|
1
|
Ali SA, Datusalia AK. Berberine Inhibits the Disruption of the Blood-Brain Barrier and Glial Cell Activation in a Rat Model of Acute Hepatic Encephalopathy. Phytother Res 2025; 39:1422-1437. [PMID: 39791947 DOI: 10.1002/ptr.8430] [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: 05/07/2024] [Revised: 11/25/2024] [Accepted: 12/08/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND AND AIM Hepatic encephalopathy (HE) is a complex neurological disorder in individuals with liver diseases, necessitating effective neuroprotective interventions to alleviate its adverse outcomes. Berberine (BBR), a natural compound with well-established anti-fibrotic and neuroprotective properties, has not been extensively studied in the context of glial activation under hyperammonaemic conditions. This study evaluates the neuroprotective potential of BBR in a thioacetamide (TAA)-induced HE rat model, focusing on its effects on glial activation and NLRP3 inflammasome signalling. METHODS Neurological impairments were assessed using open field tests and sensory analysis. Western blotting was performed to evaluate the expression of glial and neuronal markers, tight junction proteins and NLRP3 inflammasome components in the cortex and hippocampus. Histopathological and molecular changes were further examined using H&E, immunohistochemistry and immunofluorescence staining. KEY RESULTS BBR treatment significantly improved behavioural abnormalities and reduced systemic ammonia levels in TAA-exposed rats. It restored blood-brain barrier integrity, as evidenced by reduced tight junction protein degradation. BBR inhibited the expression of NLRP3 inflammasome markers, including caspase-1, IL-1β, ASC, and NF-κB, while reducing glial cell activation (IBA-1 and GFAP). Notably, BBR diminished NLRP3 expression in glial cells, indicating its potent anti-inflammatory effects. Additionally, BBR preserved neuronal integrity, as demonstrated by the maintained expression of MAP-2 and NeuN and reduced cleaved Gasdermin D levels. CONCLUSIONS These findings suggest that BBR alleviates behavioural and molecular abnormalities in HE through NLRP3 inflammasome inhibition, highlighting its potential as a therapeutic agent for managing HE.
Collapse
Affiliation(s)
- Syed Afroz Ali
- Laboratory of Molecular NeuroTherapeutics, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli, Uttar Pradesh, India
| | - Ashok Kumar Datusalia
- Laboratory of Molecular NeuroTherapeutics, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli, Uttar Pradesh, India
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli, Uttar Pradesh, India
| |
Collapse
|
|
2
|
Xu XT, Jiang MJ, Fu YL, Xie F, Li JJ, Meng QH. Gut microbiome composition in patients with liver cirrhosis with and without hepatic encephalopathy: A systematic review and meta-analysis. World J Hepatol 2025; 17:100377. [PMID: 39871903 PMCID: PMC11736471 DOI: 10.4254/wjh.v17.i1.100377] [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: 08/15/2024] [Revised: 10/26/2024] [Accepted: 11/19/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND The gut microbiome is associated with hepatic encephalopathy (HE), but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent. AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE. METHODS We searched the PubMed, Web of Science, EMBASE, and Cochrane databases using two keywords, HE, and gut microbiome. According to the inclusion and exclusion criteria, suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE. The data were analyzed using RevMan and STATA. RESULTS Seventeen studies were included: (1) A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE [-0.20, 95% confidence interval (CI): -0.28 to -0.13, I2 = 20%]; (2) The relative abundances of Lachnospiraceae (-2.73, 95%CI: -4.58 to -0.87, I2 = 38%) and Ruminococcaceae (-2.93, 95%CI: -4.29 to -1.56, I2 = 0%) in liver cirrhosis patients with HE was significantly lower than those in patients without HE; (3) In patients with HE, Enterococcus, Proteobacteria, Enterococcaceae, and Enterobacteriaceae proportions increased, but Ruminococcaceae, Lachnospiraceae, Prevotellaceae, and Bacteroidetes proportions decreased; (4) Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected; and (5) Differential gut microbiomes may serve as diagnostic and prognostic tools. CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ. Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.
Collapse
Affiliation(s)
- Xiao-Tong Xu
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Min-Jie Jiang
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong Province, China
| | - Yun-Lai Fu
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Fang Xie
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Jian-Jun Li
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Qing-Hua Meng
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China.
| |
Collapse
|
|
3
|
Shurubor YI, Keskinov AA, Yudin VS, Krasnikov BF. The Balance of Ketoacids α-Ketoglutarate and α-Ketoglutaramate Reflects the Degree of the Development of Hepatoencephalopathy in Rats. Int J Mol Sci 2024; 25:13568. [PMID: 39769330 PMCID: PMC11677448 DOI: 10.3390/ijms252413568] [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: 11/15/2024] [Revised: 12/10/2024] [Accepted: 12/13/2024] [Indexed: 01/03/2025] Open
Abstract
Hepatoencephalopathy (HE) is a liver disease that can lead to brain pathology and the impairment of human cognitive abilities. The objective assessment of HE disease severity is difficult due to the lack of reliable diagnostic markers. This paper examines the background to the emergence of HE markers and provides a brief overview of research results indicating the diagnostic value of potential markers isolated from a wide range of metabolites analyzed. It has been suggested that metabolites of the glutamate-glutamine (Glu-Gln) cycle, α-ketoglutarate (αKG), and α-ketoglutaramate (αKGM) can act as such markers of HE. The informative value of these markers was revealed during a comparative analysis of the distribution of αKG and αKGM in samples of the blood plasma and tissues (liver, kidneys, and brain) of rats exposed to the strong hepatotoxin thioacetamide (TAA). A comparative analysis of the balance of αKG and αKGM, as well as their ratio (αKG/αKGM) in the examined samples of blood plasma and animal tissues in these models, revealed their diagnostic value for assessing the severity of HE and/or monitoring the recovery process.
Collapse
Affiliation(s)
- Yevgeniya I. Shurubor
- Centre for Strategic Planning of FMBA of the Russian Federation, Pogodinskaya St., Bld. 10, 119121 Moscow, Russia; (A.A.K.); (V.S.Y.)
| | - Anton A. Keskinov
- Centre for Strategic Planning of FMBA of the Russian Federation, Pogodinskaya St., Bld. 10, 119121 Moscow, Russia; (A.A.K.); (V.S.Y.)
| | - Vladimir S. Yudin
- Centre for Strategic Planning of FMBA of the Russian Federation, Pogodinskaya St., Bld. 10, 119121 Moscow, Russia; (A.A.K.); (V.S.Y.)
| | - Boris F. Krasnikov
- Centre for Strategic Planning of FMBA of the Russian Federation, Pogodinskaya St., Bld. 10, 119121 Moscow, Russia; (A.A.K.); (V.S.Y.)
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, N.I. Pirogov Russian National Research Medical University, 1 Ostrovitianova Str., 117997 Moscow, Russia
| |
Collapse
|
|
4
|
Prasad SK, Acharjee A, Singh VV, Trigun SK, Acharjee P. Modulation of brain energy metabolism in hepatic encephalopathy: impact of glucose metabolic dysfunction. Metab Brain Dis 2024; 39:1649-1665. [PMID: 39120853 DOI: 10.1007/s11011-024-01407-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
Cerebral function is linked to a high level of metabolic activity and relies on glucose as its primary energy source. Glucose aids in the maintenance of physiological brain activities; as a result, a disruption in metabolism has a significant impact on brain function, launching a chain of events that leads to neuronal death. This metabolic insufficiency has been observed in a variety of brain diseases and neuroexcitotoxicity disorders, including hepatic encephalopathy. It is a significant neurological complication that develops in people with liver disease, ranging from asymptomatic abnormalities to coma. Hyperammonemia is the main neurotoxic villain in the development of hepatic encephalopathy and induces a wide range of complications in the brain. The neurotoxic effects of ammonia on brain function are thought to be mediated by impaired glucose metabolism. Accordingly, in this review, we provide an understanding of deranged brain energy metabolism, emphasizing the role of glucose metabolic dysfunction in the pathogenesis of hepatic encephalopathy. We also highlighted the differential metabolic profiles of brain cells and the status of metabolic cooperation between them. The major metabolic pathways that have been explored are glycolysis, glycogen metabolism, lactate metabolism, the pentose phosphate pathway, and the Krebs cycle. Furthermore, the lack of efficacy in current hepatic encephalopathy treatment methods highlights the need to investigate potential therapeutic targets for hepatic encephalopathy, with regulating deficient bioenergetics being a viable alternative in this case. This review also demonstrates the importance of the development of glucose metabolism-focused disease diagnostics and treatments, which are now being pursued for many ailments.
Collapse
Affiliation(s)
- Shambhu Kumar Prasad
- Biochemistry and Molecular Biology Unit, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
| | - Arup Acharjee
- Department of Zoology, University of Allahabad, Prayagraj, 211002, India.
| | - Vishal Vikram Singh
- Biochemistry and Molecular Biology Unit, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
| | - Surendra Kumar Trigun
- Biochemistry and Molecular Biology Unit, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
| | - Papia Acharjee
- Biochemistry and Molecular Biology Unit, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
| |
Collapse
|
|
5
|
Sharma A, Sharma A, Dheer D, Sharma RR, Puri V, Bibi S, Shamas A, Memon S, Goyal R, Priyanka, Chopra H. Stem cell transplantation therapy for advanced liver damage-associated neurodegenerative disorders. Int J Surg 2024; 110:6873-6882. [PMID: 39699862 DOI: 10.1097/js9.0000000000002001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 07/15/2024] [Indexed: 12/20/2024]
Abstract
Hepatic encephalopathy and other neurodegenerative disorders have profound implications for extensive liver impairment, calling for new ways of treating the condition. The application of stem cell transplantation to treat these severe disorders is a new and encouraging technique. This review article digs deep into the subject of stem cell transplantation therapy, neurodegenerative disorders associated with advanced liver damage, and liver transplantation. It comprehensively analyses the background, rationale, scope, and objectives of using stem cells to treat such challenging conditions. The topic of discussion includes the subtleties of neurodegenerative disorders, the function of liver transplantation, and the possible advantages and disadvantages associated with it. The relevance of patient selection, intraoperative concerns and post-transplant care is discussed. Further, the article explores how stem cell-based therapies can benefit from nanotechnology, specifically how it can improve stem cell distribution, survival, and integration for better therapeutic results. This review aims to offer a thorough analysis of regenerative medicine's present and future possibilities in dealing with the intricate relationship between neurodegeneration and liver damage. It does this by examining the efficacy, safety, and long-term impacts of stem cell transplantation in treating neurodegenerative disorders associated with advanced liver damage. This will incorporate insights from ongoing clinical trials, the patent landscape, and future directions. The goal is to pave the way for innovative and personalized treatment approaches in this evolving research and clinical practice field. Therefore, these efforts represent a promising frontier in medical research that can alleviate the burden of HE and associated neurological complications combined with liver cirrhosis.
