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Oussalah A, Haghnejad V, Silva Rodriguez M, Lagneaux A, Alix T, Filhine‐Tresarrieu P, Ferrand J, Jung J, Broseus J, Salignac S, Luc A, Baumann C, Schuetz P, Lozniewski A, Peoc'h K, Puy H, Guéant J, Bronowicki J. Mid-regional pro-adrenomedullin: A rapid sepsis biomarker for diagnosing spontaneous bacterial peritonitis in cirrhosis. Eur J Clin Invest 2025; 55:e70021. [PMID: 40052388 PMCID: PMC12066915 DOI: 10.1111/eci.70021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 02/22/2025] [Indexed: 05/13/2025]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a frequent and life-threatening complication of cirrhosis, contributing to considerable morbidity and mortality. METHODS A cross-sectional derivation study was conducted to assess the diagnostic accuracy of two sepsis-related calcitonin peptide family biomarkers, mid-regional pro-adrenomedullin (MR-pro-ADM) and procalcitonin, in ascitic fluid for identifying bacteriologically confirmed SBP (BC-SBP). In a subsequent validation study, the diagnostic performance of the 'SBP score' was evaluated in an independent patient cohort using an absolute polymorphonuclear (PMN) leukocyte count threshold of ≥250 cells/mm3 as the diagnostic benchmark for diagnosing SBP. RESULTS In the derivation study, the concentration of MR-pro-ADM in ascitic fluid was significantly higher in patients with BC-SBP compared to those without BC-SBP (3.14 nmol/L [IQR, 2.39-6.74] vs. 1.91 nmol/L [IQR, 1.33-2.80]; p = .0002). Bayesian ANOVA indicated that MR-pro-ADM was highly discriminative for diagnosing BC-SBP, with a substantial Bayes factor (BFM = 2505), whereas procalcitonin exhibited poor discriminatory performance. Receiver-operating characteristic (ROC) analysis identified an optimal MR-pro-ADM cut-off of ≥2.50 nmol/L for diagnosing BC-SBP, with an area under the ROC curve (AUROC) of 0.746 (95% CI, 0.685-0.801; p < .0001). Multivariable logistic regression identified three independent predictors of BC-SBP, which were subsequently incorporated into the 'SBP score' (MR-pro-ADM ≥2.5 nmol/L, absolute PMN count ≥250 cells/mm3 and Child-Pugh score). In the validation study, the 'SBP score' demonstrated an AUROC of 0.993 (95% CI, 0.929-1.000; p < .0001) for diagnosing SBP. CONCLUSION MR-pro-ADM in ascitic fluid emerges as a promising biomarker for SBP diagnosis. Combining MR-pro-ADM with absolute PMN count and Child-Pugh score in the 'SBP score' greatly improves the diagnostic accuracy of SBP.
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Grants
- Thermo Fisher Scientific (Asnières-sur-Seine, France) generously provided the B.R.A.H.M.S. Sensitive KRYPTOR™ immunofluorescence assays used to measure procalcitonin and mid-regional pro-adrenomedullin concentrations in ascitic fluids. The funding sources had no involvement in the study design, conduct, data collection, management, analysis, interpretation, manuscript preparation, review, approval, or the decision to submit the manuscript for publication
- INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure, F-54000 Nancy, France
- Department of Genomic Medicine, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy, F-54000 Nancy, France
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Affiliation(s)
- Abderrahim Oussalah
- Department of Genomic Medicine, Division of Biochemistry, Molecular Biology and NutritionUniversity Hospital of NancyNancyFrance
- University of LorraineINSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of NancyNancyFrance
| | - Vincent Haghnejad
- Department of Gastroenterology and HepatologyUniversity Hospital of NancyNancyFrance
| | - Maël Silva Rodriguez
- Department of Genomic Medicine, Division of Biochemistry, Molecular Biology and NutritionUniversity Hospital of NancyNancyFrance
| | | | - Tom Alix
- Department of Genomic Medicine, Division of Biochemistry, Molecular Biology and NutritionUniversity Hospital of NancyNancyFrance
| | - Pierre Filhine‐Tresarrieu
- Department of Genomic Medicine, Division of Biochemistry, Molecular Biology and NutritionUniversity Hospital of NancyNancyFrance
| | - Janina Ferrand
- Department of BacteriologyUniversity Hospital of NancyNancyFrance
| | - Jean Jung
- Department of Genomic Medicine, Division of Biochemistry, Molecular Biology and NutritionUniversity Hospital of NancyNancyFrance
| | - Julien Broseus
- University of LorraineINSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of NancyNancyFrance
- Laboratory of HematologyUniversity Hospital of NancyNancyFrance
| | | | - Amandine Luc
- Methodology, Data Management and Statistics UnitUniversity Hospital of NancyNancyFrance
| | - Cédric Baumann
- Methodology, Data Management and Statistics UnitUniversity Hospital of NancyNancyFrance
| | - Philipp Schuetz
- Medical University ClinicDepartment of Internal and Emergency Medicine and Department of Endocrinology, Diabetology and Clinical Nutrition, Kantonsspital AarauAarauSwitzerland
| | - Alain Lozniewski
- Department of BacteriologyUniversity Hospital of NancyNancyFrance
- Stress Immunity Pathogens Laboratory (EA7300), Faculty of Medicine of NancyUniversity Hospital of NancyNancyFrance
| | - Katell Peoc'h
- Laboratory of Biochemistry, Beaujon HospitalUniversity of ParisClichyFrance
| | - Hervé Puy
- Inflammation Research CenterUniversity of Paris, INSERM, CNRS, 75018 Paris, France. Laboratory of Excellence GR‐EXParisFrance
| | - Jean‐Louis Guéant
- Department of Genomic Medicine, Division of Biochemistry, Molecular Biology and NutritionUniversity Hospital of NancyNancyFrance
- University of LorraineINSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of NancyNancyFrance
| | - Jean‐Pierre Bronowicki
- University of LorraineINSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of NancyNancyFrance
- Department of Gastroenterology and HepatologyUniversity Hospital of NancyNancyFrance
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Birg A, Lin HC. The Role of Bacteria-Derived Hydrogen Sulfide in Multiple Axes of Disease. Int J Mol Sci 2025; 26:3340. [PMID: 40244174 PMCID: PMC11990059 DOI: 10.3390/ijms26073340] [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] [Received: 12/15/2024] [Revised: 03/27/2025] [Accepted: 03/27/2025] [Indexed: 04/18/2025] Open
Abstract
In this review article, we discuss and explore the role of bacteria-derived hydrogen sulfide. Hydrogen sulfide is a signaling molecule produced endogenously that plays an important role in health and disease. It is also produced by the gut microbiome. In the setting of microbial disturbances leading to disruption of intestinal homeostasis (dysbiosis), the concentration of available hydrogen sulfide can also vary leading to pathologic sequelae. The brain-gut axis is the original studied paradigm of gut microbiome and host interaction. In recent years, our understanding of microbial and host interaction has expanded greatly to include specific pathways that have branched into their own axes. These axes share a principal concept of microbiota changes, intestinal permeability, and an inflammatory response, some of which are modulated by hydrogen sulfide (H2S). In this review, we will discuss multiple axes including the gut-immune, gut-heart, and gut-endocrine axes. We will evaluate the role of H2S in modulation of intestinal barrier, mucosal healing in intestinal inflammation and tumor genesis. We will also explore the role of H2S in alpha-synuclein aggregation and ischemic injury. Finally, we will discuss H2S in the setting of metabolic syndrome as int pertains to hypertension, atherosclerosis and glucose-like peptide-1 activity. Majority of studies that evaluate hydrogen sulfide focus on endogenous production; the role of this review is to examine the lesser-known bacteria-derived source of hydrogen sulfide in the progression of diseases as it relates to these axes.
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Affiliation(s)
- Aleksandr Birg
- Medicine Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA;
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM 87106, USA
| | - Henry C. Lin
- Medicine Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA;
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM 87106, USA
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Loughrey MB. Inflammatory disorders of the peritoneum. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:1057-1071. [DOI: 10.1002/9781119423195.ch47] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Vu PQ, Thiriveedi M, Patel S, Gopal K. Spontaneous Bacterial Peritonitis: A Rare Incidence by Achromobacter xylosidans. Cureus 2024. [DOI: https:/doi.org/10.7759/cureus.67855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/11/2025] Open
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Vu PQ, Thiriveedi M, Patel S, Gopal K. Spontaneous Bacterial Peritonitis: A Rare Incidence by Achromobacter xylosidans. Cureus 2024; 16:e67855. [PMID: 39328647 PMCID: PMC11424232 DOI: 10.7759/cureus.67855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 08/25/2024] [Indexed: 09/28/2024] Open
Abstract
Liver cirrhosis results from progressive hepatic fibrosis and is generally considered irreversible. One of the many consequences of cirrhosis is spontaneous bacterial peritonitis. This typically presents in patients with decompensated cirrhosis due to bacterial translocation, most commonly from the intestinal bacterial flora seeding into the ascitic fluid. We present a rare case of spontaneous bacterial peritonitis caused by Achromobacter xylosidans. This bacterium is mostly associated with nosocomial infections, and due to its multidrug-resistant nature, treatment options are often limited. This case highlights a rare cause of spontaneous bacterial peritonitis to consider in the setting of recent hospitalization, and the importance of recognizing spontaneous bacterial peritonitis versus secondary bacterial peritonitis.
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Affiliation(s)
- Paul Q Vu
- Internal Medicine, Alabama College of Osteopathic Medicine, Dothan, USA
| | | | | | - Kalashree Gopal
- Internal Medicine, Alabama College of Osteopathic Medicine, Dothan, USA
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Nimri F, Ichkhanian Y, Shinn B, Kowalski TE, Loren DE, Kumar A, Schlachterman A, Tantau A, Arevalo M, Taha A, Shamaa O, Viales MC, Khashab MA, Simmer S, Singla S, Piraka C, Zuchelli TE. Comprehensive analysis of adverse events associated with transmural use of LAMS in patients with liver cirrhosis: International multicenter study. Endosc Int Open 2024; 12:E740-E749. [PMID: 38847015 PMCID: PMC11156515 DOI: 10.1055/a-2312-1528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 04/16/2024] [Indexed: 06/09/2024] Open
Abstract
Background and study aims Endoscopic ultrasound (EUS)-guided transmural (TM) deployment of lumen-apposing metal stents (LAMS) is considered relatively safe in non-cirrhotic patients and is cautiously offered to cirrhotic patients. Patients and methods This was a retrospective, multicenter, international matched case-control study to study the safety of EUS-guided TM deployment of LAMS in cirrhotic patients. Results Forty-three cirrhotic patients with model for end-stage liver disease score 12.5 ± 5, with 23 having ascites and 16 with varices underwent EUS-guided TM LAMS deployment, including 19 for pancreatic fluid collection (PFC) drainage, 13 gallbladder drainage, six for endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP), three for EDGI, one for endoscopic ultrasound-directed transenteric ERCP, and one postsurgical collection drainage. Technical failure occurred in one LAMS for PFC drainage. Clinical failure was encountered in another PFC. Nine adverse events (AEs) occurred. The most common AE was LAMS migration (3), followed by non-bleeding mucosal erosion (2), delayed bleeding (2), sepsis (1), and anesthesia-related complication (pulseless electrical activity) (1). Most AEs were graded as mild (6), followed by severe (2), and moderate (1); the majority were managed conservatively. On univariable comparison, risk of AE was higher when using a 20 × 10 mm LAMS and the absence of through-the-LAMS plastic stent(s). Conditional logistic regression of matched case-control patients did not show any association between potential predicting factors and occurrence of AEs. Conclusions Our study demonstrated that mainly in patients with Child-Pugh scores A and B cirrhosis and despite the presence of mild-to-moderate ascites in over half of cases, the majority of AEs were mild and could be managed conservatively. Further studies are warranted to verify the safety of LAMS in cirrhotic patients.
