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Engelmann C, Berg T. Management of Infectious Complications Associated with Acute-on-Chronic Liver Failure. Visc Med 2018; 34:261-268. [PMID: 30345283 DOI: 10.1159/000491107] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Introduction Acute-on-chronic liver failure (ACLF) is associated with a high susceptibility to infections leading to complications and poor prognosis. The sensitized immune system overwhelmingly responds to invading bacteria leading to organ damage. After resolution of infection or prolonged disease duration, the phagocytic system becomes irresponsive with a reduced bacterial clearance capacity promoting secondary infection. Methods This review focuses on the best management strategies for patients with ACLF and infections. Using the following terms, an extensive literature research on the Medline database was performed: 'acute-on-chronic liver failure', 'infection', 'ACLF', 'bacteria', 'multi-resistance'. Results Analysis of the literature confirmed that delayed diagnosis and treatment of infections in patients with ACLF results in a poor prognosis. Patients with ACLF should be considered as having a potential infection and should undergo a complete screening for sepsis. Once biochemical analysis indicates a potential infection, such as abnormal levels of C-reactive protein and procalcitonin, antibiotic treatment should be initiated immediately without microbiological culture results. For community-acquired infections third-generation cephalosporins are still the first choice, whereas in the nosocomial setting antibiotics with broader spectrum, such as piperacillin/combactam or carbapenems ± glycopeptides, are preferred. The patient should be re-assessed 48 h after treatment initiation in order to tailor the treatment. Non-response is suspicious, likely due to bacterial resistance or fungal infection, which should be considered when choosing further treatment strategies. Albumin substitution to prevent hepatorenal syndrome and to improve patients' outcome is mandatory in patients with spontaneous bacterial peritonitis. Prophylactic antibiotic therapy is suitable to prevent infections in high-risk patients. Conclusion The screening for infections and its treatment is an essential part of managing patients with ACLF. In order to improve patients' prognosis, antibiotic treatment should be initiated once an infection is suspected. However, preventive strategies are already established and should be applied according to the guidelines.
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Affiliation(s)
- Cornelius Engelmann
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Thomas Berg
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
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2
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The first episode of spontaneous bacterial peritonitis is a threat event in children with end-stage liver disease. Eur J Gastroenterol Hepatol 2018; 30:323-327. [PMID: 29303884 DOI: 10.1097/meg.0000000000001046] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Studies on native liver survival (NLS) after the first episode of spontaneous bacterial peritonitis (SBP) are rare. Our objective was to evaluate NLS in children up to 1 year after SBP. METHODS A historical cohort study of 18 children followed after the first episode of SBP was conducted. NLS, in-hospital mortality, causes of death, and rate of multidrug-resistant organisms were reported. RESULTS Biliary atresia was the most prevalent diagnosis (72.2%); all were Child-Pugh C, and the median age was 1.0 year. The probability of NLS was 77.8, 27.8, and 11.1% at 1, 3 and 6 months, respectively. At 9 months, no child had the native liver. In-hospital mortality was 38.9%, and the main causes of death were septic shock and acute-on-chronic liver failure. Escherichia coli was the predominant organism cultured. Multidrug-resistant organisms were not detected. The cumulative probability of NLS was 77.8% at 1 month, 27.8% at 3 months, and 11.1% at 6 months. At 9-month follow-up, none of children had their native liver. Ascites PMN count cell more than 1000 cells/mm, positive ascites culture, and prolonged international normalized ratio reached a significant value as predictive factors of NLS and were selected for multivariate analysis. We did not identify independent predictors of survival. CONCLUSION Development of SBP was a late event in children and had a high effect on NLS.
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Alexopoulou A, Agiasotelli D, Vasilieva LE, Dourakis SP. Bacterial translocation markers in liver cirrhosis. Ann Gastroenterol 2017; 30:486-497. [PMID: 28845103 PMCID: PMC5566768 DOI: 10.20524/aog.2017.0178] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 06/19/2017] [Indexed: 12/12/2022] Open
Abstract
Bacterial translocation (BT) is an important mechanism in the development of infection in liver cirrhosis. The migration and colonization of bacteria and/or bacterial products from the bowel to mesenteric lymph nodes is a controlled process in healthy persons. Increased intestinal permeability, bacterial overgrowth and defect of gut-associated lymphatic tissue promote impaired BT in cirrhotics. We reviewed the reports on markers used for the evaluation of BT published between 1987 and 2016. We focused on the clinical consequences of BT in cirrhosis, as indicated by the values of the BT markers. Patients with cirrhosis are reported to have elevated levels of surrogate markers associated with BT compared with controls. The most widely used BT parameters are C-reactive protein, procalcitonin, bacterial DNA, endotoxin or lipopolysaccharide, lipopolysaccharide binding protein, calprotectin, and bactericidal/permeability increasing protein. High levels of these factors in serum and/or ascitic fluid in humans may be associated with advanced liver disease, hemodynamic instability, high levels of proinflammatory cytokines, susceptibility to the development of severe or recurrent infections, acute-on-chronic liver failure, hepatic encephalopathy, hepatorenal syndrome and poor prognosis during follow up. In conclusion, high levels of BT markers are associated with a high inflammatory response, increased complications of liver cirrhosis and occasionally high fatality rates.
