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Silpa C, Alomar T, Wong RJ. Temporal Trends of Fungal Infections in Cirrhotic Patients: A Retrospective Cohort Study 2016-2020. J Clin Exp Hepatol 2025; 15:102469. [PMID: 39850933 PMCID: PMC11750545 DOI: 10.1016/j.jceh.2024.102469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 11/27/2024] [Indexed: 01/25/2025] Open
Abstract
Background Patients with cirrhosis are susceptible to infections due to abnormalities in humoral and cell-mediated immunity. Fungal infections are associated with delayed diagnosis and high mortality rates, emphasizing the importance of performing fungal cultures and maintaining elevated levels of suspicion in this patient population. Methods This retrospective cohort study analyzes cirrhotic patients readmitted with bacterial and fungal infections and investigates outcomes, including in-hospital mortality and hospital resource utilization. Data was acquired from the Nationwide Readmission Database (NRD) from 2016 to 2020. Total hospital costs were calculated using HCUP Cost-to-Charge Ratio files and adjusted for inflation based on the Consumer Price Index (CPI) for medical care services in the U.S., with 2020 as the reference year. The NRD dataset lacks details like ascitic fluid cell counts, antifungal/antibacterial drugs used, and treatment responses, limiting the clinical insights that can be derived. Results The study analyzed 393,195 index hospitalizations. Among these, 102,505 account for 30-day and 157,079 account for 90-day readmissions. The 30-day and 90-day readmissions for spontaneous bacterial peritonitis (SBP) are 8478 and 15,690 respectively. The 30-day and 90-day readmissions for spontaneous fungal peritonitis (SFP) are 3106 and 5798 respectively. The mean age of patients was 57.9 years (standard deviation between 57.7 and 58.1). The mean length of stay (LOS) for SBP at 30 days is 9.4 days, while SFP has ranged from 14.9 to 32.3 days for various fungal infections. Aspergilloses have the longest LOS among SFP. There is an increased rate of mortality as well as hospital charges with SFP compared to SBP (P < 0.001). The 30-day index admission total charges for SBP are $42,258 and SFP are $51,739. The 30-day readmission total charges for SBP are 64, 266 and for SFP 89,913. Conclusions There is increased mortality, LOS, and hospital costs for SFP compared to SBP. It is important to consider SFP in the diagnostic workup for patients who do not respond to antibiotics. Early recognition and administration of antifungals can be associated with improved outcomes.
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Affiliation(s)
- Choday Silpa
- Creighton University School of Medicine-Phoenix Health Sciences Campus, Phoenix, AZ, United States
| | - Talal Alomar
- Creighton University School of Medicine-Phoenix Health Sciences Campus, Phoenix, AZ, United States
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Shen D, Sha L, Yang L, Gu X. Identification of multiple complications as independent risk factors associated with 1-, 3-, and 5-year mortality in hepatitis B-associated cirrhosis patients. BMC Infect Dis 2025; 25:151. [PMID: 39891059 PMCID: PMC11786570 DOI: 10.1186/s12879-025-10566-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 01/28/2025] [Indexed: 02/03/2025] Open
Abstract
BACKGROUND Hepatitis B-associated cirrhosis (HBC) is associated with severe complications and adverse clinical outcomes. This study aimed to develop and validate a predictive model for the occurrence of multiple complications (three or more) in patients with HBC and to explore the effects of multiple complications on HBC prognosis. METHODS In this retrospective cohort study, data from 121 HBC patients treated at Nanjing Second Hospital from February 2009 to November 2019 were analysed. The maximum follow-up period was 10.75 years, with a median of 5.75 years. Eight machine learning techniques were employed to construct predictive models, including C5.0, linear discriminant analysis (LDA), least absolute shrinkage and selection operator (LASSO), k-nearest neighbour (KNN), gradient boosting decision tree (GBDT), support vector machine (SVM), generalised linear model (GLM) and naive Bayes (NB), utilising variables such as medical history, demographics, clinical signs, and laboratory test results. Model performance was evaluated via receiver operating characteristic (ROC) curve analysis, residual analysis, calibration curve analysis, and decision curve analysis (DCA). The influence of multiple complications on HBC survival time was assessed via Kaplan‒Meier curve analysis. Furthermore, LASSO and univariable and multivariable Cox regression analyses were conducted to identify independent prognostic factors for overall survival (OS) in patients with HBC, followed by ROC, C-index, calibration curve, and DCA curve analyses of the constructed prognostic nomogram model. This study utilized bootstrap resampling for internal validation and employed the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for external validation. RESULTS The GBDT model exhibited the highest area under the curve (AUC) and emerged as the optimal model for predicting the occurrence of multiple complications. The key predictive factors included posthospitalisation fever (PHF), body mass index (BMI), retinol binding protein (RBP), total bilirubin (TB) levels, and eosinophils (EOS). Kaplan-Meier analysis revealed that patients with multiple complications had significantly worse OS than those with fewer complications. Additionally, multivariable Cox regression analysis, informed by least absolute shrinkage and LASSO selection, identified hepatocellular carcinoma (HCC), multiple complications, and lactate dehydrogenase (LDH) levels as independent prognostic factors for OS. The prognostic model demonstrated 1-year, 3-year, and 5-year OS ROC AUCs of 0.802, 0.793, and 0.817, respectively. For the internal validation cohort, the corresponding AUC values were 0.797, 0.832, and 0.835. In contrast, the external validation cohort yielded a 1-year ROC AUC of 0.707. Calibration curves indicated good consistency of the model, and DCA demonstrated the model's clinical utility, showing high net benefits within certain threshold ranges. Compared with the univariable models, the multivariable ROC curves indicated higher AUC values for this prognostic model, and the model also possessed the best c-index. CONCLUSION The GBDT prediction model provides a reliable tool for the early identification of high-risk HBC patients prone to developing multiple complications. The concurrent occurrence of multiple complications is an independent prognostic factor for OS in patients with HBC. The constructed prognostic model demonstrated remarkable predictive performance and clinical applicability, indicating its crucial role in enhancing patient outcomes through timely and targeted interventions.
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Affiliation(s)
- Duo Shen
- Department of Gastroenterology, The Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
| | - Ling Sha
- Department of Neurology, Nanjing Drum Tower Hospital, Affiliated to Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Ling Yang
- Department of Central Laboratory, Jurong Hospital Affiliated to Jiangsu University, 66 Ersheng Road, Jurong, Zhenjiang, Jiangsu, 212400, China
| | - Xuefeng Gu
- Department of Central Laboratory, Jurong Hospital Affiliated to Jiangsu University, 66 Ersheng Road, Jurong, Zhenjiang, Jiangsu, 212400, China.
- Department of Infectious Diseases, Jurong Hospital Affiliated to Jiangsu University, 66 Ersheng Road, Jurong, Zhenjiang, Jiangsu, 212400, China.
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Ramachandran G, Pottakkat B. Probiotics-A Promising Novel Therapeutic Approach in the Management of Chronic Liver Diseases. J Med Food 2024; 27:467-476. [PMID: 38574254 DOI: 10.1089/jmf.2023.k.0129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024] Open
Abstract
An increased incidence of liver diseases has been observed in recent years and is associated with gut dysbiosis, which causes bacterial infection, intestinal permeability, and further leads to disease-related complications. Probiotics, active microbial strains, are gaining more clinical importance due to their beneficial effect in the management of many diseases, including liver diseases. Clinical scenarios show strong evidence that probiotics have efficacy in treating liver diseases due to their ability to improve epithelial barrier function, prevent bacterial translocation, and boost the immune system. Moreover, probiotics survive both bile and gastric acid to reach the gut and exert their health benefit. Evidence shows that probiotics are a promising approach to prevent several complications in clinical practice. Herein, we discuss the recent evidence, challenges, and appropriate use of probiotics in managing advanced liver diseases, which may have an impact on future therapeutic strategies. Furthermore, the superior effect of strain-specific probiotics and their efficacy and safety in managing liver diseases are discussed.
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Affiliation(s)
- Gokulapriya Ramachandran
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Biju Pottakkat
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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Sharma M, Alla M, Kulkarni A, Nagaraja Rao P, Nageshwar Reddy D. Managing a Prospective Liver Transplant Recipient on the Waiting List. J Clin Exp Hepatol 2024; 14:101203. [PMID: 38076359 PMCID: PMC10701136 DOI: 10.1016/j.jceh.2023.06.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 06/09/2023] [Indexed: 01/05/2025] Open
Abstract
The management of a patient in the peri-transplantation period is highly challenging, and it is even more difficult while the patient is on the transplantation waitlist. Keeping the patient alive during this period involves managing the complications of liver disease and preventing the disease's progression. Based on the pre-transplantation etiology and type of liver failure, there is a difference in the management protocol. The current review is divided into different sections, which include: the management of underlying cirrhosis and complications of portal hypertension, treatment and identification of infections, portal vein thrombosis management, and particular emphasis on the management of patients of hepatocellular carcinoma and acute liver failure in the transplantation waitlist. The review highlights special concerns in the management of patients in the Asian subcontinent also. The review also addresses the issue of delisting from the transplant waitlist to see that futility does not overtake the utility of organs. The treatment modalities are primarily expressed in tabular format for quick reference. The following review integrates the vast issues in this period concisely so that the management during this crucial period is taken care of in the best possible way.
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Affiliation(s)
- Mithun Sharma
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Manasa Alla
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Anand Kulkarni
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Padaki Nagaraja Rao
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Duvvur Nageshwar Reddy
- Department of Gastroenterology, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
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Höppner J, Krohn S, van den Munckhof EHA, Kallies R, Herber A, Zeller K, Tünnemann J, Matz-Soja M, Chatzinotas A, Böhm S, Hoffmeister A, Berg T, Engelmann C. Changes of the bacterial composition in duodenal fluid from patients with liver cirrhosis and molecular bacterascites. Sci Rep 2023; 13:23001. [PMID: 38155157 PMCID: PMC10754895 DOI: 10.1038/s41598-023-49505-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 12/08/2023] [Indexed: 12/30/2023] Open
Abstract
Small intestinal bacterial overgrowth and compositional changes of intestinal microbiota are pathomechanistic factors in liver cirrhosis leading to bacterial translocation and infectious complications. We analyzed the quantity and composition of duodenal bacterial DNA (bactDNA) in relation to bactDNA in blood and ascites of patients with liver cirrhosis. Duodenal fluid and corresponding blood and ascites samples from 103 patients with liver cirrhosis were collected. Non-liver disease patients (n = 22) served as controls. BactDNA was quantified by 16S-rRNA gene-based PCR. T-RFLP and 16S-rRNA amplicon sequencing were used to analyze bacterial composition. Duodenal bacterial diversity in cirrhosis was distinct to controls showing significantly higher abundances of Streptococcus, Enterococcus and Veillonella. Patients with bactDNA positive ascites revealed reduced spectrum of core microbiota with Streptococcus as key player of duodenal community and higher prevalence of Granulicatella proving presence of cirrhosis related intestinal dysbiosis. Regarding duodenal fluid bactDNA quantification, no significant differences were found between patients with cirrhosis and controls. Additionally, percentage of subjects with detectable bactDNA in blood did not differ between patients and controls. This study evaluated the diversity of bacterial DNA in different body specimens with potential implications on understanding how intestinal bacterial translocation may affect infectious complications in cirrhosis.