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Affiliation(s)
- Faisal Nimri
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, United States
| | - Yervant Ichkhanian
- Department of Internal Medicine, Henry Ford Hospital, Detroit, United States
| | - Brianna Shinn
- Division of Gastroenterology and Hepatology, Thomas Jefferson Hospital, Wayne, United States
| | - Thomas E. Kowalski
- Division of Gastroenterology and Hepatology, Thomas Jefferson Hospital, Wayne, United States
| | - David E. Loren
- Division of Gastroenterology and Hepatology, Thomas Jefferson Hospital, Wayne, United States
| | - Anand Kumar
- Division of Gastroenterology and Hepatology, Thomas Jefferson Hospital, Wayne, United States
| | - Alexander Schlachterman
- Division of Gastroenterology and Hepatology, Thomas Jefferson Hospital, Wayne, United States
| | - Alina Tantau
- Division of Gastroenterology and Hepatology Medical Center, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Martha Arevalo
- Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Ashraf Taha
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, United States
| | - Omar Shamaa
- Department of Internal Medicine, Henry Ford Hospital, Detroit, United States
| | | | - Mouen A. Khashab
- Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, United States
| | - Stephen Simmer
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, United States
| | - Sumit Singla
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, United States
| | - Cyrus Piraka
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, United States
| | - Tobias E. Zuchelli
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, United States
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Efremova I, Maslennikov R, Poluektova E, Medvedev O, Kudryavtseva A, Krasnov G, Fedorova M, Romanikhin F, Zharkova M, Zolnikova O, Bagieva G, Ivashkin V. Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis. World J Hepatol 2024; 16:822-831. [PMID: 38818295 PMCID: PMC11135270 DOI: 10.4254/wjh.v16.i5.822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 02/12/2024] [Accepted: 04/12/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND The gut-liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate. AIM To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection. METHODS This study included 48 patients with Child-Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii) for 3 months. RESULTS Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child-Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child-Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child-Pugh scores (P = 0.046), as well as a higher level of the Child-Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis. CONCLUSION The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut-liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Scientific, Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Moscow 119435, Russia.
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Scientific, Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Moscow 119435, Russia
| | - Oleg Medvedev
- Department of Pharmacology, Lomonosov Moscow State University, Moscow 119192, Russia
| | - Anna Kudryavtseva
- Department of Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - George Krasnov
- Department of Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - Maria Fedorova
- Department of Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - Filipp Romanikhin
- Department of Pharmacology, Lomonosov Moscow State University, Moscow 119192, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Oxana Zolnikova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Gyunay Bagieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Scientific, Scientific Community for the Promotion of the Clinical Study of the Human Microbiome, Moscow 119435, Russia
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Singh KA, Anandan S, Sharma A, Kumar SE, Solaimalai D, Veeraraghavan B, Goel A, Eapen CE, Zachariah UG. High Mortality With Non-O1/Non-O139 Vibrio cholera Bacteraemia in Patients With Cirrhosis. J Clin Exp Hepatol 2024; 14:101346. [PMID: 38371607 PMCID: PMC10869911 DOI: 10.1016/j.jceh.2024.101346] [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: 06/27/2023] [Accepted: 01/12/2024] [Indexed: 02/20/2024] Open
Abstract
Background Data on non-O1/non-O139 Vibrio cholera (NOVC) infection in liver disease is limited. We studied the clinical features and outcome of patients with cirrhosis with non-NOVC bacteraemia and/or spontaneous bacterial peritonitis (SBP) when compared to non-extended spectrum beta lactamase (non-ESBL) Escherichia coli (E. coli). Methods Hospital information system of patients with cirrhosis admitted with bacteraemia and/or SBP from 2010 to 2020 was searched to include patients with NOVC infection. Non-ESBL E. coli bacteraemia/bacterascites were chosen as a comparator group, matched for the date of admission within 5 days of index case. Propensity score matching (PSM) was done for patient's age and Child score to compare outcome at discharge between NOVC-infected and E. coli-infected cirrhotic patients. Results There were 2545 patients admitted with bacteraemia and/or SBP during the study period; 29 had NOVC isolated (M:F = 23:6; age: 39, 18-54 years; median, range; model for end-stage liver disease [MELD] score: 25, 12-38; Child score: 11, 10-12.5) from either blood (26), ascites (3), or both (8). Of these, 26 isolates were pan-sensitive to antibiotic sensitivity tests. Fifty-three patients with non-ESBL E. coli were isolated (M: F = 43:10; age: 48; 18-69 years; MELD score: 25, 20-32; Child score:12,11-13) from blood (31), ascites (17), or both (5) within the selected time frame. Of these, 48 isolates were sensitive to the empirical antibiotics initiated.After PSM, in comparison with 29 non-ESBL E. coli patients (age: 41, 18-55 years; MELD score: 24, 19-31; Child score: 12, 11-13), NOVC patients had higher incidence of circulatory failure at admission (14 [49 %] vs 4 [13 %]; P: 0.01) and significantly higher in-hospital mortality (15 [52 %] vs 6 [20 %];P: 0.028]. Conclusions Bacteraemia due to non-O1/non-O139 strains of V. cholera, is an uncommon cause of bacteraemia or bacterascites in patients with cirrhosis and is associated with high incidence of circulatory failure and significant mortality.
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Affiliation(s)
- Kunwar A. Singh
- Departments of Hepatology, Christian Medical College, Vellore, India
| | - Shalini Anandan
- Departments of Microbiology, Christian Medical College, Vellore, India
| | - Anand Sharma
- Departments of Hepatology, Christian Medical College, Vellore, India
| | - Santhosh E. Kumar
- Departments of Hepatology, Christian Medical College, Vellore, India
| | | | | | - Ashish Goel
- Departments of Hepatology, Christian Medical College, Vellore, India
| | | | - Uday G. Zachariah
- Departments of Hepatology, Christian Medical College, Vellore, India
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Ripoll C, Greinert R, Reuken P, Reichert MC, Weber SN, Hupfer Y, Staltner R, Meier Clinien M, Lammert F, Bruns T, Zipprich A. Influence of NOD2 risk variants on hepatic encephalopathy and association with inflammation, bacterial translocation and immune activation. Liver Int 2023; 43:1793-1802. [PMID: 37249050 DOI: 10.1111/liv.15627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/21/2023] [Accepted: 05/18/2023] [Indexed: 05/31/2023]
Abstract
BACKGROUND Nucleotide-binding oligomerization domain containing 2 (NOD2) risk variants lead to impaired mucosal barrier function, increased bacterial translocation (BT), and systemic inflammation. AIM To evaluate the association between the presence of NOD2 risk variants, BT, inflammation, and hepatic encephalopathy (HE). PATIENTS AND METHODS This prospective multicenter study included patients with cirrhosis and testing for NOD2 risk variants (p.R702W, p.G908R, c.3020insC, N289S, and c.-958T>C). Patients were evaluated for covert (C) and overt (O) HE. Markers of systemic inflammation (leukocytes, CRP, IL-6, LBP) and immune activation (soluble CD14) as well as bacterial endotoxin (hTRL4 activation) were determined in serum. RESULTS Overall, 172 patients (70% men; median age 60 [IQR 54-66] years; MELD 12 [IQR 9-16]; 72% ascites) were included, of whom 53 (31%) carried a NOD2 risk variant. In this cohort, 11% presented with OHE and 27% and CHE. Presence and severity of HE and surrogates of inflammation, BT, and immune activation did not differ between patients with and without a NOD2 risk variant, also not after adjustment for MELD. HE was associated with increased ammonia and systemic inflammation, as indicated by elevated CRP (w/o HE: 7.2 [2.7-16.7]; with HE 12.6 [4.5-29.7] mg/dL; p < 0.001) and elevated soluble CD14 (w/o HE 2592 [2275-3033]; with HE 2755 [2410-3456] ng/mL; p = 0.025). CONCLUSIONS The presence of NOD2 risk variants in patients with cirrhosis is not associated with HE and has no marked impact on inflammation, BT, or immune activation. In contrast, the presence of HE was linked to ammonia, the acute phase response, and myeloid cell activation.
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Affiliation(s)
- Cristina Ripoll
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Robin Greinert
- Internal Medicine I, Martin Luther University Halle-Wittenberg, Halle, Germany
| | - Philipp Reuken
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | | | - Susanne N Weber
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Yvonne Hupfer
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Raphaela Staltner
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Magdalena Meier Clinien
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | | | - Tony Bruns
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
- Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Alexander Zipprich
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
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Hamilton J, Milenkovski N, Martin K, Tully E, Peng C, Hayes I. Rare causes of abdominal pain: a primer for the admitting general surgeon. ANZ J Surg 2023; 93:1773-1779. [PMID: 37350226 DOI: 10.1111/ans.18570] [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] [Received: 12/18/2022] [Revised: 05/11/2023] [Accepted: 06/07/2023] [Indexed: 06/24/2023]
Abstract
The broad uptake of the acute surgical unit (ASU) model of surgical care in Australia has resulted in general surgeons becoming increasingly involved in the management of patients with acute abdominal pain (AAP), some of whom will be labelled as having non-specific abdominal pain (NSAP) (Kinnear N, Jolly S, Herath M, et al. The acute surgical unit: An updated systematic review and meta-analysis. review. Int. J. Surg. 2021;94:106109; Lehane CW, Jootun RN, Bennett M, Wong S, Truskett P. Does an acute care surgical model improve the management and outcome of acute cholecystitis? ANZ J. Surg. 2010;80:438-42). NSAP patients lack a clear diagnosis of surgical pathology based on standard clinical, laboratory and imaging work-up, although they may require ASU admission for pain control and assessment. This article provides a review of uncommon conditions, presenting as AAP, that could possibly be mis-labelled as NSAP, with a focus on aspects of the presentation that may aid diagnosis and management including specific demographic features, clinical findings, key investigations and initial treatment priorities for ASU clinicians. Ultimately, most of the conditions discussed will not require surgical intervention, however, they require a diagnosis to be made and initial treatment planning before on-referral to the appropriate specialty. For the on-call general surgeon, some knowledge of these conditions and an index of suspicion are invaluable for the prompt diagnosis and efficient management of these patients.