Collapse
Affiliation(s)
- Anjna Sharma
- Chitkara University School of Pharmacy, Chitkara University, Himachal Pradesh
| | - Ameya Sharma
- Chitkara University School of Pharmacy, Chitkara University, Himachal Pradesh
| | - Divya Dheer
- Chitkara University School of Pharmacy, Chitkara University, Himachal Pradesh
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Punjab, India
| | - Raghu Rai Sharma
- Chitkara University School of Pharmacy, Chitkara University, Himachal Pradesh
| | - Vivek Puri
- Chitkara University School of Pharmacy, Chitkara University, Himachal Pradesh
| | - Shabana Bibi
- Department of Biosciences, Shifa Tameer-e-Millat University, Islamabad
| | - Amina Shamas
- Department of Bioinformatics and Biosciences. Capital University of Science and Technology, Islamabad, Pakistan
| | | | - Rajat Goyal
- MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana
| | - Priyanka
- Department of Veterinary Microbiology, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Rampura Phul, Bathinda, Punjab
| | - Hitesh Chopra
- Department of Biosciences, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| |
Collapse
|
|
6
|
Bai Y, Liu J, Wu W, Zhou B, Sun B, Yao W, Liu X, Zhao H, Guo Y, Jiang X, Liang B, Yang L, Zheng C. Transjugular intrahepatic portosystemic shunt (TIPS) with variceal embolization reduces rebleeding risk for patients with portal pressure gradient over 12 mmHg: A long-term follow-up study. Eur J Radiol 2024; 181:111740. [PMID: 39288645 DOI: 10.1016/j.ejrad.2024.111740] [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: 06/14/2024] [Revised: 08/22/2024] [Accepted: 09/14/2024] [Indexed: 09/19/2024]
Abstract
OBJECTIVE The consensus on whether Transjugular intrahepatic portosystemic shunt (TIPS) should be combined with variceal embolization in the treatment of portal hypertension-induced bleeding has not yet been reached. This study aimed to compare the difference in rebleeding incidence between TIPS and TIPS combined with variceal embolization and to analyze the optimal population for variceal embolization. METHODS Clinical data of 721 patients undergoing TIPS were retrospectively collected. Patients were divided into two groups: TIPS alone (n = 155) and TIPS with embolization (TIPS+E, n = 251). Kaplan-Meier (KM) curves were used to analyze prognostic differences between the two groups, and subgroup analysis was conducted based on post-TIPS portal pressure gradient (PPG) exceeding 12 mmHg. RESULTS After TIPS placement, the mean PPG significantly decreased for all patients. A total of 51 patients (12.6 %) experienced rebleeding, with 24 cases (15.9 %) in the TIPS group and 27 cases (10.6 %) in the TIPS+E group. There was no significant difference in cumulative rebleeding incidence between the TIPS+E and TIPS groups. In the subgroup with post-TIPS PPG greater than 12 mmHg, the cumulative rebleeding incidence was significantly lower in the TIPS+E group compared to the TIPS group (HR = 0.47, 95 %CI = 0.24-0.93, Log rank P = 0.026). No significant difference was found in patients with a post-TIPS PPG less than 12 mmHg. CONCLUSION For patients with post-TIPS PPG exceeding 12 mmHg, simultaneous variceal embolization with TIPS placement significantly reduces the risk of rebleeding.
Collapse
Affiliation(s)
- Yaowei Bai
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Jiacheng Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Wenlong Wu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Binqian Zhou
- Department of Ultrasound, The Central Hospital of Wuhan, Tong ji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
| | - Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Wei Yao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xiaoming Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Hu Zhao
- Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yusheng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xin Jiang
- Hospital of Honghe State Affiliated to Kunming Medical University, Kunming 650500, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.
| | - Lian Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.
| |
Collapse
|
|
7
|
Kalo E, Read S, Baig A, Marshall K, Ma WS, Crowther H, Gofton C, Lynch KD, Sood S, Holmes J, Lubel J, Wigg A, McCaughan G, Roberts SK, Caraceni P, Ahlenstiel G, Majumdar A. Efficacy of albumin use in decompensated cirrhosis and real-world adoption in Australia. JGH Open 2024; 8:e70029. [PMID: 39301299 PMCID: PMC11410680 DOI: 10.1002/jgh3.70029] [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: 05/01/2024] [Revised: 08/26/2024] [Accepted: 09/03/2024] [Indexed: 09/22/2024]
Abstract
The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long-term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis-related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis-related complications and discuss key challenges for wide application of long-term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9-11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long-term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature.
Collapse
Affiliation(s)
- Eric Kalo
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Scott Read
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Asma Baig
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Kate Marshall
- Royal Prince Alfred Hospital Sydney New South Wales Australia
| | - Wai-See Ma
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Helen Crowther
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Cameron Gofton
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
- Department of Gastroenterology and Hepatology Royal North Shore Hospital St Leonards New South Wales Australia
| | - Kate D Lynch
- Department of Gastroenterology and Hepatology Royal Adelaide Hospital, Central Adelaide Local Health Network Adelaide South Australia Australia
- Faculty of Health and Medical Sciences University of Adelaide Adelaide South Australia Australia
| | - Siddharth Sood
- Department of Gastroenterology Northern Health Melbourne Victoria Australia
- Department of Medicine The University of Melbourne Parkville Victoria Australia
| | - Jacinta Holmes
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Department of Gastroenterology St Vincent's Hospital Fitzroy Victoria Australia
| | - John Lubel
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Alan Wigg
- Hepatology and Liver Transplant Medicine Unit Southern Adelaide Local Health Network Adelaide South Australia Australia
- Flinders University of South Australia Adelaide South Australia Australia
| | - Geoff McCaughan
- A.W. Morrow Gastroenterology and Liver Centre Centenary Research Institute for Cancer Research and Cell Biology Camperdown New South Wales Australia
- Australian National Liver Transplant Unit Royal Prince Alfred Hospital Sydney New South Wales Australia
- Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Stuart K Roberts
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Paolo Caraceni
- Unit of Semeiotics, Liver and Alcohol-Related Diseases IRCCS Azienda-Ospedaliera Universitaria di Bologna, EMR Bologna Italy
- Department of Medical and Surgical Sciences University of Bologna, EMR Bologna Italy
| | - Golo Ahlenstiel
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Avik Majumdar
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Victorian Liver transplant Unit Austin Health Heidelberg Victoria Australia
| |
Collapse
|
|
8
|
Martínez-Alarcón L, Martínez-Nicolás A, Jover-Aguilar M, López-López V, Alconchel-Gago F, Ríos A, Madrid JA, de los Ángeles Rol M, Ramírez P, Ramis G. Relationship between Circadian System Status, Child-Pugh Score, and Clinical Outcome in Cirrhotic Patients on Waiting Lists for Liver Transplantation. J Clin Med 2024; 13:4529. [PMID: 39124795 PMCID: PMC11313636 DOI: 10.3390/jcm13154529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/21/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Background/Objectives: Many patients suffering from liver cirrhosis are eventually added to waiting lists for liver transplantation whose priority is established based on scales such as the Child-Pugh score. However, two marker rhythms of the circadian system, motor activity and distal temperature, are not evaluated. Methods: To determine the relationship between the functional status of the circadian system and the Child-Pugh scale in patients awaiting liver transplantation, distal temperature, motor activity, and light exposure rhythms were monitored for a full week using a wrist device (Kronowise 6.0) in 63 patients (17 women, 46 men) aged between 20 and 76 years. Results: Circadian parameters (amplitude, regularity, and fragmentation) of motor activity rhythms, distal temperature, and light exposure worsen in close association with liver disease severity as assessed by using the Child-Pugh score. Likewise, the worsening of rhythmic parameters and liver disease is associated with a deterioration in the markers of the red series: count, hemoglobin, and hematocrit. Conclusions: These results indicate the utility of ambulatory monitoring of marker rhythms to complement the clinical information provided by the Child-Pugh scale and to help establish nutrition, physical exercise, and sleep guidelines that promote better survival and quality of life in these patients.
Collapse
Affiliation(s)
- Laura Martínez-Alarcón
- Departamento de Producción Animal, Hospital Clínico Universitario Virgen de la Arrixaca (UDICA), 30120 Murcia, Spain;
- Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain; (A.M.-N.); (M.J.-A.); (J.A.M.); (M.d.l.Á.R.)
| | - Antonio Martínez-Nicolás
- Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain; (A.M.-N.); (M.J.-A.); (J.A.M.); (M.d.l.Á.R.)
- Chronobiology Laboratory, Department of Physiology, College of Biology, University of Murcia, Mare Nostrum Campus, 30100 Murcia, Spain
- Human Physiology Area, Faculty of Sport Sciences, University of Murcia, Santiago de la Ribera-San Javier, 30720 Murcia, Spain
- Ciber Fragilidad y Envejecimiento Saludable (CIBERFES), 28029 Madrid, Spain
| | - Marta Jover-Aguilar
- Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain; (A.M.-N.); (M.J.-A.); (J.A.M.); (M.d.l.Á.R.)
| | - Víctor López-López
- Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain; (V.L.-L.); (F.A.-G.); (A.R.); (P.R.)
| | - Felipe Alconchel-Gago
- Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain; (V.L.-L.); (F.A.-G.); (A.R.); (P.R.)
| | - Antonio Ríos
- Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain; (V.L.-L.); (F.A.-G.); (A.R.); (P.R.)
| | - Juan Antonio Madrid
- Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain; (A.M.-N.); (M.J.-A.); (J.A.M.); (M.d.l.Á.R.)