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Affiliation(s)
- Jim Höppner
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Sandra Krohn
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | | | - René Kallies
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany
| | - Adam Herber
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Katharina Zeller
- Endocrinology and Nephrology, University Hospital Leipzig, Leipzig, Germany
| | - Jan Tünnemann
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Madlen Matz-Soja
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Antonis Chatzinotas
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany
| | - Stephan Böhm
- Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Ludwig Maximilians-University, Munich, Germany
| | - Albrecht Hoffmeister
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
| | - Cornelius Engelmann
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
- Institute for Liver and Digestive Health, Royal Free Campus, University College London, London, UK
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité - Universitaetsmedizin Berlin, Berlin, Germany
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Mousa N, Abdel-Razik A, Elbaz S, Salah M, Abdelaziz M, Habib A, Deib A, Gadallah AN, El-Wakeel N, Eldars W, Effat N, El-Emam O, Taha K, Elmetwalli A, Mousa E, Elhammady D. A risk score to predict 30-day hospital readmission rate in cirrhotic patients with spontaneous bacterial peritonitis. Eur J Med Res 2023; 28:168. [PMID: 37173752 PMCID: PMC10176908 DOI: 10.1186/s40001-023-01126-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 04/26/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND AND AIM There is lack of 30-day hospital readmission prediction score in patients with liver cirrhosis and SBP. The aim of this study is to recognize factors capable of predicting 30-day readmission and to develop a readmission risk score in patients with SBP. METHODS This study prospectively examined the 30-day hospital readmission for patients previously discharged with a diagnosis of SBP. Based on index hospitalization variables, a multivariable logistic regression model was implemented to recognize predictors of patient hospital readmission within 30 days. Consequently, Mousa readmission risk score was established to predict 30-day hospital readmission. RESULTS Of 475 patients hospitalized with SBP, 400 patients were included in this study. The 30-day readmission rate was 26.5%, with 16.03% of patients readmitted with SBP. Age ≥ 60, MELD > 15, serum bilirubin > 1.5 mg/dL, creatinine > 1.2 mg/dL, INR > 1.4, albumin < 2.5 g/dL, platelets count ≤ 74 (103/dL) were found to be independent predictors of 30-day readmission. Incorporating these predictors, Mousa readmission score was established to predict 30-day patient readmissions. ROC curve analysis demonstrated that at a cutoff value ≥ 4, Mousa score had optimum discriminative power for predicting the readmission in SBP with sensitivity 90.6% and specificity 92.9%. However, at cutoff value ≥ 6 the sensitivity and specificity were 77.4% and 99.7%, respectively, while a cutoff value ≥ 2 had sensitivity of 99.1% and specificity of 31.6%. CONCLUSIONS The 30-day readmission rate of SBP was 25.6%. With the suggested simple risk assessment Mousa score, patients at high risk for early readmission can be easily identified so as to possibly prevent poorer outcomes.
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Affiliation(s)
- Nasser Mousa
- Tropical Medicine Department, Mansoura University, Mansoura, Egypt.
- Damietta Cardiology and Gastroenterology Center, Damietta, Egypt.
| | | | - Sherif Elbaz
- Endemic Diseases and Gastroenterology Department, Aswan University, Aswan, Egypt
| | - Mohamed Salah
- Tropical Medicine Department, Mansoura University, Mansoura, Egypt
| | | | - Alaa Habib
- Internal Medicine Department, Mansoura University, Mansoura, Egypt
| | - Ahmed Deib
- Internal Medicine Department, Mansoura University, Mansoura, Egypt
| | | | - Niveen El-Wakeel
- Medical Microbiology and Immunology Department, Mansoura University, Mansoura, Egypt
| | - Waleed Eldars
- Medical Microbiology and Immunology Department, Mansoura University, Mansoura, Egypt
- Department of Basic Medical Sciences, Faculty of Medicine, New Mansoura University, Mansoura, Egypt
| | - Narmin Effat
- Clinical Pathology Department, Mansoura University, Mansoura, Egypt
| | - Ola El-Emam
- Clinical Pathology Department, Mansoura University, Mansoura, Egypt
| | - Khaled Taha
- Internal Medicine Department, Mansoura University, Mansoura, Egypt
| | - Alaa Elmetwalli
- Department of Clinical Trial Research Unit and Drug Discovery, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
| | - Eman Mousa
- Faculty of Dentistry, Mansoura University, Mansoura, Egypt
| | - Dina Elhammady
- Tropical Medicine Department, Mansoura University, Mansoura, Egypt
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Horvatits T, Tamminga M, Liu B, Sebode M, Carambia A, Fischer L, Püschel K, Huber S, Fischer EK. Microplastics detected in cirrhotic liver tissue. EBioMedicine 2022; 82:104147. [PMID: 35835713 PMCID: PMC9386716 DOI: 10.1016/j.ebiom.2022.104147] [Citation(s) in RCA: 236] [Impact Index Per Article: 78.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 06/22/2022] [Accepted: 06/22/2022] [Indexed: 12/11/2022] Open
Abstract
Background The contamination of ecosystem compartments by microplastics (MPs) is an ubiquitous problem. MPs have been observed in mice tissues, and recently in human blood, stool and placenta. However, two aspects remain unclear: whether MPs accumulate in peripheral organs, specifically in the liver, and if liver cirrhosis favours this process. We aimed to examine human liver tissue samples to determine whether MPs accumulate in the liver. Methods This proof-of-concept case series, conducted in Germany, Europe, analyzed tissue samples of 6 patients with liver cirrhosis and 5 individuals without underlying liver disease. A total of 17 samples (11 liver, 3 kidney and 3 spleen samples) were analyzed according to the final protocol. A reliable method for detection of MP particles from 4 to 30 µm in human tissue was developed. Chemical digestion of tissue samples, staining with Nile red, subsequent fluorescent microscopy and Raman spectroscopy were performed. Morphology, size and composition of MP polymers were assessed. Findings Considering the limit of detection, all liver, kidney and spleen samples from patients without underlying liver disease tested negative for MPs. In contrast, MP concentrations in cirrhotic liver tissues tested positive and showed significantly higher concentrations compared to liver samples of individuals without underlying liver disease. Six different microplastic polymers ranging from 4 to 30 µm in size were detected. Interpretation This proof-of-concept case series assessed the presence of MPs in human liver tissue and found six different MP polymers in the liver of individuals with liver cirrhosis, but not in those without underlying liver disease. Future studies are needed to evaluate whether hepatic MP accumulation represents a potential cause in the pathogenesis of fibrosis, or a consequence of cirrhosis and portal hypertension. Funding No funding was received for conducting this investigator driven study.
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Affiliation(s)
- Thomas Horvatits
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Matthias Tamminga
- Center for Earth System Research and Sustainability (CEN), University of Hamburg, Hamburg, Germany
| | - Beibei Liu
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marcial Sebode
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Antonella Carambia
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lutz Fischer
- Department of Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Klaus Püschel
- Institute of Legal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Samuel Huber
- I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Elke Kerstin Fischer
- Center for Earth System Research and Sustainability (CEN), University of Hamburg, Hamburg, Germany.
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Sumida K, Han Z, Chiu CY, Mims TS, Bajwa A, Demmer RT, Datta S, Kovesdy CP, Pierre JF. Circulating Microbiota in Cardiometabolic Disease. Front Cell Infect Microbiol 2022; 12:892232. [PMID: 35592652 PMCID: PMC9110890 DOI: 10.3389/fcimb.2022.892232] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 04/11/2022] [Indexed: 12/14/2022] Open
Abstract
The rapid expansion of microbiota research has significantly advanced our understanding of the complex interactions between gut microbiota and cardiovascular, metabolic, and renal system regulation. Low-grade chronic inflammation has long been implicated as one of the key mechanisms underlying cardiometabolic disease risk and progression, even before the insights provided by gut microbiota research in the past decade. Microbial translocation into the bloodstream can occur via different routes, including through the oral and/or intestinal mucosa, and may contribute to chronic inflammation in cardiometabolic disease. Among several gut-derived products identifiable in the systemic circulation, bacterial endotoxins and metabolites have been extensively studied, however recent advances in microbial DNA sequencing have further allowed us to identify highly diverse communities of microorganisms in the bloodstream from an -omics standpoint, which is termed "circulating microbiota." While detecting microorganisms in the bloodstream was historically considered as an indication of infection, evidence on the circulating microbiota is continually accumulating in various patient populations without clinical signs of infection and even in otherwise healthy individuals. Moreover, both quantitative and compositional alterations of the circulating microbiota have recently been implicated in the pathogenesis of chronic inflammatory conditions, potentially through their immunostimulatory, atherogenic, and cardiotoxic properties. In this mini review, we aim to provide recent evidence on the characteristics and roles of circulating microbiota in several cardiometabolic diseases, such as type 2 diabetes, cardiovascular disease, and chronic kidney disease, with highlights of our emerging findings on circulating microbiota in patients with end-stage kidney disease undergoing hemodialysis.
