 to present,and illustrate potential targeted therapeutic strategies.An appropriate treatment protocol should include daptomycin plus ceftaroline and meropenem,with prompt stepdown to a narrower spectrum when cultures and sensitivity data are available in order to reduce both cost and potential antibiotic resistance development.

Spontaneous fungal peritonitis: Micro-organisms, management and mortality in liver cirrhosis-A systematic review

BACKGROUND Spontaneous peritonitis is an infection of ascitic fluid without a known intraabdominal source of infection. spontaneous fungal peritonitis (SFP) is a potentially fatal complication of decompensated cirrhosis, defined as fungal infection of ascitic fluid in the presence of ascitic neutrophil count of greater than 250 cells/mL. AIM To determine the prevalence of fungal pathogens, management and outcomes (mortality) of SFP in critically ill cirrhotic patients. METHODS Studies were identified using PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Scopus databases until February 2019. Inclusion criteria included intervention trials and observation studies describing the association between SFP and cirrhosis. The primary outcome was in-hospital, 1-mo, and 6- mo mortality rates of SFP in cirrhotic patients. Secondary outcomes were fungal microorganisms identified and in hospital management by anti-fungal medications. The National Heart, Lung and Blood Institute quality assessment tools were used to assess internal validity and risk of bias for each included study. RESULTS Six observational studies were included in this systematic review. The overall quality of included studies was good. A meta-analysis of results could not be performed because of differences in reporting of outcomes and heterogeneity of the included studies. There were 82 patients with SFP described across all the included studies. Candida species, predominantly Candida albicans was the fungal pathogen in majority of the cases (48%-81.8%) followed by Candida krusei (15%- 25%) and Candida glabrata (6.66%-20%). Cryptococcus neoformans (53.3%) was the other major fungal pathogen. Antifungal therapy in SFP patients was utilized in 33.3% to 81.8% cases. The prevalence of in hospital mortality ranged from 33.3% to 100%, whereas 1-mo mortality ranged between 50% to 73.3%. CONCLUSION This systematic review suggests that SFP in end stage liver disease patient is associated with high mortality both in the hospital and at 1-mo, and that antifungal therapy is currently underutilized.

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure (ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections (BIs) trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first Bis either at admission or during hospitalization in patients with hepatitis B virus (HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016 The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4 To were community-acquired,46.4 To were healthcare-associated,and 40.2% belonged to nosocomial BIs.Pneumonia (40.7%),spontaneous bacterial peritonitis (SBP)(34.5%),and bloodstream infection (BSI)(13.4%) were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend (P=0.021).Sixty-one strains of bacteria,including 83.6% Gramnegative bacteria and 29.5% multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli (44.3%) and Klebsiella pneumoniae (23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend (ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;P <0.001).The independent predictors of the 28-doutcomes of patients with HBV-ACLF were COSSH-ACLF score (hazard ratio[HR]=1.371),acute kidney injury (HR=2.187),BSI (HR=2.339),prothrombin activity (HR=0.967),and invasive catheterization (HR=2.173).CONCLUSION For patients with HBV-ACLF combined with first BIs,pneumonia is the most common form,and the incidence of SBP decreases with increasing ACLF grade.COSSH-ACLF score,acute kidney injury,BSI,prothrombin activity,and invasive catheterization are the independent predictors of 28-d outcomes.

Molecular detection of monocyte chemotactic protein-1 polymorphism in spontaneous bacterial peritonitis patients

AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).

Association Between Proton Pump Inhibitor Therapy and Spontaneous Bacterial Peritonitis Occurrence in Cirrhotic Patients:A Clinical Review

Spontaneous bacterial peritonitis(SBP)is one of the most common complications in patients with end-stage liver disease(ESLD),which increases the risk of short-term mortality.Proton pump inhibitors(PPIs)are frequently used in patients with ESLD,in which controversies about the risk of PPI treatment in the occurrence of SBP are largely raised and the pathogenic mechanism of PPI-associated SBP remains unclear.We conducted a systematic literature search through PubMed/MEDLINE for publications mainly from 1 January 2000 to 1 January 2021.Our narrative review summarized the adverse effect of specific PPI therapy on the occurrence and prognosis of SBP in cirrhotic patients,described the potential mechanisms by which PPI induces the development of SBP,and discussed the risk factors associated with the development of SBP and the strategy of PPI therapy in cirrhotic patients.Although controversy regarding the association between PPI use and the occurrence of SBP exists,PPIs use should be restricted to patients with clear benefit indications,and be cautious for elderly patients with severe liver damage.