- Chronobiology Laboratory, Department of Physiology, College of Biology, University of Murcia, Mare Nostrum Campus, 30100 Murcia, Spain
- Ciber Fragilidad y Envejecimiento Saludable (CIBERFES), 28029 Madrid, Spain
| | - María de los Ángeles Rol
- Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain; (A.M.-N.); (M.J.-A.); (J.A.M.); (M.d.l.Á.R.)
- Chronobiology Laboratory, Department of Physiology, College of Biology, University of Murcia, Mare Nostrum Campus, 30100 Murcia, Spain
- Ciber Fragilidad y Envejecimiento Saludable (CIBERFES), 28029 Madrid, Spain
| | - Pablo Ramírez
- Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain; (V.L.-L.); (F.A.-G.); (A.R.); (P.R.)
| | - Guillermo Ramis
- Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain; (A.M.-N.); (M.J.-A.); (J.A.M.); (M.d.l.Á.R.)
- Departamento de Producción Animal, Facultad de Veterinaria, Campus de Espinardo, Universidad de Murcia, 30100 Murcia, Spain
| |
Collapse
|
|
9
|
Hu K, Xu Y, Fan J, Liu H, Di C, Xu F, Wu L, Ding K, Zhang T, Wang L, Ai H, Xie L, Wang G, Liang Y. Feasibility exploration of GSH in the treatment of acute hepatic encephalopathy from the aspects of pharmacokinetics, pharmacodynamics, and mechanism. Front Pharmacol 2024; 15:1387409. [PMID: 38887546 PMCID: PMC11181355 DOI: 10.3389/fphar.2024.1387409] [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: 02/17/2024] [Accepted: 05/06/2024] [Indexed: 06/20/2024] Open
Abstract
Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.
Collapse
Affiliation(s)
- Kangrui Hu
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Yexin Xu
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Jiye Fan
- Department of Pharmacy, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei Province, China
| | - Huafang Liu
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Chanjuan Di
- Hebei Zhitong Biopharmaceutical Co., Ltd., Gucheng, Hebei Province, China
| | - Feng Xu
- Hebei Zhitong Biopharmaceutical Co., Ltd., Gucheng, Hebei Province, China
| | - Linlin Wu
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Ke Ding
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Tingting Zhang
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Leyi Wang
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Haoyu Ai
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Lin Xie
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | | | - Yan Liang
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| |
Collapse
|
|
10
|
Milewski K, Orzeł-Gajowik K, Zielińska M. Mitochondrial Changes in Rat Brain Endothelial Cells Associated with Hepatic Encephalopathy: Relation to the Blood-Brain Barrier Dysfunction. Neurochem Res 2024; 49:1489-1504. [PMID: 35917006 PMCID: PMC11106209 DOI: 10.1007/s11064-022-03698-7] [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: 08/31/2021] [Revised: 02/17/2022] [Accepted: 07/14/2022] [Indexed: 12/06/2022]
Abstract
The mechanisms underlying cerebral vascular dysfunction and edema during hepatic encephalopathy (HE) are unclear. Blood-brain barrier (BBB) impairment, resulting from increased vascular permeability, has been reported in acute and chronic HE. Mitochondrial dysfunction is a well-documented result of HE mainly affecting astrocytes, but much less so in the BBB-forming endothelial cells. Here we review literature reports and own experimental data obtained in HE models emphasizing alterations in mitochondrial dynamics and function as a possible contributor to the status of brain endothelial cell mitochondria in HE. Own studies on the expression of the mitochondrial fusion-fission controlling genes rendered HE animal model-dependent effects: increase of mitochondrial fusion controlling genes opa1, mfn1 in cerebral vessels in ammonium acetate-induced hyperammonemia, but a decrease of the two former genes and increase of fis1 in vessels in thioacetamide-induced HE. In endothelial cell line (RBE4) after 24 h ammonia and/or TNFα treatment, conditions mimicking crucial aspects of HE in vivo, we observed altered expression of mitochondrial fission/fusion genes: a decrease of opa1, mfn1, and, increase of the fission related fis1 gene. The effect in vitro was paralleled by the generation of reactive oxygen species, decreased total antioxidant capacity, decreased mitochondrial membrane potential, as well as increased permeability of RBE4 cell monolayer to fluorescein isothiocyanate dextran. Electron microscopy documented enlarged mitochondria in the brain endothelial cells of rats in both in vivo models. Collectively, the here observed alterations of cerebral endothelial mitochondria are indicative of their fission, and decreased potential of endothelial mitochondria are likely to contribute to BBB dysfunction in HE.
Collapse
Affiliation(s)
- Krzysztof Milewski
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland.
| | - Karolina Orzeł-Gajowik
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland
| | - Magdalena Zielińska
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland.
| |
Collapse
|
|
11
|
Lee EW, Liang JJ, McNamara GP. Interventional Radiology Management of Hepatic Encephalopathy. Clin Liver Dis 2024; 28:317-329. [PMID: 38548442 DOI: 10.1016/j.cld.2024.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
Hepatic encephalopathy (HE) is a clinically severe and devastating complication of decompensated liver disease affecting mortality, quality of life for patients and families, hospital admission rates, and overall health-care costs globally. Depending on the cause of HE, several medical treatment options have been developed and become available. In some refractory HE, such as spontaneous portosystemic shunt-related HE (SPSS-HE) or posttransjugular intrahepatic portosystemic shunt HE (post-TIPS HE), advanced interventional radiology (IR) procedures have been used, and shown to be effective in these conditions. This review presents 2 effective IR procedures for managing SPSS-HE and post-TIPS HE.
Collapse
Affiliation(s)
- Edward Wolfgang Lee
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Division of Liver and Pancreas Transplant Surgery, Department of Surgery, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
| | - Justine J Liang
- Department of Anesthesiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Griffin P McNamara
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| |
Collapse
|
|
12
|
Paschoal-Jr FM, Nogueira RC, Ronconi KDAL, de Lima Oliveira M, Almeida KJ, Rocha IS, Paschoal EHA, Paschoal JKSF, D'Albuquerque LAC, Teixeira MJ, Panerai RB, Bor-Seng-Shu E. TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation. Ann Hepatol 2024; 29:101167. [PMID: 37802415 DOI: 10.1016/j.aohep.2023.101167] [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: 05/29/2023] [Revised: 08/25/2023] [Accepted: 09/25/2023] [Indexed: 10/10/2023]
Abstract
INTRODUCTION AND OBJECTIVES Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.
Collapse
Affiliation(s)
- Fernando M Paschoal-Jr
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil; Department of Neurology, Federal University of Pará Medical School, Brazil.
| | - Ricardo C Nogueira
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Karla de Almeida Lins Ronconi
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Marcelo de Lima Oliveira
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Kelson James Almeida
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | | | | | | | | | - Manoel Jacobsen Teixeira
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Ronney B Panerai
- Department of Cardiovascular Sciences, University of Leicester, United Kingdom
| | - Edson Bor-Seng-Shu
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| |
Collapse
|
|
13
|
Song J, Westover MB, Zhang R. A neural mass model for disturbance of alpha rhythm in the minimal hepatic encephalopathy. Mol Cell Neurosci 2024; 128:103918. [PMID: 38296121 DOI: 10.1016/j.mcn.2024.103918] [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: 11/27/2023] [Revised: 01/18/2024] [Accepted: 01/21/2024] [Indexed: 02/13/2024] Open
Abstract
One of the early markers of minimal hepatic encephalopathy (MHE) is the disruption of alpha rhythm observed in electroencephalogram (EEG) signals. However, the underlying mechanisms responsible for this occurrence remain poorly understood. To address this gap, we develop a novel biophysical model MHE-AWD-NCM, encompassing the communication dynamics between a cortical neuron population (CNP) and an astrocyte population (AP), aimed at investigating the relationship between alpha wave disturbance (AWD) and mechanistical principles, specifically concerning astrocyte-neuronal communication in the context of MHE. In addition, we introduce the concepts of peak power density and peak frequency within the alpha band as quantitative measures of AWD. Our model faithfully reproduces the characteristic EEG phenomenology during MHE and shows how impairments of communication between CNP and AP could promote AWD. The results suggest that the disruptions in feedback neurotransmission from AP to CNP, along with the inhibition of GABA uptake by AP from the extracellular space, contribute to the observed AWD. Moreover, we found that the variation of external excitatory stimuli on CNP may play a key role in AWD in MHE. Finally, the sensitivity analysis is also performed to assess the relative significance of above factors in influencing AWD. Our findings align with the physiological observations and provide a more comprehensive understanding of the complex interplay of astrocyte-neuronal communication that underlies the AWD observed in MHE, which potentially may help to explore the targeted therapeutic interventions for the early stage of hepatic encephalopathy.
Collapse
Affiliation(s)
- Jiangling Song
- The Medical Big Data Research Center, Northwest University, Xi'an, China
| | - M Brandon Westover
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA
| | - Rui Zhang
- The Medical Big Data Research Center, Northwest University, Xi'an, China.
| |
Collapse
|
|
14
|
Pun CK, Huang HC, Chang CC, Hsu SJ, Huang YH, Hou MC, Lee FY. Hepatic encephalopathy: From novel pathogenesis mechanism to emerging treatments. J Chin Med Assoc 2024; 87:245-251. [PMID: 38109364 DOI: 10.1097/jcma.0000000000001041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2023] Open
Abstract
Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of HE is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal, and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance, and emerging therapeutic targets of HE, such as fecal material transplantation. We also discuss different classifications and etiologies of HE.