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Affiliation(s)
- Alexandra Alexopoulou
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Danai Agiasotelli
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Larisa E Vasilieva
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Spyros P Dourakis
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
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Triantos C, Kalafateli M, Spantidea PI, Goukos D, Koutroumpakis E, Konstantakis C, Assimakopoulos SF, Gogos C, Mouzaki A, Daikos G, Thomopoulos K. Bacterial load and cytokine profile in patients with cirrhosis following therapy with proton pump inhibitors: a prospective cohort study. Ann Gastroenterol 2017; 30:450-456. [PMID: 28655984 PMCID: PMC5480000 DOI: 10.20524/aog.2017.0142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 03/08/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The aim of this study was to explore the presence of bacterial products and the cytokine profile in outpatients with cirrhosis before and after short-term (4-8 weeks) administration of proton pump inhibitors (PPIs). METHODS Seventeen patients with cirrhosis-male/female: 12/5; age: median 59.2 years (49-65); etiology: HBV±HDV 23.5%, HCV 17.7%, alcohol 41.2%, other 17.6%; Child-Pugh score: median 7.5 (5-12); Model for End-stage Liver Disease: 10.5 (7-21); ascites (%): 3 (17.7)-attending the outpatient clinics were included. None had hepatocellular carcinoma. Indications for PPIs were: esophagitis (n=6, 35.3%), peptic ulcer (n=10, 58.6%) and other (n=1, 5.9%). Bacterial DNA in serum and the levels of endotoxin, lipopolysaccharide binding protein, transforming growth factor-β, interleukin -1β, -6, -8, -12, -10, tumor necrosis factor-α and nitric oxide were assessed at baseline (time 1) and at the end of treatment (time 2). The Wilcoxon signed rank test was used to evaluate significant differences in the parameters assayed before and after PPI administration. RESULTS No patients developed infection during the study period. Bacterial DNA was not detected before or after treatment. No significant differences were observed between the concentrations of any indices between times 1 and 2 (P>0.05). Subgroup analysis according to Child-Pugh stage yielded similar results. CONCLUSION Short-term administration of PPIs had no effect on bacterial DNA, bacterial products or cytokine concentrations in patients with liver cirrhosis.
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Affiliation(s)
- Christos Triantos
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Maria Kalafateli
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Panagiota I. Spantidea
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras (Panagiota Spadidea, Athanasia Mouzaki)
| | - Dimitrios Goukos
- Department of Propedeutic Medicine, Laiko General Hospital, Athens (Dimitrios Goukos, Georgios Daikos)
| | - Efstratios Koutroumpakis
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Christos Konstantakis
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
| | - Stelios F. Assimakopoulos
- Department of Internal Medicine, University Hospital of Patras (Stelios Assimakopoulos, Charalambos Gogos), Greece
| | - Charalambos Gogos
- Department of Internal Medicine, University Hospital of Patras (Stelios Assimakopoulos, Charalambos Gogos), Greece
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras (Panagiota Spadidea, Athanasia Mouzaki)
| | - Georgios Daikos
- Department of Propedeutic Medicine, Laiko General Hospital, Athens (Dimitrios Goukos, Georgios Daikos)
| | - Konstantinos Thomopoulos
- Department of Gastroenterology, University Hospital of Patras (Christos Triantos, Maria Kalafateli, Efstratios Koutroumpakis, Christos Konstantakis, Konstantinos Thomopoulos)
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Bruns T, Reuken PA, Stengel S, Gerber L, Appenrodt B, Schade JH, Lammert F, Zeuzem S, Stallmach A. The prognostic significance of bacterial DNA in patients with decompensated cirrhosis and suspected infection. Liver Int 2016; 36:1133-42. [PMID: 26901072 DOI: 10.1111/liv.13095] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 02/11/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Circulating and peritoneal fragments of microbial DNA (bactDNA) are evidence for bacterial translocation in decompensated cirrhosis and may serve as a rational approach for antibiotic therapy when infection is suspected. METHODS Prospective multicenter study to investigate whether identification of bactDNA from blood or ascitic fluid (AF) by multiplex polymerase chain reaction (PCR) is associated with increased 90-day mortality in 218 patients with cirrhosis and signs of infection. RESULTS BactDNA in either compartment was detected in 134 (61%) patients, comprising 54 with bactDNA in blood and AF, 48 with AF bactDNA only, and 32 with blood bactDNA only. BactDNA was associated with spontaneous bacterial peritonitis and blood stream infections (SBP/BSI), acute-on-chronic liver failure (ACLF), encephalopathy and markers of inflammation. The prevalence of bactDNA in patients with proven SBP/BSI (36/49; 73%) was similar to that in patients with sterile ACLF (37/52; 71%). Actuarial 90-day survival was 56 ± 5% in the absence of bactDNA in both compartments and did not differ if bactDNA was detected in blood only (63 ± 9%), AF only (63 ± 7%), or in blood and AF (52 ± 7%). Predictors of 90-day mortality were SBP (HR = 3.10; 95% CI: 1.90-5.06), BSI (HR = 4.94; 95% CI: 2.71-9.02), and ACLF (HR = 2.20; 95% CI: 1.44-3.35). The detection of resistance genes in blood or AF in the absence of SBP/BSI (n = 11) was associated with poor 1-year survival (HR = 2.35; 95% CI: 1.03-5.35). CONCLUSIONS BactDNA in sterile body fluids did not indicate increased mortality in cirrhotic patients with suspected infection. Using multiplex PCR for risk stratification cannot be recommended in these patients.