Spontaneous bacterial peritonitis prevalence in pretransplant patients and its effect on survival and graft loss post-transplant

AIM To investigate the incidence of spontaneous bacterial peritonitis(SBP) in pre-transplant patients and its effect on post transplant mortality and graft failure. METHODS We conducted a retrospective cohort study of patient records from the organ procurement and transplant network data set. Patients were identified by the presence of SBP pre-transplant. Univariate post-transplant survival models were constructed using the Kaplan-Meier technique and multivariate models were constructed using the Cox proportional hazards model. Variables that affected post-transplant graft survival were identified in the SBP population. RESULTS Forty-seven thousand eight hundred and eighty patient records were included in the analysis for both groups, and 1966(4.11%) patients were identified in the data set as having pre-transplant SBP. Patients that had pre-transplant SBP had higher rates of graft loss from recurrent hepatitis C virus(HCV)(3.6% vs 2.0%, P < 0.0001), infections leading to graft loss(1.9% vs 1.3%, P = 0.02), primary non-function(4.3% vs 3.0%, P < 0.0001) and chronic rejection(1.1% vs 0.7%, P = 0.04). Kaplan-Meier survival analysis showed a statistically significant difference in all-cause survival in patients with a history of SBP vs those without(P < 0.0001). Pretransplant history of SBP was independently predictiveof mortality due to recurrent HCV(HR = 1.11, 95%CI: 1.02-1.21, P < 0.017) after liver transplantation.CONCLUSION HCV patients prior to the advent of directing acting anti-viral agents had a higher incidence of pre-transplant SBP than other patients on the liver transplant wait list. SBP history pre-transplant resulted in a higher rate of graft loss due to recurrent HCV infection and chronic rejection.

Spontaneous Bacterial Peritonitis and Short-Term Prognosis in a Group of Decompensated Cirrhotic Patients in Yaounde: A Cross-Sectional Study

Introduction: Spontaneous bacterial peritonitis (SBP) is among the most common infections in cirrhotic patients. Data on SBP are rare in Cameroon. This prompted us to carry out this study on patients with decompensated cirrhosis of the liver in Yaounde University Hospital Centre (YUHC). Methods: We carried out a cross-sectional study from December 2015 to June 2016 in three units of YUHC. All patients with decompensated liver cirrhosis were included. Our sampling was consecutive. Diagnosis of cirrhosis was performed, based on clinical, biological and ultrasound criteria. A neutrophil count greater than 250 cell/mm3 in ascites fluid defined an SBP. Data on socio-demography, clinical presentation, and outcomes were collected. Results: We included 34 decompensated cirrhotic patients (15 males). Patients mean age was 57.5 ± 2 years (SBP positive: 48.7 ± 21.3 versus without SBP: 59.8 ± 19.5, p = 0.22). SBP diagnosis was made in 6 (17.7%) patients. Compared to patients with decompensated liver cirrhosis and without SBP, positive SBP patients had a higher pulse rate (p = 0.002) and respiratory rate (p = 0.02). The patients with SBP were more likely to present these other clinical features: pulse rate >100 (RR: 4.2, [95% CI: 0.7 - 27.7];p = 0.02), presence of jaundice (RR: 3.4, [95% CI: 0.6 - 21.1];p = 0.09), being from female gender (RR: 3.2, [95% CI: 0.5 - 19.9]; p = 0.11), advanced liver disease (Child C class) (RR: 2.4, [95% CI: 0.4 - 14.5], p = 0.66), low-plasma albumin (less than 20 g/L) (RR: 1.7, [95% CI: 0.8 - 3.9], p = 0.08), respiratory rate > 30 (RR: 1.6, [95% CI: 0.6 - 3.3], p = 0.05) and fever/hypothermia (RR: 1.5, [95% CI: 0.6 - 3.4];p = 0.22). Evolution after a 72-hours antibiotherapy was stationary in four cases and unfavorable in two patients, resulting in death. Conclusion: SBP prevalence was 17.7%. SBP patients were younger, from female sex, tachycardia and polypnea, presenting with fever/hypothermia and signs of advanced liver disease than non-SBP patients. Improvement of our technical platform will be useful to determine the cause of cirrhosis and identify the different germs responsible for SBP.