Collapse
Affiliation(s)
- Chon Kit Pun
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hui-Chun Huang
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ching-Chih Chang
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shao-Jung Hsu
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| |
Collapse
|
|
15
|
Shah YR, Ali H, Tiwari A, Guevara-Lazo D, Nombera-Aznaran N, Pinnam BSM, Gangwani MK, Gopakumar H, Sohail AH, Kanumilli S, Calderon-Martinez E, Krishnamoorthy G, Thakral N, Dahiya DS. Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions. World J Hepatol 2024; 16:17-32. [PMID: 38313244 PMCID: PMC10835490 DOI: 10.4254/wjh.v16.i1.17] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 12/02/2023] [Accepted: 01/03/2024] [Indexed: 01/23/2024] Open
Abstract
Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.
Collapse
Affiliation(s)
- Yash R Shah
- Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, MI 48341, United States
| | - Hassam Ali
- Division of Gastroenterology and Hepatology, East Carolina University/Brody School of Medicine, Greenville, NC 27858, United States
| | - Angad Tiwari
- Department of Internal Medicine, Maharani Laxmi Bai Medical College, Jhansi 284001, India
| | - David Guevara-Lazo
- Faculty of Medicine, Universidad Peruana Cayetano Heredia, Lima 15102, Peru
| | | | - Bhanu Siva Mohan Pinnam
- Department of Internal Medicine, John H. Stroger Hospital of Cook County, Chicago, IL 60612, United States
| | - Manesh Kumar Gangwani
- Department of Internal Medicine, The University of Toledo, Toledo, OH 43606, United States
| | - Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, United States
| | - Amir H Sohail
- Department of Surgery, University of New Mexico, Albuquerque, NM 87106, United States
| | | | - Ernesto Calderon-Martinez
- Department of Internal Medicine, Universidad Nacional Autonoma de Mexico, Ciudad De Mexico 04510, Mexico
| | - Geetha Krishnamoorthy
- Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, MI 48341, United States
| | - Nimish Thakral
- Department of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY 40536, United States
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, United States.
| |
Collapse
|
|
16
|
Zahr N, Sullivan E, Pfefferbaum A. [WITHDRAWN] Serum biomarkers of liver fibrosis identify changes in striatal metabolite levels. RESEARCH SQUARE 2024:rs.3.rs-2729490. [PMID: 37034697 PMCID: PMC10081358 DOI: 10.21203/rs.3.rs-2729490/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
The full text of this preprint has been withdrawn by the authors due to author disagreement with the posting of the preprint. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
Collapse
|
|
17
|
Zhang Y, Fang XM. The pan-liver network theory: From traditional chinese medicine to western medicine. CHINESE J PHYSIOL 2023; 66:401-436. [PMID: 38149555 DOI: 10.4103/cjop.cjop-d-22-00131] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2023] Open
Abstract
In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and storing blood. According to the classic five elements theory, zang-xiang theory, yin-yang theory, meridians and collaterals theory, and the five-viscera correlation theory, the liver has essential relationships with many extrahepatic organs or tissues, such as the mother-child relationships between the liver and the heart, and the yin-yang and exterior-interior relationships between the liver and the gallbladder. The influences of the liver to the extrahepatic organs or tissues have been well-established when treating the extrahepatic diseases from the perspective of modulating the liver by using the ancient classic prescriptions of TCM and the acupuncture and moxibustion. In modern medicine, as the largest solid organ in the human body, the liver has the typical functions of filtration and storage of blood; metabolism of carbohydrates, fats, proteins, hormones, and foreign chemicals; formation of bile; storage of vitamins and iron; and formation of coagulation factors. The liver also has essential endocrine function, and acts as an immunological organ due to containing the resident immune cells. In the perspective of modern human anatomy, physiology, and pathophysiology, the liver has the organ interactions with the extrahepatic organs or tissues, for example, the gut, pancreas, adipose, skeletal muscle, heart, lung, kidney, brain, spleen, eyes, skin, bone, and sexual organs, through the circulation (including hemodynamics, redox signals, hepatokines, metabolites, and the translocation of microbiota or its products, such as endotoxins), the neural signals, or other forms of pathogenic factors, under normal or diseases status. The organ interactions centered on the liver not only influence the homeostasis of these indicated organs or tissues, but also contribute to the pathogenesis of cardiometabolic diseases (including obesity, type 2 diabetes mellitus, metabolic [dysfunction]-associated fatty liver diseases, and cardio-cerebrovascular diseases), pulmonary diseases, hyperuricemia and gout, chronic kidney disease, and male and female sexual dysfunction. Therefore, based on TCM and modern medicine, the liver has the bidirectional interaction with the extrahepatic organ or tissue, and this established bidirectional interaction system may further interact with another one or more extrahepatic organs/tissues, thus depicting a complex "pan-hepatic network" model. The pan-hepatic network acts as one of the essential mechanisms of homeostasis and the pathogenesis of diseases.
Collapse
Affiliation(s)
- Yaxing Zhang
- Department of Physiology; Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong; Issue 12th of Guangxi Apprenticeship Education of Traditional Chinese Medicine (Shi-Cheng Class of Guangxi University of Chinese Medicine), College of Continuing Education, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Xian-Ming Fang
- Department of Cardiology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine (Guangxi Hospital of Integrated Chinese Medicine and Western Medicine, Ruikang Clinical Faculty of Guangxi University of Chinese Medicine), Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| |
Collapse
|
|
18
|
Mai Z, Mao H. Causal effects of nonalcoholic fatty liver disease on cerebral cortical structure: a Mendelian randomization analysis. Front Endocrinol (Lausanne) 2023; 14:1276576. [PMID: 38027213 PMCID: PMC10646496 DOI: 10.3389/fendo.2023.1276576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 10/13/2023] [Indexed: 12/01/2023] Open
Abstract
Background Previous studies have highlighted changes in the cerebral cortical structure and cognitive function among nonalcoholic fatty liver disease (NAFLD) patients. However, the impact of NAFLD on cerebral cortical structure and specific affected brain regions remains unclear. Therefore, we aimed to explore the potential causal relationship between NAFLD and cerebral cortical structure. Methods We conducted a Mendelian randomization (MR) study using genetic predictors of alanine aminotransferase (ALT), NAFLD, and percent liver fat (PLF) and combined them with genome-wide association study (GWAS) summary statistics from the ENIGMA Consortium. Several methods were used to assess the effect of NAFLD on full cortex and specific brain regions, along with sensitivity analyses. Results At the global level, PLF nominally decreased SA of full cortex; at the functional level, ALT presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars orbitalis, and TH of pericalcarine cortex. Besides, NAFLD presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars triangularis and TH of pericalcarine cortex, but increased TH of entorhinal cortex, lateral orbitofrontal cortex and temporal pole. Furthermore, PLF presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of cuneus and lingual gyrus, but increased TH of entorhinal cortex. Conclusion NAFLD is suggestively associated with atrophy in specific functional regions of the human brain.
Collapse
Affiliation(s)
- Zhiliang Mai
- Department of Digestive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Department of Anatomy, Guangdong Medical University, Zhanjiang, China
| | - Hua Mao
- Department of Digestive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
19
|
Marti-Aguado D, Gougol A, Gomez-Medina C, Jamali A, Abo-Zed A, Morales-Arraez D, Jimenez-Sosa A, Burns K, Bawa A, Hernández A, Pujol C, Alvarado-Tapias E, Szafranska J, Chiu WK, Villagrasa A, Ventura-Cots M, Gandicheruvu H, Lluch P, Chen HW, Rachakonda V, Duarte-Rojo A, Bataller R. Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study. EClinicalMedicine 2023; 61:102046. [PMID: 37415844 PMCID: PMC10319982 DOI: 10.1016/j.eclinm.2023.102046] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 05/29/2023] [Accepted: 05/31/2023] [Indexed: 07/08/2023] Open
Abstract
Background The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3-27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05-2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31-3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36-0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02-4.64) and phenobarbital (HR = 2.99, 95% CI 1.07-8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44-3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38-4.49), and ICU admission (OR = 1.96, 95% CI 1.19-3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40-3.82), 90-day (HR = 1.78, 95% CI 1.18-2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06-2.24). Interpretation AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Collapse
Affiliation(s)
- David Marti-Aguado
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain
| | - Amir Gougol
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- University of California, San Francisco (UCSF), San Francisco, CA, USA
| | - Concepcion Gomez-Medina
- Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain
| | - Arsia Jamali
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Abdelrhman Abo-Zed
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Dalia Morales-Arraez
- Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain
| | - Alejandro Jimenez-Sosa
- Statistical Consultant Research Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Keith Burns
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aditi Bawa
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Anjara Hernández
- Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain
| | - Claudia Pujol
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Institut de Recerca Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - Edilmar Alvarado-Tapias
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Institut de Recerca Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Justyna Szafranska
- Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Wai Kan Chiu
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ares Villagrasa
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Meritxell Ventura-Cots
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Haritha Gandicheruvu
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Paloma Lluch
- Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain
| | | | | | - Andres Duarte-Rojo
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ramon Bataller
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| |
Collapse
|
|
20
|
Desai AP, Gandhi D, Xu C, Ghabril M, Nephew L, Patidar KR, Campbell NL, Chalasani N, Boustani M, Orman ES. Confusion assessment method accurately screens for hepatic encephalopathy and predicts short-term mortality in hospitalized patients with cirrhosis. Metab Brain Dis 2023; 38:1749-1758. [PMID: 36529762 PMCID: PMC10935593 DOI: 10.1007/s11011-022-01149-4] [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: 07/01/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022]
Abstract
Hepatic encephalopathy (HE), a subtype of delirium, is common in cirrhosis and associated with poor outcomes. Yet, objective bedside screening tools for HE are lacking. We examined the relationship between an established screening tool for delirium, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and short-term outcomes while comparing its performance with previously established measures of cognitive function such as West Haven criteria (WHC). Prospectively enrolled adults with cirrhosis who completed the CAM-ICU from 6/2014-6/2018 were followed for 90 days. Blinded provider-assigned West Haven Criteria (WHC) and other measures of cognitive function were collected. Logistic regression was used to test associations between CAM-ICU status and outcomes. Mortality prediction by CAM-ICU status was assessed using Area under the Receiver Operating Characteristics curves (AUROC). Of 469 participants, 11% were CAM-ICU( +), 55% were male and 94% were White. Most patients were Childs-Pugh class C (59%). CAM-ICU had excellent agreement with WHC (Kappa = 0.79). CAM-ICU( +) participants had similar demographic features to those CAM-ICU(-), but had higher MELD (25 vs. 19, p < 0.0001), were more often admitted to the ICU (28% vs. 7%, p < 0.0001), and were more likely to be admitted for HE and infection. CAM-ICU( +) participants had higher mortality (inpatient:37% vs. 3%, 30-day:51% vs. 11%, 90-day:63% vs. 23%, p < 0.001). CAM-ICU status predicted mortality with AUROC of 0.85, 0.82 and 0.77 for inpatient, 30-day and 90-day mortality, respectively. CAM-ICU easily screens for delirium/HE, has excellent agreement with WHC, and identifies a hospitalized cirrhosis cohort with high short-term mortality.
