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1
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Rao AG, Nashwan AJ. Enhancing endoscopic retrograde cholangiopancreatography safety: Predictive insights into gastric retention. World J Gastrointest Surg 2025; 17:98898. [PMID: 40162417 PMCID: PMC11948121 DOI: 10.4240/wjgs.v17.i3.98898] [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: 07/08/2024] [Revised: 12/20/2024] [Accepted: 01/02/2025] [Indexed: 02/24/2025] Open
Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is a vital tool for diagnosing and treating biliary and pancreatic disorders, but its safety and efficacy are marred by preoperative gastric retention. Jia et al retrospectively analyzed 190 patients who underwent ERCP and found that gastrointestinal obstruction, jaundice, opioid use, female sex, and primary diseases were independent predictors and risk factors of preoperative gastric retention. Based on these findings and comprehensive analysis, a proposed predictive model offers clinicians valuable tools to tailor preoperative strategies, improving the procedural safety and efficacy of ERCP. Despite having several limitations, like single-center design and limited generalizability, the study marks a significant advancement in optimizing ERCP outcomes through predictive analytics. Further research with larger populations and prospective designs is warranted to establish these findings.
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Affiliation(s)
- Asad Gul Rao
- Clinical Medicine, Dow Medical College, Karachi 74200, Pakistan
| | - Abdulqadir J Nashwan
- Department Nursing and Midwifery Research, Hamad Medical Corporation, Doha 3050, Qatar
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2
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Gulyaeva K, Nadinskaia M, Maslennikov R, Aleshina Y, Goptar I, Lukashev A, Poluektova E, Ivashkin V. Gut microbiota analysis in cirrhosis and non-cirrhotic portal hypertension suggests that portal hypertension can be main factor of cirrhosis-specific dysbiosis. Sci Rep 2025; 15:8394. [PMID: 40069378 PMCID: PMC11897210 DOI: 10.1038/s41598-025-92618-0] [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] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 03/03/2025] [Indexed: 03/15/2025] Open
Abstract
Gut dysbiosis plays an important role in cirrhosis, but the mechanism of its development was not established. The aim of the study was to test the hypothesis that portal hypertension can be the main factor in the development of gut dysbiosis in cirrhosis. This cross-sectional study included 25 patients with chronic non-cirrhotic portal hypertension due to extrahepatic portal vein obstruction after portal vein thrombosis (PVT) (NCPVT group), 29 cirrhotic patients without PVT (CirNoPVT), 15 cirrhotic patients with chronic PVT (CPVT), and 22 healthy controls. The fecal microbiota was assessed using 16S rRNA gene sequencing. The CirNoPVT and CPVT groups had largely similar differences in gut microbiota composition from the control group. Patients with NCPVT, as well as patients with cirrhosis, had a higher abundance of Streptococcus, Escherichia, Enterococcus, Enterobacteriaceae, Enterococcaceae, Streptococcaceae, Bacilli, Gammaproteobacteria, Proteobacteria, and a lower abundance of Roseburia, Faecalibacterium, Methanobrevibacter, Ruminococcaceae, Methanobacteriaceae, Clostridia, Methanobacteria, and Euryarchaeota as they were compared with healthy individuals. Patients with NCPVT had a higher abundance of Bifidobacterium, Bifidobacteriaceae, Actinobacteria, and a lower abundance of Gemmiger and Catenibacterium compared to healthy individuals, which was not observed in the cirrhosis groups. The abundance of Porphyromonadaceae with the genus Parabacteroides was reduced in both groups with PVT, but not in CirNoPVT. There were no significant differences in gut microbiota beta-diversity among the CirNoPVT, CPVT and NCPVT groups. All these groups had significant differences in beta-diversity from the control group. Portal hypertension seems be the main factor in the development of gut dysbiosis in cirrhosis.
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Affiliation(s)
- Kseniya Gulyaeva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
| | - Maria Nadinskaia
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation.
| | - Yulia Aleshina
- Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russian Federation, 19991
| | - Irina Goptar
- Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russian Federation, 19991
| | - Alexander Lukashev
- Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russian Federation, 19991
- Research Institute for Systems Biology and Medicine, Moscow, Russian Federation, 117246
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
- The Interregional Public Organization "Scientific Community for the Promotion of the Clinical Study of the Human Microbiome", Moscow, Russian Federation, 19991
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
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3
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Shah A, Spannenburg L, Thite P, Morrison M, Fairlie T, Koloski N, Kashyap PC, Pimentel M, Rezaie A, Gores GJ, Jones MP, Holtmann G. Small intestinal bacterial overgrowth in chronic liver disease: an updated systematic review and meta-analysis of case-control studies. EClinicalMedicine 2025; 80:103024. [PMID: 39844931 PMCID: PMC11751576 DOI: 10.1016/j.eclinm.2024.103024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 12/05/2024] [Accepted: 12/12/2024] [Indexed: 01/24/2025] Open
Abstract
Background Small Intestinal Bacterial Overgrowth (SIBO) has been implicated in the pathophysiology of chronic liver disease (CLD). We conducted a systematic review and meta-analysis to assess and compare the prevalence of SIBO among CLD patients (with and without with complications of end stage liver disease) and healthy controls. Methods Electronic databases were searched from inception up to July-2024 for case-control studies reporting SIBO in CLD. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with CLD and controls were calculated utilizing a random-effects model. The protocol was prospectively registered with PROSPERO (CRD42022379578). Findings The final dataset included 34 case-control studies with 2130 CLD patients and 1222 controls. Overall, the odds for SIBO prevalence in CLD patients compared to controls was 6.7 (95% CI 4.6-9.7, p < 0.001). Although the prevalence of SIBO among patients with CLD with cirrhosis was higher at 42.9% (95% CI: 35.9-50.2) compared to 36.9% (95% CI: 27.4-47.6) in those without cirrhosis, this difference failed statistical significance. However, CLD patients with decompensated cirrhosis had a significantly higher prevalence of SIBO compared to those with compensated cirrhosis, with an OR of 2.6 (95% CI: 1.5-4.5, p < 0.001). Additionally, the prevalence of SIBO was significantly higher in CLD patients with portal hypertension (PHT) than in those without PHT, with an OR of 2.1 (95% CI: 1.4-3.1, p < 0.001). The highest prevalence of SIBO was observed in patients with spontaneous bacterial peritonitis (SBP) (57.7%, 95% CI 38.8-74.5), followed by patients with hepatic encephalopathy (41.0%, 95% CI 16.0-72.3) and patients with variceal bleed (39.5%, 95% CI 12.1-75.6). Interpretation Overall, there is a significantly increased prevalence of SIBO in CLD patients compared to controls. The prevalence is even higher in CLD patients with PHT, especially those with SBP. This meta-analysis suggests that SIBO is associated with complications of CLD and potentially linked to the progression of CLD. Funding National Health and Medical Research Council, Centre for Research Excellence (APP170993).
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Affiliation(s)
- Ayesha Shah
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
| | - Liam Spannenburg
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
| | - Parag Thite
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
| | - Mark Morrison
- Faculty of Medicine, University of Queensland Frazer Institute, Woolloongabba, QLD, Australia
| | - Thomas Fairlie
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
| | - Natasha Koloski
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
| | - Purna C. Kashyap
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Mark Pimentel
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Ali Rezaie
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Michael P. Jones
- Macquarie University, Department of Psychology, Sydney, NSW, Australia
| | - Gerald Holtmann
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
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4
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Nishijima S, Stankevic E, Aasmets O, Schmidt TSB, Nagata N, Keller MI, Ferretti P, Juel HB, Fullam A, Robbani SM, Schudoma C, Hansen JK, Holm LA, Israelsen M, Schierwagen R, Torp N, Telzerow A, Hercog R, Kandels S, Hazenbrink DHM, Arumugam M, Bendtsen F, Brøns C, Fonvig CE, Holm JC, Nielsen T, Pedersen JS, Thiele MS, Trebicka J, Org E, Krag A, Hansen T, Kuhn M, Bork P. Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations. Cell 2025; 188:222-236.e15. [PMID: 39541968 DOI: 10.1016/j.cell.2024.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 07/12/2024] [Accepted: 10/14/2024] [Indexed: 11/17/2024]
Abstract
The microbiota in individual habitats differ in both relative composition and absolute abundance. While sequencing approaches determine the relative abundances of taxa and genes, they do not provide information on their absolute abundances. Here, we developed a machine-learning approach to predict fecal microbial loads (microbial cells per gram) solely from relative abundance data. Applying our prediction model to a large-scale metagenomic dataset (n = 34,539), we demonstrated that microbial load is the major determinant of gut microbiome variation and is associated with numerous host factors, including age, diet, and medication. We further found that for several diseases, changes in microbial load, rather than the disease condition itself, more strongly explained alterations in patients' gut microbiome. Adjusting for this effect substantially reduced the statistical significance of the majority of disease-associated species. Our analysis reveals that the fecal microbial load is a major confounder in microbiome studies, highlighting its importance for understanding microbiome variation in health and disease.
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Affiliation(s)
- Suguru Nishijima
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Evelina Stankevic
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Oliver Aasmets
- Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Thomas S B Schmidt
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Naoyoshi Nagata
- Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
| | - Marisa Isabell Keller
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Pamela Ferretti
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Helene Bæk Juel
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Anthony Fullam
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | | | - Christian Schudoma
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johanne Kragh Hansen
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Louise Aas Holm
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark
| | - Mads Israelsen
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Robert Schierwagen
- Department of Internal Medicine B, University of Münster, Münster, Germany
| | - Nikolaj Torp
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Anja Telzerow
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Rajna Hercog
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Stefanie Kandels
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Diënty H M Hazenbrink
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Manimozhiyan Arumugam
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Charlotte Brøns
- Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Cilius Esmann Fonvig
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens-Christian Holm
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Trine Nielsen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Medical department, University Hospital Zeeland, Køge, Denmark
| | - Julie Steen Pedersen
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Maja Sofie Thiele
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Münster, Germany; European Foundation for the Study of Chronic Liver Failure, EFCLIF, Barcelona, Spain
| | - Elin Org
- Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Aleksander Krag
- Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Michael Kuhn
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
| | - Peer Bork
- Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany; Max Delbrück Centre for Molecular Medicine, Berlin, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany.
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5
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Idalsoaga F, Ayares G, Blaney H, Cabrera D, Chahuan J, Monrroy H, Matar A, Halawi H, Arrese M, Arab JP, Díaz LA. Neurogastroenterology and motility disorders in patients with cirrhosis. Hepatol Commun 2025; 9:e0622. [PMID: 39773873 PMCID: PMC11717532 DOI: 10.1097/hc9.0000000000000622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 11/21/2024] [Indexed: 01/11/2025] Open
Abstract
Neurogastroenterology and motility disorders are complex gastrointestinal conditions that are prevalent worldwide, particularly affecting women and younger individuals. These conditions significantly impact the quality of life of people suffering from them. There is increasing evidence linking these disorders to cirrhosis, with a higher prevalence compared to the general population. However, the link between neurogastroenterology and motility disorders and cirrhosis remains unclear due to undefined mechanisms. In addition, managing these conditions in cirrhosis is often limited by the adverse effects of drugs commonly used for these disorders, presenting a significant clinical challenge in the routine management of patients with cirrhosis. This review delves into this connection, exploring potential pathophysiological links and clinical interventions between neurogastroenterology disorders and cirrhosis.
