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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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Yakut A. Gut microbiota in the development and progression of chronic liver diseases: Gut microbiota-liver axis. World J Hepatol 2025; 17:104167. [PMID: 40177197 PMCID: PMC11959663 DOI: 10.4254/wjh.v17.i3.104167] [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: 12/12/2024] [Revised: 01/28/2025] [Accepted: 02/25/2025] [Indexed: 03/26/2025] Open
Abstract
The gut microbiota (GM) is a highly dynamic ecology whose density and composition can be influenced by a wide range of internal and external factors. Thus, "How do GM, which can have commensal, pathological, and mutualistic relationships with us, affect human health?" has become the most popular research issue in recent years. Numerous studies have demonstrated that the trillions of microorganisms that inhabit the human body can alter host physiology in a variety of systems, such as metabolism, immunology, cardiovascular health, and neurons. The GM may have a role in the development of a number of clinical disorders by producing bioactive peptides, including neurotransmitters, short-chain fatty acids, branched-chain amino acids, intestinal hormones, and secondary bile acid conversion. These bioactive peptides enter the portal circulatory system through the gut-liver axis and play a role in the development of chronic liver diseases, cirrhosis, and hepatic encephalopathy. This procedure is still unclear and quite complex. In this study, we aim to discuss the contribution of GM to the development of liver diseases, its effects on the progression of existing chronic liver disease, and to address the basic mechanisms of the intestinal microbiota-liver axis in the light of recent publications that may inspire the future.
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Affiliation(s)
- Aysun Yakut
- Department of Gastroenterology, İstanbul Medipol University Sefakoy Health Practice Research Center, İstanbul 38000, Türkiye.
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Xu X, Zhu T, Jing C, Jiang M, Fu Y, Xie F, Meng Q, Li J. Hepatic encephalopathy treatment after transjugular intrahepatic portosystemic shunt: a new perspective on the gut microbiota. Front Med (Lausanne) 2025; 12:1423780. [PMID: 40124683 PMCID: PMC11926149 DOI: 10.3389/fmed.2025.1423780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) placement alleviates portal hypertension symptoms. Hepatic encephalopathy (HE) is a common complication of TIPS, impacting patient quality of life and the healthcare burden. Post-TIPS HE is associated with portosystemic shunting, elevated blood ammonia levels, and inflammation. Increasing attention has been given to the liver and intestinal circulation in recent years. An imbalance in intestinal microecology plays a role in the occurrence of HE and may be a new target for treatment. This review discusses the causes, diagnosis, and treatment strategies for post-TIPS HE and focuses on exploring treatment strategies and their relationships with the gut microbiota, suggesting an innovative approach to address this complication.
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Affiliation(s)
- Xiaotong Xu
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Tong Zhu
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Changyou Jing
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Minjie Jiang
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yunlai Fu
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Fang Xie
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jianjun Li
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Zhang D, Shi C, Wang Y, Guo J, Gong Z. Metabolic Dysregulation and Metabolite Imbalances in Acute-on-chronic Liver Failure: Impact on Immune Status. J Clin Transl Hepatol 2024; 12:865-877. [PMID: 39440217 PMCID: PMC11491507 DOI: 10.14218/jcth.2024.00203] [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: 06/18/2024] [Revised: 08/26/2024] [Accepted: 09/04/2024] [Indexed: 10/25/2024] Open
Abstract
Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.
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Affiliation(s)
- Danmei Zhang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chunxia Shi
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yukun Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jin Guo
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zuojiong Gong
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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5
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Llorente C. Commentary on the gut microbiome in alcohol use disorder and alcohol-associated liver disease. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:1466-1468. [PMID: 38825713 PMCID: PMC11305903 DOI: 10.1111/acer.15382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 05/22/2024] [Indexed: 06/04/2024]
Affiliation(s)
- Cristina Llorente
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
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Grodin EN, Burnette EM, Rodriguez C, Fulcher JA, Ray LA. The gut microbiome in alcohol use disorder and alcohol-associated liver disease: A systematic review of clinical studies. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:1221-1242. [PMID: 38719790 PMCID: PMC11827555 DOI: 10.1111/acer.15338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/01/2024] [Accepted: 04/10/2024] [Indexed: 07/11/2024]
Abstract
Evidence suggests that a relationship exists between the gut microbiome and the pathogenesis of alcohol use disorder (AUD) and alcohol-associated liver disease (AALD). This systematic review identified studies that investigated the gut microbiome in individuals with an AUD or an AALD. A search was conducted on October 27, 2022, in PubMed, Web of Science, and Embase databases. Fifty studies satisfied eligibility criteria. Most studies found evidence for gut dysbiosis in individuals with AUD and AALD. Microbiome intervention studies have mostly been conducted in AALD patients; fecal microbial transplant interventions show the most promise. Because most studies were conducted cross-sectionally, the causal relationship between the gut microbiome and alcohol use is unknown. Furthermore, almost all studies have been conducted in predominantly male populations, leaving critical questions regarding sex differences and generalizability of the findings. The study summaries and recommendations provided in this review seek to identify areas for further research and to highlight potential gut microbial interventions for treating AUD and AALD.
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Affiliation(s)
- Erica N. Grodin
- Department of Psychology, University of California, Los Angeles, Los Angeles, California, USA
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA
- Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA
| | - Elizabeth M. Burnette
- Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA
| | - Crystal Rodriguez
- Department of Psychology, University of California, Los Angeles, Los Angeles, California, USA
| | - Jennifer A. Fulcher
- Division of Infectious Diseases, David Gefen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA
| | - Lara A. Ray
- Department of Psychology, University of California, Los Angeles, Los Angeles, California, USA
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA
- Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA
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Ayoub M, Tomanguillo J, Faris C, Anwar N, Chela H, Daglilar E. SARS-CoV-2 Infection Is an Independent Risk Factor for Decompensation in Cirrhosis Patients. Diseases 2024; 12:46. [PMID: 38534970 PMCID: PMC10968826 DOI: 10.3390/diseases12030046] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/20/2024] [Accepted: 02/21/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2's impact on decompensation in previously compensated cirrhotic patients. METHODS We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX's deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months. RESULTS Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients. CONCLUSIONS SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months.
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Affiliation(s)
- Mark Ayoub
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA;
| | - Julton Tomanguillo
- Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA;
| | - Carol Faris
- Department of General Surgery, Marshall University, Huntington, WV 25755, USA
| | - Nadeem Anwar
- Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (N.A.); (H.C.)
| | - Harleen Chela
- Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (N.A.); (H.C.)
| | - Ebubekir Daglilar
- Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA; (N.A.); (H.C.)
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Lan NTN, Lieu DQ, Anh TN, Thuong LH, Tuong TTK, Bang MH. Characteristics and Related Factors of Bacterial Infection Among Patients With Cirrhosis. Mater Sociomed 2024; 36:90-96. [PMID: 38590588 PMCID: PMC10999149 DOI: 10.5455/msm.2024.36.90-96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 02/25/2024] [Indexed: 04/10/2024] Open
Abstract
Background Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome. Objective: This study aimed to identify the prevalence, essential features, and related factors of bacterial infection among patients with cirrhosis in Vietnam. Methods This retrospective study included 317 patients diagnosed with cirrhosis, who were divided into two groups: group 1 including 125 patients with bacterial infection and group 2 including 192 patients without bacterial infection. Infection was diagnosed on the basis of its localization. Results Spontaneous bacterial peritonitis (SBP; 31.2%) and pneumonia (28.8%) were the most common infections identified. The procalcitonin (PCT) level had a strong diagnostic value with an area under the curve value of 0.868. The most common type of gram-negative bacteria was Escherichia coli, while the gram-positive bacteria seen were Staphylococcus, Enterococcus, and Streptococcus among the patients with infection. In the logistic regression analysis, Child-Pugh class B and C (p<0.001, OR=4.14, CI=1.90-9.03; OR=4.76, CI=2.03-11.16, respectively) and the presence of acute kidney injury (p=0.009, OR=2.57, CI=1.27-5.22) and gastrointestinal hemorrhage (p=0.035, OR=0.39, CI=0.16-0.94) significantly differed between the groups. Conclusion The most prevalent type of bacterial infection in patients with cirrhosis is SBP, with gram-negative bacteria being the most common cause. The PCT level is useful in identifying infection in patients with cirrhosis. Decompensated cirrhosis is linked to a higher risk of infection.
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Affiliation(s)
| | - Dau Quang Lieu
- Department of Internal Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Tran Ngoc Anh
- Department of Internal Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
- Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam
| | - Le Hoai Thuong
- Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam
| | - Tran-Thi Khanh Tuong
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Mai Hong Bang
- Department of Gastroenterology, 108 Military Central Hospital, Hanoi, Vietnam
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Höppner J, Krohn S, van den Munckhof EHA, Kallies R, Herber A, Zeller K, Tünnemann J, Matz-Soja M, Chatzinotas A, Böhm S, Hoffmeister A, Berg T, Engelmann C. Changes of the bacterial composition in duodenal fluid from patients with liver cirrhosis and molecular bacterascites. Sci Rep 2023; 13:23001. [PMID: 38155157 PMCID: PMC10754895 DOI: 10.1038/s41598-023-49505-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 12/08/2023] [Indexed: 12/30/2023] Open
Abstract
Small intestinal bacterial overgrowth and compositional changes of intestinal microbiota are pathomechanistic factors in liver cirrhosis leading to bacterial translocation and infectious complications. We analyzed the quantity and composition of duodenal bacterial DNA (bactDNA) in relation to bactDNA in blood and ascites of patients with liver cirrhosis. Duodenal fluid and corresponding blood and ascites samples from 103 patients with liver cirrhosis were collected. Non-liver disease patients (n = 22) served as controls. BactDNA was quantified by 16S-rRNA gene-based PCR. T-RFLP and 16S-rRNA amplicon sequencing were used to analyze bacterial composition. Duodenal bacterial diversity in cirrhosis was distinct to controls showing significantly higher abundances of Streptococcus, Enterococcus and Veillonella. Patients with bactDNA positive ascites revealed reduced spectrum of core microbiota with Streptococcus as key player of duodenal community and higher prevalence of Granulicatella proving presence of cirrhosis related intestinal dysbiosis. Regarding duodenal fluid bactDNA quantification, no significant differences were found between patients with cirrhosis and controls. Additionally, percentage of subjects with detectable bactDNA in blood did not differ between patients and controls. This study evaluated the diversity of bacterial DNA in different body specimens with potential implications on understanding how intestinal bacterial translocation may affect infectious complications in cirrhosis.