Collapse
Affiliation(s)
- Archita P Desai
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
- Center for Health Innovation and Implementation Science, Indiana University, Indianapolis, IN, USA.
| | - Devika Gandhi
- Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, CA, USA
| | - Chenjia Xu
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Lauren Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Kavish R Patidar
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Noll L Campbell
- Center for Health Innovation and Implementation Science, Indiana University, Indianapolis, IN, USA
- Department of Pharmacy Practice, Purdue University College of Pharmacy, Indianapolis, IN, USA
- Indiana University Center for Aging Research at the Regenstrief Institute, Indianapolis, IN, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Malaz Boustani
- Center for Health Innovation and Implementation Science, Indiana University, Indianapolis, IN, USA
- Indiana University Center for Aging Research at the Regenstrief Institute, Indianapolis, IN, USA
- Division of Geriatrics, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eric S Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| |
Collapse
|
|
21
|
Zöllner HJ, Thiel TA, Füllenbach ND, Jördens MS, Ahn S, Wilms LM, Ljimani A, Häussinger D, Butz M, Wittsack HJ, Schnitzler A, Oeltzschner G. J-difference GABA-edited MRS reveals altered cerebello-thalamo-cortical metabolism in patients with hepatic encephalopathy. Metab Brain Dis 2023; 38:1221-1238. [PMID: 36729261 PMCID: PMC10897767 DOI: 10.1007/s11011-023-01174-x] [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: 09/30/2022] [Accepted: 01/17/2023] [Indexed: 02/03/2023]
Abstract
Hepatic encephalopathy (HE) is a common neurological manifestation of liver cirrhosis and is characterized by an increase of ammonia in the brain accompanied by a disrupted neurotransmitter balance, including the GABAergic and glutamatergic systems. The aim of this study is to investigate metabolic abnormalities in the cerebello-thalamo-cortical system of HE patients using GABA-edited MRS and links between metabolite levels, disease severity, critical flicker frequency (CFF), motor performance scores, and blood ammonia levels. GABA-edited MRS was performed in 35 participants (16 controls, 19 HE patients) on a clinical 3 T MRI system. MRS voxels were placed in the right cerebellum, left thalamus, and left motor cortex. Levels of GABA+ and of other metabolites of interest (glutamine, glutamate, myo-inositol, glutathione, total choline, total NAA, and total creatine) were assessed. Group differences in metabolite levels and associations with clinical metrics were tested. GABA+ levels were significantly increased in the cerebellum of patients with HE. GABA+ levels in the motor cortex were significantly decreased in HE patients, and correlated with the CFF (r = 0.73; p < .05) and motor performance scores (r = -0.65; p < .05). Well-established HE-typical metabolite patterns (increased glutamine, decreased myo-inositol and total choline) were confirmed in all three regions and were closely linked to clinical metrics. In summary, our findings provide further evidence for alterations in the GABAergic system in the cerebellum and motor cortex in HE. These changes were accompanied by characteristic patterns of osmolytes and oxidative stress markers in the cerebello-thalamo-cortical system. These metabolic disturbances are a likely contributor to HE motor symptoms in HE. In patients with hepatic encephalopathy, GABA+ levels in the cerebello-thalamo-cortical loop are significantly increased in the cerebellum and significantly decreased in the motor cortex. GABA+ levels in the motor cortex strongly correlate with critical flicker frequency (CFF) and motor performance score (pegboard test tPEG), but not blood ammonia levels (NH3).
Collapse
Affiliation(s)
- Helge Jörn Zöllner
- Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
| | - Thomas A Thiel
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Nur-Deniz Füllenbach
- Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Markus S Jördens
- Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | | | - Lena M Wilms
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Alexandra Ljimani
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Markus Butz
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Hans-Jörg Wittsack
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Georg Oeltzschner
- Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
- F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
| |
Collapse
|
|
22
|
Higuera-de-la-Tijera F, Velarde-Ruiz Velasco J, Raña-Garibay R, Castro-Narro G, Abdo-Francis J, Moreno-Alcántar R, Pérez-Hernández J, Torre A, Contreras-Omaña R, Cano-Contreras A, Castillo-Barradas M, Pérez-Escobar J, Aldana-Ledesma J, Cerda-Reyes E, Fernández-Pérez N, Meza-Cardona J, Flores-García N, Reyes-Bastidas M, Lira-Vera J, García-Jiménez E, Santana-Vargas D, Páez-Zayas V, Chávez-Tapia N, Márquez-Guillén E. Visión actual sobre el diagnóstico y los cuidados integrales en la encefalopatía hepática. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2023; 88:155-174. [DOI: 10.1016/j.rgmx.2023.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
23
|
Higuera-de-la-Tijera F, Velarde-Ruiz Velasco JA, Raña-Garibay RH, Castro-Narro GE, Abdo-Francis JM, Moreno-Alcántar R, Pérez-Hernández JL, Torre A, Contreras-Omaña R, Cano-Contreras A, Castillo-Barradas M, Pérez-Escobar J, Aldana-Ledesma JM, Cerda-Reyes E, Fernández-Pérez NJ, Meza-Cardona J, Flores-García NC, Reyes-Bastidas M, Lira-Vera JE, García-Jiménez ES, Santana-Vargas D, Páez-Zayas VM, Chávez-Tapia NC, Márquez-Guillén E. Current vision on diagnosis and comprehensive care in hepatic encephalopathy. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:155-174. [PMID: 37127462 DOI: 10.1016/j.rgmxen.2023.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 03/08/2023] [Indexed: 05/03/2023]
Abstract
The first clinical guidelines on hepatic encephalopathy were published in 2009. Almost 14 years since that first publication, numerous advances in the field of diagnosis, treatment, and special condition care have been made. Therefore, as an initiative of the Asociación Mexicana de Gastroenterología A.C., we present a current view of those aspects. The manuscript described herein was formulated by 24 experts that participated in six working groups, analyzing, discussing, and summarizing the following topics: Definition of hepatic encephalopathy; recommended classifications; epidemiologic panorama, worldwide and in Mexico; diagnostic tools; conditions that merit a differential diagnosis; treatment; and primary and secondary prophylaxis. Likewise, these guidelines emphasize the management of certain special conditions, such as hepatic encephalopathy in acute liver failure and acute-on-chronic liver failure, as well as specific care in patients with hepatic encephalopathy, such as the use of medications and types of sedation, describing those that are permitted or recommended, and those that are not.
Collapse
Affiliation(s)
- F Higuera-de-la-Tijera
- Departamento de Gastroenterología y Hepatología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico.
| | - J A Velarde-Ruiz Velasco
- Departamento de Gastroenterología, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico
| | | | - G E Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - R Moreno-Alcántar
- Departamento de Gastroenterología, Hospital de Especialidades Bernardo Sepúlveda del Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
| | - J L Pérez-Hernández
- Departamento de Gastroenterología y Hepatología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - A Torre
- Centro Médico ABC, Mexico City, Mexico
| | - R Contreras-Omaña
- Centro de Educación e Investigación en Enfermedades Hepáticas y Toxicológicas (CEIHET), Pachuca, Hidalgo, Mexico
| | - A Cano-Contreras
- Centro de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Mexico
| | - M Castillo-Barradas
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional "La Raza", IMSS, Mexico City, Mexico
| | - J Pérez-Escobar
- Instituto Nacional de Enfermedades Respiratorias (INER) "Ismael Cosío Villegas", Mexico City, Mexico
| | - J M Aldana-Ledesma
- Departamento de Gastroenterología, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico
| | - E Cerda-Reyes
- Departamento de Gastroenterología, Hospital Central Militar, Mexico City, Mexico
| | | | | | - N C Flores-García
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - J E Lira-Vera
- Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, Mexico
| | - E S García-Jiménez
- Departamento de Gastroenterología, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico
| | - D Santana-Vargas
- Clínica de Trastornos del Sueño, Departamento de Medicina Experimental, Facultad de Medicina, UNAM, Mexico City, Mexico
| | - V M Páez-Zayas
- Departamento de Gastroenterología y Hepatología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | | | - E Márquez-Guillén
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| |
Collapse
|
|
24
|
Rifaximin Improves Liver Functional Reserve by Regulating Systemic Inflammation. J Clin Med 2023; 12:jcm12062210. [PMID: 36983211 PMCID: PMC10054398 DOI: 10.3390/jcm12062210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 03/01/2023] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
Rifaximin, a non-absorbable antibiotic, has been demonstrated to be effective against hepatic encephalopathy (HE); however, its efficacy on liver functional reserve remains unknown. Here, we evaluated the efficacy of rifaximin on the liver functional reserve and serological inflammation-based markers in patients with cirrhosis. A retrospective study was conducted on patients who received rifaximin for more than three months at our hospital between November 2016 and October 2021. The recurrence and grade of HE, serological ammonia levels, Child–Pugh score (CPS), and serological inflammation-based markers such as the neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), platelet–lymphocyte ratio (PLR), C-reactive protein (CRP), and CRP to albumin ratio (CAR) were evaluated. The correlations between serological inflammation-based markers and liver functional reserve were evaluated. HE grades, serum ammonia levels, and inflammation-based markers significantly improved at three months compared with those at baseline. Patients with improved albumin levels showed significantly higher CRP improvement rates at both 3 and 12 months. Patients with an improvement in CAR at 3 months demonstrated a significant improvement in CPS at 12 months. Rifaximin improved the liver functional reserve in patients with cirrhosis. Improvements in inflammation-based markers, particularly CRP and albumin, may be involved in this process.