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Affiliation(s)
- Keiichi Sumida
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States,*Correspondence: Keiichi Sumida,
| | - Zhongji Han
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Chi-Yang Chiu
- Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Tahliyah S. Mims
- Department of Nutritional Sciences, College of Agriculture and Life Science, University of Wisconsin-Madison, Madison, WI, United States
| | - Amandeep Bajwa
- Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, School of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Ryan T. Demmer
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States,Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States
| | - Susmita Datta
- Department of Biostatistics, University of Florida, Gainesville, FL, United States
| | - Csaba P. Kovesdy
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States,Nephrology Section, Memphis Veterans Affairs (VA) Medical Center, Memphis, TN, United States
| | - Joseph F. Pierre
- Department of Nutritional Sciences, College of Agriculture and Life Science, University of Wisconsin-Madison, Madison, WI, United States
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Pörner D, Von Vietinghoff S, Nattermann J, Strassburg CP, Lutz P. Advances in the pharmacological management of bacterial peritonitis. Expert Opin Pharmacother 2021; 22:1567-1578. [PMID: 33878993 DOI: 10.1080/14656566.2021.1915288] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Bacterial peritonitis is an infection with high mortality if not treated immediately. In the absence of an intraabdominal source of infection, bacterial peritonitis may arise in patients with liver cirrhosis, in patients on peritoneal dialysis (PD) for end-stage renal disease or in patients with tuberculosis. In patients with cirrhosis, bacterial peritonitis may trigger acute on chronic liver failure with substantial mortality despite optimal treatment. In patients on PD, peritonitis may make continuation of PD impossible, necessitating the switch to hemodialysis.Areas covered: Recovery from peritonitis and prevention of complications depend on timely pharmacological management. Challenges are the broad microbiological spectrum with growing rates of antimicrobial resistance, the underlying chronic liver or kidney failure and high rates of relapse. The authors provide a review of predisposing conditions, diagnosis, and prevention of bacterial peritonitis with a particular focus on the pharmacological management.Expert opinion: Diagnosis of the type of bacterial peritonitis is essential to pharmacological management. In patients with spontaneous bacterial peritonitis, broad-spectrum antibiotics should be given intravenously in conjunction with albumin. In patients on PD, antibiotic therapy should be preferably applied intraperitoneally with empirical coverage of gram-positive and gram-negative bacteria. Secondary peritonitis usually requires surgical or interventional treatment.
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Affiliation(s)
- Daniel Pörner
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
| | - Sibylle Von Vietinghoff
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
- German Center for Infection Research (DZIF), University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
- German Center for Infection Research (DZIF), University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
| | - Philipp Lutz
- Department of Internal Medicine I, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
- German Center for Infection Research (DZIF), University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany
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10
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Antibiotic prophylaxis for prevention of spontaneous bacterial peritonitis in liver cirrhosis: systematic review. Acta Gastroenterol Belg 2021; 84:333-342. [PMID: 34217185 DOI: 10.51821/84.2.333] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Spontaneous bacterial peritonitis is a potentially life-threatening infection in patients with liver cirrhosis and ascites. Its prevention is vital to improve prognosis of cirrhotic patients. The main objective of this systematic review was to evaluate what is the most efficacious and safest antibiotic prophylactic strategy. METHODS Studies were located by searching PubMed and Cochrane Central Register of Controlled Trials in The Cochrane Library until February 2019. Randomized controlled trials evaluating primary or secondary spontaneous bacterial peritonitis prophylaxis in cirrhotic patients with ascites were included. The selection of studies was performed in two stages: screening of titles and abstracts, and assessment of the full papers identified as relevant, considering the inclusion criteria. Data were extracted in a standardized way and synthesized qualitatively. RESULTS Fourteen studies were included. This systematic review demonstrated that daily norfloxacin is effective as a prophylactic antibiotic for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis. Once weekly ciprofloxacin was not inferior to once daily norfloxacin, with good tolerance and no induced resistance. Trimethoprim-sulfamethoxazole and norfloxacin have similar efficacy for primary and secondary prophylaxis of spontaneous bacterial peritonitis, however, trimethoprim-sulfamethoxazole was associated with an increased risk of developing an adverse event. Rifaximin was more effective than norfloxacin in the secondary prophylaxis of spontaneous bacterial peritonitis, with a significant decrease in adverse events and mortality rate. CONCLUSIONS Continuous long-term selective intestinal decontamination with norfloxacin is the most widely used prophylactic strategy in spontaneous bacterial peritonitis, yet other equally effective and safe options are available.
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Badawi R, Asghar MN, Abd-Elsalam S, Elshweikh SA, Haydara T, Alnabawy SM, Elkadeem M, ElKhalawany W, Soliman S, Elkhouly R, Soliman S, Watany M, Khalif M, Elfert A. Amyloid A in Serum and Ascitic Fluid as a Novel Diagnostic Marker of Spontaneous Bacterial Peritonitis. Antiinflamm Antiallergy Agents Med Chem 2021; 19:140-148. [PMID: 30931865 PMCID: PMC7475799 DOI: 10.2174/1871523018666190401154447] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/13/2019] [Accepted: 03/21/2019] [Indexed: 12/18/2022]
Abstract
Background: Diagnosis of Spontaneous Bacterial Peritonitis (SBP) depends mainly on ascetic fluid culture which may be negative in spite of the clinical suggestion of SBP and high ascetic fluid neutrophilic count. Aims: This study aimed to evaluate the biological importance of amyloid A biomarker in both serum and ascetic fluid to diagnose SBP as early as possible and to compare it to other markers (C-reactive protein (CRP), and the neutrophil-to-lymphocyte ratio (NLR)). Methods: This study included 37 patients with hepatic ascites; twenty-two of them had SBP, and 15 patients did not have SBP. Serum and ascetic fluid amyloid A, ascetic fluid neutrophil, C-reactive protein, and neutrophil-to-lymphocyte ratio were measured in all subjects before the start of antimicrobial chemotherapy to the infected ones. Results: Both the serum and ascetic fluid amyloid and also, CRP were significantly higher in patients infected with ascetic fluid than others. The cut-off point of serum amyloid A for early detection of SBP was 9.25ug/ml with the high sensitivity and specificity. For ascetic amyloid A, the sensitivity and specificity were 90.09% and 60% at cut-off point 2.85ug/ml, respectively. Conclusion: Amyloid A in serum and ascitic fluid can be considered as a good biomarker for early diagnosis of SBP.
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Affiliation(s)
- Rehab Badawi
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Muhammad N Asghar
- Department of Biosciences, Abo Akademi University, 20500 Turku, Finland.,Department of Medical Biology, University of Quebec at Trois-Riveres, Quebec, Canada
| | - Sherief Abd-Elsalam
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | - Tamer Haydara
- Internal Medicine Department, Kafr-Elsheikh University, Kafr El- Shaikh, Egypt
| | | | - Mahmoud Elkadeem
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Walaa ElKhalawany
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Samah Soliman
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Reham Elkhouly
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Shimaa Soliman
- Public Health and Community Medicine, Faculty of Medicine, Menoufia University Menoufia, Egypt
| | - Mona Watany
- Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mai Khalif
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Asem Elfert
- Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
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12
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Chen S, Li X, Li M, Mei Q, Huang J, Wu Z, Zhang L. Mucosal expression of defensin-5, soluble phospholipase A2 and lysozyme in the intestine in a rat model of acute liver failure and its relationship to intestinal bacterial translocation. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:293-300. [PMID: 32278502 DOI: 10.1016/j.gastrohep.2020.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 10/29/2019] [Accepted: 01/09/2020] [Indexed: 11/18/2022]
Abstract
INTRODUCTION To study the expression of defensin-5 (RD-5), soluble phospholipase A2 (sPLA2) and lysozyme in the intestine in a rat model of acute liver failure and its relationship with intestinal bacterial translocation (BT). PATIENTS AND METHODS Sprague-Dawley (SD) rats were divided into two groups. The experimental group was divided into five subgroups according to the lapsing time after the model was established, which were designated accordingly as 8h, 16h, 24h, 48h, and 72h groups. Acute liver failure (ALF) model was induced by intraperitoneal injection of 10% d-galactosamine. The homogenates of mesenteric lymph nodes (MLNs), liver and spleen from each group were cultured in agar to determine the bacterial outgrowth. The mRNA expression of RD-5, sPLA2, lysozyme and the protein expression of sPLA2, lysozyme were determined. RESULTS No bacteria grew in the organ cultures from the control group while experimental groups had positive cultures. Expression of the RD-5 and sPLA2 mRNA in the experimental groups gradually increased at early time points and peaked 16h after induction of ALF, then progressively decreased. The mRNA expression of lysozyme in the experimental group peaked at 8h after ALF induction, then progressively decreased. Similar results were obtained with Western blot and immunohistochemical staining. DISCUSSION The immune barrier function of the ileal mucosa in the rat model of acute liver failure was compromised as demonstrated by the decreased expression of RD-5, sPLA2 and lysozyme in Paneth cells along with increased intestinal bacterial translocation.
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Affiliation(s)
- Silin Chen
- Department of Infectious Diseases, First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Xiaopeng Li
- Department of Infectious Diseases, First Affiliated Hospital of Nanchang University, Jiangxi, China; Key Laboratory of Liver Regeneration Medicine, Jiangxi, China
| | - Ming Li
- Department of Infectious Diseases, First Affiliated Hospital of Nanchang University, Jiangxi, China; Key Laboratory of Liver Regeneration Medicine, Jiangxi, China
| | - Qing Mei
- Department of Ultrasound, Jing Zhou Central Hospital, Hubei, China
| | - Juanjun Huang
- Department of Infectious Diseases, Ganzhou People's Hospital, Jiangxi, China
| | - Zhenping Wu
- Zhejiang University School of Medicine, First Affiliated Hospital, Zhejiang, China
| | - Lunli Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Nanchang University, Jiangxi, China; Key Laboratory of Liver Regeneration Medicine, Jiangxi, China.