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Affiliation(s)
- Francisco Idalsoaga
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Gustavo Ayares
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Universidad Finis Terrae, Escuela de Medicina, Facultad de Medicina, Universidad Fines Terrae, Santiago, Chile
| | - Hanna Blaney
- MedStar Georgetown University Hospital, Medstar Transplant Hepatology Institute, Washington, District of Columbia, USA
| | - Daniel Cabrera
- Faculty of Medicine, Universidad de los Andes, Santiago, Chile
- Centro de Estudios e Investigación en Salud y Sociedad, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad Bernardo O Higgins, Santiago, Chile
| | - Javier Chahuan
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Hugo Monrroy
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Ayah Matar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Houssam Halawi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Marco Arrese
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Luis Antonio Díaz
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA
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6
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Zhou Y, Pu S, Xiao J, Luo J, Xue L. Meta-analysis of probiotics efficacy in the treatment of minimum hepatic encephalopathy. Liver Int 2024; 44:3164-3173. [PMID: 39267392 PMCID: PMC11586888 DOI: 10.1111/liv.16081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/26/2024] [Accepted: 08/12/2024] [Indexed: 09/17/2024]
Abstract
OBJECTIVE This study aims to systematically evaluate the efficacy of probiotics in treating minimum hepatic encephalopathy (MHE). METHODS A systematic search was conducted across three major databases: PubMed, China National Knowledge Infrastructure and Wanfang. The search period spanned from the inception of each database to 9 March 2023. The objective was to identify all randomised controlled trials (RCTs) examining the efficacy of probiotic preparations in treating MHE. The search terms included 'probiotics' along with other clinically relevant terms to comprehensively capture all pertinent studies. RESULTS A total of 18 RCTs were included. The meta-analysis showed that probiotic treatment outperformed control groups in reducing blood ammonia levels (standard mean difference [MD] = -2.68, 95% confidence interval [CI]: -3.90 to -1.46, p < .0001), improving the remission rate of MHE (risk ratio [RR] = 2.79, 95% CI: 1.23-6.35, p = .01) and lowering alanine aminotransferase levels (MD = -11.10, 95% CI: -16.17 to -6.03, p < .0001). It also significantly reduced the Model for End-Stage Liver Disease scores (MD = -2.55, 95% CI: -3.56 to -1.54, p < .00001) and the incidence of MHE (RR = .18, 95% CI: .09-.34, p < .00001). CONCLUSION Our study demonstrates that probiotics effectively improve blood ammonia levels, liver function and cognitive function in patients with MHE. They significantly enhance the remission rate of MHE and effectively reduce its incidence, providing solid new evidence for treating MHE with probiotics.
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Affiliation(s)
- Yu‐Lian Zhou
- Department of Clinical LaboratoryMianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaMianyangSichuanChina
| | - Shu‐Tao Pu
- Department of Clinical LaboratoryMianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaMianyangSichuanChina
| | - Jian‐Bo Xiao
- Department of Clinical LaboratoryMianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaMianyangSichuanChina
| | - Jun Luo
- Department of Clinical LaboratoryMianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaMianyangSichuanChina
| | - Li Xue
- Department of Clinical LaboratoryMianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaMianyangSichuanChina
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7
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Philips CA. Commonly encountered symptoms and their management in patients with cirrhosis. Front Med (Lausanne) 2024; 11:1442525. [PMID: 39610685 PMCID: PMC11602333 DOI: 10.3389/fmed.2024.1442525] [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: 06/02/2024] [Accepted: 10/30/2024] [Indexed: 11/30/2024] Open
Abstract
This exhaustive review, explored the multifaceted symptoms and their management in patients with cirrhosis. Patients frequently endure pain, muscle cramps, sleep disturbances, psychological distress, and gastrointestinal issues, significantly impairing their quality of life. Pain is prevalent, often requiring analgesics, while muscle cramps affect up to 68% of patients, treated with supplements like zinc and taurine despite limited evidence. Sleep disturbances, including insomnia and excessive daytime sleepiness, afflict up to 80% of patients, managed through lactulose, melatonin, and cognitive behavioral therapies. Gastrointestinal symptoms, affecting 80%, include abdominal pain and bloating, necessitating lifestyle and dietary adjustments. Mental health disorders, such as depression and anxiety, are common, managed with a combination of pharmacotherapy and psychotherapy. Sexual dysfunction, often overlooked, profoundly impacts both men and women, requiring holistic treatment approaches. Pruritus, another distressing symptom, is managed with moisturizers and antihistamines, though many treatments show limited success. Hair loss and skin changes add to the psychological burden, highlighting the need for a comprehensive, multidisciplinary approach. The review underscores the imperative for tailored, compassionate care to enhance patient outcomes and quality of life in cirrhosis.
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Affiliation(s)
- Cyriac Abby Philips
- Department of Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Kochi, India
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8
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Dąbrowska A, Wilczyński B, Mastalerz J, Kucharczyk J, Kulbacka J, Szewczyk A, Rembiałkowska N. The Impact of Liver Failure on the Immune System. Int J Mol Sci 2024; 25:9522. [PMID: 39273468 PMCID: PMC11395474 DOI: 10.3390/ijms25179522] [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: 07/05/2024] [Revised: 08/26/2024] [Accepted: 08/28/2024] [Indexed: 09/15/2024] Open
Abstract
Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.
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Affiliation(s)
- Alicja Dąbrowska
- Faculty of Medicine, Wroclaw Medical University, Pasteura 1, 50-367 Wroclaw, Poland
| | - Bartosz Wilczyński
- Faculty of Medicine, Wroclaw Medical University, Pasteura 1, 50-367 Wroclaw, Poland
| | - Jakub Mastalerz
- Faculty of Medicine, Wroclaw Medical University, Pasteura 1, 50-367 Wroclaw, Poland
| | - Julia Kucharczyk
- Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
| | - Julita Kulbacka
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
| | - Anna Szewczyk
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
| | - Nina Rembiałkowska
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
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9
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Buttler L, Tiede A, Griemsmann M, Rieland H, Mauz J, Kahlhöfer J, Wedemeyer H, Cornberg M, Tergast TL, Maasoumy B, Hupa-Breier KL. Folic acid supplementation is associated with a decreased mortality and reduced hospital readmission in patients with decompensated alcohol-related liver cirrhosis. Clin Nutr 2024; 43:1719-1727. [PMID: 38909513 DOI: 10.1016/j.clnu.2024.05.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/24/2024] [Accepted: 05/28/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND AND AIMS Thiamine and folic acid malnutrition is highly frequent in patients with decompensated alcohol-related liver cirrhosis (aLC). Current guidelines therefore recommend vitamin supplementation in these patients. However, implementation and its impact on the clinical outcome remains unknown. Therefore, we aimed to analyze the use of thiamine and folic acid and their effects on mortality and morbidity in patients with decompensated aLC. METHODS A number of 289 consecutive patients with decompensated aLC who received a paracentesis at Hannover Medical School between 2011 and 2023 were retrospectively investigated. The use of folic acid and thiamine-containing supplements was assessed in the discharge medication. Patients were followed for up to one year regarding liver transplant (LTx)-free survival and the incidence of hepatic encephalopathy, infections and hepatic decompensation requiring rehospitalization. RESULTS Median baseline MELD was 15, median age 56.6 years. 73.0% (n = 211) were male patients. At hospital discharge, thiamine-containing supplements and folic acid were prescribed to 48.1% (n = 139) and 18.0% (n = 52) patients, respectively. Neither thiamine nor folic acid prescription were linked to improved clinical outcomes within 90 days. However, folic acid intake was associated with a higher one-year LTx-free survival (HR = 0.48; p = 0.04) in the multivariable analysis. Furthermore, folic acid substitution was linked to a decreased risk of rehospitalization within one year (HR = 0.55; p = 0.01) in the multivariable competing risk model. In contrast, thiamine prescription did neither affect LTx-free survival nor the here investigated liver-related complications. CONCLUSION Folic acid, but not thiamine substitution was linked to an improved outcome in patients with decompensated aLC.
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Affiliation(s)
- Laura Buttler
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
| | - Anja Tiede
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany.
| | - Marie Griemsmann
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
| | - Hannah Rieland
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
| | - Jim Mauz
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
| | - Julia Kahlhöfer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), HepNet Study-House/ German Liver Foundation, Hannover, Germany.
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany; RESIST Cluster of Excellence, Hannover Medical School, Hannover, Germany; Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany; Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany; TWINCORE, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
| | - Tammo L Tergast
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; German Centre for Infection Research (DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany.
| | - Katharina L Hupa-Breier
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
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10
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Elsabaawy M, Alhaddad O. Forgettable in the care of liver cirrhosis: the unseen culprits of progression from bad to worse. PRZEGLAD GASTROENTEROLOGICZNY 2024; 19:6-17. [PMID: 38571544 PMCID: PMC10985753 DOI: 10.5114/pg.2024.136361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 11/20/2023] [Indexed: 04/05/2024]
Abstract
Patients with liver cirrhosis constitute a critically ill and unique population, and their stability relies on a well-coordinated multidisciplinary team with a carefully structured plan. Overlooking any aspect of this plan can expedite disease progression, leading to severe complications. The lack of disease-specific nutritional guidance, the prevalent sedentary lifestyle among patients, and insufficient screening for hepatocellular carcinoma, oesophageal varices, sarcopaenia, minimal hepatic encephalopathy, and diabetes mellitus, along with fibrosis progression and cirrhosis decompensation, can add further complexities. Additionally, devaluing the impact of obesity in triggering liver cirrhosis can be disadvantageous. Prolonged and inappropriate use of proton pump inhibitors also poses a significant challenge with a wide range of complications. These often-unheeded aspects in the care of liver cirrhosis patients represents the unseen culprits of progression from bad to worse and warrant serious consideration.
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Affiliation(s)
- Maha Elsabaawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
| | - Omkosoum Alhaddad
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
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11
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Bruns N, Meyer F, Rischmüller K, Frost F, Tran QT, Ittermann T, Bahls M, Valentini L, Lamprecht G, Lerch MM, Aghdassi AA, Wiese ML. Nutritional status in patients with chronic pancreatitis and liver cirrhosis is related to disease conditions and not dietary habits. Sci Rep 2024; 14:4700. [PMID: 38409360 PMCID: PMC10897307 DOI: 10.1038/s41598-024-54998-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 02/19/2024] [Indexed: 02/28/2024] Open
Abstract
Malnutrition is a common complication of chronic pancreatitis (CP) and liver cirrhosis (LC). Inadequate food intake is considered a relevant driver of malnutrition in both entities. However, the contribution of habitual diet to impaired nutritional status is unclear. In a prospective, multicenter cross-sectional study, we recruited patients with confirmed CP or LC and healthy volunteers as a control group. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition criteria. We comprehensively investigated habitual dietary intake on nutrient, food group, and dietary pattern level applying two validated food frequency questionnaires. We included 144 patients (CP: n = 66; LC: n = 78) and 94 control subjects. Malnutrition was prevalent in 64% and 62% of patients with CP or LC, respectively. In both CP and LC, despite slightly altered food group consumption in malnourished and non-malnourished patients there were no differences in energy or nutrient intake as well as dietary quality. Compared to controls patients showed distinct dietary food group habits. Patients consumed less alcohol but also lower quantities of fruits and vegetables as well as whole grain products (p < 0.001, respectively). Nevertheless, overall dietary quality was comparable between patients and healthy controls. Nutritional status in CP and LC patients is rather related to disease than habitual dietary intake supporting the relevance of other etiologic factors for malnutrition such as malassimilation or chronic inflammation. Despite distinct disease-related differences, overall dietary quality in patients with CP or LC was comparable to healthy subjects, which suggests susceptibility to dietary counselling and the benefits of nutrition therapy in these entities.
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Affiliation(s)
- Niklas Bruns
- Department of Medicine A, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Fatuma Meyer
- Institute of Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, Neubrandenburg, Germany
| | - Karen Rischmüller
- Division of Gastroenterology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany
| | - Fabian Frost
- Department of Medicine A, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Quang Trung Tran
- Department of Medicine A, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Till Ittermann
- Institute for Community Medicine, University of Greifswald, Greifswald, Germany
| | - Martin Bahls
- Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
| | - Luzia Valentini
- Institute of Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, Neubrandenburg, Germany
| | - Georg Lamprecht
- Division of Gastroenterology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
- LMU University Hospital, Ludwig Maximilian Universität München, Munich, Germany
| | - Ali A Aghdassi
- Department of Medicine A, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
| | - Mats L Wiese
- Department of Medicine A, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
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12
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Yan Y, Jin Y, Cao Y, Chen C, Zhao X, Xia H, Yan L, Si Y, Zou J. Development and validation of a novel nomogram model to assess the risk of gastric contents in outpatients undergoing elective sedative gastrointestinal endoscopy procedures. Clin Res Hepatol Gastroenterol 2024; 48:102277. [PMID: 38159677 DOI: 10.1016/j.clinre.2023.102277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/24/2023] [Accepted: 12/27/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND Gastric contents may contribute to patients' aspiration during anesthesia. Ultrasound can accurately assess the risk of gastric contents in patients undergoing sedative gastrointestinal endoscopy (GIE) procedures, but its efficiency is limited. Therefore, developing an accurate and efficient model to predict gastric contents in outpatients undergoing elective sedative GIE procedures is greatly desirable. METHODS This study retrospectively analyzed 1501 patients undergoing sedative GIE procedures. Gastric contents were observed under direct gastroscopic vision and suctioned through the endoscope. High-risk gastric contents were defined as having solid content or liquid volume > 25 ml and pH < 2.5; otherwise, they were considered low-risk gastric contents. Univariate analysis and multivariate analysis were used to select the independent risk factors to predict high-risk gastric contents. Based on the selected independent risk factors, we assigned values to each independent risk factor and established a novel nomogram. The performance of the nomogram was verified in the testing cohort by the metrics of discrimination, calibration, and clinical usefulness. In addition, an online accessible web calculator was constructed. RESULTS We found BMI, cerebral infarction, cirrhosis, male, age, diabetes, and gastroesophageal reflux disease were risk factors for gastric contents. The AUROCs were 0.911 and 0.864 in the development and testing cohort, respectively. Moreover, the nomogram showed good calibration ability. Decision curve analysis and Clinical impact curve demonstrated that the predictive nomogram was clinically useful. The website of the nomogram was https://medication.shinyapps.io/dynnomapp/. CONCLUSIONS This study demonstrates that clinical variables can be combined with algorithmic techniques to predict gastric contents in outpatients. Nomogram was constructed from routine variables, and the web calculator had excellent clinical applicability to assess the risk of gastric contents accurately and efficiently in outpatients, assist anesthesiologists in assessment and identify the most appropriate patients for ultrasound.