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Affiliation(s)
- Jim Höppner
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Sandra Krohn
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | | | - René Kallies
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany
| | - Adam Herber
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Katharina Zeller
- Endocrinology and Nephrology, University Hospital Leipzig, Leipzig, Germany
| | - Jan Tünnemann
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Madlen Matz-Soja
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Antonis Chatzinotas
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany
| | - Stephan Böhm
- Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Ludwig Maximilians-University, Munich, Germany
| | - Albrecht Hoffmeister
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
| | - Cornelius Engelmann
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
- Institute for Liver and Digestive Health, Royal Free Campus, University College London, London, UK
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité - Universitaetsmedizin Berlin, Berlin, Germany
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Tada F, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, Kumada T. Efficacy and safety of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients with esophageal-gastric varices. J Gastroenterol 2023; 58:1134-1143. [PMID: 37528255 DOI: 10.1007/s00535-023-02026-2] [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: 03/18/2023] [Accepted: 07/11/2023] [Indexed: 08/03/2023]
Abstract
BACKGROUND Bevacizumab inhibits vascular endothelial growth factor-A (VEGF-A), though is known to increase bleeding risk as an adverse event (AE). This study examined whether atezolizumab/bevacizumab (Atez/Bev) for unresectable hepatocellular carcinoma (uHCC) can be used for patients with esophageal-gastric varices (EGV). METHODS From October 2020 to December 2022, 506 uHCC patients (median 74 years) underwent an upper gastrointestinal endoscopy examination were enrolled, after exclusion of those with portal vein tumor thrombus (PVTT). Patients with EGV (≧ F1) were defined as EGV positive, and the cohort was divided into non-EGV (n = 355) and EGV (n = 151). Before introducing Atez/Bev, endoscopic treatment was performed, when necessary. Prognosis was evaluated, retrospectively. RESULTS The EGV group had significantly worse hepatic function, lower platelet count, elevated alpha-fetoprotein, and lower rate of extrahepatic metastasis, and lower rate of first-line use (each P < 0.05) than the other. However, progression-free survival (PFS) was also not a significantly difference between the EGV and non-EGV groups in analyses with (PFS rate at 6/12/18 months: 60%/38%/30% vs. 65%/46%/34%, P = 0.29) or without inverse probability weighting adjustment [median: 10.6 months (95% CI 8.3-14.0) vs. 10.5 months (95% CI 7.8-13.7), P = 0.79]. As for AEs, diarrhea was more frequent in the EGV group (≧ G3: 2.0% vs. 0.3%, P = 0.036), while no significant difference was noted for EGV hemorrhage (≧ G3: 1.3% vs. 0.6%, P = 0.345). Of 28 patients who underwent endoscopic treatments before introducing Atez/Bev, none showed EGV-associated hemorrhage. CONCLUSIONS Atez/Bev might be an effective therapeutic option in patients with EGV, when appropriate endoscopic treatment for EGV is performed.
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Affiliation(s)
- Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-cho, Matsuyama, Ehime, 790-0024, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-cho, Matsuyama, Ehime, 790-0024, Japan.
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Kazuya Kariyama
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Joji Tani
- Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Shinya Fukunishi
- Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama, Japan
| | - Hironori Ochi
- Center of Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan
| | - Takashi Nishimura
- Department of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Hisashi Kosaka
- Department of Surgery, Kansai Medical University, Hirakata, Japan
| | - Tomomitsu Matono
- Department of Hepatology, Himeji St. Mary's Hospital, Himeji, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Yutaka Yata
- Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan
| | - Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-cho, Matsuyama, Ehime, 790-0024, Japan
| | - Kazuhiro Nouso
- Department of Hepatology, Okayama City Hospital, Okayama, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Keisuke Yokohama
- Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Hiroki Nishikawa
- Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Hiroko Iijima
- Department of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masaki Kaibori
- Department of Surgery, Kansai Medical University, Hirakata, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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11
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Abbas N, Rajoriya N, Elsharkawy AM, Chauhan A. Acute-on-chronic liver failure (ACLF) in 2022: have novel treatment paradigms already arrived? Expert Rev Gastroenterol Hepatol 2022; 16:639-652. [PMID: 35786130 DOI: 10.1080/17474124.2022.2097070] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Acute-on-chronic failure (ACLF) is a recognized syndrome in patients with chronic liver disease and is characterized by acute decompensation, organ failure(s), and a high short-term mortality. ACLF is often triggered by ongoing alcohol consumption, gastrointestinal bleeding and/or infections, and is pathophysiologically characterized by uncontrolled systemic inflammation coupled with paradoxical immunoparesis. Patients with ACLF require prompt and early recognition. Management requires extensive utilization of clinical resources often including escalation to intensive care. AREAS COVERED Currently, there are no specific targeted treatments for established ACLF, and management revolves around treating underlying precipitants and providing organ support. In this article, we review the epidemiology and pathophysiology of ACLF and summarize recent advances in management strategies of this syndrome, focusing specifically on novel emerging therapies. EXPERT COMMENTARY ACLF is a challenging condition with rapid clinical course, high short-term mortality and varying clinical phenotypes. Management of ACLF is broadly focused on supportive care often in an intensive care setting with liver transplantation proving to be an increasingly relevant and effective rescue therapy. This disease has clear pathogenesis and epidemiological burden, thus distinguishing it from decompensated cirrhosis; there is clear clinical need for the development of specific and nuanced therapies to treat this condition.
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Affiliation(s)
- Nadir Abbas
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Liver Research, Institute of Immunology and Inflammation, and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, the Medical School, University of Birmingham, Birmingham, UK.,National Institute for Health Research Biomedical Research Centre, University Hospitals Birmingham, Birmingham, UK
| | - Neil Rajoriya
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Liver Research, Institute of Immunology and Inflammation, and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, the Medical School, University of Birmingham, Birmingham, UK
| | - Ahmed M Elsharkawy
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Liver Research, Institute of Immunology and Inflammation, and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, the Medical School, University of Birmingham, Birmingham, UK.,National Institute for Health Research Biomedical Research Centre, University Hospitals Birmingham, Birmingham, UK
| | - Abhishek Chauhan
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK.,Centre for Liver Research, Institute of Immunology and Inflammation, and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, the Medical School, University of Birmingham, Birmingham, UK
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12
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Luo W, Guo S, Zhou Y, Zhao J, Wang M, Sang L, Chang B, Wang B. Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy. Front Microbiol 2022; 13:873160. [PMID: 35572649 PMCID: PMC9092458 DOI: 10.3389/fmicb.2022.873160] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/05/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota is gaining increasing attention, and the concept of the "gut-liver axis" is gradually being recognized. Leaky gut resulting from injury and/or inflammation can cause the translocation of flora to the liver. Microbiota-associated metabolites and components mediate the activation of a series of signalling pathways, thereby playing an important role in the development of hepatocellular carcinoma (HCC). For this reason, targeting the gut microbiota in the diagnosis, prevention, and treatment of HCC holds great promise. In this review, we summarize the gut microbiota and the mechanisms by which it mediates HCC development, and the characteristic alterations in the gut microbiota during HCC pathogenesis. Furthermore, we propose several strategies to target the gut microbiota for the prevention and treatment of HCC, including antibiotics, probiotics, faecal microbiota transplantation, and immunotherapy.
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Affiliation(s)
- Wenyu Luo
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- The Second Clinical College, China Medical University, Shenyang, China
| | - Shiqi Guo
- The Second Clinical College, China Medical University, Shenyang, China
| | - Yang Zhou
- The Second Clinical College, China Medical University, Shenyang, China
| | - Jingwen Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lixuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Bingyuan Wang
- Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
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13
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Ruault C, Zappella N, Labreuche J, Cronier P, Claude B, Garnier M, Vieillard-Baron A, Ortuno S, Mallet M, Cosic O, Crosby L, Lesieur O, Pichon N, Galbois A, Bruel C, Ekpe K, Sauneuf B, Roux D, Legriel S. Identifying early indicators of secondary peritonitis in critically ill patients with cirrhosis. Sci Rep 2021; 11:21076. [PMID: 34702902 PMCID: PMC8548403 DOI: 10.1038/s41598-021-00629-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 10/08/2021] [Indexed: 11/09/2022] Open
Abstract
Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors' functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm3 (OR 3.70; 95%CI 1.38-9.85; P = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30-15.68; P = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.
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Affiliation(s)
- Carole Ruault
- Medical-Surgical Intensive Care Unit, Versailles Hospital, 177 rue de Versailles, 78150, Le Chesnay Cedex, France
| | - Nathalie Zappella
- Anesthesiology and Critical Care Medicine Departement, DMU PARABOL, Bichat-Claude Bernard Hospital, HUPNVS, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Julien Labreuche
- Centre Hospitalier Régional et Universitaire de Lille, ULR 2694 - METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, 59000, Lille, France
| | - Pierrick Cronier
- Intensive Care Unit, Sud-Francilien Hospital Center, 91100, Corbeil-Essonnes, France
| | - Baptiste Claude
- Department of Intensive Care, University Hospital François Mitterrand, 21000, Dijon, France
| | - Marc Garnier
- Department of Anesthesiology and Critical Care Medicine, Sorbonne University, GRC 29, Assistance Publique-Hôpitaux de Paris (AP-HP), DMU DREAM, Tenon University Hospital, 75020, Paris, France
| | - Antoine Vieillard-Baron
- Medical-Surgical Intensive Care Unit, Ambroise Paré University Hospital, APHP, 92100, Boulogne-Billancourt, France
| | - Sofia Ortuno
- Medical Intensive Care Unit, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, 75015, Paris, France
| | - Maxime Mallet
- Groupe Hospitalier Universitaire APHP-Sorbonne Université, Site Pitié-Salpêtrière, Service de Pneumologie, Médecine Intensive et Réanimation (Département R3S), 75013, Paris, France
| | - Olga Cosic
- Medical-Surgical Intensive Care Unit, Hôpital Nord Franche-Comté, 90400, Trevenans, France
| | - Laura Crosby
- Intensive Care Unit, University Hospital of Pointe-à-Pitre, 97159, Pointe-à-Pitre, Guadeloupe, France.,Intensive Care Unit, Centre Hospitalier de Valence, 179 Boulevard Maréchal Juin, 26000, Valence, France
| | - Olivier Lesieur
- Intensive Care Unit, Groupement Hospitalier La Rochelle Ré Aunis, 17000, La Rochelle, France
| | - Nicolas Pichon
- Medical-Surgical Intensive Care Unit, Limoges University Hospital, 87000, Limoges, France
| | - Arnaud Galbois
- Ramsay-Générale de Santé, Hôpital Privé Claude Galien, Service de Réanimation Polyvalente, 91480, Quincy-sous-Sénart, France
| | - Cedric Bruel
- Medical and Surgical Intensive Care Unit, Groupe Hospitalier Paris Saint Joseph, 75014, Paris, France
| | - Kenneth Ekpe
- Medical Intensive Care Unit, Saint Louis Teaching Hospital, Assistance Publique Hôpitaux de Paris, 75010, Paris, France
| | - Bertrand Sauneuf
- General Intensive Care Unit, Cotentin Public Hospital Center, 50100, Cherbourg-en-Cotentin, France
| | - Damien Roux
- Department of Intensive Care, Louis Mourier University Hospital, Assistance Publique-Hôpitaux de Paris, 92700, Colombes, France
| | - Stephane Legriel
- Medical-Surgical Intensive Care Unit, Versailles Hospital, 177 rue de Versailles, 78150, Le Chesnay Cedex, France. .,Université Paris-Saclay, UVSQ, CESP, Team DevPsy, 94807, Villejuif, Inserm, France.