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Affiliation(s)
- Jordan Hamilton
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Nicole Milenkovski
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Katherine Martin
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Emma Tully
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Calvin Peng
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Ian Hayes
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
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11
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Badal BD, Silvey S, Dragilev L, O'Leary JG, Morgan TR, Cheung R, Patel A, Rogal S, Patton H, Nobbe A, Jakab SS, Liu J, Patel N, Bajaj JS. Primary prophylaxis for spontaneous bacterial peritonitis is linked to antibiotic resistance in the Veterans Health Administration. Hepatology 2023; 77:2030-2040. [PMID: 36645215 DOI: 10.1097/hep.0000000000000184] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/18/2022] [Indexed: 01/17/2023]
Abstract
Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit. AIM Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli , K. pneumoniae , and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p <0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p <0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay. E. coli ciprofloxacin sensitivity rates were 50%-87% and 43%-92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%-100% and 72%-100% for TMP-SMX. CONCLUSION Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.
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Affiliation(s)
- Bryan D Badal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Health Care System, Richmond, Virginia, USA
| | - Scott Silvey
- Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Lyuba Dragilev
- Department of Pharmacy, Captain James A Lovell Federal Health Care Center, North Chicago, Illinois, USA
| | | | - Timothy R Morgan
- Gastroenterology Service, VA Long Beach Health Care System, Long Beach, California, USA
| | - Ramsey Cheung
- VA Palo Alto Health Care System, Palo Alto, California, USA
| | - Arpan Patel
- Division of Digestive Diseases, David Geffen School of Medicine at University of California, Los Angeles, California, USA
| | - Shari Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania, USA
- Departments of Medicine and Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Heather Patton
- Gastroenterology Section, VA San Diego Health Care System, San Diego, California, USA
| | - Anna Nobbe
- Digestive Diseases Section, Cincinnati VA Medical Center, Cincinnati, Ohio, USA
| | - Sofia S Jakab
- Section of Digestive Diseases, VA Connecticut Health Care System, West Haven, Connecticut, USA
| | - Jinze Liu
- Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Nilang Patel
- Division of Nephrology, Virginia Commonwealth University and Central Virginia Veterans Health Care System, Richmond, Virginia, USA
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Health Care System, Richmond, Virginia, USA
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12
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Periplanetaamericana Extract Pretreatment Alleviates Oxidative Stress and Inflammation and Increases the Abundance of Gut Akkermansia muciniphila in Diquat-Induced Mice. Antioxidants (Basel) 2022; 11:antiox11091806. [PMID: 36139880 PMCID: PMC9495987 DOI: 10.3390/antiox11091806] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/08/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022] Open
Abstract
Studies have shown that Periplaneta americana extract (PAE) has good therapeutic effects in inflammatory disorders such as ulcerative colitis, alcoholic hepatitis, and gastric ulcers. However, whether or not PAE has good pre-protective effects has not been widely and deeply studied. In this study, we investigated the effects of PAE pretreatment for 7 days on oxidative stress and inflammation triggered by oxidative stress by using diquat-induced C57BL/6 mice as an oxidative stress model. The results showed that PAE pretreatment could significantly reduce oxidative stress in the intestine and liver by reducing the production of MDA, and improved antioxidant systems (SOD, CAT, GSH, and T-AOC). By primarily activating the anti-inflammatory cytokine (IL-10) mediated JAK1/STAT3 signaling pathway, PAE also effectively reduced oxidative stress-induced liver inflammation while also reducing liver damage, as evidenced by the reductions in serum AST and ALT. PAE pretreatment also had a significant effect on maintaining the intestinal barrier function, which was manifested by inhibiting a decrease in the expression of tight junction proteins (ZO-1 and occludin), and reducing the increased intestinal permeability (serum DAO and D-Lac) caused by diquat. The 16S rRNA sequencing analysis revealed that diquat decreased the gut microbiota diversity index and increased the abundance of pathogenic bacteria (e.g., Allobaculum, Providencia and Escherichia-Shigella), while PAE pretreatment responded to diquat-induced damage by greatly increasing the abundance of Akkermansia muciniphila. These findings elucidate potential pre-protective mechanisms of PAE in alleviating oxidative stress and inflammation, while providing a direction for the treatment of metabolic diseases by utilizing PAE to enhance the abundance of gut A. muciniphila.
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13
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Huang CH, Lee CH, Chang C. Spontaneous Bacterial Peritonitis in Decompensated Liver Cirrhosis—A Literature Review. LIVERS 2022; 2:214-232. [DOI: 10.3390/livers2030018] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/17/2025] Open
Abstract
Background: Spontaneous bacterial peritonitis (SBP) is defined as a bacterial infection of the ascitic fluid without a surgically treatable intra-abdominal infection source. SBP is a common, severe complication in cirrhosis patients with ascites, and if left untreated, in-hospital mortality may exceed 90%. However, the incidence of SBP has been lowered to approx. 20% through early diagnosis and antibiotic therapy. Clinical awareness, prompt diagnosis, and immediate treatment are advised when caring for these patients to reduce mortality and morbidity. Aim: To discuss important issues comprising types of SBP, pathogenesis, bacteriology, including the emergence of multidrug-resistant (MDR) microorganisms, prompt diagnosis, risk factors, prognosis, treatment strategies, as well as recurrence prevention through antibiotic prophylaxis until liver transplantation and future trends in treating and preventing SBP in detail. Methods: This article is a literature review and appraisal of guidelines, randomized controlled trials, meta-analyses, and other review articles found on PubMed from between 1977 and 2022. Results: There are three types of SBP. Bacterial translocation from GI tract is the most common source of SBP. Therefore, two thirds of SBP cases were caused by Gram-negative bacilli, of which Escherichia coli is the most frequently isolated pathogen. However, a trend of Gram-positive cocci associated SBP has been demonstrated in recent years, possibly related to more invasive procedures and long-term quinolone prophylaxis. A diagnostic paracentesis should be performed in all patients with cirrhosis and ascites who require emergency room care or hospitalization, who demonstrate or report consistent signs/symptoms in order to confirm evidence of SBP. Distinguishing SBP from secondary bacterial peritonitis is essential because the conditions require different therapeutic strategies. The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Albumin supplementation, especially in patients with renal impairment, is also beneficial. Selective intestinal decontamination is associated with a reduced risk of bacterial infection and mortality in high-risk group. Conclusions: The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Since the one-year overall mortality rates for SBP range from 53.9 to 78%, liver transplantation should be seriously considered for SBP survivors who are good candidates for transplantation. Further development of non-antibiotic strategies based on pathogenic mechanisms are also urgently needed.
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Affiliation(s)
- Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 333, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan
| | - Chen-Hung Lee
- College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Taoyuan 333, Taiwan
| | - Ching Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 333, Taiwan
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14
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Prasad R, Patton MJ, Floyd JL, Fortmann S, DuPont M, Harbour A, Wright J, Lamendella R, Stevens BR, Oudit GY, Grant MB. Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis. Int J Mol Sci 2022; 23:9141. [PMID: 36012406 PMCID: PMC9409329 DOI: 10.3390/ijms23169141] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/10/2022] [Accepted: 08/12/2022] [Indexed: 12/16/2022] Open
Abstract
The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n = 146) and healthy individuals (n = 47) were collected during hospitalization and routine visits. Plasma microbiome was analyzed using 16S rRNA sequencing and gut permeability markers including fatty acid binding protein 2 (FABP2), peptidoglycan (PGN), and lipopolysaccharide (LPS) in both patient cohorts. Plasma samples of both cohorts contained predominately Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria. COVID-19 subjects exhibit significant dysbiosis (p = 0.001) of the plasma microbiome with increased abundance of Actinobacteria spp. (p = 0.0332), decreased abundance of Bacteroides spp. (p = 0.0003), and an increased Firmicutes:Bacteroidetes ratio (p = 0.0003) compared to healthy subjects. The concentration of the plasma gut permeability marker FABP2 (p = 0.0013) and the gut microbial antigens PGN (p < 0.0001) and LPS (p = 0.0049) were significantly elevated in COVID-19 patients compared to healthy subjects. These findings support the notion that the intestine may represent a source for bacteremia and contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.
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Affiliation(s)
- Ram Prasad
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Michael John Patton
- Hugh Kaul Precision Medicine Institute, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Jason Levi. Floyd
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Seth Fortmann
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Mariana DuPont
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Angela Harbour
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | | | | | - Bruce R. Stevens
- Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USA
| | - Gavin Y. Oudit
- Division of Cardiology, Department of Medicine, University of Alberta, Mazankowski Alberta Heart Institute, Edmonton, AB T6G 2B7, Canada
| | - Maria B. Grant
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
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15
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Mani I, Alexopoulos T, Hadziyannis E, Tsiriga A, Vourli G, Alexopoulou A. An exploratory study of ascitic fluid lactate as prognostic factor of mortality in cirrhotic patients with spontaneous bacterial peritonitis. Eur J Gastroenterol Hepatol 2021; 33:e970-e977. [PMID: 34907985 DOI: 10.1097/meg.0000000000002332] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The diagnostic value of ascitic fluid lactate (AF lactate) was previously evaluated in spontaneous bacterial peritonitis (SBP) but its prognostic value was not established. AIM To assess the prognostic value of AF lactate in SBP. METHODS We prospectively studied 63 consecutive patients with SBP. Fifty patients with acute-on-chronic liver failure (ACLF) or acute decompensation (AD) (ACLF/AD group) without SBP and 30 with stable decompensated cirrhosis (DC) were included as controls. In SBP, mortality was recorded at 30, 90 and 180 days. RESULTS Arterial and AF lactate were significantly higher in SBP compared to other groups. Analyzing the SBP group alone, AF lactate accurately differentiated survivors from nonsurvivors in all time points. The prognostic performance of AF lactate was improved over time, with the area under the receiver operating characteristic computed at 0.894, 0.927 and 0.934 at 30, 90 and 180 days, respectively. The cutoff level of 2 mmol/L was associated with 100, 100 and 94.7% sensitivity, 57.9, 73.3 and 80% specificity, 61, 80.5 and 87.8% positive predictive value and 100, 100 and 90.9% negative predictive value, respectively. Arterial lactate, neutrophil-to-lymphocyte ratio (NLR) and Model for End-Stage Liver Disease (MELD) score predicted outcomes less accurately than AF lactate. Patients with AF lactate >2 mmol/L had a worse prognosis compared to patients with ≤2 mmol/L (log-rank P < 0.001). No case with AF lactate ≤2 mmol/L died within 90 days postSBP diagnosis. In Cox multivariate analysis at all time points, only AF lactate and NLR were independent predictors of mortality. CONCLUSION An AF lactate level of 2 mmol/L has a high ability to differentiate survivors from nonsurvivors in the first 180 days postSBP. Its prognostic value outperformed arterial-lactate, NLR and MELD.