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Affiliation(s)
- Yuqing Yan
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yuzhan Jin
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yuanyuan Cao
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Chen Chen
- Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiuxiu Zhao
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Huaming Xia
- Nanjing Xiaheng Network System Co., Ltd., Nanjing, China
| | - Libo Yan
- Jiangsu Kaiyuan Pharmaceutical Co., Ltd., Nanjing, China
| | - Yanna Si
- Department of Anesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Jianjun Zou
- Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China.
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13
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Santangeli E, Abbati C, Chen R, Di Carlo A, Leoni S, Piscaglia F, Ferri S. Pathophysiological-Based Nutritional Interventions in Cirrhotic Patients with Sarcopenic Obesity: A State-of-the-Art Narrative Review. Nutrients 2024; 16:427. [PMID: 38337711 PMCID: PMC10857546 DOI: 10.3390/nu16030427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 01/23/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024] Open
Abstract
In recent decades, following the spread of obesity, metabolic dysfunction has come to represent the leading cause of liver disease. The classical clinical presentation of the cirrhotic patient has, therefore, greatly changed, with a dramatic increase in subjects who appear overweight or obese. Due to an obesogenic lifestyle (lack of physical activity and overall malnutrition, with an excess of caloric intake together with a deficit of proteins and micronutrients), these patients frequently develop a complex clinical condition defined as sarcopenic obesity (SO). The interplay between cirrhosis and SO lies in the sharing of multiple pathogenetic mechanisms, including malnutrition/malabsorption, chronic inflammation, hyperammonemia and insulin resistance. The presence of SO worsens the outcome of cirrhotic patients, affecting overall morbidity and mortality. International nutrition and liver diseases societies strongly agree on recommending the use of food as an integral part of the healing process in the comprehensive management of these patients, including a reduction in caloric intake, protein and micronutrient supplementation and sodium restriction. Based on the pathophysiological paths shared by cirrhosis and SO, this narrative review aims to highlight the nutritional interventions currently advocated by international guidelines, as well as to provide hints on the possible role of micronutrients and nutraceuticals in the treatment of this multifaceted clinical condition.
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Affiliation(s)
- Ernestina Santangeli
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (E.S.); (C.A.); (R.C.); (F.P.)
| | - Chiara Abbati
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (E.S.); (C.A.); (R.C.); (F.P.)
| | - Rusi Chen
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (E.S.); (C.A.); (R.C.); (F.P.)
| | - Alma Di Carlo
- Division of Internal Medicine, Hepatobiliary and Immunoallergologic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.D.C.); (S.L.)
| | - Simona Leoni
- Division of Internal Medicine, Hepatobiliary and Immunoallergologic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.D.C.); (S.L.)
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (E.S.); (C.A.); (R.C.); (F.P.)
- Division of Internal Medicine, Hepatobiliary and Immunoallergologic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.D.C.); (S.L.)
| | - Silvia Ferri
- Division of Internal Medicine, Hepatobiliary and Immunoallergologic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.D.C.); (S.L.)
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14
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Ji R. Mucormycosis mimicking portal hypertensive haemorrhage as a complication of alcoholic liver cirrhosis: a case report. BMC Infect Dis 2024; 24:136. [PMID: 38287258 PMCID: PMC10823596 DOI: 10.1186/s12879-023-08220-0] [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: 11/20/2022] [Accepted: 04/04/2023] [Indexed: 01/31/2024] Open
Abstract
Mucor is a rare cause of gastrointestinal ulcers. This case describes a case of mucormycosis that occurred in a patient with liver cirrhosis who was hospitalized to accept a splenectomy for traumatic splenic rupture. During the perioperative period, the patient developed upper gastrointestinal bleeding(UGIB), which was diagnosed as mucormycosis-related gastric ulcer according to gastroscopy. Patients with liver cirrhosis often get UGIB for Portal hypertension, but they also can develop UGIB for multiple other reasons, including infectious ulcers for immunosuppression. The case emphasizes the importance of excluding fungal-induced ulcer haemorrhage before diagnosing Portal hypertensive-induced variceal haemorrhage in patients with liver cirrhosis.
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Affiliation(s)
- Ran Ji
- Department of the Surgical Intensive Care Unit (SICU), The Second Affiliated Hospital Zhejiang, University School of Medicine, NO. 88 Jiefang Road,Shangcheng District Hangzhou, 310009, Zhejiang, China.
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15
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Zheng J, Li J, Zhang Z, Yu Y, Tan J, Liu Y, Gong J, Wang T, Wu X, Guo Z. Clinical Data based XGBoost Algorithm for infection risk prediction of patients with decompensated cirrhosis: a 10-year (2012-2021) Multicenter Retrospective Case-control study. BMC Gastroenterol 2023; 23:310. [PMID: 37704966 PMCID: PMC10500933 DOI: 10.1186/s12876-023-02949-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 09/07/2023] [Indexed: 09/15/2023] Open
Abstract
OBJECTIVES To appraise effective predictors for infection in patients with decompensated cirrhosis (DC) by using XGBoost algorithm in a retrospective case-control study. METHODS Clinical data were retrospectively collected from 6,648 patients with DC admitted to five tertiary hospitals. Indicators with significant differences were determined by univariate analysis and least absolute contraction and selection operator (LASSO) regression. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed infection risk prediction model with simple-tree XGBoost model. Finally, the simple-tree XGBoost model is compared with the traditional logical regression (LR) model. Performances of models were evaluated by area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. RESULTS Six features, including total bilirubin, blood sodium, albumin, prothrombin activity, white blood cell count, and neutrophils to lymphocytes ratio were selected as predictors for infection in patients with DC. Simple-tree XGBoost model conducted by these features can predict infection risk accurately with an AUROC of 0.971, sensitivity of 0.915, and specificity of 0.900 in training set. The performance of simple-tree XGBoost model is better than that of traditional LR model in training set, internal verification set, and external feature set (P < 0.001). CONCLUSIONS The simple-tree XGBoost predictive model developed based on a minimal amount of clinical data available to DC patients with restricted medical resources could help primary healthcare practitioners promptly identify potential infection.
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Affiliation(s)
- Jing Zheng
- Operation Management Office, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, 401320, China
| | - Jianjun Li
- Department of Cardiothoracic Surgery, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, 401320, China
| | - Zhengyu Zhang
- Medical Records Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yue Yu
- Senior Bioinformatician Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, 55905, US
| | - Juntao Tan
- Operation Management Office, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, 401320, China
| | - Yunyu Liu
- Medical Records Department, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Jun Gong
- Department of Information Center, the University Town Hospital of Chongqing Medical University, Chongqing, 401331, China
| | - Tingting Wang
- College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, China
| | - Xiaoxin Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qing Chun Road, Hangzhou, 310003, Zhejiang, China.
| | - Zihao Guo
- Department of Gastroenterology, Chongqing Banan Cancer Hospital, Chongqing, 400054, China.
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Al Nou'mani J, Al Alawi AM, Al-Maqbali JS, Al Abri N, Al Sabbri M. Prevalence, Recognition, and Risk Factors of Constipation among Medically Hospitalized Patients: A Cohort Prospective Study. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1347. [PMID: 37512158 PMCID: PMC10385149 DOI: 10.3390/medicina59071347] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/15/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023]
Abstract
Background and Objective: Constipation is a prevalent gastrointestinal condition that has a substantial impact on individuals and healthcare systems. This condition adversely affects health-related quality of life and leads to escalated healthcare expenses due to an increase in office visits, referrals to specialists, and hospital admission. This study aimed to evaluate the prevalence, recognition, risk factors, and course of constipation among hospitalized patients in medical wards. Materials and Methods: A prospective study was conducted, including all adult patients admitted to the General Medicine Unit between 1 February 2022 and 31 August 2022. Constipation was identified using the Constipation Assessment Scale (CAS), and relevant factors were extracted from the patients' medical records. Results: Among the patients who met the inclusion criteria (n = 556), the prevalence of constipation was determined to be 55.6% (95% CI 52.8-58.4). Patients with constipation were found to be older (p < 0.01) and had higher frailty scores (p < 0.01). Logistic regression analysis revealed that heart failure (Odds ratio (OR) 2.1; 95% CI 1.2-3.7; p = 0.01), frailty score (OR 1.4; 95% CI 1.2-1.5; p < 0.01), and dihydropyridines calcium channel blockers (OR 1.8; 95% CI 1.2-2.8; p < 0.01) were independent risk factors for constipation. Furthermore, the medical team did not identify constipation in 217 patients (64.01%). Conclusions: Constipation is highly prevalent among medically hospitalized patients. To ensure timely recognition and treatment, it is essential to incorporate a daily constipation assessment scale into each patient's medical records.
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Affiliation(s)
- Jawahar Al Nou'mani
- Internal Medicine Residency Training Program, Oman Medical Specialty Board, Muscat 130, Oman
| | - Abdullah M Al Alawi
- Internal Medicine Residency Training Program, Oman Medical Specialty Board, Muscat 130, Oman
- Department of Medicine, Sultan Qaboos University Hospital, Muscat 123, Oman
| | - Juhaina Salim Al-Maqbali
- Department of Pharmacy, Sultan Qaboos University Hospital, Muscat 123, Oman
- Department of Pharmacology and Clinical Pharmacy, Sultan Qaboos University, Muscat 123, Oman
| | - Nahid Al Abri
- College of Medicine and Health Science, Sultan Qaboos University, Muscat 123, Oman
| | - Maryam Al Sabbri
- College of Medicine and Health Science, Sultan Qaboos University, Muscat 123, Oman
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Patel AA, Tapper EB, Kanwal F, Woodrell CD, Hansen L, Lai JC, Rogal S, McDermott C, Rakoski M, Ufere NN. Targets and study design for symptom-focused trials aimed at patients with cirrhosis: An expert consensus. Hepatol Commun 2023; 7:e0135. [PMID: 37267219 PMCID: PMC10241502 DOI: 10.1097/hc9.0000000000000135] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 03/07/2023] [Indexed: 06/04/2023] Open
Abstract
BACKGROUND Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures. METHODS A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in future clinical trials, including for patients with cirrhosis. RESULTS The panel reached a consensus on key reporting features for clinical trials, along with considerations for study design. Nine key symptom targets (muscle cramps, pruritus, pain, fatigue, sexual dysfunction, sleep disorders, depression and anxiety, nausea/vomiting, and dyspnea/breathlessness) were identified. The panel selected instruments that can be considered for clinical trials based on psychometric validation and previous experience. The panel identified ongoing needs, including instrument validation, safety data, evidence about non-pharmacologic interventions, and comparative effectiveness studies. CONCLUSION This expert panel identified key design, reporting, and measurement elements to standardize processes and measures in future symptom-focused clinical trials in the context of cirrhosis.