Collapse
|
|
25
|
Yilmaz P, Alferink LJM, Cremers LGM, Murad SD, Niessen WJ, Ikram MA, Vernooij MW. Subclinical liver traits are associated with structural and hemodynamic brain imaging markers. Liver Int 2023; 43:1256-1268. [PMID: 36801835 DOI: 10.1111/liv.15549] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/16/2023] [Accepted: 02/18/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND & AIMS Impaired liver function affects brain health and therefore understanding potential mechanisms for subclinical liver disease is essential. We assessed the liver-brain associations using liver measures with brain imaging markers, and cognitive measures in the general population. METHODS Within the population-based Rotterdam Study, liver serum and imaging measures (ultrasound and transient elastography), metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) and fibrosis phenotypes, and brain structure were determined in 3493 non-demented and stroke-free participants in 2009-2014. This resulted in subgroups of n = 3493 for MAFLD (mean age 69 ± 9 years, 56% ♀), n = 2938 for NAFLD (mean age 70 ± 9 years, 56% ♀) and n = 2252 for fibrosis (mean age 65 ± 7 years, 54% ♀). Imaging markers of small vessel disease and neurodegeneration, cerebral blood flow (CBF) and brain perfusion (BP) were acquired from brain MRI (1.5-tesla). General cognitive function was assessed by Mini-Mental State Examination and the g-factor. Multiple linear and logistic regression models were used for liver-brain associations and adjusted for age, sex, intracranial volume, cardiovascular risk factors and alcohol use. RESULTS Higher gamma-glutamyltransferase (GGT) levels were significantly associated with smaller total brain volume (TBV, standardized mean difference (SMD), -0.02, 95% confidence interval (CI) (-0.03 to -0.01); p = 8.4·10-4 ), grey matter volumes, and lower CBF and BP. Liver serum measures were not related to small vessel disease markers, nor to white matter microstructural integrity or general cognition. Participants with ultrasound-based liver steatosis had a higher fractional anisotropy (FA, SMD 0.11, 95% CI (0.04 to 0.17), p = 1.5·10-3 ) and lower CBF and BP. MAFLD and NAFLD phenotypes were associated with alterations in white matter microstructural integrity (NAFLD ~ FA, SMD 0.14, 95% CI (0.07 to 0.22), p = 1.6·10-4 ; NAFLD ~ mean diffusivity, SMD -0.12, 95% CI (-0.18 to -0.05), p = 4.7·10-4 ) and also with lower CBF and BP (MAFLD ~ CBF, SMD -0.13, 95% CI (-0.20 to -0.06), p = 3.1·10-4 ; MAFLD ~ BP, SMD -0.12, 95% CI (-0.20 to -0.05), p = 1.6·10-3 ). Furthermore, fibrosis phenotypes were related to TBV, grey and white matter volumes. CONCLUSIONS Presence of liver steatosis, fibrosis and elevated serum GGT are associated with structural and hemodynamic brain markers in a population-based cross-sectional setting. Understanding the hepatic role in brain changes can target modifiable factors and prevent brain dysfunction.
Collapse
Affiliation(s)
- Pinar Yilmaz
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Louise J M Alferink
- Departments of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Lotte G M Cremers
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Sarwa D Murad
- Departments of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Wiro J Niessen
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
- Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Meike W Vernooij
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| |
Collapse
|
|
26
|
Tian X, Cui X, Xiao Y, Chen T, Xiao X, Wang Y. Pt/MoS 2/Polyaniline Nanocomposite as a Highly Effective Room Temperature Flexible Gas Sensor for Ammonia Detection. ACS APPLIED MATERIALS & INTERFACES 2023; 15:9604-9617. [PMID: 36762895 DOI: 10.1021/acsami.2c20299] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
A Pt/MoS2/polyaniline (Pt/MoS2/PANI) nanocomposite is successfully synthesized by the hydrothermal process combined with the in situ polymerization method, and then Pt particles are decorated on its surface. The Pt/MoS2/PANI nanocomposite is deposited on a flexible Au-interdigitated electrode of a polyimide (PI) film. The flexible sensor exhibits a higher response value and fast response/recovery time to NH3 at room temperature (RT). It results in 2.32-fold and 1.13-fold improvement in the gas-sensing response toward 50 ppm NH3 compared to those of PANI and MoS2/PANI-based gas sensors. The detection limit is 250 ppb. The enhancement sensing mechanisms are attributed to the p-n heterojunction and the Schottky barrier between the three components, which has been confirmed by the current-voltage (I-V) curves. A satisfactory selectivity to NH3 against trimethylamine (TMA) and triethylamine (TEA) is obtained according to density functional theory (DFT), Bader's analysis, and differential charge density to illustrate the adsorption behavior and charge transfer of gas molecules on the surface of the sensing materials. The sensor retains the excellent sensing response value even under high relative humidity and sensing stability at higher bending angle/numbers to NH3 gas. Hence, Pt/MoS2/PANI can be regarded as a promising sensing material for high-performance NH3 detection at room temperature applied in flexible wearable electronics.
Collapse
Affiliation(s)
- Xu Tian
- National Center for International Research on Photoelectric and Energy Materials, School of Materials and Energy, Yunnan University, Kunming6500504, People's Republic of China
| | - Xiuxiu Cui
- National Center for International Research on Photoelectric and Energy Materials, School of Materials and Energy, Yunnan University, Kunming6500504, People's Republic of China
| | - Yawei Xiao
- National Center for International Research on Photoelectric and Energy Materials, School of Materials and Energy, Yunnan University, Kunming6500504, People's Republic of China
| | - Ting Chen
- Institute of Materials Science & Devices, School of Materials Science and Engineering, Suzhou University of Science and Technology, Suzhou215009, People's Republic of China
| | - Xuechun Xiao
- Key Lab of Quantum Information of Yunnan Province, Yunnan University, Kunming6500504, People's Republic of China
| | - Yude Wang
- National Center for International Research on Photoelectric and Energy Materials, School of Materials and Energy, Yunnan University, Kunming6500504, People's Republic of China
- Yunnan Key Laboratory of Carbon Neutrality and Green Low-Carbon Technologies, Yunnan University, Kunming650504, People's Republic of China
| |
Collapse
|
|
27
|
Abdulmajeed F, Hamandi M, Malaiyandi D, Shutter L. Neurocritical Care in the General Intensive Care Unit. Crit Care Clin 2023; 39:153-169. [DOI: 10.1016/j.ccc.2022.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
|
|
28
|
Margaryan SR, Razumovsky AY, Mitupov ZB, Gurevich AI, Titova EA. [Reconstruction of total portosystemic shunt into selective portosystemic shunt in a child]. Khirurgiia (Mosk) 2023:140-146. [PMID: 38088852 DOI: 10.17116/hirurgia2023121140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
To date, side-to-side splenorenal shunt (SRS) and its analogues (splenosuprarenal shunts (SSRS)) are mainly used for portal hypertension. These are total portosystemic shunts characterized by total blood shunt from portal vein into inferior vena cava. The latter is fraught with a significant risk of complications such as pulmonary hypertension, decreased portal liver perfusion, liver failure and hepatic encephalopathy. Prevention of these complications is still an urgent problem in modern surgery. However, we proposed a new method of treatment, i.e. reconstruction of SRS and SSRS into selective shunt. This procedure was performed in 37 patients after 2020. We present laparoscopic reconstruction in an 11-year-old girl with portal hypertension and signs of hepatic encephalopathy identified after previous SSRS.
Collapse
Affiliation(s)
- S R Margaryan
- Pirogov Russian National Research Medical University, Moscow, Russia
- Children's City Clinical Hospital named after N.F. Filatov, Moscow, Russia
| | - A Yu Razumovsky
- Pirogov Russian National Research Medical University, Moscow, Russia
- Children's City Clinical Hospital named after N.F. Filatov, Moscow, Russia
| | - Z B Mitupov
- Pirogov Russian National Research Medical University, Moscow, Russia
- Children's City Clinical Hospital named after N.F. Filatov, Moscow, Russia
| | - A I Gurevich
- Children's City Clinical Hospital named after N.F. Filatov, Moscow, Russia
| | - E A Titova
- Children's City Clinical Hospital named after N.F. Filatov, Moscow, Russia
| |
Collapse
|
|
29
|
Margaryan SR, Mitupov ZB, Razumovsky AY. [Hepatic encephalopathy after portosystemic bypass surgery]. Khirurgiia (Mosk) 2023:57-65. [PMID: 37379406 DOI: 10.17116/hirurgia202307157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Abstract
The most effective modern treatment for gastrointestinal bleeding following portal hypertension is portosystemic bypass surgery. Hepatic encephalopathy after these procedures is still an urgent problem in modern pediatric surgery, and radical treatment is unknown. To optimize treatment outcomes in children with hepatic encephalopathy, we should choose adequate treatment considering the risk of hepatic encephalopathy in the future. In this review, the authors discuss modern data on hepatic encephalopathy regarding symptoms, advantages and disadvantages of various treatment methods. Risk of hepatic encephalopathy with and without surgical treatment, as well as methods of diagnosis and treatment are particularly analyzed. Total portosystemic bypass surgery, especially portocaval shunt, is followed by higher risk of hepatic encephalopathy compared to selective shunts and physiological mesoportal bypass. The last two approaches are advisable to improve treatment outcomes in children with hepatic encephalopathy.