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Affiliation(s)
- Iliana Mani
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital, Athens
| | - Theodoros Alexopoulos
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital, Athens
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital, Athens
| | | | - Georgia Vourli
- Department of Hygiene, Epidemiology & Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Alexopoulou
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital, Athens
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16
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Hepatorenal syndrome: pathophysiology and evidence-based management update. ROMANIAN JOURNAL OF INTERNAL MEDICINE 2021; 59:227-261. [DOI: 10.2478/rjim-2021-0006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 11/20/2022] Open
Abstract
Abstract
Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.
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17
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Birg A, Lin HC, Kanagy N. Portal Venous Flow Is Increased by Jejunal but Not Colonic Hydrogen Sulfide in a Nitric Oxide-Dependent Fashion in Rats. Dig Dis Sci 2021; 66:2661-2668. [PMID: 32918175 PMCID: PMC8022870 DOI: 10.1007/s10620-020-06597-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 08/29/2020] [Indexed: 12/09/2022]
Abstract
Hydrogen sulfide (H2S) is a recently discerned endogenous signaling molecule that modulates the vascular system. Endogenous hydrogen sulfide has been shown to dilate both the mesenteric and portal vasculature. Gut microbiome, via sulfur reducing bacteria, is another source of H2S production within the gut lumen; this source of H2S is primarily produced and detoxified in the colon under physiologic conditions. Nitric oxide (NO), a major endogenous vasodilator in the portal circulation, participates in H2S-induced vasodilation in some vascular beds. We hypothesize that jejunal but not colonic H2S increases portal vein flow in a NO-dependent fashion. To evaluate the effects of luminal H2S, venous blood flow, portal venous pressure, and systemic venous pressure were measured in rats after administration of either vehicle or an H2S donor (NaHS) into the jejunum or the colon. We found that portal venous pressure and systemic pressure did not change and were similar between the three study groups. However, portal venous blood flow significantly increased following jejunal administration of NaHS but not in response to colonic NaHS or vehicle administration. To test the contribution of NO production to this response, another group of animals was treated with either an NO synthase inhibitor (N-Ω-nitro-L-arginine, L-NNA) or saline prior to jejunal NaHS infusion. After L-NNA pretreatment, NaHS caused a significant fall rather than increase in portal venous flow compared to saline pretreatment. These data demonstrate that H2S within the small intestine significantly increases portal venous blood flow in a NO-dependent fashion.
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Affiliation(s)
- Aleksandr Birg
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MSC10-5550, 1 University of New Mexico, Albuquerque, NM, 87131, USA.
| | - Henry C Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MSC10-5550, 1 University of New Mexico, Albuquerque, NM, 87131, USA
- New Mexico VA Health Care System, Albuquerque, NM, 87108, USA
| | - Nancy Kanagy
- Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, 87131, USA
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18
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Prasad R, Patton MJ, Floyd JL, Vieira CP, Fortmann S, DuPont M, Harbour A, Jeremy CS, Wright J, Lamendella R, Stevens BR, Grant MB. Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2021. [PMID: 33851159 DOI: 10.1101/2021.04.06.438634] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal ( GI ) symptoms. We asked whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n=30) and healthy control (n=16) were collected during hospitalization. Plasma microbiome was analyzed using 16S rRNA sequencing, metatranscriptomic analysis, and gut permeability markers including FABP-2, PGN and LPS in both patient cohorts. Almost 65% (9 out 14) COVID-19 patients showed abnormal presence of gut microbes in their bloodstream. Plasma samples contained predominately Proteobacteria, Firmicutes, and Actinobacteria . The abundance of gram-negative bacteria ( Acinetobacter, Nitrospirillum, Cupriavidus, Pseudomonas, Aquabacterium, Burkholderia, Caballeronia, Parabhurkholderia, Bravibacterium, and Sphingomonas ) was higher than the gram-positive bacteria ( Staphylococcus and Lactobacillus ) in COVID-19 subjects. The levels of plasma gut permeability markers FABP2 (1282±199.6 vs 838.1±91.33; p=0.0757), PGN (34.64±3.178 vs 17.53±2.12; p<0.0001), and LPS (405.5±48.37 vs 249.6±17.06; p=0.0049) were higher in COVID-19 patients compared to healthy subjects. These findings support that the intestine may represent a source for bacteremia and may contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.
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19
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Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies. Biosci Rep 2021; 40:224145. [PMID: 32406491 PMCID: PMC7276520 DOI: 10.1042/bsr20193890] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 05/12/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
Background: Proton pump inhibitor (PPI) is commonly used in patients with cirrhosis. However, some studies demonstrated that PPI use was associated with adverse outcome in patients with cirrhosis. We aimed to perform a meta-analysis of cohort studies to evaluate the association between PPI use and mortality in cirrhotic patients. Methods: Relevant studies were obtained via search of PubMed and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses were performed to evaluate the source of heterogeneity. Results: Overall, 21 cohort studies with 20,899 patients and 7457 death events were included. The pooled results with a randomized-effect model showed that PPI use was associated with significantly increased risk of mortality in patients with cirrhosis (adjusted relative risk [RR] = RR: 1.39, P<0.001) with considerable heterogeneity (I2=73%). Subgroup analyses showed that characteristics such as patient ethnicity, sample size, definition of PPI use, and complications of patients did not affect the association. However, the association between PPI use and mortality was independent of study characteristics including patient ethnicity, sample size, complications, definition of PPI use, and follow-up duration. However, the association between PPI use and mortality in cirrhotic patients was significant in retrospective studies (RR: 1.40, P<0.001), but not in prospective studies (RR: 1.34, P=0.33). Conclusions: PPI use may be associated with moderately increased mortality in cirrhotic patients. Although prospective cohort studies are needed to validate our findings, PPI should only prescribed to cirrhotic patients with indications for the treatment.
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20
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Fan Y, Li Y, Chu Y, Liu J, Cui L, Zhang D. Toll-Like Receptors Recognize Intestinal Microbes in Liver Cirrhosis. Front Immunol 2021; 12:608498. [PMID: 33708204 PMCID: PMC7940369 DOI: 10.3389/fimmu.2021.608498] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 01/11/2021] [Indexed: 12/15/2022] Open
Abstract
Liver cirrhosis is one major cause of mortality in the clinic, and treatment of this disease is an arduous task. The scenario will be even getting worse with increasing alcohol consumption and obesity in the current lifestyle. To date, we have no medicines to cure cirrhosis. Although many etiologies are associated with cirrhosis, abnormal intestinal microbe flora (termed dysbiosis) is a common feature in cirrhosis regardless of the causes. Toll-like receptors (TLRs), one evolutional conserved family of pattern recognition receptors in the innate immune systems, play a central role in maintaining the homeostasis of intestinal microbiota and inducing immune responses by recognizing both commensal and pathogenic microbes. Remarkably, recent studies found that correction of intestinal flora imbalance could change the progress of liver cirrhosis. Therefore, correction of intestinal dysbiosis and targeting TLRs can provide novel and promising strategies in the treatment of liver cirrhosis. Here we summarize the recent advances in the related topics. Investigating the relationship among innate immunity TLRs, intestinal flora disorders, and liver cirrhosis and exploring the underlying regulatory mechanisms will assuredly have a bright future for both basic and clinical research.
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Affiliation(s)
- Yujing Fan
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunpeng Li
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yanjie Chu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jing Liu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lin Cui
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dekai Zhang
- Center for Infectious and Inflammatory Diseases, Texas A&M University, Houston, TX, United States
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21
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Abstract
Biliary atresia (BA) is a fibro-obliterative condition of the biliary tree, presenting in infancy. The bilioenteric conduit formed at Kasai portoenterostomy (KPE), achieves restoration of bile flow in approximately 60% of infants. Even if the operation is successful, cirrhosis and its associated complications are, however, common. BA remains the leading cause for liver transplantation (LT) in children. Antibiotic, choleretic, and steroid therapy post-KPE have not convincingly reduced LT rates. Advances in molecular technology have enabled characterisation of the encoded genes of the gut microbiota (gut microbiome). The gut microbiome plays an important role in host metabolism, nutrition, and immune function, with alterations in its diversity and/or composition, known as dysbiosis, being described in disease states, including liver disease. Liver-gut microbiome exploration in adulthood largely focuses on nonalcoholic liver disease, cirrhosis (mainly alcohol- or viral-based aetiology) and cholestatic liver diseases (eg, primary sclerosing cholangitis), with microbial signatures correlating to disease severity. Investigation of the gut microbiota in BA had been limited to culture-based methodology, but molecular studies are emerging, and although in their infancy, highlight a potential pathogenic role for Enterobacteriaceae and Streptococcus, and a potential beneficial role for Bifidobacteria. Bacterial translocation, and the production of gut microbiome-derived metabolites, are key host-microbiome-mechanistic pathways in liver disease pathogenesis. Microbiome-targeted therapeutics for liver disease are in development, with faecal microbiota transplantation showing promise in cirrhosis. Could the gut microbiome be a novel modifiable risk factor in BA, reducing the need for LT?
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22
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Carrion AF, Martin P. Keeping Patients with End-Stage Liver Disease Alive While Awaiting Transplant: Management of Complications of Portal Hypertension. Clin Liver Dis 2021; 25:103-120. [PMID: 33978573 DOI: 10.1016/j.cld.2020.08.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Complications of portal hypertension such as gastroesophageal variceal hemorrhage, ascites, and spontaneous bacterial peritonitis, as well as pulmonary complications, are often responsible for diminished quality of life, excess morbidity and mortality, increased health care resource use and expenditure, and dropout from the liver transplant (LT) waiting list. Therefore, the care of LT candidates on the waiting list must be centered on anticipation and prompt intervention for these complications.
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Affiliation(s)
- Andres F Carrion
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, Office 1189, Miami, FL 33136, USA.
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 Northwest 14th #1115, Miami, FL 33136, USA
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Sasso R, Rockey DC. Non-selective beta-blocker use in cirrhotic patients is associated with a reduced likelihood of hospitalisation for infection. Aliment Pharmacol Ther 2021; 53:418-425. [PMID: 33314175 DOI: 10.1111/apt.16156] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/01/2020] [Accepted: 10/21/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Non-selective beta-blockers (NSBBs) reduce enteric bacterial translocation rates and the frequency of spontaneous bacterial peritonitis (SBP) in animal models. AIM To evaluate the effect of NSBBs on infection-related admissions. METHODS We performed a case-control study of cirrhotic patients' first in-patient admission between 1 January 2011 and 31 December 2016. We examined NSBB use and the development of infection. We performed a propensity score-matched analysis in those with NSBB use vs no use and calculated odds ratios on this matched cohort to determine the odds of outcomes based on NSBB use. RESULTS We identified 2165 cirrhotic patients who met our inclusion criteria. Most patients were Caucasian (69%), male (62%). Admission Model for End stage Liver Disease (MELD) score, Charlson comorbidity index and Child-Pugh score were 12 ± 1, 4 ± 2, and 8 ± 2, respectively. Ascites was the most common complication of portal hypertension (44%); 23% of patients used NSBBs at home. Infections occurred in 33% of admissions. In the propensity score-matched cohort, the use of NSBBs at home was associated with lower overall, and specific, infections. The effect was similar in patients taking NSBBs for either primary or secondary oesophageal variceal prophylaxis and for those on NSBBs for other indications. Patients not on NSBBs had higher odds of infection (OR = 2.5), SBP (OR = 4.0), and bacteraemia (OR = 6.0). CONCLUSION Home use of NSBBs by patients with cirrhosis was associated with fewer infection-related admissions. The data suggest that NSBBs in this group of patients reduce the risk of infection.