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Affiliation(s)
- Tony Bruns
- The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.,Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
| | - Philipp A Reuken
- The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.,Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
| | - Sven Stengel
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
| | - Ludmila Gerber
- Department of Internal Medicine I, Frankfurt University Hospital, Frankfurt, Germany
| | - Beate Appenrodt
- Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany
| | - Johannes H Schade
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
| | - Frank Lammert
- Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine I, Frankfurt University Hospital, Frankfurt, Germany
| | - Andreas Stallmach
- The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.,Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
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Santiago A, Pozuelo M, Poca M, Gely C, Nieto JC, Torras X, Román E, Campos D, Sarrabayrouse G, Vidal S, Alvarado-Tapias E, Guarner F, Soriano G, Manichanh C, Guarner C. Alteration of the serum microbiome composition in cirrhotic patients with ascites. Sci Rep 2016; 6:25001. [PMID: 27112233 PMCID: PMC4845009 DOI: 10.1038/srep25001] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Accepted: 04/08/2016] [Indexed: 01/01/2023] Open
Abstract
The progression of cirrhosis is associated with alterations in the composition of the gut microbiome. To assess microbial translocation, we compared the serum microbial composition of patients with and without ascites and characterized the ascitic fluid microbiome using 16S rDNA high-throughput sequencing data. A complex and specific microbial community was detected in the serum and ascitic fluid of patients with cirrhosis but barely detectable in the serum of healthy controls. The serum microbiome of patients with ascites presented higher levels of lipopolysaccharide binding protein, a marker of microbial translocation, associated with higher diversity and relative abundance of Clostridiales and an unknown genus belonging to the Cyanobacteria phylum compared to patients without ascites. The composition of the fecal microbiome was also more altered in patients with than without ascites, confirming previous studies on fecal microbiome. We propose that alteration of the serum and fecal microbiome composition be considered indicators of cirrhosis progression.
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Affiliation(s)
- Alba Santiago
- Department of Gastroenterology, Vall d’Hebron Research Institute, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain
| | - Marta Pozuelo
- Department of Gastroenterology, Vall d’Hebron Research Institute, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain
| | - Maria Poca
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Centro de Investigaciòn Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Cristina Gely
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Juan Camilo Nieto
- Department of Immunology, Institut de Recerca-IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Xavier Torras
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Centro de Investigaciòn Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Eva Román
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Centro de Investigaciòn Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
- Escola Universitària d’Infermeria EUI-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - David Campos
- Department of Gastroenterology, Vall d’Hebron Research Institute, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain
| | - Guillaume Sarrabayrouse
- Department of Gastroenterology, Vall d’Hebron Research Institute, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain
| | - Silvia Vidal
- Department of Immunology, Institut de Recerca-IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | | | - Francisco Guarner
- Department of Gastroenterology, Vall d’Hebron Research Institute, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain
- Centro de Investigaciòn Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - German Soriano
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Centro de Investigaciòn Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Chaysavanh Manichanh
- Department of Gastroenterology, Vall d’Hebron Research Institute, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain
- Centro de Investigaciòn Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Carlos Guarner
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Centro de Investigaciòn Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
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7
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Martínez-Esparza M, Tristán-Manzano M, Ruiz-Alcaraz AJ, García-Peñarrubia P. Inflammatory status in human hepatic cirrhosis. World J Gastroenterol 2015; 21:11522-11541. [PMID: 26556984 PMCID: PMC4631958 DOI: 10.3748/wjg.v21.i41.11522] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 07/31/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis.