Collapse
Affiliation(s)
- S R Margaryan
- Pirogov Russian National Research Medical University, Moscow, Russia
- N.F. Filatov Children's City Clinical Hospital, Moscow, Russia
| | - Z B Mitupov
- Pirogov Russian National Research Medical University, Moscow, Russia
- N.F. Filatov Children's City Clinical Hospital, Moscow, Russia
| | - A Yu Razumovsky
- Pirogov Russian National Research Medical University, Moscow, Russia
- N.F. Filatov Children's City Clinical Hospital, Moscow, Russia
| |
Collapse
|
|
30
|
Kwong AJ, Zahr NM. Serum biomarkers of liver fibrosis identify globus pallidus vulnerability. Neuroimage Clin 2023; 37:103333. [PMID: 36868044 PMCID: PMC9996367 DOI: 10.1016/j.nicl.2023.103333] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 01/12/2023] [Accepted: 01/19/2023] [Indexed: 01/28/2023]
Abstract
The CNS manifestation of chronic liver disease can include magnetic resonance (MR) signal hyperintensities in basal ganglia structures. Here, relations between liver (serum-derived fibrosis scores) and brain (regional T1-weighted signal intensities and volumes) integrity were evaluated in a sample of 457 individuals including those with alcohol use disorders (AUD), people living with human immunodeficiency virus (HIV), those comorbid for AUD and HIV, and healthy controls. Liver fibrosis was identified from cutoff scores as follows: aspartate aminotransferase to platelet ratio index (APRI) > 0.7 in 9.4% (n = 43) of the cohort; fibrosis score (FIB4) > 1.5 in 28.0% (n = 128) of the cohort; and non-alcoholic fatty liver disease fibrosis score (NFS) > -1.4 in 30.2% (n = 138) of the cohort. Presence of serum-derived liver fibrosis was associated with high signal intensities selective to basal ganglia (i.e., caudate, putamen, and pallidum) structures. High signal intensities in the pallidum, however, explained a significant portion of the variance in APRI (25.0%) and FIB4 (23.6%) cutoff scores. Further, among the regions evaluated, only the globus pallidus showed a correlation between greater signal intensity and smaller volume (r = -0.44, p <.0001). Finally, higher pallidal signal intensity correlated worse ataxia (eyes open ρ = -0.23, p =.0002; eyes closed ρ = -0.21, p =.0005). This study suggests that clinically relevant serum biomarkers of liver fibrosis such as the APRI may identify individuals vulnerable to globus pallidus pathology and contribute to problems with postural balance.
Collapse
Affiliation(s)
- Allison J Kwong
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, School of Medicine, Redwood City, CA 94063, USA
| | - Natalie M Zahr
- Department of Psychiatry & Behavioral Sciences, Stanford University, School of Medicine, 401 Quarry Rd. Stanford, CA 94305, USA; Neuroscience Program, SRI International, Menlo Park, CA 94025, USA.
| |
Collapse
|
|
31
|
Bouzbib C, El Mourabit H, Wendum D, Lasnier E, Mouri S, Housset C, Thabut D, Weiss N, Rudler M. ATP-binding cassette transporters expression in rats with cirrhosis and hepatic encephalopathy. Clin Res Hepatol Gastroenterol 2022; 46:101784. [PMID: 34384925 DOI: 10.1016/j.clinre.2021.101784] [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] [Received: 07/16/2021] [Accepted: 08/06/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pathophysiology of acute encephalopathy in cirrhotic patients is not completely understood. Factors implicated include ammonia, inflammation, various metabolic disorders and drug toxicity. Recent studies have evidenced an increased permeability of the blood-brain barrier (BBB) in models of chronic liver disease and encephalopathy, either to solutes, or to leukocytes. A modification of the expression of BBB ATP-Binding Cassette (ABC) transporters, actively transporting endogenous and exogenous components through the BBB, has been described in models of acute liver failure. We hypothesized that a modification of ABC transporters expression may contribute to drug-induced acute encephalopathy in cirrhosis. MATERIEL AND METHODS A rat model of cirrhosis induced by Bile Duct Ligation (BDL) was studied, and compared to a SHAM rat model. Rats were sacrificed and brains studied after decapitation. Genic expression of ABC transporters, including P-gp, BCRP, MRP1, MRP2, MRP4 and MRP5 was evaluated by RT-qPCR on isolated brain microvessels. Encephalopathy was assessed 6 weeks after surgery by a trail suspension test and an Open Field Test. RESULTS BDL rats developed a histologically proven cirrhosis and displayed a higher ammonemia than SHAM rats (183 µmol/L vs 53 µmol/L, p = 0.0003). BDL rats presented with encephalopathy shown by neurobehavioral tests. MRP2 was not detected neither in BDL nor in SHAM rats. There was a decrease in the genic expression of MRP5 6 weeks after surgery. Expressions of P-gp, BCRP, MRP1 and MRP4 were not different between the 2 groups. CONCLUSION We suggest that acute encephalopathy in cirrhotic BDL rats may be associated to a modification of ABC transporter MRP5 on the BBB, that could be responsible for a decrease clearance of neurotoxic agents.
Collapse
Affiliation(s)
- Charlotte Bouzbib
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | - Haquima El Mourabit
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Dominique Wendum
- AP-HP.Sorbonne Université, Department of Pathology, Saint-Antoine Hospital, 184 rue du Faubourg-Saint-Antoine, 75012 Paris, France
| | - Elisabeth Lasnier
- AP-HP.Sorbonne Université, Department of Biochemistry, Saint-Antoine Hospital, 184 rue du Faubourg-Saint-Antoine, 75012 Paris, France
| | - Sarah Mouri
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | - Chantal Housset
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Dominique Thabut
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France.
| | - Nicolas Weiss
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Neurological Intensive Care Unit, Neurology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France.
| | - Marika Rudler
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| |
Collapse
|
|
32
|
Abdelghffar EAR, El-Nashar HAS, Fayez S, Obaid WA, Eldahshan OA. Ameliorative effect of oregano (Origanum vulgare) versus silymarin in experimentally induced hepatic encephalopathy. Sci Rep 2022; 12:17854. [PMID: 36284120 PMCID: PMC9596437 DOI: 10.1038/s41598-022-20412-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 09/13/2022] [Indexed: 01/20/2023] Open
Abstract
Hepatic encephalopathy (HE) is a deterioration of brain function in patients suffering from chronic liver disease, cirrhosis as a result of elevated blood ammonia and the production of pseudo-neurotransmitters. Herein, we investigated the chemical composition of hexane extract from Origanum vulgare (O. vulgare) leaves as well as its possible protective effects against thioacetamide (TAA)-induced HE in rats. GC-MS analysis of the extract revealed tentative identification of twenty-five compounds (82.93%), predominated by cholesten-3-one (27.30%), followed by γ-tocopherol (13.52%), α-tocopherol (5.01%), β-amyrin (5.24%) and α-amyrin (4.89%). Albino rats were distributed into seven groups (n = 7). G1 served as negative control; G2 and G3 served as controls treated with O. vulgare (100 and 200 mg/kg/p.o b.w, respectively); G4 served as TAA-positive control group (100 mg/kg/day/i.p., three alternative days per week for six weeks); G5, G6, and G7 served as TAA -induced HE rat model that received O. vulgare 100, O. vulgare 200, and silymarin (100 mg/kg of SILY, as standard drug), respectively. TAA showed depressive and anxiety-like behaviors in forced swimming test (FST) and reduction of cognitive score in elevated plus-maze test (EPMT) as well as impairment of locomotor and exploratory activities in open-field test (OFT). TAA caused a significant decline in body weight gain; however, the relative liver weight and brain water content were statistically increased. TAA-intoxicated rats showed significant increase of serum biomarker enzymes, proinflammatory cytokines, blood ammonia levels, brain serotonin, acetyl cholinesterase and cellular lipid peroxidation with significant decrease of brain dopamine, norepinephrine, antioxidant status. The hepatoprotective/neuro-protective activities of O. vulgare was found to be comparable with that of SILY in HE rats model. Where, treatment of TAA-intoxicated rats with O. vulgare attenuated anxiety, depressive-related behaviors, and reduced the biochemical changes in HE-induced by TAA. Therefore, O. vulgare could be an excellent hepato-/neuroprotective against hepatic injury and HE via improving the oxidative/inflammatory status through its antioxidant and neuro-modulatory properties and its effect is equal to that of SILY.