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Affiliation(s)
- Roula Sasso
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA
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Skinner C, Thompson AJ, Thursz MR, Marchesi JR, Vergis N. Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention. Therap Adv Gastroenterol 2020; 13:1756284820942616. [PMID: 33149761 PMCID: PMC7580143 DOI: 10.1177/1756284820942616] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/25/2020] [Indexed: 02/04/2023] Open
Abstract
Increased bacterial translocation (BT) across the gut barrier due to greater intestinal permeability (IP) is seen across a range of conditions, including alcohol-related liver disease (ArLD). The phenomenon of BT may contribute to both the pathogenesis and the development of complications in ArLD. There are a number of methods available to assess IP and in this review we look at their various advantages and limitations. The knowledge around BT and IP in ArLD is also reviewed, as well as the therapeutic strategies currently in use and in development.
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Affiliation(s)
- Charlotte Skinner
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
| | - Alex J. Thompson
- Department of Surgery & Cancer, St. Mary’s Hospital Campus, Imperial College London, London, UK
| | - Mark R. Thursz
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
| | - Julian R. Marchesi
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
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Chang CF, Chen TL, Chen TW, Yang WC, Lin CC. Recurrent Dialysis-Associated Aeromonas hydrophila Peritonitis: Reports of Two Cases and Review of the Literature. Perit Dial Int 2020. [DOI: 10.1177/089686080502500516] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Chao-Fu Chang
- Division of Nephrology, Yang-Ming University Taipei, Taiwan
- Department of Medicine Taipei Veterans General Hospital School of Medicine, Yang-Ming University Taipei, Taiwan
| | - Te-Li Chen
- Division of Infectious Diseases, Yang-Ming University Taipei, Taiwan
- Department of Medicine Taipei Veterans General Hospital School of Medicine, Yang-Ming University Taipei, Taiwan
| | - Tzen-Wen Chen
- Division of Nephrology, Yang-Ming University Taipei, Taiwan
- Department of Medicine Taipei Veterans General Hospital School of Medicine, Yang-Ming University Taipei, Taiwan
| | - Wu-Chang Yang
- Division of Nephrology, Yang-Ming University Taipei, Taiwan
- Department of Medicine Taipei Veterans General Hospital School of Medicine, Yang-Ming University Taipei, Taiwan
| | - Chih-Ching Lin
- Division of Nephrology, Yang-Ming University Taipei, Taiwan
- Department of Medicine Taipei Veterans General Hospital School of Medicine, Yang-Ming University Taipei, Taiwan
- Institute of Clinical Medicine National Yang-Ming University Taipei, Taiwan
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26
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Miyashita H, Okamoto K, Kobayashi T, Wakabayashi Y, Kitaura S, Ikeuchi K, Ishigaki K, Nakai Y, Okugawa S, Koike K, Moriya K. Bacterial peritonitis in a patient with malignant ascites caused by pancreatic carcinoma: Case report and review of literature. J Infect Chemother 2019; 25:473-476. [PMID: 30738726 DOI: 10.1016/j.jiac.2019.01.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 01/07/2019] [Accepted: 01/20/2019] [Indexed: 11/21/2022]
Abstract
Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.
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Affiliation(s)
- Hirotaka Miyashita
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Koh Okamoto
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan.
| | - Tatsuya Kobayashi
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | | | - Satoshi Kitaura
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Kazuhiko Ikeuchi
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Kazunaga Ishigaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yosuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shu Okugawa
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kyoji Moriya
- Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan
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27
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Menshawy A, Mattar O, Barssoum K, AboEl-Naga AM, Salim HM, Mohamed AMF, Elgebaly A, Abd-Elsalam S. Safety and Efficacy of Rifaximin in Prophylaxis of Spontaneous Bacterial Peritonitis: A Systematic Review and Meta-analysis. Curr Drug Targets 2019; 20:380-387. [PMID: 30246636 DOI: 10.2174/1389450119666180924145156] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 09/12/2018] [Accepted: 09/17/2018] [Indexed: 01/22/2023]
Abstract
AIM The role of rifaximin in the prevention of Spontaneous Bacterial Peritonitis (SBP) is not well studied. The aim of this meta-analysis was to evaluate the role of rifaximin in the prevention of SBP. METHODS A computerized literature search for relevant clinical trials was conducted during August 2017. Data on Frequency of SBP, the success rate of prevention of SBP, mortality rate, hepatorenal syndrome, septic shock, hepatic encephalopathy, and GIT bleeding were extracted and pooled as Risk Ratio (RR) with their 95% Confidence Interval (CI) in a meta-analysis model. Heterogeneity was assessed by Chi-square test. RESULTS Six studies involving 973 patients were included in the final analysis. The pooled effect estimate showed that the rifaximin plus norfloxacin group had less incidence of SBP (RR 0.58, 95% CI[0.37, 0.92], P=0.02) and hepatic encephalopathy (RR 0.38, 95% CI[0.17, 0.84], P=0.02) than the norfloxacin-based regimen group. No significant difference between rifaximin and norfloxacin in terms of frequency of SBP and success rate of primary prevention of SBP (RR 0.49, 95% CI [0.24, 1.01], P=0.05; RR1.21, 95% CI [0.95, 1.55], P=0.13, respectively). CONCLUSION Based on our analysis, Rifaximin is a promising drug and appears to be a good alternative to norfloxacin in the prevention of SBP.
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Affiliation(s)
- Amr Menshawy
- Medical Research Education and Practice Association (MREP), Cairo, Egypt
- Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Omar Mattar
- Medical Research Education and Practice Association (MREP), Cairo, Egypt
- Kasr Al-Ainy School of Medicine, Cairo University, Egypt
| | - Kirolos Barssoum
- Medical Research Education and Practice Association (MREP), Cairo, Egypt
- Department of medicine, Rochester general hospital, Rochester, NY, 14621, United States
| | - Ammar M AboEl-Naga
- Medical Research Education and Practice Association (MREP), Cairo, Egypt
- Oberlin College, Lorain, OH, 44074, United States
| | - Haitham Mohamed Salim
- Medical Research Education and Practice Association (MREP), Cairo, Egypt
- Faculty of Medicine, Ain Shams University, Egypt
| | - Ahmed Mesbah Fahmy Mohamed
- Medical Research Education and Practice Association (MREP), Cairo, Egypt
- Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ahmed Elgebaly
- Medical Research Education and Practice Association (MREP), Cairo, Egypt
- Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Sherief Abd-Elsalam
- Department of Tropical Medicine & Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
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28
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Single versus double experimental bile duct ligation model for inducing bacterial translocation. Am J Surg 2018; 218:380-387. [PMID: 30470552 DOI: 10.1016/j.amjsurg.2018.09.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 09/10/2018] [Accepted: 09/18/2018] [Indexed: 11/23/2022]
Abstract
BACKGROUND Double common bile duct ligation plus section in rats is used as a model for bacterial translocation, a phenomenon that has been correlated with the degree of liver damage. This study analyzes whether a simpler variant of the technique is also a valid model to study bacterial translocation. METHODS Fifty-six male Sprague Dawley rats underwent one of three surgical interventions: a) proximal double ligation and section of the common bile duct; b) proximal simple ligation of the bile duct; and c) sham operation. Bacterial translocation was measured by cultures of mesenteric lymph nodes, blood, spleen and liver. Stool culture and histological analysis of liver damage were also performed. RESULTS The incidence of bacterial translocation in SBL and DBDL groups was 23,5% and 25% respectively. Mortality was similar between ligation groups (11.2% versus 10%). Liver cirrhosis developed in the group of double ligation and section (100% of the animals at 4 weeks), while portal hypertension appeared starting at week 3. None of the animals submitted to simple ligation developed liver cirrhosis. CONCLUSIONS Simple bile duct ligation is associated with a similar incidence of bacterial translocation as double ligation, but without cirrhosis or portal hypertension.
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29
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Gómez-Hurtado I, Gimenez P, García I, Zapater P, Francés R, González-Navajas JM, Manichanh C, Ramos JM, Bellot P, Guarner F, Such J. Norfloxacin is more effective than Rifaximin in avoiding bacterial translocation in an animal model of cirrhosis. Liver Int 2018; 38:295-302. [PMID: 28834270 DOI: 10.1111/liv.13551] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 08/09/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Norfloxacin administration is useful in preventing bacterial infections in cirrhosis but associated to the generation of resistant species. Rifaximin is known to reach high concentrations in the intestinal lumen without generating relevant resistance in the intestinal flora. Our aim was to compare the effect of Norfloxacin and Rifaximin on intestinal flora composition, bacterial translocation and survival in cirrhotic rats. METHODS Cirrhosis was induced in rats by oral administration of CCl4 . Animals were divided into three groups: only CCl4 (group I, n = 10); CCl4 + Norfloxacin (group II, n = 17) and CCl4 + Rifaximin (group III, n = 14). Gut bacterial composition, bacterial translocation and cytokine levels were measured. RESULTS Forty-one rats were finally included. The incidence of viable and non-viable bacterial translocation was significantly reduced in animals receiving Norfloxacin; Rifaximin also decreased the incidence of viable and non-viable bacterial translocation, but did not reach statistical significance. Serum TNF-α levels were significantly lower in antibiotic groups. Norfloxacin modified intestinal microbiota, depleting significantly more pathobionts than Rifaximin. CONCLUSION Norfloxacin is more effective than Rifaximin in preventing bacterial translocation in rats with cirrhosis probably because of its capacity to reduce pathobionts from intestinal microbiota.