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13
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Mohandas S, Vairappan B. Pregnane X receptor activation by its natural ligand Ginkgolide-A improves tight junction proteins expression and attenuates bacterial translocation in cirrhosis. Chem Biol Interact 2019; 315:108891. [PMID: 31697926 DOI: 10.1016/j.cbi.2019.108891] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/02/2019] [Accepted: 10/30/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Pregnane X receptor (PXR) is a ligand-activated transcription factor and nuclear receptor expressed ubiquitously along gut-liver-axis. Inflammatory bowel disorders have been reported to implicate PXR in maintaining tight junction (TJ) integrity and countering inflammation. However, the hepatoprotective role of PXR activation in soothing bacterial translocation in liver cirrhosis has not been explored. Ginkgolide A (GA), a terpene trilactone from Ginkgo Biloba extract, is a natural ligand of rodent and human PXR. This study aims to investigate the effect of GA in activating PXR and improving associated tight junction integrity and reducing bacterial translocation in gut-liver axis of CCl4 induced cirrhosis model. METHODS Swiss albino mice were administered with CCl4 (0.5 ml/kg body weight, i.p) in corn oil for 12 weeks at an interval of two times a week. Following ascites induction, mice were randomized & administered 100 mg/kg body weight of GA through oral gavage for 2 weeks. At termination, blood, gut and liver tissues were collected for biochemical and molecular studies. RESULTS When compared to naïve mice, protein expression of hepatic and small intestinal PXR, CYP3A, ZO-1 and occludin were found to be significantly (p < 0.01) decreased in CCl4 induced cirrhotic mice. Treatment with GA to cirrhotic mice significantly (p < 0.05) induced the expression of both hepatic and small intestinal PXR, CYP3A, ZO-1 and Occludin. Furthermore, increased (p < 0.01) hepatic and small intestinal NFκB was observed in CCl4 induced cirrhotic mice that was significantly (p < 0.05) lowered following GA treatment. Over expression of TLR4/MyD88/NFκB axis and its downstream pro-inflammatory mediators TNF-α, IL6 and IFN-γ were observed in CCl4 induced mice, and these indices were abrogated significantly after GA treatment. Furthermore, significantly increased plasma levels of bacterial translocation markers LBP and procalcitonin were found in CCl4 mice, which were reduced significantly (p < 0.05 & p < 0.0001) after GA treatment. CONCLUSION In conclusion, our data supports the hypothesis that, GA treatment to CCl4 induced cirrhotic mice, activated hepatic and small intestinal PXR and diminished inflammation, thereby improving tight junction integrity and attenuating bacterial translocation.
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Affiliation(s)
- Sundhar Mohandas
- Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India
| | - Balasubramaniyan Vairappan
- Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India.
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14
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Abstract
The recent explosion of scientific interest in the gut microbiota has dramatically advanced our understanding of the complex pathophysiological interactions between the gut and multiple organs in health and disease. Emerging evidence has revealed that the gut microbiota is significantly altered in patients with chronic kidney disease (CKD), along with impaired intestinal barrier function. These alterations allow translocation of various gut-derived products into the systemic circulation, contributing to the development and progression of CKD and cardiovascular disease (CVD), partly mediated by chronic inflammation. Among potentially toxic gut-derived products identifiable in the systemic circulation, bacterial endotoxin and gut metabolites (e.g., p-cresyl sulfate and trimethylamine-N-oxide) have been extensively studied for their immunostimulatory and atherogenic properties. Recent studies have also suggested similar biological properties of bacterial DNA fragments circulating in the blood of patients with CKD, even in the absence of overt infections. Despite the accumulating evidence of the gut microbiota in CKD and its therapeutic potential for CVD, the precise mechanisms for multidirectional interactions between the gut, kidney, and heart remain poorly understood. This review aims to provide recent evidence on the associations between the gut microbiota, CKD, and CVD, and summarize current understanding of the potential pathophysiological mechanisms underlying the “gut–kidney–heart” axis in CKD.
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Affiliation(s)
- K Sumida
- 1 Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - CP Kovesdy
- 1 Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
- 2 Nephrology Section, Memphis VA Medical Center, Memphis, TN, USA
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15
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Wong YJ, Kalki RC, Lin KW, Kumar R, Tan J, Teo EK, Li JW, Ang TL. Short- and long-term predictors of spontaneous bacterial peritonitis in Singapore. Singapore Med J 2019; 61:419-425. [PMID: 31363784 DOI: 10.11622/smedj.2019085] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is the commonest complication of liver cirrhosis. Timely and appropriate treatment of SBP is crucial, particularly with the rising worldwide prevalence of multidrug-resistant organisms (MDROs). We aimed to investigate the clinical outcomes of SBP in Singapore. METHODS All cirrhotic patients with SBP diagnosed between January 2014 and December 2017 were included. Nosocomial SBP (N-SBP) was defined as SBP diagnosed more than 48 hours after hospitalisation. Clinical outcomes were analysed as categorical outcomes using univariate and multivariate analysis. RESULTS There were 33 patients with 39 episodes of SBP. Their mean age was 64.5 years and 69.7% were male. The commonest aetiology of cirrhosis was hepatitis B (27.3%). The Median Model for End-stage Liver Disease (MELD) score was 17; 33.3% had acute-on-chronic liver failure and 60.6% had septic shock at presentation. N-SBP occurred in 25.6% of SBP cases. N-SBP was more commonly associated with MDROs, previous antibiotic use in the past three months (p = 0.014) and longer length of stay (p = 0.011). The 30-day and 90-day mortality among SBP patients was 30.8% and 51.3%, respectively. MELD score > 20 was a predictor for 30-day mortality. N-SBP and MELD score > 20 were predictors for 90-day mortality. CONCLUSION N-SBP was significantly associated with recent antibiotic use, longer hospitalisation, more resistant organisms and poorer survival among patients with SBP. N-SBP and MELD score predict higher mortality in SBP. Judicious use of antibiotics may reduce N-SBP and improve survival among cirrhotic patients.
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Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | | | - Kenneth Weicong Lin
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Jessica Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - James Weiquan Li
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
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Ding X, Yu Y, Chen M, Wang C, Kang Y, Lou J. Causative agents and outcome of spontaneous bacterial peritonitis in cirrhotic patients: community-acquired versus nosocomial infections. BMC Infect Dis 2019; 19:463. [PMID: 31122192 PMCID: PMC6533661 DOI: 10.1186/s12879-019-4102-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 05/16/2019] [Indexed: 02/08/2023] Open
Abstract
Background Spontaneous bacterial peritonitis (SBP) is a serious complication and common cause of death in patients with liver cirrhosis. This study was conducted to compare the microbiological characteristics, drug resistance, and treatment outcomes for nosocomial SBP and community-acquired SBP. Methods A retrospective study was performed on 334 patients with culture-positive SBP at Beijing Youan Hospital, China, between January 2012 and December 2016. The medical records for these patients were reviewed, and their clinical and laboratory data were analyzed. Results A total of 155 (46.4%) patients with nosocomial SBP and 179 (53.6%) with community-acquired SBP were included in this study. From the patients’ ascitic fluids, 334 pathogenic strains, including 178 Gram-negative bacterial strains, 138 Gram-positive bacterial strains and 18 other microbial strains were isolated. E. coli was the major pathogen (24.3%), followed by Klebsiella pneumoniae (12.0%) and Enterococcus faecium (10.5%). The proportion of Enterococcus was significantly higher in the patients with nosocomial SBP (6.1% vs. 27.7%, P < 0.001) than in the patients with community-acquired SBP. The main pathogens isolated from the nosocomial infections were significantly more resistant to the first-line recommended drug. Compared with community-acquired SBP, nosocomial SBP had a poorer outcome (36.8% vs. 24.6%; P = 0.016). The independent predictors for 30-day mortality included nosocomial infection, Child-Pugh classification, hepatocellular carcinoma, renal failure and hepatic encephalopathy. Conclusion Gram-negative bacteria were the major pathogens involved in SBP in the cirrhotic patients. The strains isolated from the patients with nosocomial SBP displayed higher drug resistance than those isolated from patients with community-acquired SBP. Compared with community-acquired SBP, nosocomial SBP had a poorer outcome. When choosing drug treatments, the acquisition site of infection and the local epidemiological situation should be taken into account.
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Affiliation(s)
- Xiurong Ding
- Department of Clinical Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Yanhua Yu
- Department of Clinical Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Ming Chen
- Department of Clinical Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Chen Wang
- Department of Clinical Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Yanfang Kang
- Department of Clinical Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Jinli Lou
- Department of Clinical Laboratory, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
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17
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Zhong HJ, Lin D, Lu ZY, Yang WY, Chen Y. Use of gastric-acid suppressants may be a risk factor for enteric peritonitis in patients undergoing peritoneal dialysis: A meta-analysis. J Clin Pharm Ther 2019; 44:209-215. [PMID: 30332507 DOI: 10.1111/jcpt.12769] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 08/23/2018] [Accepted: 09/13/2018] [Indexed: 12/14/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Mounting evidence suggests that long-term use of gastric-acid suppressants (GASs) may be associated with adverse effects. Whether GAS use increases the risk of enteric peritonitis in patients undergoing peritoneal dialysis (PD) is not known. The aim of this meta-analysis was to evaluate the association between GAS use and enteric peritonitis in PD patients. METHODS We searched PubMed, Embase and Cochrane Library databases from inception to 23 January 2018 to identify eligible studies. The primary outcome was an association between GAS use and enteric peritonitis in PD patients. RESULTS AND DISCUSSION Six studies involving 829 people were included in this meta-analysis. Pooled data showed that GAS use in PD patients was associated with an increased risk of enteric peritonitis (odds ratio [OR] = 1.27; 95% confidence interval [CI]: 1.02-1.57, I2 = 48%). Subgroup analyses based on GAS type revealed that histamine-2 receptor antagonists (H2 RAs) might increase the risk of enteric peritonitis in PD patients (OR = 1.40; 95% CI: 1.01-1.93; I2 = 8%), but proton pump inhibitors (PPIs) might not (1.13; 0.72-1.77; 6; 34%). WHAT IS NEW AND CONCLUSION Gastric-acid suppressants use might be a risk factor for enteric peritonitis in PD patients. In particular, H2 RAs increased the risk of enteric peritonitis, but PPIs did not. Therefore, to prevent enteric peritonitis, H2 RAs should probably be prescribed with caution for PD patients.
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Affiliation(s)
- Hao-Jie Zhong
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, China
- Guangdong Medical University, Guangdong, China
| | - Da Lin
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, China
| | - Zhi-Yong Lu
- Department of Dermatology, Qingyuan Hospital of Traditional Chinese Medicine, Guangdong, China
| | | | - Yu Chen
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, China
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18
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Abstract
Liver cancer is the sixth most common cancer worldwide, and the third most common cause of cancer-related death. Hepatocellular carcinoma (HCC), which accounts for more than 90% of primary liver cancers, is an important public health problem. In addition to cirrhosis caused by hepatitis B viral (HBV) or hepatitis C viral (HCV) infection, non-alcoholic fatty liver disease (NAFLD) is becoming a major risk factor for liver cancer because of the prevalence of obesity. Non-alcoholic steatohepatitis (NASH) will likely become the leading indication for liver transplantation in the future. It is well recognized that gut microbiota is a key environmental factor in the pathogenesis of liver disease and cancer. The interplay between gut microbiota and liver disease has been investigated in animal and clinical studies. In this article, we summarize the roles of gut microbiota in the development of liver disease as well as gut microbiota-targeted therapies.