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Affiliation(s)
- Arpan A. Patel
- Tamar and Vatche Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California, USA
- VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Fasiha Kanwal
- Baylor College of Medicine and Michael E DeBakey VA Medical Center, Houston, Texas, USA
| | - Christopher D. Woodrell
- Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Geriatric Research, Education and Clinical Center, James J. Peters VA Medical Center, Bronx, New York, USA
| | - Lissi Hansen
- Oregon Health & Science University, School of Nursing, Portland, Oregon, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, University of California, San Francisco, California, USA
| | - Shari Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Cara McDermott
- Division of Geriatrics, Department of Medicine, Duke University, Durham, New Carolina, USA
- Geriatric Research, Education and Clinical Center, Durham VA Medical Center, Durham, New Carolina, USA
| | - Mina Rakoski
- Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California, USA
| | - Nneka N. Ufere
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachussetts, USA
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18
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Development and validation of the Adult cirrhosiS Knowledge Questionnaire. Eur J Gastroenterol Hepatol 2023; 35:333-341. [PMID: 36708305 DOI: 10.1097/meg.0000000000002493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Assessing a patient's knowledge regarding liver cirrhosis is important to improve patient outcomes. This study aimed to develop and validate the Adult cirrhosiS Knowledge Questionnaire (ASK-Q) to assess patients' knowledge regarding liver cirrhosis from multiple aspects. METHODS A 24-item ASK-Q with four domains: self-understanding (5 items), aetiology (5 items), complications (5 items) and management (9 items) of liver cirrhosis was developed based on literature review and expert panel input. It was then piloted in five English-speaking patients with liver cirrhosis. These patients commented that the font size was too small. Hence, the font was enlarged and the final version of the ASK-Q was administered to English-speaking patients with liver cirrhosis, aged ≥18 years, with or without decompensation, at a tertiary hospital, from September 2020 to November 2021, at baseline and fortnight later. Patients with encephalopathy were excluded. RESULTS 120/135 patients agreed to participate (response rate = 88.9%). The overall median score was 59.1 (45.6-68.2). A total of 7/22 (31.8%) items were "easy", 14/22 (63.6%) items were "moderately easy" and 1/22 (4.5%) items were "difficult". Exploratory factor analysis extracted nine factors, and two items were omitted. The ASK-Q was able to discriminate the knowledge level of patients with and without tertiary education [59.1 (50.0-72.7) vs. 54.5 (36.4-63.6); P < 0.05]. The overall Kuder-Richardson coefficient was 0.760, indicating adequate internal consistency. At retest, 77/120 patients participated (response rate = 64.2%) and 15/22 items were not statistically significant, indicating adequate reliability. CONCLUSIONS The ASK-Q was found to be a valid and reliable questionnaire for evaluating the knowledge of liver cirrhosis among English-speaking adult patients.
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Lopez-Delgado JC, Putzu A, Landoni G. The importance of liver function assessment before cardiac surgery: A narrative review. Front Surg 2022; 9:1053019. [PMID: 36561575 PMCID: PMC9764862 DOI: 10.3389/fsurg.2022.1053019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 11/15/2022] [Indexed: 12/12/2022] Open
Abstract
The demand for cardiac surgery procedures is increasing globally. Thanks to an improvement in survival driven by medical advances, patients with liver disease undergo cardiac surgery more often. Liver disease is associated with the development of heart failure, especially in patients with advanced cirrhosis. Cardiovascular risk factors can also contribute to the development of both cardiomyopathy and liver disease and heart failure itself can worsen liver function. Despite the risk that liver disease and cirrhosis represent for the perioperative management of patients who undergo cardiac surgery, liver function is often not included in common risk scores for preoperative evaluation. These patients have worse short and long-term survival when compared with other cardiac surgery populations. Preoperative evaluation of liver function, postoperative management and close postoperative follow-up are crucial for avoiding complications and improving results. In the present narrative review, we discuss the pathophysiological components related with postoperative complications and mortality in patients with liver disease who undergo cardiac surgery and provide recommendations for the perioperative management.
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Affiliation(s)
- Juan C. Lopez-Delgado
- Hospital Clinic de Barcelona, Area de Vigilancia Intensiva (ICMiD), Barcelona, Spain,IDIBELL (Institut d’Investigació Biomèdica Bellvitge; Biomedical Investigation Institute of Bellvitge), L’Hospitalet de Llobregat, Barcelona, Spain,Correspondence: Juan C. Lopez-Delgado Alessandro Putzu
| | - Alessandro Putzu
- Division of Anesthesiology, Department of Acute Medicine, Geneva University Hospitals, Geneva, Switzerland,Correspondence: Juan C. Lopez-Delgado Alessandro Putzu
| | - Giovanni Landoni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy,Vita-Salute San Raffaele University, Milan, Italy
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20
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Zhang J, Luo W, Miao C, Zhong J. Hypercatabolism and Anti-catabolic Therapies in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome. Front Nutr 2022; 9:941097. [PMID: 35911117 PMCID: PMC9326442 DOI: 10.3389/fnut.2022.941097] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/21/2022] [Indexed: 12/06/2022] Open
Abstract
Owing to the development of intensive care units, many patients survive their initial insults but progress to chronic critical illness (CCI). Patients with CCI are characterized by prolonged hospitalization, poor outcomes, and significant long-term mortality. Some of these patients get into a state of persistent low-grade inflammation, suppressed immunity, and ongoing catabolism, which was defined as persistent inflammation, immunosuppression, and catabolism syndrome (PICS) in 2012. Over the past few years, some progress has been made in the treatment of PICS. However, most of the existing studies are about the role of persistent inflammation and suppressed immunity in PICS. As one of the hallmarks of PICS, hypercatabolism has received little research attention. In this review, we explore the potential pathophysiological changes and molecular mechanisms of hypercatabolism and its role in PICS. In addition, we summarize current therapies for improving the hypercatabolic status and recommendations for patients with PICS.
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Affiliation(s)
- Jinlin Zhang
- Department of Anesthesiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Wenchen Luo
- Department of Anesthesiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Changhong Miao
- Department of Anesthesiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Jing Zhong
- Department of Anesthesiology, Zhongshan Hospital Fudan University, Shanghai, China
- Fudan Zhangjiang Institute, Shanghai, China
- Department of Anesthesiology, Zhongshan Wusong Hospital, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China
- *Correspondence: Jing Zhong,
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Li Y, Hu H, Yang H, Lin A, Xia H, Cheng X, Kong M, Liu H. Vine Tea (
Ampelopsis grossedentata
) extract attenuates CCl
4
‐induced liver injury by restoring gut microbiota dysbiosis in mice. Mol Nutr Food Res 2022; 66:e2100892. [PMID: 35188709 DOI: 10.1002/mnfr.202100892] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/29/2021] [Indexed: 11/11/2022]
Affiliation(s)
- Ying Li
- College of Basic Medical Sciences Hubei University of Chinese Medicine Huangjiahu West Road 16 Wuhan 430065 PR China
| | - Haiming Hu
- College of Basic Medical Sciences Hubei University of Chinese Medicine Huangjiahu West Road 16 Wuhan 430065 PR China
| | - Huabing Yang
- College of Basic Medical Sciences Hubei University of Chinese Medicine Huangjiahu West Road 16 Wuhan 430065 PR China
| | - Aizhen Lin
- Hubei Provincial Hospital of Traditional Chinese Medicine Wuhan 430061 P.R. China
- Hubei Province Academy of Traditional Chinese Medicine Wuhan 430074 P.R. China
| | - Hui Xia
- College of Basic Medical Sciences Hubei University of Chinese Medicine Huangjiahu West Road 16 Wuhan 430065 PR China
| | - Xue Cheng
- College of Basic Medical Sciences Hubei University of Chinese Medicine Huangjiahu West Road 16 Wuhan 430065 PR China
| | - Mingwang Kong
- College of Basic Medical Sciences Hubei University of Chinese Medicine Huangjiahu West Road 16 Wuhan 430065 PR China
| | - Hongtao Liu
- College of Basic Medical Sciences Hubei University of Chinese Medicine Huangjiahu West Road 16 Wuhan 430065 PR China
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22
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Gurol KC, Aschner M, Smith DR, Mukhopadhyay S. Role of excretion in manganese homeostasis and neurotoxicity: a historical perspective. Am J Physiol Gastrointest Liver Physiol 2022; 322:G79-G92. [PMID: 34786983 PMCID: PMC8714252 DOI: 10.1152/ajpgi.00299.2021] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The essential metal manganese (Mn) induces incurable neurotoxicity at elevated levels that manifests as parkinsonism in adults and fine motor and executive function deficits in children. Studies on Mn neurotoxicity have largely focused on the role and mechanisms of disease induced by elevated Mn exposure from occupational or environmental sources. In contrast, the critical role of excretion in regulating Mn homeostasis and neurotoxicity has received less attention although 1) studies on Mn excretion date back to the 1920s; 2) elegant radiotracer Mn excretion assays in the 1940s to 1960s established the routes of Mn excretion; and 3) studies on patients with liver cirrhosis in the 1990s to 2000s identified an association between decreased Mn excretion and the risk of developing Mn-induced parkinsonism in the absence of elevated Mn exposure. Notably, the last few years have seen renewed interest in Mn excretion largely driven by the discovery that hereditary Mn neurotoxicity due to mutations in SLC30A10 or SLC39A14 is caused, at least in part, by deficits in Mn excretion. Quite remarkably, some of the recent results on SLC30A10 and SLC39A14 provide explanations for observations made ∼40-50 years ago. The goal of the current review is to integrate the historic studies on Mn excretion with more contemporary recent work and provide a comprehensive state-of-the-art overview of Mn excretion and its role in regulating Mn homeostasis and neurotoxicity. A related goal is to discuss the significance of some of the foundational studies on Mn excretion so that these highly consequential earlier studies remain influential in the field.
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Affiliation(s)
- Kerem C. Gurol
- 1Division of Pharmacology & Toxicology, College of Pharmacy, and Institute for Neuroscience, The University of Texas at Austin, Austin, Texas
| | - Michael Aschner
- 2Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York
| | - Donald R. Smith
- 3Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California
| | - Somshuvra Mukhopadhyay
- 1Division of Pharmacology & Toxicology, College of Pharmacy, and Institute for Neuroscience, The University of Texas at Austin, Austin, Texas
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23
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Kadiri DD, Peela S, Ganguli D. Effect of cirrhosis and hepatitis on the prognosis of liver cancer. THERANOSTICS AND PRECISION MEDICINE FOR THE MANAGEMENT OF HEPATOCELLULAR CARCINOMA 2022:51-72. [DOI: 10.1016/b978-0-323-98806-3.00002-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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24
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Abdel Moneim M, Abdelaziz DH, Ibrahim Nagy Y, Abdel Baki A, Attia AS, Sabry N. Rifaximin microbial resistance and its efficacy and safety as a secondary prophylaxis of hepatic encephalopathy in patients with hepatitis C virus-related cirrhosis. Int J Clin Pract 2021; 75:e14807. [PMID: 34487412 DOI: 10.1111/ijcp.14807] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/14/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIM Rifaximin is an oral antibiotic with promising efficacy in the reduction of hepatic encephalopathy (HE) recurrence. Development of microbial resistance to rifaximin is not studied yet in HE. The study aim was to assess the microbial resistance, safety and efficacy of rifaximin as secondary prophylaxis of HE. METHOD In this open-label parallel, prospective interventional study, 100 patients were randomly allocated either to receive 400 mg rifaximin 3 times/d plus 30-45 mL lactulose 3 times/d (intervention group) or to receive the standard of care only which is lactulose alone (control group) for 6 months. The primary outcome of the study was the difference between minimum inhibitory concentration (MIC) of rifaximin among the two studied groups at the end of treatment. The secondary outcomes included the time to first episode of HE, time to first hospitalisation, and patient's survival. RESULTS The MIC did not differ significantly after treatment exposure compared with baseline either between groups or within the same group. The time to new episode of HE was 18.84 ± 6.49 weeks (mean ± SD) in the intervention group and was significantly longer (P = .002) than that in the control group 14 ± 7.52 weeks. Moreover, only 23 (46%) patients developed overt HE in the intervention group compared with 35 patients (70%) in the control group (P = .005). Also, there was an observed 32% reduction in the risk of hospitalisation in intervention group compared with control group. CONCLUSION Rifaximin succeeded to maintain remission from new episodes of HE in hepatitis C virus cirrhotic patients with limited potential for development of microbial resistance over the study period. ClinicalTrials.gov Identifier: NCT04736836.