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14
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Kilincalp S, Papachrysos N. Letter: confounders and outcomes in studies of beta-blockers in liver disease-role of PPIs? Aliment Pharmacol Ther 2021; 54:90. [PMID: 34109674 DOI: 10.1111/apt.16306] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Serta Kilincalp
- Division of Gastroenterology/Hepatology, Department of Medicine, Sahlgrenska University Hospital/East, Gothenburg, Sweden
| | - Nikolaos Papachrysos
- Division of Gastroenterology/Hepatology, Department of Medicine, Sahlgrenska University Hospital/East, Gothenburg, Sweden
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15
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Eom JA, Kwon GH, Kim NY, Park EJ, Won SM, Jeong JJ, Raja G, Gupta H, Asmelash Gebru Y, Sharma S, Choi YR, Kim HS, Yoon SJ, Hyun JY, Jeong MK, Park HJ, Min BH, Choi MR, Kim DJ, Suk KT. Diet-Regulating Microbiota and Host Immune System in Liver Disease. Int J Mol Sci 2021; 22:6326. [PMID: 34199182 PMCID: PMC8231888 DOI: 10.3390/ijms22126326] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/07/2021] [Accepted: 06/10/2021] [Indexed: 02/07/2023] Open
Abstract
The gut microbiota has been known to modulate the immune responses in chronic liver diseases. Recent evidence suggests that effects of dietary foods on health care and human diseases are related to both the immune reaction and the microbiome. The gut-microbiome and intestinal immune system play a central role in the control of bacterial translocation-induced liver disease. Dysbiosis, small intestinal bacterial overgrowth, translocation, endotoxemia, and the direct effects of metabolites are the main events in the gut-liver axis, and immune responses act on every pathways of chronic liver disease. Microbiome-derived metabolites or bacteria themselves regulate immune cell functions such as recognition or activation of receptors, the control of gene expression by epigenetic change, activation of immune cells, and the integration of cellular metabolism. Here, we reviewed recent reports about the immunologic role of gut microbiotas in liver disease, highlighting the role of diet in chronic liver disease.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Ki Tae Suk
- Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24253, Korea; (J.A.E.); (G.H.K.); (N.Y.K.); (E.J.P.); (S.M.W.); (J.J.J.); (G.R.); (H.G.); (Y.A.G.); (S.S.); (Y.R.C.); (H.S.K.); (S.J.Y.); (J.Y.H.); (M.K.J.); (H.J.P.); (B.H.M.); (M.R.C.); (D.J.K.)
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16
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Madsen M, Kimer N, Bendtsen F, Petersen AM. Fecal microbiota transplantation in hepatic encephalopathy: a systematic review. Scand J Gastroenterol 2021; 56:560-569. [PMID: 33840331 DOI: 10.1080/00365521.2021.1899277] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction that ranges in severity from subclinical alterations to coma. Patients with chronic liver disease are predisposed to HE due to metabolic failure and portosystemic shunting of toxins, of which ammonia is believed to be the main toxic chemical. Fecal microbiota transplantation (FMT) may reduce ammonia synthesis by altering the gut microbiota composition to a taxon low in urease, diminish uptake of ammonia by reestablishing the integrity of the intestinal barrier and increase ammonia clearance by improving liver function. In this systematic review, we summarize the insights of the current literature examining FMT as a treatment for HE.PubMed and EMBASE were searched on 08 February 2021 using the MeSH terms 'fecal microbiota transplantation & hepatic encephalopathy' and the abbreviations 'FMT & HE'.Eight studies fulfilled our inclusion criteria, comprising two randomized clinical trials, three case reports and three rodent studies. Thirty-nine patients with HE were treated with FMT. Thirty-nine rodents received FMT in laboratory tests. FMT improved neurocognitive test results in four human studies and two rodent studies. Microbiota originating from donors was found in human recipients one year post-FMT. Readmission of patients was lower after treatment with FMT compared to standard of care.FMT may improve neurocognitive function and reduce serious adverse events in patients with HE, but the studies conducted so far have been small and their long-term follow-up is limited. Large-scale, randomized and controlled trials are needed to validate and help standardize the clinical application of FMT in cases of HE.
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Affiliation(s)
- Mathias Madsen
- Gastro Unit, Medical Division, Hvidovre University Hospital, Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Hvidovre University Hospital, Copenhagen, Denmark.,Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Hvidovre University Hospital, Copenhagen, Denmark
| | - Andreas Munk Petersen
- Gastro Unit, Medical Division, Hvidovre University Hospital, Copenhagen, Denmark.,Department of Clinical Microbiology, Hvidovre University Hospital, Copenhagen, Denmark
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17
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Lężyk-Ciemniak E, Tworkiewicz M, Wilczyńska D, Szaflarska-Popławska A, Krogulska A. Usefulness of Testing for Fecal Calprotectin in Pediatric Gastroenterology Clinical Practice. Med Princ Pract 2021; 30:311-319. [PMID: 33120396 PMCID: PMC8436627 DOI: 10.1159/000512631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 10/25/2020] [Indexed: 01/11/2023] Open
Abstract
Gastrointestinal tract symptoms such as abdominal pain, constipation, diarrhea, and fever are common reasons for which parents take children to the pediatrician. An increasing prevalence of chronic diseases of the gastrointestinal tract and a decrease in the median age of their onset indicate the need to search for new diagnostic methods for differentiating inflammatory bowel diseases (IBDs) from other gastrointestinal tract diseases. An example of a novel biomarker is fecal calprotectin (FC), which is considered a noninvasive and useful marker of intestinal inflammation. This review summarizes currently available information on the use of FC in the diagnosis and monitoring of IBD in children. Additionally, it attempts to determine the course of action depending on the concentration of FC. Application of FC determination within the framework of primary medical care can decrease the number of children unnecessarily referred either to endoscopic or radiologic examination. There is a double advantage of calprotectin screening; for patients, it reduces delays in diagnosis and unnecessary exposure to endoscopy, and for doctors, it reduces pressure on endoscopy testing and facilitates decision-making. We emphasize the role of FC as a noninvasive marker, primarily in patients with IBD, in monitoring disease activity, predicting relapse, monitoring therapy efficacy, and monitoring postoperative relapses.
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Affiliation(s)
- Eliza Lężyk-Ciemniak
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Magdalena Tworkiewicz
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Dominika Wilczyńska
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Anna Szaflarska-Popławska
- Department of Pediatric Endoscopy and Gastrointestinal Function Testing, NCU Toruń, Bydgoszcz, Poland
| | - Aneta Krogulska
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
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18
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Labenz C, Kostev K, Galle PR, Wörns MA, Labenz J, Tanislav C, Adarkwah CC. Proton pump inhibitor use is associated with a variety of infections in patients with liver cirrhosis. Medicine (Baltimore) 2020; 99:e23436. [PMID: 33327272 PMCID: PMC7738005 DOI: 10.1097/md.0000000000023436] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
There is evidence that intake of proton pump inhibitors (PPI) increases the risk for spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis. However, data regarding the impact of PPI intake on occurrence of infections other than SBP are still lacking.We hypothesized that PPI use is associated with a higher rate of infections other than SBP in patients with liver cirrhosis.The current case-control study sample included patients with liver cirrhosis from the Disease Analyzer database (IQVIA), which compiles data such as risk factors, drug prescriptions and diagnoses obtained from general practitioners and specialists in Germany. In total, 2,823 patients with infections were matched with 2,823 patients without infections by propensity scores. For quantification of PPI use the prescribed quantity of PPI during the past 12 months before index date was analyzed.Frequency of PPI users was significantly higher in patients with infections than in patients without infections (47.9% vs 37.9%). In regression analysis, PPI use was significantly associated with the occurrence of infections overall (OR 1.55, 95% CI 1.39-1.72, P < .001), and associated with the occurrence of lower respiratory tract infections, urinary tract infections and infectious gastroenteritis. There was no association between PPI use and skin infections. Pantoprazole and omeprazole were the most frequently prescribed PPIs and were both independently associated with the occurrence of infections.PPI use may be associated with infections other than SBP in patients with liver cirrhosis. Prescription of PPI should be limited to patients with a clear indication.
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Affiliation(s)
- Christian Labenz
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz
| | | | - Peter R. Galle
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz
| | - Marcus-Alexander Wörns
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz
| | | | | | - Charles Christian Adarkwah
- Department of General Practice and Family Medicine, Philipps-University, Marburg
- CAPHRI School for Public Health and Primary Care, Department of Health Services Research, Maastricht University, Maastricht, The Netherlands
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19
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Li Q, Wang J, Lu M, Qiu Y, Lu H. Acute-on-Chronic Liver Failure From Chronic-Hepatitis-B, Who Is the Behind Scenes. Front Microbiol 2020; 11:583423. [PMID: 33365018 PMCID: PMC7750191 DOI: 10.3389/fmicb.2020.583423] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/13/2020] [Indexed: 12/12/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is an acute syndrome accompanied with decompensation of cirrhosis, organ failure with high 28-day mortality rate. Systemic inflammation is the main feature of ACLF, and poor outcome is closely related with exacerbated systemic inflammatory responses. It is well known that severe systemic inflammation is an important event in chronic hepatitis B (CHB)-ACLF, which eventually leads to liver injury. However, the initial CHB-ACLF events are unclear; moreover, the effect of these events on host immunity as well as that of immune imbalance on CHB-ACLF progression are unknown. Here, we investigate the initial events of ACLF progression, discuss possible mechanisms underlying ACLF progression, and provide a new model for ACLF prediction and treatment. We review the characteristics of ACLF, and consider its plausible immune predictors and alternative treatment strategies.
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Affiliation(s)
- Qian Li
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Jun Wang
- Center of Clinical Laboratory, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, China
| | - Mengji Lu
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
| | - Yuanwang Qiu
- Department of Hepatology, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, China
| | - Hongzhou Lu
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
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20
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GUIMARÃES VM, SANTOS VN, BORGES PSDA, DE FARIAS JLR, GRILLO P, PARISE ER. PERIPHERAL BLOOD ENDOTOXIN LEVELS ARE NOT ASSOCIATED WITH SMALL INTESTINAL BACTERIAL OVERGROWTH IN NONALCOHOLIC FATTY LIVER DISEASE WITHOUT CIRRHOSIS. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:471-476. [DOI: 10.1590/s0004-2803.202000000-82] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
ABSTRACT BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease worldwide. Approximately 20% of individuals with NAFLD develop nonalcoholic steatohepatitis (NASH), which is associated with increased risk of cirrhosis, portal hypertension, and hepatocellular carcinoma. Intestinal microflora, including small intestinal bacterial overgrowth (SIBO), appear to play an important role in the pathogenesis of the disease, as demonstrated in several clinical and experimental studies, by altering intestinal permeability and allowing bacterial endotoxins to enter the circulation. OBJECTIVE: To determine the relationship between SIBO and endotoxin serum levels with clinical, laboratory, and histopathological aspects of NAFLD and the relationship between SIBO and endotoxin serum levels before and after antibiotic therapy. METHODS: Adult patients with a histological diagnosis of NAFLD, without cirrhosis were included. A comprehensive biochemistry panel, lactulose breath test (for diagnosis of SIBO), and serum endotoxin measurement (chromogenic LAL assay) were performed. SIBO was treated with metronidazole 250 mg q8h for 10 days and refractory cases were given ciprofloxacin 500 mg q12h for 10 days. RESULTS: Overall, 42 patients with a histopathological diagnosis of NAFLD were examined. The prevalence of SIBO was 26.2%. Comparison of demographic and biochemical parameters between patients with SIBO and those without SIBO revealed no statistically significant differences, except for use of proton pump inhibitors, which was significantly more frequent in patients with positive breath testing. The presence of SIBO was also associated with greater severity of hepatocellular ballooning on liver biopsy. Although the sample, as a whole, have elevated circulating endotoxin levels, we found no significant differences in this parameter between the groups with and without SIBO. Endotoxin values before and after antibiotic treatment did not differ, even on paired analysis, suggesting absence of any relationship between these factors. Serum endotoxin levels were inversely correlated with HDL levels, and directly correlated with triglyceride levels. CONCLUSION: Serum endotoxin levels did not differ between patients with and without SIBO, nor did these levels change after antibacterial therapy, virtually ruling out the possibility that elevated endotoxinemia in non-cirrhotic patients with NAFLD is associated with SIBO. Presence of SIBO was associated with greater severity of ballooning degeneration on liver biopsy, but not with a significantly higher prevalence of NASH. Additional studies are needed to evaluate the reproducibility and importance of this finding in patients with NAFLD and SIBO.