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Affiliation(s)
- Isabel Gómez-Hurtado
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Paula Gimenez
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Irma García
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
| | - Pedro Zapater
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
- Departamento Farmacología Clínica, UMH, Alicante, Spain
| | - Rubén Francés
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
- Departamento Medicina Clínica, UMH, Alicante, Spain
| | - José M González-Navajas
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Chaysavanh Manichanh
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Departamento Gastroenterología, VHIR, Barcelona, Spain
| | - José M Ramos
- Departamento Medicina Interna, HGUA, Alicante, Spain
| | - Pablo Bellot
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Francisco Guarner
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Departamento Gastroenterología, VHIR, Barcelona, Spain
| | - José Such
- Cleveland Clinic, Digestive Disease institute, Abu Dhabi, UAE
- Lerner School of Medicine, Case Western Reserve University, Cleveland, OH, USA
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30
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Temporary Intra-Operative Portocaval Shunts, Post-Operative Infections, and Mid-Term Survival after Cava-Sparing Liver Transplantation. Surg Infect (Larchmt) 2017; 18:803-809. [DOI: 10.1089/sur.2017.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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31
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Sánchez E, Nieto JC, Vidal S, Santiago A, Martinez X, Sancho FJ, Sancho-Bru P, Mirelis B, Corominola H, Juárez C, Manichanh C, Guarner C, Soriano G. Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 reduces bacterial translocation in rats treated with carbon tetrachloride. Sci Rep 2017; 7:45712. [PMID: 28368023 PMCID: PMC5377325 DOI: 10.1038/srep45712] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 03/06/2017] [Indexed: 02/06/2023] Open
Abstract
Probiotics can prevent pathological bacterial translocation by modulating intestinal microbiota and improving the gut barrier. The aim was to evaluate the effect of a fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 on bacterial translocation in rats with carbon tetrachloride (CCl4)-induced cirrhosis. Sprague-Dawley rats treated with CCl4 were randomized into a probiotic group that received fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 in drinking water or a water group that received water only. Laparotomy was performed one week after ascites development. We evaluated bacterial translocation, intestinal microbiota, the intestinal barrier and cytokines in mesenteric lymph nodes and serum. Bacterial translocation decreased and gut dysbiosis improved in the probiotic group compared to the water group. The ileal β-defensin-1 concentration was higher and ileal malondialdehyde levels were lower in the probiotic group than in water group. There were no differences between groups in serum cytokines but TNF-α levels in mesenteric lymph nodes were lower in the probiotic group than in the water group. Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 decreases bacterial translocation, gut dysbiosis and ileal oxidative damage and increases ileal β-defensin-1 expression in rats treated with CCl4, suggesting an improvement in the intestinal barrier integrity.
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Affiliation(s)
- Elisabet Sánchez
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
| | - Juan C. Nieto
- Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
- Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
- Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Silvia Vidal
- Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
- Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
- Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Alba Santiago
- Digestive System Research Unit, Vall d’Hebron Research Institute, Barcelona, Spain
| | - Xavier Martinez
- Digestive System Research Unit, Vall d’Hebron Research Institute, Barcelona, Spain
| | - Francesc J. Sancho
- Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Pau Sancho-Bru
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Institut Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain
| | - Beatriz Mirelis
- Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
- Department of Microbiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | | | - Candido Juárez
- Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
- Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
- Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Chaysavanh Manichanh
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Digestive System Research Unit, Vall d’Hebron Research Institute, Barcelona, Spain
| | - Carlos Guarner
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
| | - German Soriano
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Institut d´Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
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Noor MT, Manoria P. Immune Dysfunction in Cirrhosis. J Clin Transl Hepatol 2017; 5:50-58. [PMID: 28507927 PMCID: PMC5411357 DOI: 10.14218/jcth.2016.00056] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 01/20/2017] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body. Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity, due to defects in the local immunity of liver as well as in systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic phenomenon, comprised of both increased systemic inflammation and immunodeficiency, and is responsible for 30% mortality. It also plays an important role in acute as well as chronic decompensation. Immune paralysis can accompany it, which is characterized by increase in anti-inflammatory cytokines and suppression of proinflammatory cytokines. There is also presence of increased gut permeability, reduced gut motility and altered gut flora, all of which leads to increased bacterial translocation. This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome, sepsis, multiorgan failure and death. The gut microbiota of cirrhotic patients has more pathogenic microbes than that of non-cirrhotic individuals, and this disturbs the homeostasis and favors gut translocation. Prompt diagnosis and treatment of such infections are necessary for better survival. We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis. Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates.
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Affiliation(s)
- Mohd Talha Noor
- Department of Gastroenterology, Sri Aurobindo Medical College and Post Graduate Institute, Indore, India
- *Correspondence to: Mohd Talha Noor, Department of Gastroenterology, Sri Aurobindo Medical College and Post Graduate Institute, Indore 453 111, India. Tel: +91-7314231751, +91-8305421496, Fax: +91-7314231012, E-mail: ,
| | - Piyush Manoria
- Department of Gastroenterology, Sri Aurobindo Medical College and Post Graduate Institute, Indore, India
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Salerno F, Borzio M, Pedicino C, Simonetti R, Rossini A, Boccia S, Cacciola I, Burroughs AK, Manini MA, La Mura V, Angeli P, Bernardi M, Dalla Gasperina D, Dionigi E, Dibenedetto C, Arghittu M. The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study. Liver Int 2017; 37:71-79. [PMID: 27364035 DOI: 10.1111/liv.13195] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Accepted: 06/17/2016] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation. RESULTS Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone-resistant Gram-negative isolates were 48%, 44% were extended-spectrum beta-lactamase producers and 9% carbapenem resistant. In 83/313 culture-positive infections (27%), multidrug-resistant agents (MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in-hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)-spectrum therapy (P=.038). During a 3-month follow-up, 56/203 culture-positive patients (27.6%) died, 24/63 who have had MDRA-related infections (38%) and 32/140 who have had antibiotic-susceptible infections (22.8%) (P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension-related complications independent predictors of death. CONCLUSIONS Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy.
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Affiliation(s)
- Francesco Salerno
- Medicina Interna, IRCCS San Donato, Università degli studi di Milano, San Donato Milanese, Milano, Italy
| | - Mauro Borzio
- Unità di Gastroenterologia e Microbiologia, Ospedale Predabissi, Melegnano, Italy
| | - Claudia Pedicino
- Unità di Gastroenterologia e Microbiologia, Ospedale Predabissi, Melegnano, Italy
| | - Rosa Simonetti
- Unità di Medicina 2, Ospedali Riuniti, Villa Sofia Cervello, Palermo, Italy
| | - Angelo Rossini
- Unità di Epatologia, Dipartimento di Medicina, Azienda Ospedaliera Spedali Civili, Brescia, Italy
| | - Sergio Boccia
- Unità di Gastroenterologia, Azienda Universitaria Ospedaliera di Ferrara, Ferrara, Italy
| | - Irene Cacciola
- Unità di Epatologia Clinica e Biomolecolare, Policlinico Universitario, Messina, Italy
| | | | - Matteo A Manini
- Gastroenterologia-1, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Vincenzo La Mura
- Medicina Interna, IRCCS San Donato, Università degli studi di Milano, San Donato Milanese, Milano, Italy
| | - Paolo Angeli
- Medicina Clinica e Sperimentale, Policlinico Universitario, Padova, Italy
| | - Mauro Bernardi
- Unità di Semeiotica Medica, Department of Clinical Medicine, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Daniela Dalla Gasperina
- Sezione di Malattie Infettive, Dipartimento di Medicina Clinica, Università dell'Insubria, Varese, Italy
| | - Elena Dionigi
- Unità di Gastroenterologia e Microbiologia, Ospedale Predabissi, Melegnano, Italy
| | - Clara Dibenedetto
- Unità di Gastroenterologia e Microbiologia, Ospedale Predabissi, Melegnano, Italy
| | - Milena Arghittu
- Unità di Gastroenterologia e Microbiologia, Ospedale Predabissi, Melegnano, Italy
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Cole HL, Pennycook S, Hayes PC. The impact of proton pump inhibitor therapy on patients with liver disease. Aliment Pharmacol Ther 2016; 44:1213-1223. [PMID: 27774677 DOI: 10.1111/apt.13827] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Revised: 08/21/2016] [Accepted: 09/21/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Proton pump inhibitor (PPI) therapy has been reported to be an independent mortality risk factor in patients with cirrhosis. AIM To identify the prevalence of PPI prescription, the appropriateness of this therapy and to investigate the relationship between PPI therapy and overall survival in patients with liver disease. METHODS This retrospective cohort study used patient data for 2012 to 2014 collected from the Scottish Liver Transplant Unit and the Hepatology Ward at the New Royal Infirmary of Edinburgh. RESULTS A total of 64% of the 198 patients discharged from the Hepatology ward were prescribed a PPI. Of the 206 patients assessed and listed for orthotopic liver transplant (OLT), 55% were prescribed a PPI. These percentages are significant, particularly as the majority had no recorded appropriate indication for this therapy. For patients listed for OLT, a logistic regression model revealed significant associations between PPI treatment and male sex, higher model of end-stage liver disease (MELD) scores and patient encephalopathy. A multivariate Cox regression model showed that MELD and UK model for end-stage liver disease scores were independent predictors of patient mortality, while alcoholic liver disease aetiology was a protective factor. There was no statistically significant difference in survival between patients who were prescribed a PPI at assessment and those who were not. CONCLUSION Associations between PPI use, encephalopathy and higher MELD scores imply caution should be exercised in prescribing gastric acid suppressants to patients with cirrhosis, particularly in the absence of clear indications.
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Affiliation(s)
- H L Cole
- University of Edinburgh, Edinburgh, UK
| | | | - P C Hayes
- University of Edinburgh, Edinburgh, UK
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Kim T, Hong SI, Park SY, Jung J, Chong YP, Kim SH, Lee SO, Kim YS, Woo JH, Lim YS, Sung H, Kim MN, Choi SH. Clinical Features and Outcomes of Spontaneous Bacterial Peritonitis Caused by Streptococcus pneumoniae: A Matched Case-Control Study. Medicine (Baltimore) 2016; 95:e3796. [PMID: 27258513 PMCID: PMC4900721 DOI: 10.1097/md.0000000000003796] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Streptococcus pneumoniae is a well-known cause of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. However, little information is available regarding clinical characteristics and outcomes of SBP caused by S. pneumoniae. It has been suggested that spontaneous pneumococcal peritonitis (SPP) often spreads hematogenously from concomitant pneumococcal pneumonia, and is associated with a higher rate of mortality.During the period between January 1997 and December 2013, 50 SPP cases were identified. These cases were then age/sex-matched with 100 patients with SBP due to causes other than S. pneumoniae (controls).SPP accounted for 4.3% (50/1172) of all culture-proven SBPs. The baseline Child-Pugh class, etiology of cirrhosis, and model for end-stage liver disease scores were comparable for the 2 groups. SPP patients were more likely than control patients to have a community-acquired infection (90.0% vs. 76.0%; P = 0.04), concurrent bacteremia (84.0% vs. 59.0%; P = 0.002), and to present with variceal bleeding (10.0% vs. 1.0%; P = 0.02). None of the study patients had pneumococcal pneumonia. The most common initial empirical therapy for both groups was third-generation cephalosporins (96.0% vs. 91.0%; P = 0.34) which was active against a significantly higher proportion of the cases than of the controls (97.8% vs. 78.7%; P = 0.003). Thirty-day mortality was significantly lower in the case group than in the control group (10.0% vs. 24.0%; P = 0.04).SPP was not associated with pneumococcal pneumonia and showed lower mortality than SBP caused by other organisms. However, the present study was constrained by the natural limitations characteristic of a small, retrospective study. Therefore, large-scale, well-controlled studies are required to demonstrate the influence of SPP on mortality, which was marginal in the present study.