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Affiliation(s)
- Mai Abdel Moneim
- Clinical Pharmacy Department, The National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Doaa H Abdelaziz
- Clinical Pharmacy Department, The National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt
| | - Yosra Ibrahim Nagy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Amin Abdel Baki
- Hepatology, Gastroenterology and Infectious Diseases Department, The National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed S Attia
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Nirmeen Sabry
- Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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25
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De Muynck K, Vanderborght B, Van Vlierberghe H, Devisscher L. The Gut-Liver Axis in Chronic Liver Disease: A Macrophage Perspective. Cells 2021; 10:2959. [PMID: 34831182 PMCID: PMC8616442 DOI: 10.3390/cells10112959] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic liver disease (CLD) is a growing health concern which accounts for two million deaths per year. Obesity, alcohol overconsumption, and progressive cholestasis are commonly characterized by persistent low-grade inflammation and advancing fibrosis, which form the basis for development of end-stage liver disease complications, including hepatocellular carcinoma. CLD pathophysiology extends to the intestinal tract and is characterized by intestinal dysbiosis, bile acid dysregulation, and gut barrier disruption. In addition, macrophages are key players in CLD progression and intestinal barrier breakdown. Emerging studies are unveiling macrophage heterogeneity and driving factors of their plasticity in health and disease. To date, in-depth investigation of how gut-liver axis disruption impacts the hepatic and intestinal macrophage pool in CLD pathogenesis is scarce. In this review, we give an overview of the role of intestinal and hepatic macrophages in homeostasis and gut-liver axis disruption in progressive stages of CLD.
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Affiliation(s)
- Kevin De Muynck
- Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium; (K.D.M.); (B.V.)
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium;
| | - Bart Vanderborght
- Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium; (K.D.M.); (B.V.)
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium;
| | - Hans Van Vlierberghe
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium;
| | - Lindsey Devisscher
- Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium; (K.D.M.); (B.V.)
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Fukui H. Leaky Gut and Gut-Liver Axis in Liver Cirrhosis: Clinical Studies Update. Gut Liver 2021; 15:666-676. [PMID: 33071239 PMCID: PMC8444108 DOI: 10.5009/gnl20032] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 06/09/2020] [Accepted: 06/09/2020] [Indexed: 12/12/2022] Open
Abstract
Portal blood flows into the liver containing the gut microbiome and its products such as endotoxin and bacterial DNA. The cirrhotic liver acts and detoxifies as the initial site of microbial products. In so-called "leaky gut," the increased intestinal permeability for bacteria and their products constitutes an important pathogenetic factor for major complications in patients with liver cirrhosis. Prolonged gastric and small intestinal transit may induce intestinal bacterial overgrowth, a condition in which colonic bacteria translocate into the small gut. Cirrhotic patients further show gut dysbiosis characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous nonpathogenic bacteria. Pathological bacterial translocation (BT) is a contributing factor in the development of various severe complications. Bile acids (BAs) undergo extensive enterohepatic circulation and play important roles in the gut-liver axis. BT-induced inflammation prevents synthesis of BAs in the liver through inhibition of BA-synthesizing enzyme CYP7A1. A lower abundance of 7α-dehydroxylating gut bacteria leads to decreased conversion of primary to secondary BAs. Decreases in total and secondary BAs may play an important role in the gut dysbiosis characterized by a proinflammatory and toxic gut microbiome inducing BT and endotoxemia, as addressed in my previous reviews. Selective intestinal decontamination by the use of various antimicrobial drugs for management of complications has a long history. Lactobacillus GG decreasing endotoxemia is reported to improve the microbiome with beneficial changes in amino acid, vitamin and secondary BA metabolism. Current approaches for hepatic encephalopathy are the use of nonabsorbable antibiotics and disaccharides. Probiotics may become an additional therapeutic option for advanced liver cirrhosis.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Nara Medical University, Kashihara, Japan
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27
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Hutin D, Long AS, Sugamori K, Shao P, Singh SK, Rasmussen M, Olafsen NE, Pettersen S, Grimaldi G, Grant DM, Matthews J. 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)-Inducible Poly-ADP-Ribose Polymerase (TIPARP/PARP7) Catalytic Mutant Mice (TiparpH532A) Exhibit Increased Sensitivity to TCDD-Induced Hepatotoxicity and Lethality. Toxicol Sci 2021; 183:154-169. [PMID: 34129049 PMCID: PMC8404992 DOI: 10.1093/toxsci/kfab075] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-adenosine diphosphate (ADP)-ribose polymerase (TIPARP/PARP7), an aryl hydrocarbon receptor (AHR) target gene and mono-ADP-ribosyltransferase, acts as part of a negative feedback loop to repress AHR signaling. This process is prevented by a single H532A mutation in TIPARP that destroys its catalytic activity. We hypothesized that the loss of TIPARP catalytic activity would increase sensitivity to TCDD-induced toxicity in vivo. To test this, we created a catalytically deficient mouse line (TiparpH532A) by introducing a single H532A mutation in TIPARP. Treatment of mouse embryonic fibroblasts or hepatocytes isolated from TiparpH532A mice confirmed the increased TCDD-induced expression of the AHR target genes Cyp1a1, Cyp1b1, and Tiparp. TiparpH532A mice given a single injection of 10 µg/kg TCDD, a nonlethal dose in Tiparp+/+ mice, did not survive beyond day 10. All Tiparp+/+ mice survived the 30-day treatment. TCDD-treated TiparpH532A mice displayed increased expression of AHR target genes, increased steatohepatitis and hepatotoxicity. Hepatic RNA-sequencing revealed 7-fold more differentially expressed genes in TiparpH532A mice than in Tiparp+/+ mice (4542 vs 647 genes) 6 days after TCDD treatment. Differentially expressed genes included genes involved in xenobiotic metabolism, lipid homeostasis and inflammation. Taken together, these data further support TIPARP as a critical negative regulator of AHR activity and show that loss of its catalytic activity is sufficient to increase sensitivity to TCDD-induced steatohepatitis and lethality. Since TIPARP inhibition has recently emerged as a potential anticancer therapy, the impact on AHR signaling, TCDD and polycyclic aromatic hydrocarbon toxicity will need to be carefully considered under conditions of therapeutic TIPARP inhibition.
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Affiliation(s)
- David Hutin
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8 Ontario, Canada
| | - Alexandra S Long
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8 Ontario, Canada
| | - Kim Sugamori
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8 Ontario, Canada
| | - Peng Shao
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8 Ontario, Canada
| | | | - Marit Rasmussen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
| | - Ninni Elise Olafsen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
| | - Solveig Pettersen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
| | - Giulia Grimaldi
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
| | - Denis M Grant
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8 Ontario, Canada
| | - Jason Matthews
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, M5S 1A8 Ontario, Canada.,Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
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The Gut Microbiota-Derived Immune Response in Chronic Liver Disease. Int J Mol Sci 2021; 22:ijms22158309. [PMID: 34361075 PMCID: PMC8347749 DOI: 10.3390/ijms22158309] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/29/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
In chronic liver disease, the causative factor is important; however, recently, the intestinal microbiome has been associated with the progression of chronic liver disease and the occurrence of side effects. The immune system is affected by the metabolites of the microbiome, and diet is the primary regulator of the microbiota composition and function in the gut–liver axis. These metabolites can be used as therapeutic material, and postbiotics, in the future, can increase or decrease human immunity by modulating inflammation and immune reactions. Therefore, the excessive intake of nutrients and the lack of nutrition have important effects on immunity and inflammation. Evidence has been published indicating that microbiome-induced chronic inflammation and the consequent immune dysregulation affect the development of chronic liver disease. In this research paper, we discuss the overall trend of microbiome-derived substances related to immunity and the future research directions.
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A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy. J Hepatol 2021; 75:98-107. [PMID: 33894327 DOI: 10.1016/j.jhep.2021.03.012] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 03/07/2021] [Accepted: 03/09/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND & AIMS Golexanolone is a novel small molecule GABA-A receptor-modulating steroid antagonist under development for the treatment of cognitive and vigilance disorders caused by allosteric over-activation of GABA-A receptors by neurosteroids. It restored spatial learning and motor coordination in animal models of hepatic encephalopathy (HE) and mitigated the effects of intravenous allopregnanolone in healthy adults in a dose-dependent fashion. Herein, we report data on the safety, pharmacokinetics (PK) and efficacy of golexanolone in adult patients with cirrhosis. METHODS Following single/multiple ascending dose studies, adults with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening were randomized to 3 weeks' dosing with golexanolone (10, 40 or 80 mg BID) or placebo. CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalogram (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]) were obtained at baseline, 10, and 21 days. RESULTS Golexanolone exhibited satisfactory safety and PK. Baseline characteristics were similar between the 12 and 33 patients randomized to placebo or golexanolone, respectively. By prespecified analyses, golexanolone was associated with directionally favourable changes vs. placebo in ESS (p = 0.047), MDF (p = 0.142) and DT/AB (p = 0.021). All patients also showed directionally favourable changes in CRT, PHES and ANT, but with no statistical difference between golexanolone and placebo. Post hoc analyses taking into account the variability and improvement in CRT, PHES and ANT observed between screening and baseline suggested an efficacy signal by cognitive measures as well. CONCLUSION Golexanolone was well tolerated and associated with improvement in cognitive performance. These results implicate GABA-A receptor-modulating neurosteroids in the pathogenesis of HE and support the therapeutic potential of golexanolone. LAY SUMMARY Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug. CLINICAL TRIAL REGISTRATION NUMBER EudraCT 2016-003651-30.
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30
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Sun L, Barter Z, von Moltke L, Rowland Yeo K. Using physiologically-based pharmacokinetic modeling for predicting the effects of hepatic impairment on the pharmacokinetics of olanzapine and samidorphan given as a combination tablet. CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY 2021; 10:1071-1080. [PMID: 34185436 PMCID: PMC8452299 DOI: 10.1002/psp4.12675] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 05/14/2021] [Accepted: 05/19/2021] [Indexed: 12/15/2022]
Abstract
A combination of olanzapine and samidorphan (OLZ/SAM) was recently approved by the US Food and Drug Administration for treatment of patients with schizophrenia or bipolar I disorder. The effects of moderate hepatic impairment on the pharmacokinetics (PKs) of olanzapine and samidorphan after a single dose of OLZ/SAM were characterized in a clinical study. Physiologically-based pharmacokinetic (PBPK) modeling was used to extend the clinical findings to predict the effects of varying degrees of hepatic impairment on the PKs of olanzapine and samidorphan. A previously developed PBPK model for OLZ/SAM was refined to recover the observed pharmacokinetic differences between individuals with moderate hepatic impairment and healthy controls. The optimized model was applied to predict changes in olanzapine and samidorphan PKs after multiple once-daily doses of OLZ/SAM in subjects with mild, moderate, and severe hepatic impairment relative to healthy controls. Modifications to model parameters, including absorption rate constant and fraction unbound to plasma protein, were made to recover the observed change in the PKs of olanzapine and samidorphan in individuals with moderate hepatic impairment. In applying the optimized model, mild, moderate, and severe hepatic impairment were predicted to increase steady-state total systemic exposures by 1.1-, 1.5-, and 1.6-fold, respectively, for olanzapine, and by 1.2-, 1.9-, and 2.3-fold, respectively, for samidorphan. PBPK modeling allowed for prediction of untested clinical scenarios of varying degrees of hepatic impairment in lieu of additional clinical studies.
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Affiliation(s)
- Lei Sun
- Clinical Pharmacology, Alkermes, Inc., Waltham, Massachusetts, USA
| | - Zoe Barter
- Simcyp Division, Certara UK Limited, Sheffield, UK
| | - Lisa von Moltke
- Clinical Pharmacology, Alkermes, Inc., Waltham, Massachusetts, USA.,Seres Therapeutics, Cambridge, Massachusetts, USA
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Nishimura N, Kaji K, Kitagawa K, Sawada Y, Furukawa M, Ozutsumi T, Fujinaga Y, Tsuji Y, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Fukui H, Yoshiji H. Intestinal Permeability Is a Mechanical Rheostat in the Pathogenesis of Liver Cirrhosis. Int J Mol Sci 2021; 22:ijms22136921. [PMID: 34203178 PMCID: PMC8267717 DOI: 10.3390/ijms22136921] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/22/2021] [Accepted: 06/24/2021] [Indexed: 12/12/2022] Open
Abstract
Recent studies have suggested that an alteration in the gut microbiota and their products, particularly endotoxins derived from Gram-negative bacteria, may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, which means higher translocation of bacteria and their products and components, including endotoxins, the so-called "leaky gut". Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases, including alcoholic liver disease and nonalcoholic liver disease. A decrease in commensal nonpathogenic bacteria including Ruminococaceae and Lactobacillus and an overgrowth of pathogenic bacteria such as Bacteroidaceae and Enterobacteriaceae are observed in cirrhotic patients. The decreased diversity of the gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of post-transplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via Toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is a major receptor activated by the binding of endotoxins in macrophages, and its downstream signal induces proinflammatory cytokines. The expression of TLR4 is also observed in nonimmune cells in the liver, such as hepatic stellate cells, which play a crucial role in the progression of liver fibrosis that develops into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression. In this review, we summarize the findings for the role of gut-derived endotoxemia underlying the progression of liver pathogenesis.