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Ding JH, Jin Z, Yang XX, Lou J, Shan WX, Hu YX, Du Q, Liao QS, Xie R, Xu JY. Role of gut microbiota via the gut-liver-brain axis in digestive diseases. World J Gastroenterol 2020; 26:6141-6162. [PMID: 33177790 PMCID: PMC7596643 DOI: 10.3748/wjg.v26.i40.6141] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/29/2020] [Accepted: 09/18/2020] [Indexed: 02/06/2023] Open
Abstract
The gut-brain axis is a bidirectional information interaction system between the central nervous system (CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut- liver-brain axis.
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Affiliation(s)
- Jian-Hong Ding
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Zhe Jin
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Xiao-Xu Yang
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Jun Lou
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Wei-Xi Shan
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Yan-Xia Hu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Qian Du
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Qiu-Shi Liao
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Rui Xie
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Jing-Yu Xu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
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Elevated serum procalcitonin levels and their association with the prognosis of patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2020; 32:1222-1228. [PMID: 31851098 DOI: 10.1097/meg.0000000000001644] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Bacterial infection is a major complication in patients with liver cirrhosis. Procalcitonin is an early diagnostic marker of bacterial infection. This study aimed to investigate the association between the serum procalcitonin levels and the prognosis of patients with liver cirrhosis. METHODS We retrospectively analyzed the serum procalcitonin levels in 236 hospitalized patients with liver cirrhosis. The impact of the serum procalcitonin level on their prognoses was evaluated using multivariate Cox proportional hazards analyses and the Kaplan-Meier method. RESULTS The serum procalcitonin level was higher (≥0.05 ng/mL) in 151 (64%) patients, and it was significantly higher in the patients with Child-Turcotte-Pugh class C than in those with Child-Turcotte-Pugh classes A/B. Patients with refractory ascites, hepatic encephalopathy, gastrointestinal bleeding, and bacterial infections had elevated serum procalcitonin levels. The multivariate analyses showed a serum procalcitonin level ≥0.05 ng/mL was an independent prognostic factor for liver cirrhosis (hazard ratio = 1.64; 95% confidence interval = 1.07-2.53; P = 0.024). During a median follow-up interval of 2.1 years, the three-year cumulative survival rates for the patients with normal and elevated serum procalcitonin levels were 72.9 and 56.0%, respectively (P < 0.001). The subgroup analyses that stratified the patients according to age, the Child-Turcotte-Pugh classification, and the presence of liver cancer showed the serum procalcitonin level was significantly associated with their prognoses. CONCLUSIONS The patients with liver cirrhosis had higher serum procalcitonin levels, regardless of local bacterial infections, and higher procalcitonin levels were associated with poor prognoses.
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Current Status and Prospects of Spontaneous Peritonitis in Patients with Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3743962. [PMID: 32724800 PMCID: PMC7364234 DOI: 10.1155/2020/3743962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 06/03/2020] [Indexed: 12/14/2022]
Abstract
Spontaneous bacterial peritonitis (SBP) is a common cirrhotic ascites complication which exacerbates the patient's condition. SBP is caused by gram-negative bacilli and, to a lesser extent, gram-positive cocci. Hospital-acquired infections show higher levels of drug-resistant bacteria. Geographical location influences pathogenic bacteria distribution; therefore, different hospitals in the same country record different bacteria strains. Intestinal changes and a weak immune system in patients with liver cirrhosis lead to bacterial translocation thus causing SBP. Early diagnosis and timely treatment are important in SBP management. When the treatment effect is not effective, other rare pathogens should be explored.
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Wongtrakul W, Charoenngnam N, Ungprasert P. Use of proton pump inhibitors is associated with a higher risk of pneumonia in cirrhotic patients: a systematic review and meta-analysis. Ann Gastroenterol 2020; 33:277-284. [PMID: 32382231 PMCID: PMC7196626 DOI: 10.20524/aog.2020.0483] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 03/04/2020] [Indexed: 12/15/2022] Open
Abstract
Background Proton pump inhibitors (PPIs) are commonly prescribed for cirrhotic patients. However, the use of PPIs in these patients may increase the risk of bacterial infection. The current study aimed to investigate the risk of developing pneumonia among cirrhotic patients exposed to PPIs. Methods A literature search was independently conducted by 2 investigators using the MEDLINE and EMBASE databases up to September 2019. To be eligible, a study had to be an observational (cohort, case-control or cross-sectional) study that included one group of cirrhotic patients with PPI use and another group of cirrhotic patients without PPI use. Effect estimates of the association between PPI use and pneumonia had to be reported. Point estimates and standard errors from each eligible study were combined together using the generic inverse variance method of DerSimonian and Laird. Results Of 1947 articles identified from the 2 databases, 3 cohort and 5 cross-sectional studies with 40,295 participants met the eligibility criteria and were included in the meta-analysis. The pooled analysis found that cirrhotic patients with a history of PPI use had a significantly higher risk of developing pneumonia than those without PPI use, with a pooled risk ratio of 1.36 (95% confidence interval 1.00-1.85; I2 47%). Conclusion A significantly increased risk of pneumonia among cirrhotic patients exposed to PPIs was demonstrated in this study.
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Affiliation(s)
| | | | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine (Patompong Ungprasert), Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Schwarzer R, Reiberger T, Mandorfer M, Kivaranovic D, Hametner S, Hametner S, Paternostro R, Scheiner B, Schneeweiss-Friedl J, Trauner M, Schoefl R, Maieron A. The von Willebrand Factor antigen to platelet ratio (VITRO) score predicts hepatic decompensation and mortality in cirrhosis. J Gastroenterol 2020; 55:533-542. [PMID: 31832759 DOI: 10.1007/s00535-019-01656-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 11/30/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND The ratio of von Willebrand Factor to platelets (VITRO) reflects the severity of fibrosis and portal hypertension and might thus hold prognostic value. METHODS Patients with compensated cirrhosis were recruited. VITRO, Child-Pugh score (CPS) and MELD were determined at study entry. Hepatic decompensation was defined as variceal bleeding, ascites or hepatic encephalopathy. Liver transplantation and death were recorded. RESULTS One hundred and ninety-four patients with compensated cirrhosis (CPS-A 89%, B 11%; 56% male; median age 56 years; 50% with varices) were included. During a median follow-up of 45 months (IQR 29-61), decompensation occurred in 35 (18%) patients and 14 (7%) patients deceased. The risk of hepatic decompensation was significantly increased in the n = 88 (45%) patients with a VITRO ≥ 2.5 (p < 0.001). Patients with a VITRO ≥ 2.5 had a higher probability of decompensation at 1-year 9% (95% CI 3-16) vs. 0% (95% CI 0-0) and at 2-years 18% (95% CI 10-27%), vs. 4% (95% CI 0-8%) as compared to patients with VITRO < 2.5. Patients with VITRO ≥ 2.5, the estimated 1-year/2-year survival rates were at 98% (95% CI 95-100%) and 94% (95% CI 88-99%) as compared to 100% (95% CI 100-100%) both in the patients with a VITRO < 2.5 (p < 0.001). After adjusting for age, albumin and MELD, VITRO ≥ 2.5 remained as significant predictor of transplant-free mortality (HR 1.38, CI 1.09-1.76; p = 0.007). Patients with compensated cirrhosis and VITRO > 2.1 after hepatitis C eradication remained at significantly increased risk for decompensation (p = 0.033). CONCLUSIONS VITRO is a valuable prognostic tool for estimating the risk of decompensation and mortality in patients with compensated cirrhosis-including the setting after hepatitis C eradication.
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Affiliation(s)
- Rémy Schwarzer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Danijel Kivaranovic
- Department of Statistics and Operations Research, University of Vienna, Oskar-Morgenstern-Platz 1, 1090, Vienna, Austria
| | - Silvia Hametner
- Division of Gastroenterology and Hepatology, Ordensklinikum Linz, Fadingerplatz 1, 4020, Linz, Austria
| | - Stephanie Hametner
- Division of Gastroenterology and Hepatology, Ordensklinikum Linz, Fadingerplatz 1, 4020, Linz, Austria
| | - Rafael Paternostro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | | | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Rainer Schoefl
- Division of Gastroenterology and Hepatology, Ordensklinikum Linz, Fadingerplatz 1, 4020, Linz, Austria
| | - Andreas Maieron
- Division of Gastroenterology and Hepatology, Ordensklinikum Linz, Fadingerplatz 1, 4020, Linz, Austria.
- Internal Medicine II, Gastroenterology and Hepatology, Karl Landsteiner University of Health Sciences, University Hospital of St. Pölten, Dunant Platz 1, 3100, St. Pölten, Austria.
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Chen Z, Xie Y, Zhou F, Zhang B, Wu J, Yang L, Xu S, Stedtfeld R, Chen Q, Liu J, Zhang X, Xu H, Ren J. Featured Gut Microbiomes Associated With the Progression of Chronic Hepatitis B Disease. Front Microbiol 2020; 11:383. [PMID: 32265857 PMCID: PMC7098974 DOI: 10.3389/fmicb.2020.00383] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 02/20/2020] [Indexed: 12/11/2022] Open
Abstract
Dysbiosis of gut microbiota during the progression of HBV-related liver disease is not well understood, as there are very few reports that discuss the featured bacterial taxa in different stages. The aim of this study was to reveal the featured bacterial species whose abundances are directly associated with HBV disease progression, that is, progression from healthy subjects to, chronic HBV infection, chronic hepatitis B to liver cirrhosis. Approximately 400 fecal samples were collected, and 97 samples were subjected to 16S rRNA gene sequencing after age and BMI matching. Compared with the healthy individuals, significant gut microbiota alterations were associated with the progression of liver disease. LEfSe results showed that the HBV infected patients had higher Fusobacteria, Veillonella, and Haemophilus abundance while the healthy individuals had higher levels of Prevotella and Phascolarctobacterium. Indicator analysis revealed that 57 OTUs changed as the disease progressed, and their combination produced an AUC value of 90% (95% CI: 86-94%) between the LC and non-LC groups. In addition, the abundances of OTU51 (Dialister succinatiphilus) and OTU50 (Alistipes onderdonkii) decreased as the disease progressed, and these results were further verified by qPCR. The LC patients had the higher bacterial network complexity, which was accompanied with a lower abundance of potential beneficial bacterial taxa, such as Dialister and Alistipes, while they had a higher abundance of pathogenic species within Actinobacteria. The compositional and network changes in the gut microbiota in varied CHB stages, suggest the potential contributions of gut microbiota in CHB disease progression.