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Affiliation(s)
- Taeeun Kim
- From the Department of Infectious Diseases (TK, SIH, SYP, JJ, YPC, S-HK, S-OL, YSK, JHW, S-HC); Department of Gastroenterology (Y-SL); and Department of Laboratory Medicine (HS, M-NK), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Abstract
Bloodstream infections (BSI) carry a heavy burden of morbidity and mortality in modern internal medicine wards (IMW). These wards are often filled with elderly subjects with several risk factors for BSI, such as multiple comorbidities, polypharmacy, immunosuppression, and indwelling devices. Diagnosing BSI in such a setting might require a high degree of suspicion, since the clinical presentation could be affected by underlying conditions and concomitant medications, which might delay the administration of an appropriate antimicrobial therapy, an event strongly and unfavorably influencing survival. Furthermore, selecting the appropriate antimicrobial therapy to treat these patients is becoming an increasingly complex task in which all possible benefits and costs should be carefully analyzed from patient and public health perspectives. Only a specialized, continuous, and interdisciplinary approach could really improve the management of IMW patients in an era of increasing antimicrobial resistance and complexity of care.
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Affiliation(s)
- Valerio Del Bono
- a Clinica Malattie Infettive, IRCCS AOU San Martino-IST, Università di Genova , Genova , Italy
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Clinical Significance and Characterization of Streptococcus tigurinus Isolates in an Adult Population. J Clin Microbiol 2015; 53:3574-9. [PMID: 26354809 DOI: 10.1128/jcm.01551-15] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Accepted: 08/30/2015] [Indexed: 11/20/2022] Open
Abstract
Streptococcus tigurinus is a newly described member of the Streptococcus mitis group. Due to the difficulty in distinguishing viridans group streptococci (VGS) by phenotype, analysis of 16S rRNA sequences is necessary for the accurate identification of most species. Through a laboratory policy of analyzing all clinically significant isolates from the VGS group by16S rRNA gene sequencing, we identified 14 S. tigurinus isolates from 11 patients. The Vitek 2 system most commonly gave an excellent rating to an incorrect identification (e.g., Streptococcus mitis), as did matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (e.g., Streptococcus oralis). S. tigurinus strains were recovered from numerous body sites, including the blood, peritoneal fluid, bone, synovial fluid, a perianal abscess, and an arm wound. Retrospective chart review indicated that most isolates were clinically significant, with bacteremia (n = 5), soft tissue infections (n = 3) osteomyelitis (n = 2), infected joint prosthesis (n = 2), and peritonitis (n = 2) being the most common, thus expanding the spectrum of disease associated with S. tigurinus.
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Dever JB, Sheikh MY. Review article: spontaneous bacterial peritonitis--bacteriology, diagnosis, treatment, risk factors and prevention. Aliment Pharmacol Ther 2015; 41:1116-31. [PMID: 25819304 DOI: 10.1111/apt.13172] [Citation(s) in RCA: 121] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Revised: 02/02/2015] [Accepted: 03/03/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with cirrhosis and ascites. AIM To review the known and changing bacteriology, risk factors, ascitic fluid interpretation, steps in performing paracentesis, treatment, prophylaxis and evolving perspectives related to SBP. METHODS Information was obtained from reviewing medical literature accessible on PubMed Central. The search term 'spontaneous bacterial peritonitis' was cross-referenced with 'bacteria', 'risk factors', 'ascites', 'paracentesis', 'ascitic fluid analysis', 'diagnosis', 'treatment', 'antibiotics', 'prophylaxis', 'liver transplantation' and 'nutrition'. RESULTS Gram-positive cocci (GPC) such as Staphylococcus, Enterococcus as well as multi-resistant bacteria have become common pathogens and have changed the conventional approach to treatment of SBP. Health care-associated and nosocomial SBP infections should prompt greater vigilance and consideration for alternative antibiotic coverage. Acid suppressive and beta-adrenergic antagonist therapies are strongly associated with SBP in at-risk individuals. CONCLUSIONS Third-generation, broad-spectrum cephalosporins remain a good initial choice for SBP treatment. Levofloxacin is an acceptable alternative for patients not receiving long-term flouroquinolone prophylaxis or for those with a penicillin allergy. For uncomplicated SBP, early oral switch therapy is reasonable. Alternative antibiotics such as pipercillin-tazobactam should be considered for patients with nosocomial SBP or for patients who fail to improve on traditional antibiotic regimens. Selective albumin supplementation remains an important adjunct in SBP treatment. Withholding acid suppressive medication deserves strong consideration, and discontinuing beta-adrenergic antagonist therapy in patients with end-stage liver disease and resistant ascites is standard care. Liver transplant evaluation should be undertaken for patients who develop SBP barring contraindications.
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Affiliation(s)
- J B Dever
- Department of Gastroenterology, VA San Diego Healthcare System, San Diego, CA, USA
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Sánchez E, Soriano G, Mirelis B, Gonzalez B, Nieto JC, Vidal S, Guarner-Argente C, Juárez C, Monés J, Guarner C. Effect of long-term acid gastric inhibition on bacterial translocation in cirrhotic rats. Eur J Gastroenterol Hepatol 2015; 27:570-576. [PMID: 25822866 DOI: 10.1097/meg.0000000000000319] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Bacterial translocation (BT) related to intestinal bacterial overgrowth (IBO) plays an important role in the pathogenesis of bacterial infections in cirrhosis. Inhibition of acid gastric secretion promotes IBO and might favor BT. We evaluated the effect of long-term inhibition of acid gastric secretion on BT in cirrhotic rats. METHODS Cirrhotic rats with and without ascites induced by oral CCl4 and controls were randomized to treatment with a daily subcutaneous injection of placebo, ranitidine (50 mg/kg), or pantoprazole (8 mg/kg) during 2 weeks. Continuous pH-metry was performed for 2 h before and at the end of treatment; thereafter, a laparotomy to obtain samples of blood, mesenteric lymph nodes, ascites, spleen, liver, and cecal stools was performed. RESULTS Ranitidine and pantoprazole increased gastric pH as compared with placebo (P<0.001). However, antisecretory drugs increased the incidence of BT only in ascitic rats treated with ranitidine (P<0.05) or pantoprazole (P=0.07) when compared with placebo-treated ascitic rats or cirrhotic rats without ascites treated with the same drug. Cirrhotic ascitic rats treated with pantoprazole showed a trend toward an increased incidence of IBO (P=0.08), a higher ileal malondialdehyde level (P<0.01), and an increased production of tumor necrosis factor-α (P<0.05). CONCLUSION Although inhibition of acid gastric secretion increased gastric pH in all animals, the incidence of BT increased only in ascitic rats, and it was associated with a trend toward an increase in IBO incidence, a higher ileal malondialdehyde level, and an increased production of serum tumor necrosis factor-α. Therefore, antisecretory drugs should be carefully administered to cirrhotic ascitic patients.
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Affiliation(s)
- Elisabet Sánchez
- Departments of aGastroenterology, Liver Unit bMicrobiology cImmunology, Hospital de la Santa Creu i Sant Pau dInstitut d´Investigacions Biomédiques de Sant Pau (IIB) eUniversitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona fCentro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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Sánchez E, Nieto JC, Boullosa A, Vidal S, Sancho FJ, Rossi G, Sancho-Bru P, Oms R, Mirelis B, Juárez C, Guarner C, Soriano G. VSL#3 probiotic treatment decreases bacterial translocation in rats with carbon tetrachloride-induced cirrhosis. Liver Int 2015; 35:735-745. [PMID: 24750552 DOI: 10.1111/liv.12566] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Accepted: 04/17/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Probiotics can prevent pathological bacterial translocation in cirrhosis by modulating intestinal microbiota and improving gut barrier and immune disturbances. To evaluate the effect of probiotic VSL#3 on bacterial translocation, intestinal microbiota, gut barrier and inflammatory response in rats with experimental cirrhosis. METHODS Forty-six Sprague-Dawley rats with CCl4 -induced cirrhosis were randomized into two groups: VSL#3 group (n = 22) that received VSL#3 in drinking water, and water group (n = 24) that received water only. Treatment began at week 6 of cirrhosis induction and continued until laparotomy, performed 1 week after development of ascites or at week 20. A control group included 11 healthy rats. At this study end, we evaluated bacterial translocation, intestinal flora, intestinal barrier (ileal claudin-2 and 4, β-defensin-1, occludin and malondialdehyde as index of oxidative damage) and serum cytokines. RESULTS Mortality during this study was similar in the VSL#3 group (10/22, 45%) and the water group (10/24, 42%) (P = 1). The incidence of bacterial translocation was 1/12 (8%) in the VSL#3 group, 7/14 (50%) in the water group (P = 0.03 vs. VSL#3 group) and 0/11 in the control group (P = 0.008 vs. water group). The concentration of ileal and caecal enterobacteria and enterococci was similar in the two groups of cirrhotic rats. The ileal occludin concentration was higher and ileal malondialdehyde and serum levels of TNF-α were lower in the VSL#3 group than in the water group (P < 0.05). CONCLUSIONS VSL#3 decreases bacterial translocation, the pro-inflammatory state and ileal oxidative damage and increases ileal occludin expression in rats with experimental cirrhosis.
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Affiliation(s)
- Elisabet Sánchez
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
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Giannelli V, Di Gregorio V, Iebba V, Giusto M, Schippa S, Merli M, Thalheimer U. Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis. World J Gastroenterol 2014; 20:16795-16810. [PMID: 25492994 PMCID: PMC4258550 DOI: 10.3748/wjg.v20.i45.16795] [Citation(s) in RCA: 168] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 07/26/2014] [Accepted: 09/30/2014] [Indexed: 02/06/2023] Open
Abstract
Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.
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Abstract
Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) usually mandate management within an intensive care unit (ICU). Even though the conditions bear some similarities, precipitating causes, and systemic complications management practices differ. Although early identification of ALF and ACLF, improvements in ICU management, and the widespread availability of liver transplantation have improved mortality, optimal management practices have not been defined. This article summarizes current ICU management practices and identifies areas of management that require further study.
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Affiliation(s)
- M Shadab Siddiqui
- Section of Hepatology, Hume-Lee Transplant Center, Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA 23222, USA
| | - R Todd Stravitz
- Section of Hepatology, Hume-Lee Transplant Center, Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA 23222, USA.
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Wen JB, Zhu FQ, Chen WG, Jiang LP, Chen J, Hu ZP, Huang YJ, Zhou ZW, Wang GL, Lin H, Zhou SF. Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats. PLoS One 2014; 9:e106082. [PMID: 25171482 PMCID: PMC4149463 DOI: 10.1371/journal.pone.0106082] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 07/31/2014] [Indexed: 12/11/2022] Open
Abstract
Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5% glucose solution (vehicle). The blank group (n = 10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-κB p65, TNF-α, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that oxymatrine improves intestinal barrier function via NF-κB-mediated signaling pathway and may be used as a new protecting agent for cirrhosis-associated intestinal mucosal damage.