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Enderes J, Teschke J, Manekeller S, Vilz TO, Kalff JC, Glowka TR. Chronic Liver Disease Increases Mortality Following Pancreatoduodenectomy. J Clin Med 2021; 10:jcm10112521. [PMID: 34200183 PMCID: PMC8201140 DOI: 10.3390/jcm10112521] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 05/29/2021] [Accepted: 06/02/2021] [Indexed: 12/13/2022] Open
Abstract
According to the International Study Group of Pancreatic Surgery (ISGPS), data about the impact of pre-existing liver pathologies on delayed gastric emptying (DGE) after pancreatoduodenectomy (PD) according to the definitions of the International Study Group of Pancreatic Surgery (ISGPS) are lacking. We therefore investigated the impact of DGE after PD according to ISGPS in patients with liver cirrhosis (LC) and advanced liver fibrosis (LF). Patients were analyzed with respect to pre-existing liver pathologies (LC and advanced LF, n = 15, 6% vs. no liver pathologies, n = 240, 94%) in relation to demographic factors, comorbidities, intraoperative characteristics, mortality and postoperative complications, with special emphasis on DGE. DGE was equally distributed (DGE grade A, p = 1.000; B, p = 0.396; C, p = 0.607). Particularly, the first day of solid food intake (p = 0.901), the duration of intraoperative administered nasogastric tube (NGT) (p = 0.812), the rate of re-insertion of NGT (p = 0.072), and the need for parenteral nutrition (p = 0.643) did not differ. However, patients with LC and advanced LF showed a higher ASA (American Society of Anesthesiologists) score (p = 0.016), intraoperatively received more erythrocyte transfusions (p = 0.029), stayed longer in the intensive care unit (p = 0.010) and showed more intraabdominal abscess formation (p = 0.006). Moreover, we did observe a higher mortality rate amongst patients with pre-existing liver diseases (p = 0.021), and reoperation was a risk factor for higher mortality (p ≤ 0.001) in the multivariate analysis. In our study, we could not detect a difference with respect to DGE classified by ISGPS; however, we did observe a higher mortality rate amongst these patients and thus, they should be critically evaluated for PD.
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Bakr RO, Shahat EA, Elissawy AE, Fayez AM, Eldahshan OA. Evaluation of the hepatoprotective activity of Pulicaria incisa subspecies candolleana and in silico screening of its isolated phenolics. JOURNAL OF ETHNOPHARMACOLOGY 2021; 271:113767. [PMID: 33444722 DOI: 10.1016/j.jep.2020.113767] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 11/05/2020] [Accepted: 12/24/2020] [Indexed: 05/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Pulicaria incisa sub. candolleana E. Gamal-Eldin (Asteraceae) was traditionally used by Bedouins as a refreshing tea and as hypoglycemic, in gastrointestinal ailments, sinusitis and headache. Recently a great correlation has been established between liver cirrhosis and gastrointestinal dysfunction reflected by abdominal bloating, pain, diarrhea, constipation, besides decreased food intake. So far, the hepatoprotective effect of P. incisa sub. candolleana E. Gamal-Eldin was not studied before although other Pulicaria species have previously shown hepatoprotective and antioxidant effects. AIM OF THE STUDY In this study, we aimed to identify the phytochemical constituents of the P. incisa sub. candolleana E. Gamal-Eldin hydroethanolic extract (PICE), as well as to evaluate the hepatoprotective, anti-inflammatory and antioxidant activities in methotrexate (MTX)- intoxicated rats. Besides, the molecular interaction between the isolated compounds and cyclooxygenase-2 (COX-2) and phospholipase 2 (PLA-2) were assessed by in-silico screening. MATERIAL AND METHODS The main phytoconstituents were characterized using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Vacuum liquid chromatography (VLC) aided by preparative high-performance liquid chromatography (HPLC) were also used to isolate the major phenolics from the hydroethanolic extract. Their structures were elucidated using different spectroscopic analysis methods, including 1D and 2D nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI/MS). The hepatoprotective activity of three doses (100, 250, 500 mg/kg) of PICE in MTX-intoxicated rats was assessed and compared to silymarin as a standard. Additionally, in silico docking study on cyclooxygenase-2 (COX-2) and phospholipase 2 (PLA-2) was performed to justify the anti-inflammatory activity of the isolated compounds. RESULTS Thirteen compounds were tentatively identified, including flavonoids and phenolic acids. Four main isolated compounds were identified as, eugenol-1-O-β-glucoside, 5-O-caffeoylquinic acid, 3, 5-di-O-caffeoylquinic acid and quercetin-3-O-β-glucoside. Treatment of MTX-intoxicated rats with the 250 mg/kg extract reversed the altered levels of biochemical markers of liver damage, ameliorated the oxidant status and reduced the inflammatory mediators, similar to treatment with silymarin. Quercetin-3-O-β-glucoside showed the best docking energy score of -19.12 kcal/mol against COX-2, forming four binding interactions with residues Leu 353, Arg 121, Tyr 356 and Ala 528, followed by 3,5-di-O-caffeoylquinic acid (-18.01 kcal/mol). CONCLUSION This study reveals P. incisa sub. candolleana as a rich source of phenolics including flavonoids, supporting its anti-inflammatory and hepatoprotective effects and suggesting its usage as a promising candidate in inflammatory conditions.
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Affiliation(s)
- Riham O Bakr
- Pharmacognosy Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt
| | - Esraa A Shahat
- Pharmacognosy Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt
| | - Ahmed E Elissawy
- Pharmacognosy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Center for Drug Discovery Research and Development, Ain Shams University, Egypt
| | - Ahmed M Fayez
- Pharmacology Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt
| | - Omayma A Eldahshan
- Pharmacognosy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Center for Drug Discovery Research and Development, Ain Shams University, Egypt.
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Montoro-Huguet MA, Belloc B, Domínguez-Cajal M. Small and Large Intestine (I): Malabsorption of Nutrients. Nutrients 2021; 13:1254. [PMID: 33920345 PMCID: PMC8070135 DOI: 10.3390/nu13041254] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Numerous disorders can alter the physiological mechanisms that guarantee proper digestion and absorption of nutrients (macro- and micronutrients), leading to a wide variety of symptoms and nutritional consequences. Malabsorption can be caused by many diseases of the small intestine, as well as by diseases of the pancreas, liver, biliary tract, and stomach. This article provides an overview of pathophysiologic mechanisms that lead to symptoms or complications of maldigestion (defined as the defective intraluminal hydrolysis of nutrients) or malabsorption (defined as defective mucosal absorption), as well as its clinical consequences, including both gastrointestinal symptoms and extraintestinal manifestations and/or laboratory abnormalities. The normal uptake of nutrients, vitamins, and minerals by the gastrointestinal tract (GI) requires several steps, each of which can be compromised in disease. This article will first describe the mechanisms that lead to poor assimilation of nutrients, and secondly discuss the symptoms and nutritional consequences of each specific disorder. The clinician must be aware that many malabsorptive disorders are manifested by subtle disorders, even without gastrointestinal symptoms (for example, anemia, osteoporosis, or infertility in celiac disease), so the index of suspicion must be high to recognize the underlying diseases in time.
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Affiliation(s)
- Miguel A. Montoro-Huguet
- Departamento de Medicina, Psiquiatría y Dermatología, Facultad de Ciencias de la Salud y del Deporte, University of Zaragoza, 50009 Zaragoza, Spain
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| | - Blanca Belloc
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
| | - Manuel Domínguez-Cajal
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge de Huesca, 22004 Huesca, Spain; (B.B.); (M.D.-C.)
- Aragonese Institute of Health Sciences (IACS), 50009 Zaragoza, Spain
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Chen Y, Guo J, Chen C, Shi D, Fang D, Ji F, Li L. Characterization of the Gastric Mucosal Microbiota in Patients with Liver Cirrhosis and Its Associations with Gastrointestinal Symptoms. ENGINEERING 2021; 7:507-514. [DOI: 10.1016/j.eng.2020.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Motamed F, Heidari G, Heirati B, Rahmani P. Diagnostic Performance of Noninvasive Methods for Liver Biopsy by Fibroscan in Pediatric. JOURNAL OF CHILD SCIENCE 2021. [DOI: 10.1055/s-0041-1725079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
AbstractLiver biopsy is the gold standard for the diagnosis and management of various liver diseases; however, noninvasive diagnostic modalities may help prevent adverse effects of anesthesia, prolonged hospitalization, sampling error, and other serious complications, particularly in pediatric patients. The aim of this study is to compare the results of liver biopsy and fibroscan in children with chronic liver diseases. All patients presenting chronic liver disease admitted in the ward or clinic of Tehran's Children Medical Center were enrolled in the study. Required laboratory tests were performed to diagnose the disease, followed by elastography using fibroscan 402 (M-probe) Echosens machine and liver biopsy using Menghini technique. Samples were scored by using METAVIR scoring system. Thirty-two patients were reported (68.8%, female) with autoimmune hepatitis (18.8%), Wilson disease (12.5%), and glycogen storage disease (12.5%). The most common pathologic stage and fibroscan result was stage III and F0 (46.9%), respectively. Association between pathology and fibroscan results was not significant. Nonetheless, age and diagnosis, age and Fibroscan score, and pathology and liver function test were significantly associated with each other. Fibroscan cannot be used as an alternative to liver biopsy; however, it can be a useful accessory tool.
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Affiliation(s)
- Farzaneh Motamed
- Pediatric Gastroenterology and Hepatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghobad Heidari
- Department of Pediatric, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Bita Heirati
- Department of Pediatric, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Rahmani
- Pediatric Gastroenterology and Hepatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Shi Y, Leng Y, Liu D, Liu X, Ren Y, Zhang J, Chen F. Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2021; 49:413-435. [PMID: 33622215 DOI: 10.1142/s0192415x21500191] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).
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Affiliation(s)
- Yajing Shi
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China
| | - Yufang Leng
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China
- The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
| | - Disheng Liu
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China
- The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
| | - Xin Liu
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China
- The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
| | - Yixing Ren
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China
| | - Jianmin Zhang
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China
| | - Feng Chen
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China
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Dos Santos ALS, Anastácio LR. The impact of L-branched-chain amino acids and L-leucine on malnutrition, sarcopenia, and other outcomes in patients with chronic liver disease. Expert Rev Gastroenterol Hepatol 2021; 15:181-194. [PMID: 32993404 DOI: 10.1080/17474124.2021.1829470] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Metabolic and hormonal disorders resulting from chronic liver diseases culminate in increased proteolysis and decreased protein synthesis, which contributes to the development and progression of malnutrition and, consequently, sarcopenia. Nutritional management of sarcopenia in liver cirrhosis is a continuously evolving field and data on essential amino acid supplementation in chronic liver diseases is scarce. AREAS COVERED This review encompasses the current literature on oral amino acids supplementation in patients with chronic liver disease or patients with liver cirrhosis to try to elucidate the possible effects of L-branched-chain amino acids and isolated L-leucine as a therapeutic approach to malnutrition and sarcopenia. EXPERT COMMENTARY To ensure an optimal nutritional status and to reduce sarcopenia, it is necessary to assess nutritional status in all patients with liver cirrhosis and to apply nutritional interventions accordingly. The supply of calories, proteins, and essential amino acids is necessary for the maintenance of muscle mass and function. Although supplementation of L-branched-chain amino acids plays an important role in liver disease, L-leucine has been described as the main amino acid involved in protein turnover, reducing proteolysis, and stimulating protein synthesis.