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Affiliation(s)
- Zhangran Chen
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
- College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
| | - Yurou Xie
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Fei Zhou
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Bangzhou Zhang
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Jingtong Wu
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Luxi Yang
- School of Life Sciences, Xiamen University, Xiamen, China
| | - Shuangbin Xu
- Fisheries College, Jimei University, Xiamen, China
| | - Robert Stedtfeld
- Civil and Environmental Engineering, Michigan State University, East Lansing, MI, United States
| | - Qiongyun Chen
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Jingjing Liu
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Xiang Zhang
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Hongzhi Xu
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
| | - Jianlin Ren
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China
- Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen, China
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Jiang S, Xiao G, Koh AY, Kim J, Li Q, Zhan X. A Bayesian zero-inflated negative binomial regression model for the integrative analysis of microbiome data. Biostatistics 2019; 22:522-540. [PMID: 31844880 DOI: 10.1093/biostatistics/kxz050] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 10/07/2019] [Accepted: 10/09/2019] [Indexed: 12/13/2022] Open
Abstract
Microbiome omics approaches can reveal intriguing relationships between the human microbiome and certain disease states. Along with identification of specific bacteria taxa associated with diseases, recent scientific advancements provide mounting evidence that metabolism, genetics, and environmental factors can all modulate these microbial effects. However, the current methods for integrating microbiome data and other covariates are severely lacking. Hence, we present an integrative Bayesian zero-inflated negative binomial regression model that can both distinguish differentially abundant taxa with distinct phenotypes and quantify covariate-taxa effects. Our model demonstrates good performance using simulated data. Furthermore, we successfully integrated microbiome taxonomies and metabolomics in two real microbiome datasets to provide biologically interpretable findings. In all, we proposed a novel integrative Bayesian regression model that features bacterial differential abundance analysis and microbiome-covariate effects quantifications, which makes it suitable for general microbiome studies.
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Affiliation(s)
- Shuang Jiang
- Department of Statistical Science, Southern Methodist University, Dallas, TX 75275, USA
| | - Guanghua Xiao
- Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Andrew Y Koh
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Jiwoong Kim
- Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Qiwei Li
- Department of Mathematical Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA
| | - Xiaowei Zhan
- Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Abstract
BACKGROUND AND AIMS Bacterial infections arising in patients with liver cirrhosis are associated with life-threatening complications such as hepatic encephalopathy and spontaneous bacterial peritonitis in relation to bacterial translocation. To investigate the state of bacterial translocation, we surveyed the peripheral blood microbiota by 16S rRNA gene sequencing and analysed the blood microbial profiles. METHODS Sixty-six patients with liver cirrhosis were enrolled in this study, whereas 14 healthy individuals were also analysed as controls. Total RNA was purified from the peripheral blood, and an approximately 430 base pair genomic locus which included the V3-V4 region of the 16s rRNA gene was amplified and assessed using bacterial pyrosequencing. RESULTS At the genus level, a total of 183 operational taxonomic units were identified in cirrhotic patients, whereas 123 units in controls. Intergroup differences in gut microbiota were analysed by the linear discriminant analysis effect size, which showed that the abundance of Enterobacteriaceae was significantly higher in cirrhotics. On the contrary, the abundance of Akkermansia, Rikenellaceae and Erysipelotrichales were significantly lower in cirrhotics (relative abundance of Akkermansia in cirrhotics and controls: 0% and 0.2%, respectively; Rikenellaceae: 0.1% and 0.92%; Erysipelotrichales: 0.58% and 1.21%). CONCLUSION The present study has demonstrated that various circulating bacteria are present in cirrhotic patients, and the diversity of such bacteria is consistent with the presence of dysbiosis in cirrhotics. Although the clinical significance of the findings remains to be clarified, the findings may potentially facilitate diagnostic and therapeutic attempts to comprehend and furthermore to manipulate bacterial infections in cirrhotic patients.
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Sorribas M, Jakob MO, Yilmaz B, Li H, Stutz D, Noser Y, de Gottardi A, Moghadamrad S, Hassan M, Albillos A, Francés R, Juanola O, Spadoni I, Rescigno M, Wiest R. FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis. J Hepatol 2019; 71:1126-1140. [PMID: 31295531 DOI: 10.1016/j.jhep.2019.06.017] [Citation(s) in RCA: 167] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 05/26/2019] [Accepted: 06/19/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Pathological bacterial translocation (PBT) in cirrhosis is the hallmark of spontaneous bacterial infections, increasing mortality several-fold. Increased intestinal permeability is known to contribute to PBT in cirrhosis, although the role of the mucus layer has not been addressed in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined, but we hypothesize that the recently described gut-vascular barrier (GVB) is impaired in experimental portal hypertension, leading to increased accessibility of the vascular compartment for translocating bacteria. MATERIALS Cirrhosis was induced in mouse models using bile-duct ligation (BDL) and CCl4. Pre-hepatic portal-hypertension was induced by partial portal vein ligation (PPVL). Intestinal permeability was compared in these mice after GFP-Escherichia coli or different sized FITC-dextrans were injected into the intestine. RESULTS Healthy and pre-hepatic portal-hypertensive (PPVL) mice lack translocation of FITC-dextran and GFP-E. coli from the small intestine to the liver, whereas BDL and CCl4-induced cirrhotic mice demonstrate pathological translocation, which is not altered by prior thoracic-duct ligation. The mucus layer is reduced in thickness, with loss of goblet cells and Muc2-staining and expression in cirrhotic but not PPVL mice. These changes are associated with bacterial overgrowth in the inner mucus layer and pathological translocation of GFP-E. coli through the ileal epithelium. GVB is profoundly altered in BDL and CCl4-mice with Ileal extravasation of large-sized 150 kDa-FITC-dextran, but only slightly altered in PPVL mice. This pathological endothelial permeability and accessibility in cirrhotic mice is associated with augmented expression of PV1 in intestinal vessels. OCA but not fexaramine stabilizes the GVB, whereas both FXR-agonists ameliorate gut to liver translocation of GFP-E. coli. CONCLUSIONS Cirrhosis, but not portal hypertension per se, grossly impairs the endothelial and muco-epithelial barriers, promoting PBT to the portal-venous circulation. Both barriers appear to be FXR-modulated, with FXR-agonists reducing PBT via the portal-venous route. LAY SUMMARY For intestinal bacteria to enter the systemic circulation, they must cross the mucus and epithelial layer, as well as the gut-vascular barrier. Cirrhosis disrupts all 3 of these barriers, giving bacteria access to the portal-venous circulation and thus, the gut-liver axis. Diminished luminal bile acid availability, cirrhosis and the associated reduction in farnesoid x receptor (FXR) signaling seem, at least partly, to mediate these changes, as FXR-agonists reduce bacterial translocation via the portal-venous route to the liver in cirrhosis.
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Affiliation(s)
- Marcel Sorribas
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - Manuel O Jakob
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Bahtiyar Yilmaz
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - Hai Li
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - David Stutz
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Yannik Noser
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Andrea de Gottardi
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Sheida Moghadamrad
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - Moshin Hassan
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - Agustin Albillos
- Department of Gastroenterology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, CIBEREHD, Madrid, Spain
| | - Ruben Francés
- Hepatic and Intestinal Immunobiology Group, Universidad Miguel Hernández-CIBERehd, San Juan, Spain
| | - Oriol Juanola
- Hepatic and Intestinal Immunobiology Group, Universidad Miguel Hernández-CIBERehd, San Juan, Spain
| | - Ilaria Spadoni
- Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini, 20090 Pieve Emanuele, MI, Italy
| | - Maria Rescigno
- Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini, 20090 Pieve Emanuele, MI, Italy; Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, MI, Italy
| | - Reiner Wiest
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland; Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
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Simbrunner B, Mandorfer M, Trauner M, Reiberger T. Gut-liver axis signaling in portal hypertension. World J Gastroenterol 2019; 25:5897-5917. [PMID: 31660028 PMCID: PMC6815800 DOI: 10.3748/wjg.v25.i39.5897] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 08/15/2019] [Accepted: 09/28/2019] [Indexed: 02/06/2023] Open
Abstract
Portal hypertension (PHT) in advanced chronic liver disease (ACLD) results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition (structural component) and intrahepatic vasoconstriction (functional component). PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding. Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns (PAMPs) that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways. Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability: The intestinal barrier function is affected by impaired microcirculation, neoangiogenesis, and abnormal vascular and mucosal permeability. The close bidirectional relationship between the gut and the liver has been termed “gut-liver axis”. Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function, intestinal barrier integrity, as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects. The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments, however, further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed. In this review, we summarize the clinical impact of PHT on the course of liver disease, discuss the underlying pathophysiological link of PHT to gut-liver axis signaling, and provide insight into molecular mechanisms that may represent novel therapeutic targets.
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Affiliation(s)
- Benedikt Simbrunner
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna 1180, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1180, Austria
| | - Mattias Mandorfer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna 1180, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1180, Austria
| | - Michael Trauner
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna 1180, Austria
| | - Thomas Reiberger
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna 1180, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1180, Austria
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31
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Yousif MM, Sadek AMEM, Farrag HA, Selim FO, Hamed EF, Salama RI. Associated vitamin D deficiency is a risk factor for the complication of HCV-related liver cirrhosis including hepatic encephalopathy and spontaneous bacterial peritonitis. Intern Emerg Med 2019; 14:753-761. [PMID: 30706253 DOI: 10.1007/s11739-019-02042-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 01/19/2019] [Indexed: 02/07/2023]
Abstract
The influence of vitamin D, 25-hydroxyvitamin D (25(OH)D), deficiency on hepatitis C virus (HCV)-related cirrhosis had been poorly elucidated especially in patients with hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). We aimed to investigate the association between vitamin D deficiency and the risk of SBP or HE, including the mortality rate. Serum 25(OH)D levels were prospectively determined in 135 patients. Of them, 45 patients had complications with HE and 45 patients had complications with SBP; 45 cirrhotic patients without complication served as the control group. Vitamin D deficiency was defined as 25(OH)D levels < 20 ng/ml. Receiver operating characteristic (ROC) and Kaplan-Meier method with log-rank test were used in our statistical analysis. Predictors of survival were determined using Cox regression analysis. Serum 25(OH)D levels were significantly (P < 0.05) lower in the HE and SBP groups than in the control group (6.81 ± 2.75, 7.15 ± 2.10, 16.28 ± 6.60, respectively). Moreover, serum 25(OH)D levels were significantly lower in the high HE grade than in the low grade (P < 0.001). Regarding the SBP group, classic SBP was associated with lower 25(OH)D levels compared to other types (P < 0.001). ROC curve revealed that lower 25(OH)D levels less than 7.1 ng/ml and 6.6 ng/ml could predict the mortality in SBP and HE patients, respectively, with high sensitivity and specificity. Serum 25(OH)D levels < 5 ng/ml were associated with significant higher mortality rate (HR = 2.76, P = 0.001). Lower 25(OH)D levels were associated with HE and SBP in cirrhotic patients. In addition, it may be considered a prognostic parameter for the severity of liver cirrhosis.