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Affiliation(s)
- Lijun Wang
- Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA,The College of Life Science, Yangtze University, Jingzhou, Hubei, China
| | - Yu-Jui Yvonne Wan
- Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA,Corresponding author. Department of medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA. (Y.-J.Y. Wan)
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19
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Maraolo AE, Buonomo AR, Zappulo E, Scotto R, Pinchera B, Gentile I. Unsolved Issues in the Treatment of Spontaneous Peritonitis in Patients with Cirrhosis: Nosocomial Versus Community-acquired Infections and the Role of Fungi. Rev Recent Clin Trials 2019; 14:129-135. [PMID: 30514194 DOI: 10.2174/1574887114666181204102516] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 11/26/2018] [Accepted: 11/27/2018] [Indexed: 06/09/2023]
Abstract
INTRODUCTION Historically, spontaneous bacterial peritonitis (SBP) has represented one of the most frequent and relevant infectious complications of advanced liver disease, and this is still valid today. Nevertheless, in recent years the role of fungi as causative pathogens of primary peritonitis in patients with cirrhosis has become not negligible. Another issue is linked with the traditional distinction, instrumental in therapeutic choice, between community-acquired and nosocomial forms, according to the onset. Between these two categories, another one has been introduced: the so-called "healthcare-associated infections". OBJECTIVE To discuss the most controversial aspects in the management of SBP nowadays in the light of best available evidence. METHODS A review of recent literature through MEDLINE was performed. RESULTS The difference between community-acquired and nosocomial infections is crucial to guide empiric antibiotic therapy, since the site of acquisition impact on the likelihood of multidrug-resistant bacteria as causative agents. Therefore, third-generation cephalosporins cannot be considered the mainstay of treatment in each episode. Furthermore, the distinction between healthcare-associated and nosocomial form seems very subtle, especially in areas wherein antimicrobial resistance is widespread, warranting broad-spectrum antibiotic regimens for both. Finally, spontaneous fungal peritonitis is a not common but actually underestimated entity, linked to high mortality. Especially in patients with septic shock and/or failure of an aggressive antibiotic regimen, the empiric addition of an antifungal agent might be considered. CONCLUSION Spontaneous bacterial peritonitis is one of the most important complications in patients with cirrhosis. A proper empiric therapy is crucial to have a positive outcome. In this respect, a careful assessment of risk factors for multidrug-resistant pathogens is crucial. Likewise important, mostly in nosocomial cases, is not to overlook the probability of a fungal ascitic infection, namely a spontaneous fungal peritonitis.
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Affiliation(s)
- Alberto Enrico Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131, Naples, Italy
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Metwally K, Fouad T, Assem M, Abdelsameea E, Yousery M. Predictors of Spontaneous Bacterial Peritonitis in Patients with Cirrhotic Ascites. J Clin Transl Hepatol 2018; 6:372-376. [PMID: 30637213 PMCID: PMC6328737 DOI: 10.14218/jcth.2018.00001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 06/07/2018] [Accepted: 06/22/2018] [Indexed: 12/14/2022] Open
Abstract
Background and Aims: Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis and a prognostic model to predict it is needed. This study was designed to test the ability of different laboratory tests and the new scoring system by Wehmeyer and colleagues (consisting of age, C-reactive protein (CRP) and platelet count) to predict it. Methods: Three-hundred patients admitted to the National Liver Institute, University of Menoufia, Egypt (2015-2016) with liver cirrhosis and ascites were included in our study. SBP was diagnosed if ascetic neutrophil count was ≥250/µL with no sign of secondary peritonitis. Results: The patient population had age range of 29-81 years old, was 60% men and showed a majority (91.7%) with primary cause of liver disease being hepatitis C. By univariate analysis, associations with age, total bilirubin, aspartate aminotransferase level, creatinine level, international normalized ratio, model for end-stage liver disease score, total leucocytic count, platelet count and CRP level were significant. By multivariate analysis, independent predictors were age, platelet count and CRP level (p = 0.004, 0.013 and <0.001, respectively). CRP at a cut-off point ≥13.5 mg/L could predict SBP (sensitivity of 86.4% and specificity of 66.0%). Wehmeyer's SBP scoring system was predictive (p < 0.001); only 4% of patients with 0 score developed SBP (CRP cut-off of 30 mg/L), while 92.8% with score of 3 or 4 developed SBP. By using our modified Wehmeyer score with CRP cut-off value of 13.5 mg/L, no patient with 0 score developed SBP. Conclusions: Age, CRP level and platelet count are independent predictors for SBP and a scoring system including them could easily predict the condition. SBP diagnosis could be excluded in patients with 0 score, using CRP cut-off value of 13.5 mg/L.
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Affiliation(s)
- Khaled Metwally
- Hepatology and Gastroenterology department, National Liver Institute, Menoufia University, Egypt
- *Correspondence to: Khaled Metwally, Liver and Gastroenterology Unit, National Liver Institute, University of Menoufyia, Menofyia Governorate, Egypt. Tel: +20-100-0486019, Fax: + 20-48-2222740, E-mail:
| | - Tamer Fouad
- Hepatology and Gastroenterology department, National Liver Institute, Menoufia University, Egypt
| | - Medhat Assem
- Hepatology and Gastroenterology department, National Liver Institute, Menoufia University, Egypt
| | - Eman Abdelsameea
- Hepatology and Gastroenterology department, National Liver Institute, Menoufia University, Egypt
| | - Mohamed Yousery
- Hepatology and Gastroenterology department, National Liver Institute, Menoufia University, Egypt
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21
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Mohr R, Lutz P. How to reduce mortality of bacterascites-That is the question. Liver Int 2018; 38:2129-2131. [PMID: 30480379 DOI: 10.1111/liv.13976] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 09/12/2018] [Indexed: 01/13/2023]
Affiliation(s)
- Raphael Mohr
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research (DZIF), University of Bonn, Bonn, Germany
| | - Philipp Lutz
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research (DZIF), University of Bonn, Bonn, Germany
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22
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Sadat Mazloom S, Khoramian MK, Mohsenian L. Spontaneous Bacterial Peritonitis in Afebrile Cirrhotic Patients; Report from a Referral Transplantation Center. Bull Emerg Trauma 2018; 6:363-366. [PMID: 30402527 PMCID: PMC6215066 DOI: 10.29252/beat-060415] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is a complication of liver cirrhosis with adverse effect on patient prognosis. Early diagnosis and treatment is highly important, especially in patients without remarkable manifestations. We designed this study to determine the prevalence of SBP among afebrile cirrhotic patients and identify high-risk subgroups in a referral center in southern Iran. This cross-sectional study evaluated all afebrile cirrhotic patients, admitted to the gastroenterology ward of Namazi hospital (affiliated with Shiraz University of Medical Sciences, Shiraz, Iran) over a 6-month period in 2017, for the presence and correlates of SBP. Demographic data, clinical findings, and comorbidities were recorded. Ascitic fluid white blood cells (WBC) count >500 and neutrophil count >250 indicated bacterial peritonitis. In total, 97 afebrile cirrhotic patients comprising of 63 (64.9%) men and 34 (35.1%) women were included. All patients had ascites and 89 (91.8%) had abdominal tenderness. Accordingly, abdominal distension was the top presentation. Confirmed etiologies or comorbidities such as HBS, HCV, and liver cancer or metastasis existed in 46 patients. Thirteen (13.4%) had SBP. The correlations of gender (p=0.331), decreased level of consciousness (p=0.145), tenderness (p=0.315). With regards to the type of presentations, only DLOC showed to be significantly higher in SBP negative patients (p=0.022, OR=0.09. 95%CI=0.01–0.62). Also, using binary logistic regression, the correlation of age with SBP was statistically non-significant (coefficient= ⎼0.013, p=0.595). Our findings indicated that routine paracentesis in all cirrhotic patients regardless of fever can help diagnose a number of potentially neglected patients and improve their outcome.
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Affiliation(s)
- Sara Sadat Mazloom
- Department of Emergency Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Leila Mohsenian
- Department of Emergency Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Oliver A, Wong M, Sanchez C. Role of Rifaximin in Spontaneous Bacterial Peritonitis Prevention. South Med J 2018; 111:660-665. [PMID: 30392000 DOI: 10.14423/smj.0000000000000887] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Cirrhosis affects millions of people around the world and is associated with increased morbidity and mortality. Spontaneous bacterial peritonitis (SBP) is a common complication of liver disease with cirrhosis and accounts for up to 30% of infections in patients with cirrhosis. Patients with a history of SBP and those deemed to be at high risk often are prescribed antibiotics to reduce the incidence of SBP. Fluoroquinolones and sulfamethoxazole-trimethoprim are commonly used antibiotics for long-term prevention for these specified populations; however, these antibiotics are associated with several adverse effects and interactions that may be harmful to patients. In addition, resistance development may decrease the efficacy of SBP treatment and prophylaxis. Given these limitations, rifaximin, a nonabsorbable, broad-spectrum antibiotic that is used for hepatic encephalopathy, may serve as a prophylactic alternative to conventional therapy. This review discusses guideline-recommended therapy and the evidence for using rifaximin for SBP prophylaxis.