Microbiological Characteristics and Antibiotic Susceptibility in Liver Cirrhosis Patients With Nosocomial Spontaneous Bacterial Peritonitis Caused by Escherichia coli:A Multicenter Study

Escherichia coli is a prevalent causative pathogen of spontaneous bacterial peritonitis(SBP).In this retrospective study,we investigated the microbiological characteristics and antibiotic susceptibility of E.coli clinical isolates obtained from liver cirrhosis patients suffering from nosocomial SBP.Our results showed that extended-spectrum b-lactamase(ESBL)-producing E.coli accounted for 47%of the cases,while 62%of the isolates were multi-drug resistant(MDR)pathogens.ESBL-producing and MDR isolates showed high incidences of resistance to third-generation cephalosporins,but they displayed susceptibility to carbapenems,b-lactamase inhibitors,and aminoglycosides.Importantly,liver cirrhosis patients with MDR E.coli SBP showed a significantly higher death rate than patients with non-MDR infections(P=0.021).The 30-day mortality of nosocomial SBP was independently correlated with female gender[odds ratio(OR)=5.200,95%confidence interval(CI)=1.194–22.642],liver failure(OR=9.609,95%CI=1.914–48.225),hepatocellular carcinoma(OR=8.176,95%CI=2.065–32.364),hepatic encephalopathy(OR=8.176,95%CI=2.065–32.364),model of end-stage liver disease score(OR=1.191,95%CI=1.053–1.346),white blood cell count(OR=0.847,95%CI=0.737–0.973),and ascites polymorphonuclear(OR=95.903,95%CI=3.410–2697.356).In conclusion,third-generation cephalosporins may be inappropriate for empiric treatment of nosocomial SBP caused by E.coli,due to the widespread presence of ESBLs and high incidence of MDR pathogens.

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/mm3 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.

Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis

BACKGROUND Proton pump inhibitors(PPIs)are widely prescribed,often without clear indications.There are conflicting data on its association with mortality risk and hepatic decompensation in cirrhotic patients.Furthermore,PPI users and PPI exposure in some studies have been poorly defined with many confounding factors.AIM To examine if PPI use increases mortality and hepatic decompensation and the impact of cumulative PPI dose exposure.METHODS Data from patients with decompensated liver cirrhosis were extracted from a hospital database between 2013 to 2017.PPI users were defined as cumulative defined daily dose(cDDD)≥28 within a landmark period,after hospitalisation for hepatic decompensation.Cox regression analysis for comparison was done after propensity score adjustment.Further risk of hepatic decompensation was analysed by Poisson regression.RESULTS Among 295 decompensated cirrhosis patients,238 were PPI users and 57 were non-users.PPI users had higher mortality compared to non-users[adjusted HR=2.10,(1.20-3.67);P=0.009].Longer PPI use with cDDD>90 was associated with higher mortality,compared to non-users[aHR=2.27,(1.10-5.14);P=0.038].PPI users had a higher incidence of hospitalization for hepatic decompensation[aRR=1.61,(1.30-2.11);P<0.001].CONCLUSION PPI use in decompensated cirrhosis is associated with increased risk of mortality and hepatic decompensation.Longer PPI exposure with cDDD>90 increases the risk of mortality.

Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: a prospective study

AIM: To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis.METHODS: IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test.RESULTS: Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio &#x0003e; 0.07) compared to 4 (25%) healthy controls (P &#x0003c; 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival.CONCLUSION: Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study.

Development and Validation of a Prognostic Model for One-year Survival of Cirrhosis Patients with First-ever Spontaneous Bacterial Peritonitis

Background and Aims: Spontaneous bacterial peritonitis(SBP) is one of the leading causes of death in patients withliver cirrhosis. We aimed to establish a prognostic model toevaluate the 1-year survival of cirrhosis patients after thefirst episode of SBP. Methods: A prognostic model was developedbased on a retrospective derivation cohort of 309cirrhosis patients with first-ever SBP and was validated in aseparate validation cohort of 141 patients. We used Uno’sconcordance, calibration curve, and decision curve (DCA)analysis to evaluate the discrimination, calibration, and clinicalnet benefit of the model. Results: A total of 59 (19.1%)patients in the derivation cohort and 42 (29.8%) patientsin the validation cohort died over the course of 1 year. Aprognostic model in nomogram form was developed withpredictors including age [hazard ratio (HR): 1.25;95% confidenceinterval (CI): 0.92–1.71], total serum bilirubin (HR:1.66;95% CI: 1.28–2.14), serum sodium (HR: 0.94;95%CI: 0.90–0.98), history of hypertension (HR: 2.52;95% CI:1.44–4.41) and hepatic encephalopathy (HR: 2.06;95%CI: 1.13–3.73). The nomogram had a higher concordance(0.79) compared with the model end-stage liver disease(0.67) or Child-Turcotte-Pugh (0.71) score. The nomogramalso showed acceptable calibration (calibration slope, 1.12;Bier score, 0.15±0.21) and optimal clinical net benefit in thevalidation cohort. Conclusions: This prediction model developedbased on characteristics of first-ever SBP patientsmay benefit the prediction of patients’ 1-year survival.