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Affiliation(s)
- Monkez Moteih Yousif
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | | | - Hesham Ahmad Farrag
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | - Fayrouz Othman Selim
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | - Emad Fawzi Hamed
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | - Rasha Ibrahim Salama
- Tropical Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Egypt
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Lu HF, Ren ZG, Li A, Zhang H, Xu SY, Jiang JW, Zhou L, Ling Q, Wang BH, Cui GY, Chen XH, Zheng SS, Li LJ. Fecal Microbiome Data Distinguish Liver Recipients With Normal and Abnormal Liver Function From Healthy Controls. Front Microbiol 2019; 10:1518. [PMID: 31333622 PMCID: PMC6619441 DOI: 10.3389/fmicb.2019.01518] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 06/18/2019] [Indexed: 12/27/2022] Open
Abstract
Emerging evidence suggests that altered intestinal microbiota plays an important role in the pathogenesis of many liver diseases, mainly by promoting inflammation via the "intestinal microbiota-immunity-liver" axis. We aimed to investigate the fecal microbiome of liver recipients with abnormal/normal liver function using 16S rRNA gene sequencing. Fecal samples were collected from 90 liver recipients [42 with abnormal liver function (Group LT_A) and 48 with normal liver function (Group LT_N)] and 61 age- and gender-matched healthy controls (HCs). Fecal microbiomes were analyzed for comparative composition, diversity, and richness of microbial communities. Principal coordinates analysis successfully distinguished the fecal microbiomes of recipients in Group LT_A from healthy subjects, with the significant decrease of fecal microbiome diversity in recipients in Group LT_A. Other than a higher relative abundance of opportunistic pathogens such as Klebsiella and Escherichia/Shigella in all liver recipients, the main difference in gut microbiome composition between liver recipients and HC was the lower relative abundance of beneficial butyrate-producing bacteria in the recipients. Importantly, we established a fecal microbiome index (specific alterations in Staphylococcus and Prevotella) that could be used to distinguish Group LT_A from Group LT_N, with an area under the receiver operating characteristic curve value of 0.801 and sensitivity and specificity values of 0.771 and 0.786, respectively. These findings revealed unique gut microbial characteristics of liver recipients with abnormal and normal liver functions, and identified fecal microbial risk indicators of abnormal liver function in liver recipients.
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Affiliation(s)
- Hai-Feng Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhi-Gang Ren
- Department of Infectious Diseases, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ang Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Infectious Diseases, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hua Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shao-Yan Xu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jian-Wen Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
- Health Management Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Qi Ling
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Bao-Hong Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Guang-Ying Cui
- Department of Infectious Diseases, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xin-Hua Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Lan-Juan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Dam G, Vilstrup H, Andersen PK, Bossen L, Watson H, Jepsen P. Effect of proton pump inhibitors on the risk and prognosis of infections in patients with cirrhosis and ascites. Liver Int 2019; 39:514-521. [PMID: 30472808 DOI: 10.1111/liv.14012] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 10/30/2018] [Accepted: 11/17/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Many patients with cirrhosis use proton pump inhibitors. We aimed to determine their effects on the risk and prognosis of infections in patients with cirrhosis and ascites. METHODS We used data from three 1-year trials of satavaptan treatment of ascites (N = 1198) to compare incidence and 90-day mortality of first-time infections between users and nonusers of proton pump inhibitors. With standard and marginal structural Cox models, we adjusted for differences in gender, age, cirrhosis aetiology, Model for End-stage Liver Disease score, serum albumin, lactulose use, severity of ascites, and history of spontaneous bacterial peritonitis or variceal bleeding. RESULTS During the follow-up, 446 patients had an infection. At inclusion, 524 patients (44%) used proton pump inhibitors, and 645 (54%) used them at some point during the follow-up. Proton pump inhibitor use increased the rate of infections overall (adjusted hazard ratio = 1.43, 95% CI 1.18-1.74), and it also increased the rate of all specific types of infections except upper respiratory tract infections of presumably viral origin. The estimated cumulative risk of infections was 36.4% for proton pump inhibitor users vs 25.1% for nonusers at 6 months (relative risk = 1.45, 95% CI 1.22-1.73), and 45.2% vs 37.7% at 1 year (relative risk = 1.20, 95% 0.97-1.40). Use of proton pump inhibitors did not affect mortality during the 90 days following infection (adjusted hazard ratio = 0.83, 95% CI 0.53-1.31). CONCLUSIONS Approximately half of patients with cirrhosis and ascites use proton pump inhibitors. This use increases their risk of bacterial infections, but does not affect their prognosis after an infection occurs.
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Affiliation(s)
- Gitte Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Lars Bossen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
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Zainul-Abidin S, Amanatullah DF, Anderson MB, Austin M, Barretto JM, Battenberg A, Bedard NA, Bell K, Blevins K, Callaghan JJ, Cao L, Certain L, Chang Y, Chen JP, Cizmic Z, Coward J, DeMik DE, Diaz-Borjon E, Enayatollahi MA, Feng JE, Fernando N, Gililland JM, Goodman S, Goodman S, Greenky M, Hwang K, Iorio R, Karas V, Khan R, Kheir M, Klement MR, Kunutsor SK, Limas R, Morales Maldonado RA, Manrique J, Matar WY, Mokete L, Nung N, Pelt CE, Pietrzak JRT, Premkumar A, Rondon A, Sanchez M, Novaes de Santana C, Sheth N, Singh J, Springer BD, Tay KS, Varin D, Wellman S, Wu L, Xu C, Yates AJ. General Assembly, Prevention, Host Related General: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty 2019; 34:S13-S35. [PMID: 30360983 DOI: 10.1016/j.arth.2018.09.050] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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35
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Mani I, Alexopoulou A, Vasilieva L, Hadziyannis E, Agiasotelli D, Bei M, Alexopoulos T, Dourakis SP. Human beta-defensin-1 is a highly predictive marker of mortality in patients with acute-on-chronic liver failure. Liver Int 2019; 39:299-306. [PMID: 30261128 DOI: 10.1111/liv.13977] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 08/16/2018] [Accepted: 09/19/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIM Human beta-defensin-1 (hBD-1) is a natural antimicrobial peptide expressed in the epithelia of multiple tissues including the digestive tract. In the current study, hBD-1 levels were determined in different subsets of patients with decompensated cirrhosis including acute-on-chronic liver failure (ACLF). In addition, the association with mortality of hBD-1, C-reactive protein (CRP) and procalcitonin (PCT) was assessed. METHODS A total of 125 patients were divided into three groups: 39 with ACLF (derivation cohort), 46 with acute decompensation without ACLF (AD) and 40 with decompensated cirrhosis without an acute event (DC). The data from 24 different ACLF patients were used for validation and 15 healthy individuals as control group. RESULTS Serum hBD-1, CRP and PCT levels were higher in ACLF compared to both AD and DC groups (P < 0.001). Healthy controls demonstrated similar hBD-1 and PCT values compared to DC group. In ROC curve, the performance of hBD-1 to predict 60-day mortality in ACLF group was similar in derivation and validation cohorts (c-statistic 0.834 and 0.879, respectively). CRP was a poor predictor of mortality. In ACLF group, patients with high hBD-1 (>36.625 ng/mL) had a poor prognosis at 60 days compared to those with lower values (log-rank P = 0.001). In Cox multivariate regression analysis, only hBD-1 (HR 1.020, 95%CI 1.006-1.035, P = 0.006) emerged as an independent predictor of death in ACLF group. In AD group, neither hBD-1 nor PCT or CRP variables were associated with mortality. CONCLUSIONS High hBD-1 was detected at presentation in patients with ACLF who died during follow-up period. hBD-1 is an accurate predictor of short-term mortality in patients with ACLF.
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Affiliation(s)
- Iliana Mani
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Alexopoulou
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Larisa Vasilieva
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Danai Agiasotelli
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Myrianthi Bei
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodoros Alexopoulos
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Spyros P Dourakis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Abstract
Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.
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Affiliation(s)
- Danielle Adebayo
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Shuet Fong Neong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Florence Wong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
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37
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Tariq R, Wahab A, Singal AK. Editorial: direct anti-viral agents, hepatitis C virus eradication, and gut-liver axis-another mechanistic piece to the puzzle. Aliment Pharmacol Ther 2018; 48:1321-1322. [PMID: 30488623 DOI: 10.1111/apt.15047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Raseen Tariq
- Department of Medicine, Rochester General Hospital, Rochester, New York
| | - Abdul Wahab
- Department of Medicine, Unity Hospital, Rochester, New York
| | - Ashwani K Singal
- Department of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama
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Lin H, He QY, Shi L, Sleeman M, Baker MS, Nice EC. Proteomics and the microbiome: pitfalls and potential. Expert Rev Proteomics 2018; 16:501-511. [PMID: 30223687 DOI: 10.1080/14789450.2018.1523724] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Human symbiotic microbiota are now known to play important roles in human health and disease. Significant progress in our understanding of the human microbiome has been driven by recent technological advances in the fields of genomics, transcriptomics, and proteomics. As a complementary method to metagenomics, proteomics is enabling detailed protein profiling of the microbiome to decipher its structure and function and to analyze its relationship with the human body. Fecal proteomics is being increasingly applied to discover and validate potential health and disease biomarkers, and Therapeutic Goods Administration (TGA)-approved instrumentation and a range of clinical assays are being developed that will collectively play key roles in advancing personalized medicine. Areas covered: This review will introduce the complexity of the microbiome and its role in health and disease (in particular the gastrointestinal tract or gut microbiome), discuss current genomic and proteomic methods for studying this system, including the discovery of potential biomarkers, and outline the development of clinically accepted protocols leading to personalized medicine. Expert commentary: Recognition of the important role the microbiome plays in both health and disease is driving current research in this key area. A proteogenomics approach will be essential to unravel the biologies underlying this complex network.
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Affiliation(s)
- Huafeng Lin
- a Department of Biotechnology , College of Life Science and Technology, Jinan University , Guangzhou , Guangdong , China.,b Institute of Food Safety and Nutrition Research , Jinan University , Guangzhou , China
| | - Qing-Yu He
- c Institute of Life and Health Engineering, College of Life Science and Technology , Jinan University , Guangzhou , China
| | - Lei Shi
- b Institute of Food Safety and Nutrition Research , Jinan University , Guangzhou , China
| | - Mark Sleeman
- d Biomedicine Discovery Institute , Monash University , Melbourne , Australia
| | - Mark S Baker
- e Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , Macquarie University , Sydney , Australia
| | - Edouard C Nice
- f Department of Biochemistry and Molecular Biology , Monash University , Melbourne , Victoria , Australia
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Oikonomou T, Papatheodoridis GV, Samarkos M, Goulis I, Cholongitas E. Clinical impact of microbiome in patients with decompensated cirrhosis. World J Gastroenterol 2018; 24:3813-3820. [PMID: 30228776 PMCID: PMC6141334 DOI: 10.3748/wjg.v24.i34.3813] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 07/11/2018] [Accepted: 07/21/2018] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are trying to clarify the role of microbiome in clinical exacerbation of patients with decompensated cirrhosis. Nowadays, it is accepted that patients with cirrhosis have altered salivary and enteric microbiome, characterized by the presence of dysbiosis. This altered microbiome along with small bowel bacterial overgrowth, through translocation across the gut, is associated with the development of decompensating complications. Studies have analyzed the correlation of certain bacterial families with the development of hepatic encephalopathy in cirrhotics. In general, stool and saliva dysbiosis with reduction of autochthonous bacteria in patients with cirrhosis incites changes in bacterial defenses and higher risk for bacterial infections, such as spontaneous bacterial peritonitis, and sepsis. Gut microbiome has even been associated with oncogenic pathways and under circumstances might promote the development of hepatocarcinogenesis. Lately, the existence of the oral-gut-liver axis has been related with the development of decompensating events. This link between the liver and the oral cavity could be via the gut through impaired intestinal permeability that allows direct translocation of bacteria from the oral cavity to the systemic circulation. Overall, the contribution of the microbiome to pathogenesis becomes more pronounced with progressive disease and therefore may represent an important therapeutic target in the management of cirrhosis.