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Koutsounas I, Kaltsa G, Siakavellas SI, Bamias G. Markers of bacterial translocation in end-stage liver disease. World J Hepatol 2015; 7:2264-2273. [PMID: 26380651 PMCID: PMC4568487 DOI: 10.4254/wjh.v7.i20.2264] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 08/13/2015] [Accepted: 08/30/2015] [Indexed: 02/06/2023] Open
Abstract
Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.
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Affiliation(s)
- Ioannis Koutsounas
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
| | - Garyfallia Kaltsa
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
| | - Spyros I Siakavellas
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
| | - Giorgos Bamias
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
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9
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Bellot P, Francés R, Such J. Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and clinical implications. Liver Int 2013; 33:31-9. [PMID: 23121656 DOI: 10.1111/liv.12021] [Citation(s) in RCA: 183] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2012] [Accepted: 08/27/2012] [Indexed: 02/13/2023]
Abstract
Bacterial translocation (BT) is defined by the passage of viable indigenous bacteria from the intestinal lumen to mesenteric lymph nodes (MLNs) and other territories, and its diagnostic criteria rely on the isolation of viable bacteria in MLNs. Small intestinal overgrowth, increased intestinal permeability and immunological alterations are the main factors involved in its pathogenesis. BT is obviously difficult to identify in patients with cirrhosis, and alternative methods have been proposed instead. Bacterial DNA detection and species identification in serum or ascitic fluid has been proposed as a reliable marker of BT. Bacterial products, such as endotoxin, or bacterial DNA can translocate to extra-intestinal sites and promote an immunological response similar to that produced by viable bacteria. Therefore, pathological BT plays an important role in the pathogenesis of the complications of cirrhosis, not only in infections, but by exerting a profound inflammatory state and exacerbating the haemodynamic derangement. This may promote in turn the development of hepatorenal syndrome, hepatic encephalopathy and other portal hypertension-related complications. Therapeutic approaches for the prevention of BT in experimental and human cirrhosis are summarized. Finally, new investigations are needed to better understand the pathogenesis and consequences of translocation by viable bacteria (able to grow in culture), or non-viable BT (detection of bacterial fragments with negative culture) and open new therapeutic avenues in patients with cirrhosis.
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Affiliation(s)
- Pablo Bellot
- Liver Unit, Hospital General Universitario de Alicante and Miguel Hernández University, Elche, Alicante, Spain
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Identification of bacterial pathogens in ascitic fluids from patients with suspected spontaneous bacterial peritonitis by use of broad-range PCR (16S PCR) coupled with high-resolution melt analysis. J Clin Microbiol 2012; 50:2428-32. [PMID: 22573594 DOI: 10.1128/jcm.00345-12] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Spontaneous bacterial peritonitis (SBP) can be a severe complication occurring in patients with cirrhosis and ascites, with associated mortality often as high as 40%. Traditional diagnostics for SBP rely on culture techniques for proper diagnosis, although recent reports suggest that the presence of bacterial DNA in peritoneal fluid in patients with cirrhosis and ascites is an indicator of SBP. A previously published broad-range PCR (16S PCR) coupled with high-resolution melt analysis (HRMA) was compared with standard culture techniques for diagnosis of SBP in 106 peritoneal fluid samples from patients with suspected SBP. The sensitivity and specificity for 16S PCR for detecting eubacterial DNA compared with those of standard culture techniques were 100% (17/17) and 91.5% (85/89), respectively. Overall, HRMA concordance with species identification was 70.6% (12/17), although the 5 samples that were discordant at the species level were SBP resulting from a polymicrobial infection, and species-level identification for polymicrobial infections is outside the capability of HRMA. Both the broad-range 16S PCR and HRMA analysis provide useful diagnostic adjunctive assays for clinicians in detecting and identifying pathogens responsible for SBP.
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