Antibiotic prophylaxis in patients with cirrhosis: Current evidence for clinical practice

Patients with cirrhosis show an increased susceptibility to infection due to disease-related immune-dysfunction.Bacterial infection therefore represents a common,often detrimental event in patients with advanced liver disease,since it can worsen portal hypertension and impair the function of hepatic and extrahepatic organs.Among pharmacological strategies to prevent infection,antibiotic prophylaxis remains the first-choice,especially in high-risk groups,such as patients with acute variceal bleeding,low ascitic fluid proteins,and prior episodes of spontaneous bacterial peritonitis.Nevertheless,antibiotic prophylaxis has to deal with the changing bacterial epidemiology in cirrhosis,with increased rates of gram-positive bacteria and multidrug resistant rods,warnings about quinolonesrelated side effects,and low prescription adherence.Short-term antibiotic prophylaxis is applied in many other settings during hospitalization,such as before interventional or surgical procedures,but often without knowledge of local bacterial epidemiology and without strict adherence to antimicrobial stewardship.This paper offers a detailed overview on the application of antibiotic prophylaxis in cirrhosis,according to the current evidence.

血清IL-12、IL-18、CRP联合检测对肝硬化并发自发性细菌性腹膜炎患者预后的评估价值

目的探讨血清白细胞介素12(interleukin 12,IL-12)、白细胞介素18(interleukin 18,IL-18)、C反应蛋白(C-reactive protein,CRP)联合检测对肝硬化并发自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)患者的预后评估价值。方法选择2021年8月至2022年8月在承德医学院附属医院确诊并接受治疗的120例肝硬化并发SBP患者为研究对象,均给予相应的对症治疗,分别于入院当天和治疗14 d后采集患者空腹肘静脉血5 ml,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清IL-12、IL-18水平,采用速率散射免疫比浊法检测血清CRP水平,分析治疗前后患者血清IL-12、IL-18、CRP水平变化情况。治疗结束后随访90 d,根据预后将患者分为存活组和死亡组,比较两组患者各项临床资料并采用Cox回归分析影响肝硬化并发SBP患者90 d内死亡的危险因素,绘制受试者工作特征(receiver operating characteristic,ROC)曲线评估血清IL-12、IL-18、CRP联合检测对肝硬化并发SBP患者预后的预测价值。结果120例患者均完成治疗,随访期间死亡21例,存活99例。治疗后患者血清IL-12[(36.67±4.57)ng/L比(67.53±8.16)ng/L]、IL-18[(60.19±7.04)ng/L比(111.06±12.58)ng/L]、CRP[(19.56±2.24)mg/L比(42.65±5.53)mg/L]水平均较治疗前显著降低(P均<0.05)。死亡组患者肝性脑病[33.33%(7/21)比14.14%(14/99)]、肝肾综合征[42.86%(9/21)比18.18%(18/99)]比例以及白蛋白[(22.34±2.52)g/L比(25.53±2.64)g/L]、总胆红素[(47.56±4.90)μmol/L比(33.34±3.58)μmol/L]、治疗后IL-12[(40.01±4.16)ng/L比(35.96±4.02)ng/L]、治疗后IL-18[(65.28±7.02)ng/L比(59.11±6.31)ng/L]、治疗后CRP[(23.19±3.34)mg/L比(18.79±2.36)mg/L]水平均高于存活组(P均<0.05)。Cox回归分析显示,肝性脑病(HR=1.893,95%CI:1.379~2.406,P<0.001)、肝肾综合征(HR=1.749,95%CI:1.225~2.273,P<0.001)、低白蛋白(HR=1.756,95%CI:1.108~2.404,P<0.001)、治疗后IL-12(HR=1.996,95%CI:1.226~2.765,P<0.001)、IL-18(HR=1.564,95%CI:1.117~2.010,P<0.001)、CRP(HR=2.385,95%CI:1.856~2.913,P<0.001)水平高均是导致肝硬化并发SBP患者90 d内死亡的危险因素。治疗后血清IL-12、IL-18、CRP水平联合预测肝硬化并发SBP患者90 d内死亡的ROC曲线下面积为0.906,约登指数为0.638,高于治疗后单独血清IL-12、IL-18、CRP预测的ROC曲线下面积(0.791、0.805、0.802;z值分别为2.996、2.819、2.847,P值分别为0.022、0.031、0.027)。结论血清IL-12、IL-18、CRP水平升高与肝硬化并发SBP患者90 d内死亡有关,可用于预测肝硬化并发SBP患者的死亡风险,三者联合的预测价值更高。