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Affiliation(s)
- Theodora Oikonomou
- Fourth Department of Internal Medicine, Hippokration General Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Michael Samarkos
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokration General Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
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Dinya T, Tornai T, Vitalis Z, Tornai I, Balogh B, Tornai D, Antal-Szalmas P, Sumegi A, Andrikovics H, Bors A, Tordai A, Papp M. Functional polymorphisms of innate immunity receptors are not risk factors for the non-SBP type bacterial infections in cirrhosis. Liver Int 2018; 38:1242-1252. [PMID: 29235260 DOI: 10.1111/liv.13664] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 11/28/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Pattern recognition receptors (PRRs) have a key role in the innate host defense. Functional polymorphisms of various PRRs have been established to contribute to an increased susceptibility to spontaneous bacterial peritonitis (SBP). Their role in the development of cirrhosis-associated bacterial infections (BI), beyond SBP or progressive disease course related to pathological bacterial translocation (BT) remains unknown. METHODS Three hundred and forty-nine patients with cirrhosis were genotyped for common NOD2 (R702W, G908R and L1007PfsinsC), TLR2 (-16934T>A), and TLR4 (D299G) variants. Incidence of BIs, decompensating events and liver-related death were assessed in a 5-year follow-up observational study. Pathological BT was assessed based on the presence of antimicrobial antibodies or lipopolysaccharide-binding protein (LBP) level. RESULTS In patients with ascites (n = 88) only NOD2 gene variants were associated with an increased cumulative probability of SBP (76.9% ± 19.9%) compared to wild-type (30.9% ± 6.9%, PLogRank = .047). Individual or combined PRR genetic profiles were associated with the risk of non-SBP type BI. Advanced disease stage (HR [95% CI]: 2.11 [1.38-3.25]) and prior history of a BI episode (HR: 2.42 [1.58-3.72]) were the major clinical risk factors of a subsequent BI. The risk of a non-SBP type BI in patients with advanced disease and a prior BI was even higher (HR: 4.74 [2.68-8.39]). The frequency of antimicrobial antibodies and LBP levels did not differ between various PRR genotypes. Correspondingly, PRR genetic profile was not able to predict the long-term disease course. CONCLUSIONS In cirrhosis, functional polymorphisms of PRRs did not improve the identification of patients with high risk of BI beyond SBP or progressive diseases course.
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Affiliation(s)
- Tamas Dinya
- Faculty of Medicine, Institute of Surgery, University of Debrecen, Debrecen, Hungary
| | - Tamas Tornai
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsuzsanna Vitalis
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Istvan Tornai
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Boglárka Balogh
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - David Tornai
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Peter Antal-Szalmas
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Andrea Sumegi
- Vascular Biology, Thrombosis and Haemostasis Research Group, Hungarian Academy of Sciences, Debrecen, Hungary
| | | | - Andras Bors
- Hungarian National Blood Transfusion Service, Budapest, Hungary
| | - Attila Tordai
- Department of Pathophysiology, Semmelweis University, Budapest, Hungary
| | - Maria Papp
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Liu Y, Li J, Jin Y, Zhao L, Zhao F, Feng J, Li A, Wei Y. Splenectomy Leads to Amelioration of Altered Gut Microbiota and Metabolome in Liver Cirrhosis Patients. Front Microbiol 2018; 9:963. [PMID: 29867867 PMCID: PMC5962811 DOI: 10.3389/fmicb.2018.00963] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 04/24/2018] [Indexed: 12/12/2022] Open
Abstract
Dysbiosis of gut microbiota and metabolome is a frequently encountered condition in liver cirrhosis (LC) patients. The severity of liver dysfunction was found to be correlated with the degree of microbial dysbiosis. Several clinical studies have indicated liver function improvement after therapeutic splenectomy for LC-induced hypersplenism. We sought to determine whether such post-splenectomy outcome is pertinent to modulation of the abnormal gut microenvironment in LC patients. A cross-sectional study including 12 LC patients and 16 healthy volunteers was first conducted, then a before-after study in the cohort of patients was carried out before and 6 months after splenectomy. Fecal samples were collected in hospital. Temporal bacterial (n = 40) and metabolomics (n = 30) profiling was performed using 16s rRNA gene sequencing and ultra performance liquid chromatography/mass spectrometer (UPLC/MS), respectively. Our results revealed that microbial composition in patients was clearly different from that in healthy controls (HCs), evidenced by considerable taxonomic variation. Along with improved liver function (Child-Pugh score), the patients also displayed similar gut microbiota profile and predicted metagenome function to that of HCs after splenectomy. Enterobacteriaceae and Streptococcaceae, two LC-enriched families showing positive relation with Child-Pugh score, exhibited significantly decreased abundance after splenectomy. At the genus level, 11 genera were differentially abundant between patients and HCs, but 9 genera of them restituted to normal levels by certain degree after splenectomy. PICRUSt analysis showed that the relative abundance of 17 KEGG pathways was partially restored after splenectomy. Four of them were amino acid-related pathways: lysine degradation, tryptophan degradation, amino acid metabolism, and protein digestion and absorption. These findings were supported by metabonomics results which showed that relative abundance of amino acid and corresponding catabolites changed toward normal. In addition to the variations in the relative abundances of bacteria and metabolites, the correlation between them also altered in patients after splenectomy. Dysbiosis in gut microbiome and related metabolism of LC patients was partially corrected after splenectomy. Whether the improved gut microenvironment could prevent LC-related complications and delay the progress of LC is a propitious objective for future study. TRIAL REGISTRATION ChiCTR-OOB-15007409. Registered November 15, 2015.
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Affiliation(s)
| | | | | | | | | | | | | | - Yunwei Wei
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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Liu Y, Jin Y, Li J, Zhao L, Li Z, Xu J, Zhao F, Feng J, Chen H, Fang C, Shilpakar R, Wei Y. Small Bowel Transit and Altered Gut Microbiota in Patients With Liver Cirrhosis. Front Physiol 2018; 9:470. [PMID: 29780327 PMCID: PMC5946013 DOI: 10.3389/fphys.2018.00470] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 04/13/2018] [Indexed: 12/13/2022] Open
Abstract
Disturbance of the gut microbiota is common in liver cirrhosis (LC) patients, the underlying mechanisms of which are yet to be unfolded. This study aims to explore the relationship between small bowel transit (SBT) and gut microbiota in LC patients. Cross-sectional design was applied with 36 LC patients and 20 healthy controls (HCs). The gut microbiota was characterized by 16S rRNA gene sequencing. The Firmicutes/Bacteroidetes (F/B) ratio and the Microbial Dysbiosis index (MDI) were used to evaluate the severity of microbiota dysbiosis. The scintigraphy method was performed in patients to describe the objective values of SBT. Patients were then subdivided according to the Child–Pugh score (threshold = 5) or SBT value (threshold = 0.6) for microbiota analysis. LC patients were characterized by an altered gut microbiota; F/B ratios and MDI were higher than HC in both Child_5 (14.00 ± 14.69 vs. 2.86 ± 0.99, p < 0.01; 0.49 ± 0.80 vs. -0.47 ± 0.69, p < 0.01) and Child_5+ (15.81 ± 15.11 vs. 2.86±0.99, p < 0.01; 1.11 ± 1.05 vs. -0.47 ± 0.69, p < 0.01) sub-groups in patients. Difference in the gut microbiota between Child_ 5 and Child_5+ patients was inappreciable, but the SBT was relatively slower in Child_5+ patients (43 ± 26% vs. 80 ± 15%, p < 0.05). Compared with the Child–Pugh score indicators, SBT showed stronger associations with bacterial genera. A clear difference in the gut microbiota was observed between SBT_0.6- and SBT_0.6+ patients [Pr(>F) = 0.0068, pMANOVA], with higher F/B ratios and MDI in SBT_0.6- patients (19.71 ± 16.62 vs. 7.33 ± 6.65, p < 0.01; 1.02 ± 0.97 vs. 0.20 ± 0.58, p < 0.01). Similar results were observed between the SBT_0.6- and SBT_0.6+ sub-groups of patients with normal liver function and a Child–Pugh score of 5. SBT was negatively correlated with both the F/B ratio and MDI (r = -0.34, p < 0.05; r = -0.38, p < 0.05). Interestingly, an increased capacity for the inferred pathway “bacterial invasion of epithelial cells” in patients, was highly negatively correlated with SBT (r = -0.57, p < 0.01). The severity of microbiota dysbiosis in LC patients depends on SBT rather than Child–Pugh score. SBT per se might be significantly related to the gut microbiota abnormalities observed in patients with LC.
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Affiliation(s)
- Yang Liu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ye Jin
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jun Li
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lei Zhao
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhengtian Li
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jun Xu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Fuya Zhao
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jing Feng
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huinan Chen
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chengyuan Fang
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Rojina Shilpakar
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunwei Wei
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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Liu CP, Chiang TT, Liu YM, Kuo SC, Yang YS, Lee YT, Chen TL, Shih SC. A multicenter study on clinical characteristics of Acinetobacter bacteremia in patients with liver cirrhosis. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2018; 52:956-965. [PMID: 29731384 DOI: 10.1016/j.jmii.2018.03.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 12/14/2017] [Accepted: 03/15/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clinical characteristics and risk factors for mortality of Acinetobacter bacteremia in cirrhotic patients have not been investigated. METHODS Acinetobacter bacteremia cases from four medical centers were collected from 2009 to 2014, to compare between patients with and without liver cirrhosis. Risk factors for mortality of Acinetobacter bacteremia among cirrhotic patients were identified using multivariate logistic regression. RESULTS Among the patients with Acinetobacter bacteremia, 72 had liver cirrhosis and 816 had not. Patients with cirrhosis were younger (57.5 [50-71] vs. 72 [50.25-71], p < 0.001), had more solid tumor (51.4% vs. 31.4%, p = 0.001), lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (17 [12-24] vs. 20 [13-28], p = 0.012), less sourced from pneumonia (19.4% vs. 35.8%, p = 0.008), and less caused by Acinetobacterbaumannii (33.3% vs. 50.6%, p = 0.007) than those without. After matching for age, sex, and causative pathogens, the 30-day mortality (34.7% vs. 29.2%, p = 0.592) and APACHE II scores (17 vs. 17, p = 0.769) were not significant. APACHE II score (odds ratio [OR], 1.146; 95% confidence interval [CI], 1.035-1.268; p = 0.009), bacteremia caused by A. baumannii (OR, 20.501; 95% CI, 2.301-182.649; p = 0.007), and solid tumor (OR, 18.073; 95% CI, 1.938-168.504; p = 0.011) were independent risk factors for 30-day mortality of cirrhotic patients with Acinetobacter bacteremia. CONCLUSION Even though cirrhotic patients with Acinetobacter bacteremia were younger and had lower APACHE II scores than non-cirrhotic patients, the mortality rates were insignificantly different between the two groups.