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Affiliation(s)
- Ana Luiza Soares Dos Santos
- Food Science Post-Graduation Program, Pharmacy School, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil
| | - Lucilene Rezende Anastácio
- Food Science Post-Graduation Program, Pharmacy School, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil
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Puri P, Dhiman RK, Taneja S, Tandon P, Merli M, Anand AC, Arora A, Acharya SK, Benjamin J, Chawla YK, Dadhich S, Duseja A, Eapan C, Goel A, Kalra N, Kapoor D, Kumar A, Madan K, Nagral A, Pandey G, Rao PN, Saigal S, Saraf N, Saraswat VA, Saraya A, Sarin SK, Sharma P, Shalimar, Shukla A, Sidhu SS, Singh N, Singh SP, Srivastava A, Wadhawan M. Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver. J Clin Exp Hepatol 2021; 11:97-143. [PMID: 33679050 PMCID: PMC7897902 DOI: 10.1016/j.jceh.2020.09.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.
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Key Words
- ACLF, acute on chronic liver failure
- ASM, appendicular skeletal muscle mass
- BCAA, branched chain amino acids
- BIA, bioimpedance analysis
- BMD, bone mineral densitometry
- BMI, body mass index
- CLD, chronic liver disease
- CS, corn-starch
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- DEXA, dual-energy X-ray absorptiometry
- EASL, European Association for the Study of the Liver
- ESPEN, European society for Clinical Nutrition and Metabolism
- GSD, glycogen storage disease
- HGS, hand-grip strength
- IBW, ideal body weight
- IEM, inborn error of metabolism
- INASL, Indian National Association for Study of the Liver
- L3, third lumbar
- LFI, Liver Frailty Index
- MCT, medium-chain triglyceride
- MELD, model for end-stage liver disease
- MLD, metabolic liver disease
- MRI, magnetic resonance imaging
- RDA, recommended daily allowance
- REE, NASH
- RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool
- SMI, skeletal muscle index
- Sarcopenia
- TEE, total energy expenditure
- chronic liver disease
- cirrhosis
- malnutrition
- non-alcoholic liver disease, resting energy expenditure
- nutrition
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Radha K. Dhiman
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Puneeta Tandon
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, 00185, Italy
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Anil Arora
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Subrat K. Acharya
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Jaya Benjamin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Yogesh K. Chawla
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Sunil Dadhich
- Department of Gastroenterology SN Medical College, Jodhpur, 342003, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - C.E. Eapan
- Department of Gastroenterology, Christian Medical College, Vellore, 632004, India
| | - Amit Goel
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Naveen Kalra
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad, 500004, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Kaushal Madan
- Max Smart Super Speciality Hospital, New Delhi, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital, Mumbai, 400026, India
| | - Gaurav Pandey
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Padaki N. Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, 500082, India
| | - Sanjiv Saigal
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Vivek A. Saraswat
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | - Sandeep S. Sidhu
- Department of Gastroenterology, SPS Hospital, Ludhiana, 141001, India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, 753007, India
| | - Anshu Srivastava
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases, BL Kapur Memorial Hospital, New Delhi, 110005, India
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Chapman B, Sinclair M, Gow PJ, Testro AG. Malnutrition in cirrhosis: More food for thought. World J Hepatol 2020; 12:883-896. [PMID: 33312416 PMCID: PMC7701970 DOI: 10.4254/wjh.v12.i11.883] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 10/08/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications. The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multiple and interrelated. Anorexia and liver decompensation symptoms lead to poor dietary intake; metabolic changes characterised by elevated energy expenditure, reduced glycogen storage, an accelerated starvation response and protein catabolism result in muscle and fat wasting; and, malabsorption renders the cirrhotic patient unable to fully absorb or utilise food that has been consumed. Malnutrition is therefore a considerable challenge to manage effectively, particularly as liver disease progresses. A high energy, high protein diet is recognised as standard of care, yet patients struggle to follow this recommendation and there is limited evidence to guide malnutrition interventions in cirrhosis and liver transplantation. In this review, we seek to detail the factors which contribute to poor nutritional status in liver disease, and highlight complexities far greater than "poor appetite" or "reduced oral intake" leading to malnutrition. We also discuss management strategies to optimise nutritional status in this patient group, which target the inter-related mechanisms unique to advanced liver disease. Finally, future research requirements are suggested, to develop effective treatments for one of the most common and debilitating complications afflicting cirrhotic patients.
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Affiliation(s)
- Brooke Chapman
- Nutrition and Dietetics Department, Austin Health, Heidelberg 3084, Australia.
| | - Marie Sinclair
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
| | - Paul J Gow
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
| | - Adam G Testro
- Liver Transplant Unit, Austin Health, Heidelberg 3084, Australia
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Caballero-Mateos AM, García Márquez J, Ortiz Sánchez A, Roa Colomo A, Rodríguez Acosta C. Is gastroparesis that is often detected in patients with alcoholic chronic liver disease a manifestation of an autonomic dysfunction syndrome? A preliminary study. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 113:269-271. [PMID: 33233909 DOI: 10.17235/reed.2020.7303/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND the autonomic dysfunction defines the neuropathy of the autonomic nervous system. The prevalence of the gastric dysmotility and its relationship with the autonomic dysfunction in patients with alcohol chronic liver disease is not well known. METHODS thirty-six patients with alcohol chronic liver disease and 25 healthy controls were evaluated, in order to detect an autonomic dysfunction through different cardiovascular reflexes and gastric emptying tests. RESULTS ninety-four per cent of the patients showed an impaired R index (variations in heart rate during six deep inspirations-expirations per minute) and/or S/S-HR (variations in heart rate when standing from a supine position). Seventy-five per cent of the patients showed gastroparesis (T1/2: gastric half-emptying time was delayed). There was a correlation between the R index and T1/2 (r = -0.49; p < 0.01). CONCLUSIONS we suggest that gastroparesis detected in alcoholic chronic liver disease is another clinical manifestation of the autonomic parasympathetic dysfunction.
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Sarcopenia Severity Based on Computed Tomography Image Analysis in Patients with Cirrhosis. Nutrients 2020; 12:nu12113463. [PMID: 33187310 PMCID: PMC7696263 DOI: 10.3390/nu12113463] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 10/25/2020] [Accepted: 11/09/2020] [Indexed: 12/15/2022] Open
Abstract
Standardized sex-specific cut-offs for sarcopenia in cirrhosis are needed to identify the risk of clinical complications and to discriminate the severity of sarcopenia. We aimed to compare clinical characteristics between patients with cirrhosis categorized according to the severity of sarcopenia. Computed tomography images were taken at the 3rd lumbar vertebra from 603 patients with cirrhosis and 129 adult donors for living liver transplantation. Patients with skeletal muscle index (SMI) two standard deviations (SD) below the sex-specific mean value of young donors (18-40 years old) were categorized as having severe sarcopenia whereas patients with SMI between -1 and -2 SD of the sex-specific young adult mean values were categorized as having sarcopenia. In the cirrhosis group, 408 patients (68%) were male with the mean age of 57 ± 0.4 years, and MELD score of 14 ± 0.4. Patients were divided into three groups: severe-sarcopenic (SMI < 30 cm2/m2 in females and <42 cm2/m2 in males), sarcopenic (30 ≤ SMI < 37 cm2/m2 in females and 42 ≤ SMI < 50 cm2/m2 in males) and non-sarcopenic (SMI ≥ 37 cm2/m2 in females and ≥50 cm2/m2 in males). Patients with cirrhosis and severe sarcopenia had lower muscle radiodensity and higher plasma neutrophil as well as neutrophil to lymphocyte ratio levels than both non- and sarcopenic groups. The frequency of alcohol-induced cirrhosis, refractory ascites, hepatic encephalopathy, CRP > 20 mg/mL, and severe malnutrition was also higher in severe-sarcopenic patients. The interval between sarcopenia and severe sarcopenia may reflect a window of opportunity in which to intervene and mitigate muscle wasting to improve patient outcomes.
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Yoon U, Topper J, Goldhammer J. Preoperative Evaluation and Anesthetic Management of Patients With Liver Cirrhosis Undergoing Cardiac Surgery. J Cardiothorac Vasc Anesth 2020; 36:1429-1448. [PMID: 32891522 DOI: 10.1053/j.jvca.2020.08.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 07/30/2020] [Accepted: 08/09/2020] [Indexed: 12/13/2022]
Abstract
Preoperative evaluation and anesthetic management of patients with liver cirrhosis undergoing cardiac surgery remain a clinical challenge because of its high risk for perioperative complications. This narrative review article summarizes the pathophysiology and anesthetic implication of liver cirrhosis on each organ system. It will help physicians to evaluate surgical candidates, to optimize intraoperative management, and to anticipate complications in liver cirrhosis patients undergoing cardiac surgery. Morbidity typically results from bleeding, sepsis, multisystem organ failure, or hepatic insufficiency. These complications occur as a result of the presence of coagulopathy, poor nutritional status, immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction that occur with liver cirrhosis. Therefore, liver cirrhosis should not be seen as a single disease, but one that manifests with multiorgan dysfunction. Cardiac surgery in patients with liver cirrhosis increases the risk of perioperative complications, and it presents a particular challenge to the anesthesiologist in that nearly every aspect of normally functioning physiology may be jeopardized in a unique way. Accurately classifying the extent of liver disease, preoperative optimization, and surgical risk communication with the patient are crucial. In addition, all teams involved in the surgery should communicate openly and coordinate in order to ensure optimal care. To reduce perioperative complications, consider using off-pump cardiopulmonary bypass techniques and optimal perfusion modalities to mimic current physiologic conditions.
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Affiliation(s)
- Uzung Yoon
- Department of Anesthesiology, Thomas Jefferson University Hospital, Philadelphia, PA.
| | - James Topper
- Department of Anesthesiology, Thomas Jefferson University Hospital, Philadelphia, PA
| | - Jordan Goldhammer
- Department of Anesthesiology, Thomas Jefferson University Hospital, Philadelphia, PA
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Meyer F, Bannert K, Wiese M, Esau S, Sautter LF, Ehlers L, Aghdassi AA, Metges CC, Garbe LA, Jaster R, Lerch MM, Lamprecht G, Valentini L. Molecular Mechanism Contributing to Malnutrition and Sarcopenia in Patients with Liver Cirrhosis. Int J Mol Sci 2020; 21:E5357. [PMID: 32731496 PMCID: PMC7432938 DOI: 10.3390/ijms21155357] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 07/24/2020] [Accepted: 07/24/2020] [Indexed: 02/07/2023] Open
Abstract
Liver cirrhosis is frequently accompanied by disease-related malnutrition (DRM) and sarcopenia, defined as loss of skeletal muscle mass and function. DRM and sarcopenia often coexist in cirrhotic patients and are associated with increased morbidity and mortality. The clinical manifestation of both comorbidities are triggered by multifactorial mechanisms including reduced nutrient and energy intake caused by dietary restrictions, anorexia, neuroendocrine deregulation, olfactory and gustatory deficits. Maldigestion and malabsorption due to small intestinal bacterial overgrowth, pancreatic insufficiency or cholestasis may also contribute to DRM and sarcopenia. Decreased protein synthesis and increased protein degradation is the cornerstone mechanism to muscle loss, among others mediated by disease- and inflammation-mediated metabolic changes, hyperammonemia, increased myostatin and reduced human growth hormone. The concise pathophysiological mechanisms and interactions of DRM and sarcopenia in liver cirrhosis are not completely understood. Furthermore, most knowledge in this field are based on experimental models, but only few data in humans exist. This review summarizes known and proposed molecular mechanisms contributing to malnutrition and sarcopenia in liver cirrhosis and highlights remaining knowledge gaps. Since, in the prevention and treatment of DRM and sarcopenia in cirrhotic patients, more research is needed to identify potential biomarkers for diagnosis and development of targeted therapeutic strategies.