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Affiliation(s)
- Ashley Oliver
- From the South Texas Veterans Health Care System, and the Department of Pharmacotherapy, University of Texas, Austin
| | - Mark Wong
- From the South Texas Veterans Health Care System, and the Department of Pharmacotherapy, University of Texas, Austin
| | - Chelsea Sanchez
- From the South Texas Veterans Health Care System, and the Department of Pharmacotherapy, University of Texas, Austin
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24
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Ferstl PG, Müller M, Filmann N, Hogardt M, Kempf VA, Wichelhaus TA, Lange CM, Vermehren J, Zeuzem S, Reinheimer C, Waidmann O. Noninvasive screening identifies patients at risk for spontaneous bacterial peritonitis caused by multidrug-resistant organisms. Infect Drug Resist 2018; 11:2047-2061. [PMID: 30464547 PMCID: PMC6223386 DOI: 10.2147/idr.s172587] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background and aims Spontaneous bacterial peritonitis (SBP) is a severe complication of decompensated cirrhosis. The prevalence of multidrug-resistant organisms (MDROs) in patients with cirrhosis is increasing. Identification of patients at risk for SBP due to MDROs (ie, SBP with the evidence of MDROs or Stenotrophomonas maltophilia in ascitic culture, MDRO-SBP) is crucial to the early adaptation of antibiotic treatment in such patients. We therefore investigated whether MDROs found in ascitic cultures can also be found in specimens determined by noninvasive screening procedures. Patients and methods This retrospective study was conducted at the liver center of the University Hospital Frankfurt, Germany. Between 2011 and 2016, patients with cirrhosis were included upon diagnosis of SBP and sample collection of aerobic/anaerobic ascitic cultures. Furthermore, the performance of at least one complete MDRO screening was mandatory for study inclusion. Results Of 133 patients diagnosed with SBP, 75 (56.4%) had culture-positive SBP and 22 (16.5%) had MDRO-SBP. Multidrug-resistant Escherichia coli (10/22; 45.5%) and vancomycin-resistant enterococci (7/22; 36.4%) resembled the major causatives of MDRO-SBP. Rectal swabs identified MDROs in 17 of 22 patients (77.3%) who developed MDRO-SBP with a time-dependent sensitivity of 77% and 87% after 30 and 90 days upon testing, while negative predictive value was 83% and 76%, respectively. The majority of patients were included from intensive care unit or intermediate care unit. Conclusion MDRO screening may serve as a noninvasive diagnostic tool to identify patients at risk for MDRO-SBP. Patients with decompensated cirrhosis should be screened for MDROs from the first day of inpatient treatment onward.
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Affiliation(s)
- Philip G Ferstl
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Mona Müller
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Natalie Filmann
- Institute of Biostatistics and Mathematical Modeling, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Michael Hogardt
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Volkhard Aj Kempf
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Thomas A Wichelhaus
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Christian M Lange
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Johannes Vermehren
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Stefan Zeuzem
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
| | - Claudia Reinheimer
- University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany, .,Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.,University Center of Competence for Infection Control at the Universities Frankfurt, Giessen, and Marburg, Frankfurt am Main, State of Hesse, Germany
| | - Oliver Waidmann
- Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany, .,University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany,
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25
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Maraolo AE, Gentile I, Pinchera B, Nappa S, Borgia G. Current and emerging pharmacotherapy for the treatment of bacterial peritonitis. Expert Opin Pharmacother 2018; 19:1317-1325. [PMID: 30071176 DOI: 10.1080/14656566.2018.1505867] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Spontaneous bacterial peritonitis (SBP) is the quintessential model of bacterial infection in cirrhotic patients. In these particularly frail subjects, infections clearly worsen prognosis increasing substantially mortality. Furthermore, treatment of SBP has become more challenging because of the growing impact of multidrug-resistant (MDR) bacteria. AREAS COVERED This review addresses the reasons behind the change in therapeutic recommendations for SBP that have occurred in the past few years, by focusing on the following aspects: the importance of an early appropriate empirical treatment, the difference between nosocomial and non-nosocomial forms and the overall microbiological shift (rise of Gram-positive bacteria and MDR strains) that have affected SBP. EXPERT OPINION Until recently, third-generation cephalosporins have represented the cornerstone of SBP treatment, a safe choice covering the most important causative agents, namely Enterobacteriaceae. Unfortunately, massive exposure to health systems makes cirrhotic patients prone to MDR infections, which poses significant challenges, all the while not forgetting to strike a balance between effective antimicrobial activity and the risk of toxicity in these fragile subjects. Moreover, there is sparse information about new antibiotics in cirrhotic patients and about drugs levels in ascitic fluid. Therefore, further research is needed to optimize the treatment of SBP.
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Affiliation(s)
- Alberto Enrico Maraolo
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Ivan Gentile
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Biagio Pinchera
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Salvatore Nappa
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
| | - Guglielmo Borgia
- a Department of Clinical Medicine and Surgery, Section of Infectious Diseases , University of Naples Federico II , Naples , Italy
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26
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Hüsing-Kabar A, Meister T, Köhler M, Domschke W, Kabar I, Wilms C, Hild B, Schmidt HH, Heinzow HS. Is de novo hepatocellular carcinoma after transjugular intrahepatic portosystemic shunt increased? United European Gastroenterol J 2018; 6:413-421. [PMID: 29774155 PMCID: PMC5949971 DOI: 10.1177/2050640617732886] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 08/30/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Portal hypertension is a major complication of liver cirrhosis. Transjugular intrahepatic portosystemic shunt is effective in treatment of portal hypertension. However, decreased parenchymal portal venous flow after transjugular intrahepatic portosystemic shunt insertion favours ischaemic liver injury which has been discussed to induce hepatocarcinogenesis causing hepatocellular cancer. AIM This study aimed to explore the association between transjugular intrahepatic portosystemic shunt placement and the development of hepatocellular cancer. METHODS A total of 1338 consecutive liver cirrhosis patients were included in this retrospective study between January 2004-December 2015. Data were analysed with regard to development of hepatocellular cancer during follow-up. Binary logistic regression and Kaplan-Meier analyses were conducted for the assessment of risk factors for hepatocellular cancer development. In a second step, to rule out confounders of group heterogeneity, case-control matching was performed based on gender, age, model of end-stage liver disease score and underlying cause of cirrhosis (non-alcoholic steatohepatitis, alcoholic liver disease and viral hepatitis). RESULTS Besides established risk factors such as older age, male gender and underlying viral hepatitis, statistical analysis revealed the absence of transjugular intrahepatic portosystemic shunt insertion as a risk factor for hepatocellular cancer development. Furthermore, matched-pair analysis of 432 patients showed a significant difference (p = 0.003) in the emergence of hepatocellular cancer regarding transjugular intrahepatic portosystemic shunt placement versus the non-transjugular intrahepatic portosystemic shunt cohort. CONCLUSION In patients with end-stage liver disease, transjugular intrahepatic portosystemic shunt insertion is significantly associated with reduced rates of hepatocellular cancer development.
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Affiliation(s)
- A Hüsing-Kabar
- Department of Transplant Medicine, University Hospital
Muenster, Muenster, Germany
| | - T Meister
- Department of Gastroenterology, HELIOS
Albert-Schweitzer-Hospital Northeim, Northeim, Germany
| | - M Köhler
- Department of Clinical Radiology, University Hospital
Muenster, Muenster, Germany
| | - W Domschke
- Department of Medicine B, University Hospital
Muenster, Muenster, Germany
| | - I Kabar
- Department of Transplant Medicine, University Hospital
Muenster, Muenster, Germany
| | - C Wilms
- Department of Transplant Medicine, University Hospital
Muenster, Muenster, Germany
| | - B Hild
- Department of Transplant Medicine, University Hospital
Muenster, Muenster, Germany
| | - HH Schmidt
- Department of Transplant Medicine, University Hospital
Muenster, Muenster, Germany
| | - HS Heinzow
- Department of Transplant Medicine, University Hospital
Muenster, Muenster, Germany
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27
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Abstract
This narrative review summarises the benefits, risks and appropriate use of acid-suppressing drugs (ASDs), proton pump inhibitors and histamine-2 receptor antagonists, advocating a rationale balanced and individualised approach aimed to minimise any serious adverse consequences. It focuses on current controversies on the potential of ASDs to contribute to infections-bacterial, parasitic, fungal, protozoan and viral, particularly in the elderly, comprehensively and critically discusses the growing body of observational literature linking ASD use to a variety of enteric, respiratory, skin and systemic infectious diseases and complications (Clostridium difficile diarrhoea, pneumonia, spontaneous bacterial peritonitis, septicaemia and other). The proposed pathogenic mechanisms of ASD-associated infections (related and unrelated to the inhibition of gastric acid secretion, alterations of the gut microbiome and immunity), and drug-drug interactions are also described. Both probiotics use and correcting vitamin D status may have a significant protective effect decreasing the incidence of ASD-associated infections, especially in the elderly. Despite the limitations of the existing data, the importance of individualised therapy and caution in long-term ASD use considering the balance of benefits and potential harms, factors that may predispose to and actions that may prevent/attenuate adverse effects is evident. A six-step practical algorithm for ASD therapy based on the best available evidence is presented.
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28
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Oey RC, de Man RA, Erler NS, Verbon A, van Buuren HR. Microbiology and antibiotic susceptibility patterns in spontaneous bacterial peritonitis: A study of two Dutch cohorts at a 10-year interval. United European Gastroenterol J 2017; 6:614-621. [PMID: 29881617 PMCID: PMC5987276 DOI: 10.1177/2050640617744456] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 10/24/2017] [Indexed: 12/20/2022] Open
Abstract
Background Recent investigations suggest an increasing prevalence of Gram-positive and antibiotic-resistant bacteria causing spontaneous bacterial peritonitis (SBP), probably related to changes in antibiotic prescription patterns, in particular more widespread and long-term use of antibiotic prophylaxis with quinolones. Objective The primary objective of this study was to assess potential changes in the microbiology of SBP in two patient cohorts studied at a 10-year interval. Further aims were to study prognostic factors and outcome of SBP. Methods A retrospective double-cohort study, including all ascitic cultures from patients with cirrhosis obtained 2003–2005 and 2013–2014, was conducted. Results In total 312 patients were included, 125 patients in the first and 187 patients in the second cohort. SBP was diagnosed in 132 of 840 analyzed ascitic fluid samples; 62 samples were culture positive. An increase of Gram-positive bacterial isolates was noted from 26% to 46% between cohorts (p = 0.122). The prevalence of multidrug-antibiotic–resistant pathogens increased from 25% to 32% (p = 0.350). Survival after SBP among the two cohorts was comparable. Conclusion This single-center study in the Netherlands found a modest but nonsignificant increase in the proportion of patients with SBP caused by Gram-positive bacteria and multidrug-antibiotic–resistant bacteria over a 10-year period. Our findings differ from reported data in other countries and suggest empiric antibiotic prophylaxis and treatment of SBP should be based on national and regional microbiological findings and resistance patterns.