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Affiliation(s)
- Jian-Bo Wen
- Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
- * E-mail: (JBW); (SFZ)
| | - Fang-Qing Zhu
- Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Wei-Guo Chen
- Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Li-Ping Jiang
- Animal Laboratory, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Jie Chen
- Department of Pharmacology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Zhao-Peng Hu
- Department of Pathology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Yong-Jian Huang
- Department of Clinical Laboratory, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Zhi-Wei Zhou
- Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida, United States of America
| | - Gui-Liang Wang
- Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Hao Lin
- Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China
| | - Shu-Feng Zhou
- Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida, United States of America
- * E-mail: (JBW); (SFZ)
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Abstract
Providing artificial nutrition is an important part of caring for critically ill patients. However, because of a paucity of robust data, the practice has been highly variable and often based more on dogma than evidence. A number of studies have been published investigating many different aspects of critical care nutrition. Although the influx of data has better informed the practice, the results have often been conflicting or counter to prevailing thought, resulting in discordant opinions and different interpretations by experts in the field. In this article, we review and summarize the data from a number of the published studies, including studies investigating enteral vs parenteral nutrition, supplementing enteral with parenteral nutrition, and use of immunonutrition. In addition, published studies informing the practice of how best to provide enteral nutrition will be reviewed, including the use of trophic feedings, gastric residual volumes, and gastric vs postpyloric tube placement.
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Affiliation(s)
- Svetang V Desai
- Division of Gastroenterology, Duke University Medical Center, Durham, NC
| | - Stephen A McClave
- Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, Louisville, KY
| | - Todd W Rice
- Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN.
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Wehmeyer MH, Krohm S, Kastein F, Lohse AW, Lüth S. Prediction of spontaneous bacterial peritonitis in cirrhotic ascites by a simple scoring system. Scand J Gastroenterol 2014; 49:595-603. [PMID: 24673156 DOI: 10.3109/00365521.2013.848471] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with liver cirrhosis. The aim of this prospective study was to identify predictors of SBP in order to develop a noninvasive method to identify or exclude an episode of SBP. PATIENTS AND METHODS Three hundred and ninety-two consecutive patients, who underwent paracentesis from March 2008 through January 2012 in our department due to cirrhotic ascites, were screened. Ninety-six patients were excluded, mostly due to prior application of antibiotics. SBP was defined by an absolute neutrophil count≥250 cells/µL ascites. We evaluated various clinical and laboratory parameters as potential predictors of SBP. A scoring system was developed in a training set of 220 and validated in a second set of 76 patients. RESULTS Fifty-eight patients (26%) in the training set and 17 patients in the validation set (22%) suffered from SBP. Thrombocytopenia≤100,000 cells/µL, age>60 years and CRP>60 mg/L were identified as independent predictors of SBP. A scoring system combining these three parameters (weighting thrombocytopenia and age with 1 point each, but CRP with 2 points) reaches a positive predictive value for the diagnosis of SBP of 81.8% with a specificity of 98.8% (score≥3). The negative predictive value at a threshold of 1 point is 93.5% with a sensitivity of 87.9%. Notably, a high MELD score is not associated with SBP (p=0.3344). CONCLUSIONS Combination of age, CRP and platelet count in a simple scoring system helps in the rapid diagnosis or exclusion of SBP.
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Affiliation(s)
- Malte H Wehmeyer
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf , Hamburg , Germany
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Role of pentoxifylline and sparfloxacin in prophylaxis of spontaneous bacterial peritonitis in cirrhotic patients. ISRN GASTROENTEROLOGY 2014; 2014:595213. [PMID: 24729879 PMCID: PMC3963113 DOI: 10.1155/2014/595213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 02/19/2014] [Indexed: 02/06/2023]
Abstract
This study was directed to evaluate the role of sparfloxacin and pentoxifylline in the prophylaxis of spontaneous bacterial peritonitis in cirrhotic patients. Forty cirrhotic patients with ascites were included in the study. Patients were randomized into four groups in a blind fashion; each group consists of ten patients. Group one received ciprofloxacin (control group), group two received sparfloxacin, group three received pentoxifylline, and group four received a combination of sparfloxacin and pentoxifylline. Treatment duration was six months. Serum TNF-α level was the primary inflammatory marker of the study to evaluate the effect of the used medications. In group two, TNF-α level showed a statistically significant decrease in comparison with group one (P = 0.001), while in group three, TNF-α level showed nonsignificant difference in comparison with the control group (P > 0.05). In addition, group four showed a statistically significant decrease in TNF-α level compared to the other three groups (P < 0.05). The finding from our study indicates that sparfloxacin as well as pentoxifylline could be used in prophylaxis of spontaneous bacterial peritonitis. Combination of sparfloxacin and pentoxifylline showed some of synergism which may be useful in decreasing emergence of resistant strains.
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Ge PS, Runyon BA. The changing role of beta-blocker therapy in patients with cirrhosis. J Hepatol 2014; 60:643-53. [PMID: 24076364 DOI: 10.1016/j.jhep.2013.09.016] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 09/13/2013] [Accepted: 09/17/2013] [Indexed: 12/11/2022]
Abstract
Cirrhosis is a leading cause of death in the United States and worldwide. Beta-blockers have been established in numerous studies as part of the cornerstone of the medical management of cirrhosis, particularly in the primary and secondary prevention of variceal hemorrhage. However, new evidence has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites. In this article, we review the beneficial effects of beta-blocker therapy, the potential harms of aggressive beta-blocker therapy, and provide suggestions regarding the appropriate use of this class of medications in patients with cirrhosis.
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Affiliation(s)
- Phillip S Ge
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
| | - Bruce A Runyon
- Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
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Cuenca S, Sanchez E, Santiago A, El Khader I, Panda S, Vidal S, Camilo Nieto J, Juárez C, Sancho F, Guarner F, Soriano G, Guarner C, Manichanh C. Microbiome composition by pyrosequencing in mesenteric lymph nodes of rats with CCl4-induced cirrhosis. J Innate Immun 2013; 6:263-271. [PMID: 24296725 PMCID: PMC6741495 DOI: 10.1159/000356454] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 10/18/2013] [Accepted: 10/18/2013] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The cross talk between the gut microbiota and the immune system, which is essential to maintain homeostasis, takes place at the intestinal lymphoid tissue such as the mesenteric lymph nodes (MLNs). Here, we investigated the presence of bacterial DNA in MLNs of control and cirrhotic rats and its relationship with inflammatory responses. METHODS The MLN microbiome of cirrhotic rats with ascites, which was induced by carbon tetrachloride (CCl4), was compared to that of control rats using quantitative real-time PCR and pyrosequencing of the 16S rRNA gene. Cytokines in blood samples were assessed by ELISA. RESULTS Unexpectedly, sequence analysis revealed a high microbial diversity in the MLNs of both control and cirrhotic rats with Proteobacteria as one of the most dominant phylum. CCl4-induced liver injury was not associated with a change in bacterial load, but it was linked to a decrease in microbial diversity (p < 0.05) and alterations in the microbial community in MLNs. A high proportion of Bifidobacterium animalis was also positively correlated with elevated interleukin-10 expression (p = 0.002, false discovery rate = 0.03, r = 0.94). CONCLUSIONS For the first time, the high microbial diversity observed in MLNs of both controls and CCl4-induced cirrhotic rats provides evidence that bacterial translocation is more than a mere dichotomic phenomenon.
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Affiliation(s)
- Silvia Cuenca
- Digestive System Research Unit, Vall d'Hebron Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Elisabet Sanchez
- Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
- Universitat Autònoma de Barcelona, Bellaterra, Spain
- Institut d'Investigacions Biomédiques de Sant Pau (IIB), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Liver Section, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Alba Santiago
- Digestive System Research Unit, Vall d'Hebron Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Ismail El Khader
- Digestive System Research Unit, Vall d'Hebron Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Suchita Panda
- Digestive System Research Unit, Vall d'Hebron Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Silvia Vidal
- Institut d'Investigacions Biomédiques de Sant Pau (IIB), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Juan Camilo Nieto
- Institut d'Investigacions Biomédiques de Sant Pau (IIB), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Liver Section, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Cándido Juárez
- Institut d'Investigacions Biomédiques de Sant Pau (IIB), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Francesc Sancho
- Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Francisco Guarner
- Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
- Digestive System Research Unit, Vall d'Hebron Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - German Soriano
- Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
- Universitat Autònoma de Barcelona, Bellaterra, Spain
- Institut d'Investigacions Biomédiques de Sant Pau (IIB), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Liver Section, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Carlos Guarner
- Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
- Universitat Autònoma de Barcelona, Bellaterra, Spain
- Institut d'Investigacions Biomédiques de Sant Pau (IIB), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Liver Section, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Chaysavanh Manichanh
- Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
- Digestive System Research Unit, Vall d'Hebron Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
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Abstract
One of the most important factors affecting outcome and recovery from surgical trauma is preoperative nutritional status. Research in perioperative nutritional support has suffered from a lack of consensus as to the definition of malnutrition, no recognition of which nutrients are important to surgical healing, and a paucity of well-designed studies. In the past decade, there has been some activity to address this situation, recognizing the importance of nutrition as a therapy before surgery, after surgery, and possibly even during surgery.
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Affiliation(s)
- T Miko Enomoto
- Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, UHS-2, Portland, OR 97239, USA
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50
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Alexopoulou A, Papadopoulos N, Eliopoulos DG, Alexaki A, Tsiriga A, Toutouza M, Pectasides D. Increasing frequency of gram-positive cocci and gram-negative multidrug-resistant bacteria in spontaneous bacterial peritonitis. Liver Int 2013; 33:975-81. [PMID: 23522099 DOI: 10.1111/liv.12152] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Accepted: 02/22/2013] [Indexed: 02/13/2023]
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is historically caused by Gram-negative bacteria (GNB) almost exclusively Enterobacteriaceae. Recently, an increasing rate of infections with Gram-positive cocci (GPC) and multidrug-resistant (MDR) microorganisms was demonstrated. AIMS To assess possible recent changes of the bacteria causing SBP in cirrhotic patients. METHODS We retrospectively recorded 47 cases (66% males) during a 4-year-period (2008-2011). RESULTS Twenty-eight (60%) patients had healthcare-associated infections while 15 (32%) received prophylactic quinolone treatment. GPC were found to be the most frequent cause (55%). The most prevalent organisms in a descending order were Streptococcus spp (n = 10), Enterococcus spp (n = 9), Escherichia coli (n = 8), Klebsiella pneumonia (n = 5), methicillin-sensitive Staphylococcus aureus (n = 4) and coagulase-negative Staphylococcus spp (n = 3). Nine of the isolated bacteria (19%) were MDR, including carbapenemase-producing K. pneumonia (n = 4), followed by extended-spectrum beta-lactamase-producing E. coli (n = 3) and Pseudomonas aeruginosa (n = 2). MDR bacteria were more frequently isolated in healthcare-associated than in community-acquired infections (100% vs 50%, P = 0.006), in patients receiving long-term quinolone prophylaxis (67% vs 24%, P = 0.013) and in those with advanced liver disease as suggested by higher MELD score (28 vs 19, P = 0.012). More infections with GNB than GPC were healthcare-associated (81% vs 42%, P = 0.007). Third-generation cephalosporin resistance was observed in 49% and quinolone resistance in 47%. CONCLUSIONS GPC were the most frequent bacteria in culture-positive SBP and a variety of drug-resistant microorganisms have emerged. As a result of high rates of resistance in currently recommended therapy and prophylaxis, the choice of optimal antibiotic therapy is vital in the individual patient.
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