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Affiliation(s)
- Fatuma Meyer
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
| | - Karen Bannert
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Mats Wiese
- Division of Gastroenterology, Endocrinology and Nutritional Medicine, Department of Internal Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany; (M.W.); (A.A.A.); (M.M.L.)
| | - Susanne Esau
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
| | - Lea F. Sautter
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Luise Ehlers
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Ali A. Aghdassi
- Division of Gastroenterology, Endocrinology and Nutritional Medicine, Department of Internal Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany; (M.W.); (A.A.A.); (M.M.L.)
| | - Cornelia C. Metges
- Institute of Nutritional Physiology ‘Oskar Kellner’, Leibniz Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, Germany;
| | - Leif-A. Garbe
- Department of Agriculture and Food Sciences, University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany;
| | - Robert Jaster
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Markus M. Lerch
- Division of Gastroenterology, Endocrinology and Nutritional Medicine, Department of Internal Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany; (M.W.); (A.A.A.); (M.M.L.)
| | - Georg Lamprecht
- Division of Gastroenterology and Endocrinology, Department of Internal Medicine II, University Medicine Rostock, 18057 Rostock, Germany; (K.B.); (L.E.); (R.J.); (G.L.)
| | - Luzia Valentini
- Department of Agriculture and Food Sciences, Neubrandenburg Institute for Evidence-Based Dietetics (NIED), University of Applied Sciences Neubrandenburg, 17033 Neubrandenburg, Germany; (F.M.); (S.E.); (L.F.S.)
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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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Wan S, Luo F, Huang C, Liu C, Luo Q, Zhu X. Ursolic acid reverses liver fibrosis by inhibiting interactive NOX4/ROS and RhoA/ROCK1 signalling pathways. Aging (Albany NY) 2020; 12:10614-10632. [PMID: 32496208 PMCID: PMC7346053 DOI: 10.18632/aging.103282] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023]
Abstract
Liver fibrosis is the reversible deposition of extracellular matrix (ECM) and scar formation after liver damage by various stimuli. The interaction between NOX4/ROS and RhoA/ROCK1 in liver fibrosis is not yet clear. Ursolic acid (UA) is a traditional Chinese medicine with anti-fibrotic effects, but the molecular mechanism underlying these effects is still unclear. We investigated the interaction between NOX4/ROS and RhoA/ROCK1 during liver fibrosis and whether these molecules are targets for the anti-fibrotic effects of UA. First, we confirmed that UA reversed CCl4-induced liver fibrosis. In the NOX4 intervention and RhoA intervention groups, related experimental analyses confirmed the decrease in CCl4-induced liver fibrosis. Next, we determined that the expression of NOX4 and RhoA/ROCK1 was decreased in UA-treated liver fibrotic mice. Furthermore, RhoA/ROCK1 expression was decreased in the NOX4 intervention group, but there was no significant change in the expression of NOX4 in the RhoA intervention group. Finally, we found that liver fibrotic mice showed a decline in their microbiota diversity and abundance, a change in their microbiota composition, and a reduction in the number of potential beneficial bacteria. However, in UA-treated liver fibrotic mice, the microbiota dysbiosis was ameliorated. In conclusion, the NOX4/ROS and RhoA/ROCK1 signalling pathways are closely linked to the development of liver fibrosis. UA can reverse liver fibrosis by inhibiting the NOX4/ROS and RhoA/ROCK1 signalling pathways, which may interact with each other.
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Affiliation(s)
- Sizhe Wan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Fangyun Luo
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Chenkai Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Cong Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Qingtian Luo
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Snell DB, Cohen-Mekelburg S, Weg R, Ghosh G, Buckholz AP, Mehta A, Ma X, Christos PJ, Jesudian AB. Gastric food retention at endoscopy is associated with severity of liver cirrhosis. World J Hepatol 2019; 11:725-734. [PMID: 31772719 PMCID: PMC6856021 DOI: 10.4254/wjh.v11.i11.725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 08/22/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis. Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis. However, the contributing factors have not been fully elucidated. Retained gastric food on esophagogastroduodenoscopy (EGD) has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity. Therefore, we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease. Additionally, we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis.
AIM To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors.
METHODS We performed a retrospective case-control study of cirrhotic subjects who underwent EGD at an academic medical center between 2000 and 2015. Three hundred sixty-four patients with confirmed cirrhosis, who underwent a total of 1044 EGDs for the indication of esophageal variceal screening or surveillance, were identified. During the same period, 519 control patients without liver disease, who underwent a total of 881 EGDs for the indication of anemia, were identified. The presence of retained food on EGD was used as a surrogate for delayed gastric emptying. The relative frequency of delayed gastric emptying among cirrhotics was compared to non-cirrhotics. Characteristics of patients with and without retained food on EGD were compared using univariable and multivariable logistic regression analysis to identify associated factors.
RESULTS Overall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics were more likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P < 0.001). Characteristics associated with retained food on univariable analysis included age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004), Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P = 0.007), and lower platelet count (P = 0.027). On multivariate logistic regression analysis, in addition to the presence of cirrhosis (adjusted OR = 5.83; 95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34; 95%CI: 1.08-5.06, P = 0.031), opioid use (OR = 3.08; 95%CI: 1.29-7.34, P = 0.011), and Child-Pugh class C (OR = 4.29; 95%CI: 1.43-12.9, P = 0.01) were also associated with a higher likelihood of food retention on EGD.
CONCLUSION Cirrhotics have a higher frequency of retained food at EGD than non-cirrhotics. Decompensated cirrhosis, defined by Child-Pugh class C, is associated with a higher likelihood of delayed gastric emptying.
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Affiliation(s)
- David B Snell
- Division of Gastroenterology and Hepatology, New York University, New York, NY 10016, United States
| | - Shirley Cohen-Mekelburg
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Russell Weg
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY 14642, United States
| | - Gaurav Ghosh
- Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY 10065, United States
| | - Adam P Buckholz
- Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY 10065, United States
| | - Amit Mehta
- Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Xiaoyue Ma
- Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY 10065, United States
| | - Paul J Christos
- Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY 10065, United States
| | - Arun B Jesudian
- Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
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Fukui H. Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far? Diseases 2019; 7:diseases7040058. [PMID: 31726747 PMCID: PMC6956030 DOI: 10.3390/diseases7040058] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 10/29/2019] [Accepted: 10/29/2019] [Indexed: 02/07/2023] Open
Abstract
Accumulating evidence supports that gut dysbiosis may relate to various liver diseases. Alcoholics with high intestinal permeability had a decrease in the abundance of Ruminnococcus. Intestinal dysmotility, increased gastric pH, and altered immune responses in addition to environmental and genetic factors are likely to cause alcohol-associated gut microbial changes. Alcohol-induced dysbiosis may be associated with gut barrier dysfunction, as microbiota and their products modulate barrier function by affecting epithelial pro-inflammatory responses and mucosal repair functions. High levels of plasma endotoxin are detected in alcoholics, in moderate fatty liver to advanced cirrhosis. Decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal, stimulating IL-10 secretion and inhibiting IL-12 and interferon-γ expression. Proteobacteria, Enterobacteriaceae, and Escherichia were reported to be increased in NAFLD (nonalcoholic fatty liver disease) patients. Increased abundance of fecal Escherichia to elevated blood alcohol levels in these patients and gut microbiota enriched in alcohol-producing bacteria produce more alcohol (alcohol hypothesis). Some undetermined pathological sequences related to gut dysbiosis may facilitate energy-producing and proinflammatory conditions for the progression of NAFLD. A shortage of autochthonous non-pathogenic bacteria and an overgrowth of potentially pathogenic bacteria are common findings in cirrhotic patients. The ratio of the amounts of beneficial autochthonous taxa (Lachnospiraceae + Ruminococaceae + Veillonellaceae + Clostridiales Incertae Sedis XIV) to those of potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) was low in those with early death and organ failure. Cirrhotic patients with decreased microbial diversity before liver transplantation were more likely to develop post-transplant infections and cognitive impairment related to residual dysbiosis. Patients with PSC had marked reduction of bacterial diversity. Enterococcus and Lactobacillus were increased in PSC patients (without liver cirrhosis.) Treatment-naive PBC patients were associated with altered composition and function of gut microbiota, as well as a lower level of diversity. As serum anti-gp210 antibody has been considered as an index of disease progression, relatively lower species richness and lower abundance of Faecalibacterium spp. in gp210-positive patients are interesting. The dysbiosis-induced altered bacterial metabolites such as a hepatocarcinogenesis promotor DCA, together with a leaky gut and bacterial translocation. Gut protective Akkermansia and butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early hepatocellular carcinoma (HCC) patients.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8522, Japan
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Wan SZ, Liu C, Huang CK, Luo FY, Zhu X. Ursolic Acid Improves Intestinal Damage and Bacterial Dysbiosis in Liver Fibrosis Mice. Front Pharmacol 2019; 10:1321. [PMID: 31736766 PMCID: PMC6838135 DOI: 10.3389/fphar.2019.01321] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 10/15/2019] [Indexed: 12/12/2022] Open
Abstract
Liver fibrosis is a reversible process of extracellular matrix deposition or scar formation after liver injury. Intestinal damage and bacterial dysbiosis are important concomitant intestinal changes in liver fibrosis and may in turn accelerate the progression of liver fibrosis through the gut-liver axis. RhoA, an important factor in the regulation of the cytoskeleton, plays an important role in intestinal damage. We investigated the effects of ursolic acid (UA), a traditional Chinese medicine with anti-fibrotic effects, on intestinal damage and bacterial disorder through the RhoA pathway. UA treatment reduced intestinal damage by inhibiting the inflammatory factor TNF-α and increasing the expression of tight junction proteins and antibacterial peptides to protect the intestinal barrier. Moreover, the corrective effect of UA on bacterial dysbiosis was also confirmed by sequencing of the 16S rRNA gene. Potential beneficial bacteria, such as the phylum Firmicutes and the genera Lactobacillus and Bifidobacterium, were increased in the UA group compared to the CCl4 group. In liver fibrosis mice with RhoA inhibition via injection of adeno-associated virus, the liver fibrosis, intestinal damage, and flora disturbances were improved. Moreover, UA inhibited the expression of RhoA pathway components. In conclusion, UA improves intestinal damage and bacterial dysbiosis partly via the RhoA pathway. This may be a potential mechanism by which UA exerts its anti-fibrotic effects and provides effective theoretical support for the future use of UA in clinical practice.
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Affiliation(s)
- Si-Zhe Wan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Cong Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Chen-Kai Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fang-Yun Luo
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Aller MA, Arias N, Blanco-Rivero J, Arias J. Metabolism in Acute-On-Chronic Liver Failure: The Solution More than the Problem. Arch Med Res 2019; 50:271-284. [PMID: 31593852 DOI: 10.1016/j.arcmed.2019.09.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 09/09/2019] [Indexed: 12/13/2022]
Abstract
Chronic inflammatory liver disease with an acute deterioration of liver function is named acute-on-chronic inflammation and could be regulated by the metabolic impairments related to the liver dysfunction. In this way, the experimental cholestasis model is excellent for studying metabolism in both types of inflammatory responses. Along the evolution of this model, the rats develop biliary fibrosis and an acute-on-chronic decompensation. The acute decompensation of the liver disease is associated with encephalopathy, ascites, acute renal failure, an acute phase response and a splanchnic increase of pro- and anti-inflammatory cytokines. This multiorgan inflammatory dysfunction is mainly associated with a splanchnic and systemic metabolic switch with dedifferentiation of the epithelial, endothelial and mesothelial splanchnic barriers. Furthermore, a splanchnic infiltration by mast cells occurs, which suggests that these cells could carry out a compensatory metabolic role, especially through the modulation of hepatic and extrahepatic mitochondrial-peroxisome crosstalk. For this reason, we propose the hypothesis that mastocytosis in the acute-on-chronic hepatic insufficiency could represent the development of a survival metabolic mechanisms that mitigates the noxious effect of the hepatic functional deficit. A better understanding the pathophysiological response of the mast cells in liver insufficiency and portal hypertension would help to find new pathways for decreasing the high morbidity and mortality rate of these patients.
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Affiliation(s)
- Maria-Angeles Aller
- Department of Surgery, School of Medicine, Complutense University of Madrid, Madrid, Spain.
| | - Natalia Arias
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; INEUROPA (Instituto de Neurociencias del Principado de Asturias), Oviedo, Spain
| | - Javier Blanco-Rivero
- Department of Physiology, School of Medicine, Autonoma University of Madrid, Madrid, Spain, Instituto de Investigación Biomédica La Paz (IdIPAZ), Madrid, España; Centro de Investigación Biomédica en Red (Ciber) de Enfermedades Cardiovasculares, Madrid, España
| | - Jaime Arias
- Department of Surgery, School of Medicine, Complutense University of Madrid, Madrid, Spain
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