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Affiliation(s)
- Rosalie C Oey
- 1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Robert A de Man
- 1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Nicole S Erler
- 2Department of Biostatistics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.,3Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Annelies Verbon
- 4Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.,5Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Henk R van Buuren
- 1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
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29
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Malikowski TM, Podboy AJ, Sweetser S. 57-Year-Old Woman With Abdominal Pain. Mayo Clin Proc 2017. [PMID: 28647225 DOI: 10.1016/j.mayocp.2016.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Thomas M Malikowski
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Alexander J Podboy
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Seth Sweetser
- Advisor to residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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30
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Sidhu GS, Go A, Attar BM, Mutneja HR, Arora S, Patel SA. Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis: a systematic review. BMJ Open Gastroenterol 2017; 4:e000154. [PMID: 28944070 PMCID: PMC5606119 DOI: 10.1136/bmjgast-2017-000154] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 06/26/2017] [Accepted: 06/30/2017] [Indexed: 02/07/2023] Open
Abstract
Aim The aim of this systematic review is to evaluate the efficacy and safety of rifaximin in the prophylaxis of spontaneous bacterial peritonitis (SBP) as compared with norfloxacin. Methods We searched MEDLINE, CINAHL, Google Scholar and Cochrane databases from inception to January 2017. Reference lists of articles as well as conference proceedings were manually screened. We included studies that recruited patients with cirrhosis and ascites who met the criteria for primary or secondary SBP prophylaxis as defined by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases. Two independent investigators reviewed the studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was occurrence of SBP. Secondary outcomes included mortality and adverse events with therapy. Results Of the 435 studies identified, a total of five were included for full-text review. Four studies were eligible for the systematic review, three of which were randomised controlled trials and one was a prospective observational study. The population examined in majority of studies was primarily hepatitis C cirrhosis. The results of individual studies indicated either superior efficacy of rifaximin or no statistical difference between rifaximin and norfloxacin for SBP prophylaxis. Conclusions Moderate-quality evidence shows that long-term use of rifaximin appears to be a reasonable alternative to norfloxacin for SBP prevention in hepatitis C cirrhosis.
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Affiliation(s)
| | - Andrew Go
- University of Illinois at Chicago, Chicago, IL, USA
| | - Bashar M Attar
- Cook County Health and Hospitals System, Chicago, IL, USA
| | | | - Shilpa Arora
- Cook County Health and Hospitals System, Chicago, IL, USA
| | - Sanjay A Patel
- Cook County Health and Hospitals System, Chicago, IL, USA
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31
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Fiore M, Maraolo AE, Gentile I, Borgia G, Leone S, Sansone P, Passavanti MB, Aurilio C, Pace MC. Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review. World J Gastroenterol 2017; 23:4654-4660. [PMID: 28740354 PMCID: PMC5504381 DOI: 10.3748/wjg.v23.i25.4654] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Revised: 03/31/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODS A literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: "spontaneous" AND "peritonitis". RESULTS The initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSION N-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.
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32
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Bacterial translocation aggravates CCl 4-induced liver cirrhosis by regulating CD4 + T cells in rats. Sci Rep 2017; 7:40516. [PMID: 28134306 PMCID: PMC5278361 DOI: 10.1038/srep40516] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 12/06/2016] [Indexed: 02/08/2023] Open
Abstract
Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3+CD4+CD25+Foxp3+), Th17 (CD3+CD4+IL-17+), and Th1 (CD3+CD4+IFN-γ+) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl4. We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT. We found that BT may cause increase of Treg cells in the proximal small intestine and decrease of Th17 cells in the whole intestine and blood in cirrhotic rats. It may also aggravate the CCl4-induced decrease in Th1 cells in the whole intestine, liver, caecum, and blood and the CCl4-induced increase in Th17 cells in the liver and Tregs in the distal small intestine, colon, and liver. Our data suggest that BT may aggravate liver injury and decrease liver function via an interaction with CD4+ T Cells. The results of this study may be helpful for the development of new treatments for liver cirrhosis.
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33
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Lutz P, Nischalke HD, Krämer B, Goeser F, Kaczmarek DJ, Schlabe S, Parcina M, Nattermann J, Hoerauf A, Strassburg CP, Spengler U. Antibiotic resistance in healthcare-related and nosocomial spontaneous bacterial peritonitis. Eur J Clin Invest 2017; 47:44-52. [PMID: 27861767 DOI: 10.1111/eci.12701] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 11/07/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) can be life threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP. MATERIALS AND METHODS We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively. RESULTS Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequencies of these microorganisms were comparable for healthcare-related and nosocomial SBP (14% vs. 11%, 14% vs. 8%, 14% vs. 5% and 10% vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30% vs. 11% for piperacillin-tazobactam; P > 0·05), but comparable concerning third-generation cephalosporins (30% vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n = 3) and Candida albicans (n = 1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; P = 0·002). CONCLUSION Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP.
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Affiliation(s)
- Philipp Lutz
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Hans Dieter Nischalke
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Benjamin Krämer
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Felix Goeser
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Dominik J Kaczmarek
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Stefan Schlabe
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Marijo Parcina
- German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany.,Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Achim Hoerauf
- German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany.,Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany.,German Center for Infection Research, partner site Bonn-Cologne, Bonn, Germany
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McGillen KL, Boos J, Nathavitharana R, Brook A, Sun MR, Siewert B, Raptopoulos V, Kane R, Sheiman R, Brook OR. Diagnostic yield and clinical impact of microbiologic diagnosis from CT-guided drainage in patients previously treated with empiric antibiotics. Abdom Radiol (NY) 2017; 42:298-305. [PMID: 27654990 DOI: 10.1007/s00261-016-0833-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE The purpose of the study was to evaluate diagnostic yield and the added value of culture results on the clinical management of patients empirically treated with antibiotics prior to CT-guided drainage. METHODS This retrospective, HIPAA-compliant, IRB-approved study reviewed records of 300 consecutive patients who underwent CT-guided aspiration or drainage for suspected infected fluid collection while on empiric antibiotics (11/2011 to 9/2013) at a single institution. Patient imaging and clinical characteristics were evaluated by an abdominal imaging fellow and culture results, and patient management were evaluated by an infectious diseases fellow. RESULTS After exclusion of 14/300 (4.6%) patients who were not on empiric antibiotics and 8/300 (2.6%) patients in which no culture was acquired, 278 patients (average age 55 ± 16 years; M:F ratio 54:46) constituted the final study cohort. Leukocytosis was present in 163/278 (59%), and fever in 65/278 (24%). The average collection size was 8.5 ± 4.2 cm with gas present in 140/278 (50%) of collections; median amount drained was 35 mL, and visibly purulent material was obtained in 172/278 (63%). 236/278 (85%) received drains and the remainder were aspirated only. Average time between initiation of antibiotics and start of the drainage procedure was 4.1 ± 6.4 days (median 1.7 days). Cultures were positive in 205/278 (74%) patients with a resulting change in management in 181/278 (65%) cases. The change in management included change of antibiotics in 71/278 (26%), narrowing the antibiotic regimen in 94/278 (34%), and cessation of antibiotics in 16/278 (6%). Multidrug-resistant bacteria were cultured in 53/278 (19%). Several factors were found to be statistically significant predictors of positive cultures: patient leukocytosis (sens 62%, spec 53%), gas in the collection on CT (sens 59%, spec 77%), purulent material aspiration (sens 76%, spec 76%), and presence of polymorphonuclear cells in the specimen. CONCLUSIONS Despite predrainage antibiotic therapy, CT-guided drainage demonstrates a high yield of positive cultures and influences clinical management in the majority of patients.
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Liu M, Wang P, Zhao M, Liu DY. Intestinal Dendritic Cells Are Altered in Number, Maturity and Chemotactic Ability in Fulminant Hepatic Failure. PLoS One 2016; 11:e0166165. [PMID: 27832135 PMCID: PMC5104363 DOI: 10.1371/journal.pone.0166165] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Accepted: 10/23/2016] [Indexed: 01/01/2023] Open
Abstract
Fulminant hepatic failure (FHF) is defined as rapid acute liver injury, often complicated with spontaneous bacterial peritonitis (SBP). The precise onset of FHF with SBP is still unknown, but it is thought that SBP closely correlates with a weakened intestinal barrier. Dendritic cells (DCs) play a crucial role in forming the intestinal immune barrier, therefore the number, maturity and chemotactic ability of intestinal DCs were studied in FHF. Mouse intestinal and spleen DCs were isolated by magnetic-activated cell sorting (MACS) and surface markers of DCs, namely CD11c, CD74, CD83 and CD86, were identified using flow cytometry. Immunohistochemistry and Western blotting were performed to detect the distribution and expression of CC-chemokine receptor 7 (CCR7) and CC-chemokine receptor 9 (CCR9), as well as their ligands-CC-chemokine ligand 21 (CCL21) and CC-chemokine ligand 25 (CCL25). Real-time PCR was used to detect CCR7 and CCR9 mRNA, along with their ligands-CCL21 and CCL25 mRNA. Flow cytometry analysis showed that the markers CD74, CD83 and CD86 of CD11c+DCs were lower in the D-galactosamine (D-GalN) group and were significantly decreased in the FHF group, while there were no significant changes in the expression of these markers in the lipopolysaccharide (LPS) group. Immunohistochemistry results showed that staining for CCR7 and CCR9, as well as their ligands CCL21 and CCL25, was significantly weaker in the D-GalN and FHF groups compared with the normal saline (NS) group or the LPS group; the FHF group even showed completely unstained parts. Protein expression of CCR7 and CCR9, as well as their ligands- CCL21 and CCL25, was also lower in the D-GalN group and decreased even more significantly in the FHF group. At the gene level, CCR7 and CCR9, along with CCL21 and CCL25 mRNA expression, was lower in the D-GalN group and significantly decreased in the FHF group compared to the NS and LPS groups, consisting with the protein expression. Our study indicated that intestinal DCs were decreased in number, maturity and chemotactic ability in FHF and might contribute to a decreased function of the intestinal immune barrier in FHF.