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Affiliation(s)
- Chang-Pan Liu
- Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; MacKay College of Medicine, Nursing and Management, Taipei, Taiwan; Infection Control Committee, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
| | - Tsung-Ta Chiang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yuag-Meng Liu
- Division of Infectious Diseases, Department of Internal Medicine, Changhua Christian Hospital, Changhua County, Taiwan
| | - Shu-Chen Kuo
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan
| | - Ya-Sung Yang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
| | - Yi-Tzu Lee
- School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
| | - Te-Li Chen
- Division of Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Shou-Chuan Shih
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; MacKay College of Medicine, Nursing and Management, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
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Mancini A, Campagna F, Amodio P, Tuohy KM. Gut : liver : brain axis: the microbial challenge in the hepatic encephalopathy. Food Funct 2018; 9:1373-1388. [PMID: 29485654 DOI: 10.1039/c7fo01528c] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatic encephalopathy (HE) is a debilitating neuropsychiatric condition often associated with acute liver failure or cirrhosis. Advanced liver diseases are characterized by a leaky gut and systemic inflammation. There is strong evidence that the pathogenesis of HE is linked to a dysbiotic gut microbiota and to harmful microbial by-products, such as ammonia, indoles, oxindoles and endotoxins. Increased concentrations of these toxic metabolites together with the inability of the diseased liver to clear such products is thought to play an important patho-ethiological role. Current first line clinical treatments target microbiota dysbiosis by decreasing the counts of pathogenic bacteria, blood endotoxemia and ammonia levels. This review will focus on the role of the gut microbiota and its metabolism in HE and advanced cirrhosis. It will critically assess data from different clinical trials measuring the efficacy of the prebiotic lactulose, the probiotic VSL#3 and the antibiotic rifaximin in treating HE and advanced cirrhosis, through gut microbiota modulation. Additionally data from Randomised Controlled Trials using pre-, pro- and synbiotic will be also considered by reporting meta-analysis studies. The large amount of existing data showed that HE is a clear example of how an altered gut microbiota homeostasis can influence and impact on physiological functions outside the intestine, with implication for host health at the systems level. Nevertheless, a strong effort should be made to increase the information on gut microbiota ecology and its metabolic function in liver diseases and HE.
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Affiliation(s)
- Andrea Mancini
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all'Adige, Trento, Italy.
| | - Francesca Campagna
- Department of Medicine (DIMED), University of Padova, 35128 Padova, Italy
| | - Piero Amodio
- Department of Medicine (DIMED), University of Padova, 35128 Padova, Italy
| | - Kieran M Tuohy
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all'Adige, Trento, Italy.
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Zhang T, Wang Y, Huang L, Lang R, Jiang W. Disruption of the gut-liver axis in the pathogenesis of acute-on-chronic liver failure. Eur J Gastroenterol Hepatol 2018; 30:130-135. [PMID: 29200007 PMCID: PMC5738259 DOI: 10.1097/meg.0000000000001026] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is characterized by organ failure mediated by acute decompensation of cirrhosis. Recent studies have highlighted the importance of the gut-liver axis (GLS) and its association with ACLF pathogenesis. In this review, we discuss the mechanisms related to the alteration of the GLA and their involvement in ACLF pathogenesis and suggest some possible therapeutic options that could modulate the GLA dysfunction. This knowledge may provide information useful for the design of therapeutic strategies for gut dysbiosis and its complications in ACLF.
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Affiliation(s)
- Tao Zhang
- The First Affiliated Hospital of Hu-Nan University of Chinese Medicine, Changsha, China, 410007
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA, 29425
| | - Ya Wang
- The First Affiliated Hospital of Hu-Nan University of Chinese Medicine, Changsha, China, 410007
| | - Lei Huang
- The 302 Hospital of PLA, Treatment and Research Center for Infectious Diseases, Beijing, China, 100039
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China, 10020
| | - Wei Jiang
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA, 29425
- Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA, 29425
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Gentile I, Buonomo AR, Scotto R, Zappulo E, Borgia G. Infections worsen prognosis of patients with cirrhosis irrespective of the liver disease stage. Eur J Intern Med 2017; 46:e45-e47. [PMID: 28918985 DOI: 10.1016/j.ejim.2017.09.014] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Revised: 09/07/2017] [Accepted: 09/11/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
| | - Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy.
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
| | - Guglielmo Borgia
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
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Xu H, Xiong J, Xu J, Li S, Zhou Y, Chen D, Cai X, Ping J, Deng M, Chen J. Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl 4-Induced Cirrhotic Rats. Dig Dis Sci 2017; 62:2801-2811. [PMID: 28815345 DOI: 10.1007/s10620-017-4704-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 07/29/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats. METHODS A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl4). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting. RESULTS Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1. CONCLUSIONS Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.
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Affiliation(s)
- Hong Xu
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China
| | - Jingfang Xiong
- Department of Geriatrics, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Jianjun Xu
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China
| | - Shuiming Li
- Key Laboratory of Marine Bioresources and Ecology, College of Life Science, Shenzhen University, Shenzhen, China
| | - Yang Zhou
- Liver Cirrhosis Section, Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Dongya Chen
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China
| | - Xinjun Cai
- Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Jian Ping
- Liver Cirrhosis Section, Department of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Min Deng
- Department of Emergency, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China.
| | - Jianyong Chen
- Department of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, 208 Huancheng Dong Road, Hangzhou, 310003, China.
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Narciso-Schiavon JL, Pereira JG, Silva TE, Bansho ETO, Morato EF, Pinheiro JT, Muraro-Wildner L, Bazzo ML, Dantas-Corrêa EB, Schiavon LL. Circulating levels of pentraxin-3 (PTX3) in patients with liver cirrhosis. Ann Hepatol 2017; 16:780-787. [PMID: 28809733 DOI: 10.5604/01.3001.0010.2789] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Despite the circulating levels of PTX3 were related to the severity of various diseases, there are no studies investigating its role in patients with liver cirrhosis. We aimed to study PTX3 levels in patients with liver cirrhosis. MATERIAL AND METHODS A prospective cohort study included 130 patients hospitalized for acute decompensation of liver cirrhosis, 29 stable cirrhotic outpatients and 32 healthy controls evaluated in a tertiary hospital in Southern Brasil. RESULTS The median PTX3 level was significantly higher in stable cirrhotic patients compared to controls (2.6 vs. 1.1 ng/mL; p < 0.001), hospitalized cirrhotic patients compared to controls (3.8 vs. 1.1 ng/mL; p < 0.001), and hospitalized cirrhotic patients compared to stable cirrhotic patients (3.8 vs. 2.6 ng/mL; p = 0.001). A positive correlation was found between PTX3 and serum creatinine (r = 0.220; p = 0.012), Chronic Liver Failure - Sequential Organ Failure Assessment score (CLIF-SOFA) (r = 0.220; p = 0.010), MELD (r = 0.279; p = 0.001) and Child-Pugh score (r = 0.224; p = 0.010). Significantly higher levels of PTX3 were observed in patients on admission with ACLF (8.9 vs. 3.1 ng/mL; p < 0.001) and MELD score ≥ 20 (6.6 vs. 3.4 ng/mL; p = 0.002). Death within 90 days occurred in 30.8% of patients and was associated with higher levels of PTX3 (5.3 vs. 3.4 ng/mL; p = 0.009). The probability of Kaplan-Meier survival was 77.0% in patients with PTX-3 < 5.3 ng mL (upper tercile) and 53.5% in those with PTX3 ≥ 5.3 ng/mL (p = 0.002). CONCLUSION These results indicate the potential for use of PTX3 as an inflammatory biomarker for the prognosis of patients with hepatic cirrhosis.
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Affiliation(s)
- Janaína L Narciso-Schiavon
- Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Núcleo de Estudos em Gastroenterologia e Hepatologia, Department of Internal Medicine
| | - Jéssica G Pereira
- Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Núcleo de Estudos em Gastroenterologia e Hepatologia, Department of Internal Medicine
| | - Telma Erotides Silva
- Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Núcleo de Estudos em Gastroenterologia e Hepatologia, Department of Internal Medicine
| | - Emília T O Bansho
- Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Núcleo de Estudos em Gastroenterologia e Hepatologia, Department of Internal Medicine
| | - Edelton F Morato
- University Hospital Polydoro Ernani de São Thiago - Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Postgraduate Program in Medical Sciences
| | - José T Pinheiro
- University Hospital Polydoro Ernani de São Thiago - Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Center for Assessment of Allergic Type Reactions to Drugs
| | - Letícia Muraro-Wildner
- University Hospital Polydoro Ernani de São Thiago - Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Clinical Analysis Laboratory
| | - Maria Luiza Bazzo
- Department of Clinical Analysis. Federal University of Santa Catarina. Brasil
| | | | - Leonardo L Schiavon
- Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Núcleo de Estudos em Gastroenterologia e Hepatologia, Department of Internal Medicine
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Buechler C, Haberl EM, Rein-Fischboeck L, Aslanidis C. Adipokines in Liver Cirrhosis. Int J Mol Sci 2017; 18:E1392. [PMID: 28661458 PMCID: PMC5535885 DOI: 10.3390/ijms18071392] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 06/23/2017] [Accepted: 06/27/2017] [Indexed: 12/12/2022] Open
Abstract
Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively.
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Affiliation(s)
- Christa Buechler
- Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany.
| | - Elisabeth M Haberl
- Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany.
| | - Lisa Rein-Fischboeck
- Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany.
| | - Charalampos Aslanidis
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93042 Regensburg, Germany.
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Jhan SW, Lu YD, Lee MS, Lee CH, Wang JW, Kuo FC. The risk factors of failed reimplantation arthroplasty for periprosthetic hip infection. BMC Musculoskelet Disord 2017; 18:255. [PMID: 28606121 PMCID: PMC5469052 DOI: 10.1186/s12891-017-1622-1] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 06/06/2017] [Indexed: 01/01/2023] Open
Abstract
Background Two-stage reimplantation arthroplasty is one of the standard treatments for chronic periprosthetic joint infection (PJI). Scanty data exist regarding the risk factors for failure after two-stage reimplantation for periprosthetic hip infection. The purpose of this study was to investigate and identify the risk factors associated with failure after two-stage reimplantation hip arthroplasty. Methods Sixty-two patients with hip PJI treated with a two-stage reimplantation protocol at our institution from 2005 to 2012 were reviewed. Patients requiring medical treatment or reoperation for recurrent infection were defined as treatment failure. A multivariate Cox proportional hazards model was used to analyze the risk factors associated with treatment failure. Results Of the 62 patients, 11 (17.7%) patients had developed reinfection after the two-stage reimplantation with a mean follow-up of 5.7 years. The implant survival was 82.2% (95% confidence interval [CI] 75.19−92.55) at 10 years. Multivariate analysis revealed BMI ≥30 kg/m2 (hazard ratio [HR] 9.16; 95% CI 1.51−55.3; p = 0.0158), liver cirrhosis (HR 6.39; 95% CI 1.09−37.4; p = 0.0398), gram-negative organism (HR 5.68; 95% CI 1.18−27.4; p = 0.0303), and presence of sinus tract (HR 18.2; 95% CI 2.15−153; p = 0.0077) as the independent risk factors for treatment failure. Conclusions We found obesity, liver cirrhosis, gram-negative organism, and the presence of sinus tract were significantly related to the risks of failure after reimplantation arthroplasties.
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Affiliation(s)
- Shun-Wun Jhan
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, No. 123, Ta Pei Road, Niao Sung Dist, Kaohsiung City, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Der Lu
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, No. 123, Ta Pei Road, Niao Sung Dist, Kaohsiung City, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Mel S Lee
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, No. 123, Ta Pei Road, Niao Sung Dist, Kaohsiung City, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chen-Hsiang Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jun-Wen Wang
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, No. 123, Ta Pei Road, Niao Sung Dist, Kaohsiung City, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Feng-Chih Kuo
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, No. 123, Ta Pei Road, Niao Sung Dist, Kaohsiung City, 833, Taiwan. .,Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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