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MESH Headings
- Animals
- Antigens, CD/immunology
- Antigens, CD/metabolism
- Antigens, Differentiation, B-Lymphocyte/immunology
- Antigens, Differentiation, B-Lymphocyte/metabolism
- B7-2 Antigen/immunology
- B7-2 Antigen/metabolism
- Blotting, Western
- CD11c Antigen/immunology
- CD11c Antigen/metabolism
- Cell Count
- Chemokine CCL21/genetics
- Chemokine CCL21/immunology
- Chemokine CCL21/metabolism
- Chemokines, CC/genetics
- Chemokines, CC/immunology
- Chemokines, CC/metabolism
- Chemotaxis/immunology
- Dendritic Cells/immunology
- Dendritic Cells/metabolism
- Flow Cytometry
- Gene Expression/immunology
- Histocompatibility Antigens Class II/immunology
- Histocompatibility Antigens Class II/metabolism
- Immunoglobulins/immunology
- Immunoglobulins/metabolism
- Immunohistochemistry
- Intestines/immunology
- Liver Failure, Acute/genetics
- Liver Failure, Acute/immunology
- Liver Failure, Acute/metabolism
- Male
- Membrane Glycoproteins/immunology
- Membrane Glycoproteins/metabolism
- Mice, Inbred BALB C
- Receptors, CCR/genetics
- Receptors, CCR/immunology
- Receptors, CCR/metabolism
- Receptors, CCR7/genetics
- Receptors, CCR7/immunology
- Receptors, CCR7/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- CD83 Antigen
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Affiliation(s)
- Mei Liu
- Medical Research Center, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, China
| | - Peng Wang
- The second department of urology, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, China
| | - Min Zhao
- Medical Research Center, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, China
| | - DY Liu
- Medical Research Center, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, China
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The role of the neutrophil Fcγ receptor I (CD64) index in diagnosing spontaneous bacterial peritonitis in cirrhotic patients. Int J Infect Dis 2016; 49:154-60. [PMID: 27381937 DOI: 10.1016/j.ijid.2016.06.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 05/18/2016] [Accepted: 06/28/2016] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVE To investigate the role of the neutrophil Fcγ receptor I (CD64) index in the diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. METHODS A total of 123 cirrhotic patients with ascites who fulfilled the inclusion criteria were enrolled in this study. Ascites and blood samples were collected; the polymorphonuclear neutrophil (PMN) count, bacterial culture, and related laboratory tests were performed. The CD64 index was determined for each sample using flow cytometry. RESULTS The neutrophil CD64 index results were significantly higher in cirrhotic patients with SBP than in those without SBP (p<0.001). There was a positive correlation between the neutrophil CD64 index and the PMN count in ascites. In the receiver operating characteristic curve (ROC) analysis, the area under the curve (AUC) was 0.894 (95% confidence interval 0.823-0.964, p<0.001). The optimal cut-off value for the neutrophil CD64 index was 2.02. The sensitivity and specificity of the neutrophil CD64 index for cirrhotic patients with SBP were 80.49% and 93.90%, respectively. The elevated neutrophil CD64 index was down-regulated by antibiotic therapy (p=0.002). CONCLUSIONS The neutrophil CD64 index could be used as a sensitive and specific indicator for the diagnosis of SBP in cirrhotic patients with ascites and is also modulated by antibiotic therapy.
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Andersen K, Kesper MS, Marschner JA, Konrad L, Ryu M, Kumar Vr S, Kulkarni OP, Mulay SR, Romoli S, Demleitner J, Schiller P, Dietrich A, Müller S, Gross O, Ruscheweyh HJ, Huson DH, Stecher B, Anders HJ. Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation. J Am Soc Nephrol 2016; 28:76-83. [PMID: 27151924 DOI: 10.1681/asn.2015111285] [Citation(s) in RCA: 166] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 03/14/2016] [Indexed: 11/03/2022] Open
Abstract
CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3-deficient mice with Alport syndrome-related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen-presenting cells, CD4 and CD8 T cells, and Th17- or IFNγ-producing T cells in the spleen as well as regulatory T cell suppression. CKD-related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD-related systemic inflammation and its consequences.
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Affiliation(s)
- Kirstin Andersen
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Marie Sophie Kesper
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Julian A Marschner
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Lukas Konrad
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Mi Ryu
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Santhosh Kumar Vr
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Onkar P Kulkarni
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Shrikant R Mulay
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Simone Romoli
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
| | - Jana Demleitner
- Walther Straub Institut für Pharmakologie und Toxikologie and
| | - Patrick Schiller
- Max von Pettenkofer Institut, Universität München, Munich, Germany.,German Center for Infection Research, Ludwig Maximilians University Munich, Munich, Germany
| | | | - Susanna Müller
- Pathologisches Institut, Ludwig Maximilians Universität, Munich, Germany
| | - Oliver Gross
- Clinic of Nephrology and Rheumatology, University Medical Centre Göttingen, Göttingen, Germany; and
| | | | - Daniel H Huson
- Centre for Bioinformatics, Tübingen University, Tübingen, Germany
| | - Bärbel Stecher
- Max von Pettenkofer Institut, Universität München, Munich, Germany.,German Center for Infection Research, Ludwig Maximilians University Munich, Munich, Germany
| | - Hans-Joachim Anders
- Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität and
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Kim JH, Jeon YD, Jung IY, Ahn MY, Ahn HW, Ahn JY, Ku NS, Han SH, Choi JY, Ahn SH, Song YG, Han KH, Kim JM. Predictive Factors of Spontaneous Bacterial Peritonitis Caused by Gram-Positive Bacteria in Patients With Cirrhosis. Medicine (Baltimore) 2016; 95:e3489. [PMID: 27124049 PMCID: PMC4998712 DOI: 10.1097/md.0000000000003489] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is typically caused by gram-negative bacteria. However, the number of SBP cases due to gram-positive bacteria is steadily increasing. To date, little is known about the predictive factors involved in SBP infections.We performed a retrospective cohort study of patients (>18 years) with SBP due to gram-positive and -negative bacteria who were enrolled from January 2006 to December 2013 at Severance Hospital in Seoul, Korea where the incidences of hepatitis B virus associated chronic liver disease, cirrhosis, and hepatocellular carcinoma are high. Only the 1st SBP episode for each patient within the study period was included in our analysis.We identified 77 patients with cirrhosis and SBP. Of these, 27 patients (35%) had gram-positive bacterial infections and 50 patients (65%) had gram-negative bacterial infections. Our univariate analysis revealed that an early stage of cirrhosis (P = 0.004), lower creatinine level (P = 0.011), lower Sequential Organ Failure Assessment (SOFA) score (P = 0.001), lower Model for End-Stage Liver Disease score (P = 0.005), and use of systemic antibiotics within 30 days before SBP diagnosis (P = 0.03) were significantly associated with gram-positive bacterial infections. Our multivariate analysis indicated that the use of systemic antibiotics within 30 days before SBP diagnosis (odds ratio, 3.94; 95% CI, 1.11-13.96; P = 0.033) and a lower SOFA score (odds ratio, 0.56; 95% CI, 0.37-0.86; P = 0.007) were independent predictive factors of SBP caused by gram-positive bacterial infections in patients with cirrhosis. However, we did not observe a statistically significant difference in the 28-day mortality between the gram-positive and -negative bacterial infection groups (40.7% vs 46.0%, respectively; P = 0.407).In this study, the incidence rate of SBP caused by gram-positive bacteria in patients with cirrhosis was similar to the rates reported in recently published studies. Furthermore, the use of systemic antibiotics within 30 days before SBP diagnosis and a lower SOFA score were significantly associated with SBP caused by gram-positive bacteria in patients with cirrhosis.
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Affiliation(s)
- Jung Ho Kim
- From the Department of Internal Medicine (JHK, YDJ, IYJ, MYA, HWA, JYA, NSK, SHH, JYC, SHA, YGS, KHH, JMK); and AIDS Research Institute, Severance Hospital (YDJ, MYA, HWA, JYA, NSK, SHH, JYC, YGS, JMK), Yonsei University College of Medicine, Seoul, Republic of Korea
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Abstract
BACKGROUND Diagnosis of spontaneous bacterial peritonitis in cirrhosis can be made when a patient has an ascites polymorphonuclear leukocyte count ≥250/mm3. However, symptomatic bacterascites, which is a variant of spontaneous bacterial peritonitis with signs of infection but an ascites polymorphonuclear leukocyte count <250/mm3, cannot be confirmed until the time-consuming ascites culture becomes positive. Currently, early indicators for symptomatic bacterascites remain undetermined. AIMS To develop a quick screening model for early detection of symptomatic bacterascites in cirrhosis. MATERIALS AND METHODS Data on patients with cirrhotic ascites from two hospitals (from 2010 to 2014) were collected retrospectively. Patients with symptomatic bacterascites were enrolled in the case group and compared with patients without any infection in the control group. Logistic regression analysis was used to build a model for screening symptomatic bacterascites, and a receiver operating characteristics curve was used to assess the model. RESULTS In total, 103 patients were enrolled in the case group and 204 patients were enrolled in the control group. A screening model was constructed based on body temperature, abdominal tenderness, blood neutrophil percentage, blood total bilirubin, prothrombin time, and ascites nucleated leukocyte count. The area under the receiver operating characteristic curve was 0.939; a screening score of 0.328 was the best cutoff value. CONCLUSION Patients with suspected symptomatic bacterascites can be quickly screened according to the developed model, and a screening score ≥0.328 indicates symptomatic bacterascites.
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Affiliation(s)
- Long-Chuan Zhu
- Department of Digestion, The First Affiliated Hospital of Nanchang University, Jiangxi, China,Department of Hepatology, Infectious Disease Hospital of Nanchang University, Jiangxi, China
| | - Long Xu
- Department of Hepatology, Infectious Disease Hospital of Nanchang University, Jiangxi, China
| | - Wen-Hua He
- Department of Digestion, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Wei Wu
- Department of Digestion, Children's Hospital of Jiangxi Province, Jiangxi, China
| | - Xuan Zhu
- Department of Digestion, The First Affiliated Hospital of Nanchang University, Jiangxi, China,Address for correspondence: Prof. Xuan Zhu, Department of Digestion, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. E-mail:
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Dirchwolf M, Ruf AE. Role of systemic inflammation in cirrhosis: From pathogenesis to prognosis. World J Hepatol 2015; 7:1974-1981. [PMID: 26261687 PMCID: PMC4528271 DOI: 10.4254/wjh.v7.i16.1974] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 06/15/2015] [Accepted: 07/02/2015] [Indexed: 02/06/2023] Open
Abstract
The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted.
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