Collapse
Affiliation(s)
- Eman A. R. Abdelghffar
- grid.7269.a0000 0004 0621 1570Department of Zoology, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Heba A. S. El-Nashar
- grid.7269.a0000 0004 0621 1570Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt ,grid.7269.a0000 0004 0621 1570Centre of Drug Discovery Research and Development, Ain Shams University, Cairo, Egypt
| | - Shaimaa Fayez
- grid.7269.a0000 0004 0621 1570Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt ,grid.7269.a0000 0004 0621 1570Centre of Drug Discovery Research and Development, Ain Shams University, Cairo, Egypt
| | - Wael A. Obaid
- grid.412892.40000 0004 1754 9358Department of Biology, College of Science, Taibah University, Al-Madīnah Al-Munawarah, Saudi Arabia
| | - Omayma A. Eldahshan
- grid.7269.a0000 0004 0621 1570Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt ,grid.7269.a0000 0004 0621 1570Centre of Drug Discovery Research and Development, Ain Shams University, Cairo, Egypt
| |
Collapse
|
|
33
|
Roy S, Chakrabarti M, Dasgupta H, Mahale A, Tripathi S, Sharma V, Banerjee M, Kulkarni OP. Inhibition of Autotaxin Ameliorates LPA-Mediated Neuroinflammation and Alleviates Neurological Dysfunction in Acute Hepatic Encephalopathy. ACS Chem Neurosci 2022; 13:2829-2841. [PMID: 36112416 DOI: 10.1021/acschemneuro.2c00046] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Growing evidence suggests an essential role of neuroinflammation in behavioral abnormalities associated with hepatic encephalopathy (HE). Here, we report the involvement of autotaxin-lysophosphatidic acid (LPA) signaling in HE's pathogenesis. We demonstrate that the autotaxin (ATX) inhibitor PF-8380 attenuates neuroinflammation and improves neurological dysfunction in the mouse model of HE. In the thioacetamide (TAA)-induced model of HE, we found a twofold increase in the levels of ammonia in the brain and in plasma along with a significant change in HE-related behavioral parameters. Mice with HE show an increased brain weight, increased levels of tumor necrosis factor-α (TNF-α), IL-1β (interleukin-1β), interleukin-6 (IL-6), and LPA 18:0 in the cerebral cortex and hippocampus, and increased levels of LPA 18:0 in plasma. Treatment with the autotaxin inhibitor (ATXi) did not affect liver injury, as we observed no change in liver function markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) and no change in ammonia levels in the brain and plasma. However, ATXi treatment significantly ameliorated the neuroinflammation, reduced the levels of LPA 18:0 in the cerebral cortex and hippocampus in the brain and plasma, and reduced brain edema and the levels of IL1β, IL-6, and TNF-α. The neurobehavioral symptoms for HE such as the cognitive and motor function deficit and overall clinical grading score were significantly improved in ATXi-treated mice. Mouse astrocytes and microglia stimulated with NH4CL with or without ATXi showed significant attenuation of oxidative stress and the neuroinflammatory effect of NH4CL in ATXi-treated cells.
Collapse
Affiliation(s)
- Subhasis Roy
- TCG Life Sciences Private Ltd., Biolab, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091, West Bengal, India
| | - Monali Chakrabarti
- TCG Life Sciences Private Ltd., Biolab, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091, West Bengal, India
| | - Hemantika Dasgupta
- TCG Life Sciences Private Ltd., Biolab, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091, West Bengal, India
| | - Ashutosh Mahale
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani-Hyderabad Campus, Hyderabad 500078, India
| | - Shraddha Tripathi
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani-Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Ranga Reddy District, Hyderabad 500078, India
| | - Vivek Sharma
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani-Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Ranga Reddy District, Hyderabad 500078, India
| | - Manish Banerjee
- TCG Life Sciences Private Ltd., Biolab, Bengal Intelligent Park Ltd., Block EP and GP, Sector V, Salt Lake, Kolkata 700091, West Bengal, India
| | - Onkar Prakash Kulkarni
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani-Hyderabad Campus, Hyderabad 500078, India
| |
Collapse
|
|
34
|
Aidar FJ, Fraga GS, Getirana-Mota M, Marçal AC, Santos JL, de Souza RF, Vieira-Souza LM, Ferreira ARP, de Matos DG, de Almeida-Neto PF, Garrido ND, Díaz-de-Durana AL, Knechtle B, de Araújo Tinoco Cabral BG, Murawska-Ciałowicz E, Nobari H, Silva AF, Clemente FM, Badicu G. Evaluation of Ibuprofen Use on the Immune System Indicators and Force in Disabled Paralympic Powerlifters of Different Sport Levels. Healthcare (Basel) 2022; 10:healthcare10071331. [PMID: 35885857 PMCID: PMC9323516 DOI: 10.3390/healthcare10071331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Paralympic powerlifting (PP) training is typically intense and causes fatigue and alterations in the immune system. Objective: To analyze whether IBU would affect performance and the immune system after training in PP. Methodology: 10 athletes at the national level (NL) and 10 at the regional level (RL) participated in the study, where force and blood indicators were evaluated after training. The study took place over three weeks: (1) familiarization and (2 and 3) comparison between recovery methods, with ibuprofen or placebo (IBU vs. PLA), 800 mg. In the evaluation of the force, the peak torque (PT), fatigue index (FI), and blood immune system biomarkers were analyzed. The training consisted of five sets of five repetitions with 80% of one maximum repetition (5 × 5, 80% 1RM) on the bench press. Results: The PT at the national level using IBU was higher than with PLA (p = 0.007, η2p = 0.347), and the FI in the NL was lower with IBU than with PLA (p = 0.002, η2p = 0.635), and when comparing the use of IBU, the NL showed less fatigue than the regional level (p = 0.004, η2p = 0.414). Leukocytes, with the use of IBU in the NL group, were greater than in the RL (p = 0.001, η2p = 0.329). Neutrophils, in the NL with IBU, were greater than in the RL with IBU and PLA (p = 0.025, η2p = 0.444). Lymphocytes, in NL with IBU were lower than in RL with IBU and PLA (p = 0.001, η2p = 0.491). Monocytes, in the NL with IBU and PLA, were lower than in the RL with IBU (p = 0.049, η2p = 0.344). For hemoglobin, hematocrit, and erythrocyte, the NL with IBU and PLA were higher than the RL with IBU and PLA (p < 0.05). Ammonia, with the use of IBU in the NL, obtained values higher than in the RL (p = 0.007), and with the use of PLA, the NL was higher than the RL (p = 0.038, η2p = 0.570). Conclusion: The training level tends to influence the immune system and, combined with the use of the IBU, it tends to improve recovery and the immune system.
Collapse
Affiliation(s)
- Felipe J. Aidar
- Graduate Program of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil; (F.J.A.); (G.S.F.); (M.G.-M.); (A.C.M.); (J.L.S.); (R.F.d.S.); (L.M.V.-S.)
- Group of Studies and Research of Performance, Sport, Health and Paralympic Sports (GEPEPS), Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
- Department of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
- Graduate Program of Physiological Science, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
| | - Guacira S. Fraga
- Graduate Program of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil; (F.J.A.); (G.S.F.); (M.G.-M.); (A.C.M.); (J.L.S.); (R.F.d.S.); (L.M.V.-S.)
| | - Márcio Getirana-Mota
- Graduate Program of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil; (F.J.A.); (G.S.F.); (M.G.-M.); (A.C.M.); (J.L.S.); (R.F.d.S.); (L.M.V.-S.)
- Group of Studies and Research of Performance, Sport, Health and Paralympic Sports (GEPEPS), Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
| | - Anderson Carlos Marçal
- Graduate Program of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil; (F.J.A.); (G.S.F.); (M.G.-M.); (A.C.M.); (J.L.S.); (R.F.d.S.); (L.M.V.-S.)
- Group of Studies and Research of Performance, Sport, Health and Paralympic Sports (GEPEPS), Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
| | - Jymmys L. Santos
- Graduate Program of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil; (F.J.A.); (G.S.F.); (M.G.-M.); (A.C.M.); (J.L.S.); (R.F.d.S.); (L.M.V.-S.)
- Group of Studies and Research of Performance, Sport, Health and Paralympic Sports (GEPEPS), Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
| | - Raphael Fabricio de Souza
- Graduate Program of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil; (F.J.A.); (G.S.F.); (M.G.-M.); (A.C.M.); (J.L.S.); (R.F.d.S.); (L.M.V.-S.)
- Group of Studies and Research of Performance, Sport, Health and Paralympic Sports (GEPEPS), Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
- Department of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
| | - Lucio Marques Vieira-Souza
- Graduate Program of Physical Education, Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil; (F.J.A.); (G.S.F.); (M.G.-M.); (A.C.M.); (J.L.S.); (R.F.d.S.); (L.M.V.-S.)
- Group of Studies and Research of Performance, Sport, Health and Paralympic Sports (GEPEPS), Federal University of Sergipe (UFS), São Cristovão 49100-000, Brazil
- Department of Physical Education, State Univerity of Minas Gerais (UEMG), Passos 37900-106, Brazil
| | | | - Dihogo Gama de Matos
- Cardiovascular & Physiology of Exercise Laboratory, University of Manitoba, Winnipeg, MB R3T 2N2, Canada;
| | - Paulo Francisco de Almeida-Neto
- Department of Physical Education, Federal University of Rio Grande do Norte, Natal 59064-741, Brazil; (P.F.d.A.-N.); (B.G.d.A.T.C.)
| | - Nuno Domingos Garrido
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Trás-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal;
| | - Alfonso López Díaz-de-Durana
- Sports Department, Physical Activity and Sports Faculty-INEF, Universidad Politécnica de Madrid, 28040 Madrid, Spain;
| | - Beat Knechtle
- Institute of Primary Care, University of Zurich, 8091 Zurich, Switzerland;
- Medbase St. Gallen Am Vadianplatz, 9001 St. Gallen, Switzerland
| | | | - Eugenia Murawska-Ciałowicz
- Physiology and Biochemistry Department, Wroclaw University of Health and Sport Sciences, 51-612 Wroclaw, Poland;
| | - Hadi Nobari
- Department of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil 56199-11367, Iran;
- Faculty of Sport Sciences, University of Extremadura, 10003 Cáceres, Spain
| | - Ana Filipa Silva
- Escola Superior de Desporto e Lazer, Instituto Politécnico de Viana do Castelo, Rua Escola Industrial e Comercial de Nun’Álvares, 4900-347 Viana do Castelo, Portugal; (A.F.S.); (F.M.C.)
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), Polytechnic Institute of Maia, Maia, 5001-801 Vila Real, Portugal
| | - Filipe Manuel Clemente
- Escola Superior de Desporto e Lazer, Instituto Politécnico de Viana do Castelo, Rua Escola Industrial e Comercial de Nun’Álvares, 4900-347 Viana do Castelo, Portugal; (A.F.S.); (F.M.C.)
- Instituto de Telecomunicações, Delegação da Covilhã, 1049-001 Lisboa, Portugal
| | - Georgian Badicu
- Department of Physical Education and Special Motricity, Transilvania University of Brasov, 500068 Brasov, Romania
- Correspondence:
| |
Collapse
|
|
35
|
García-Martínez R, Diaz-Ruiz R, Poncela M. Management of Hepatic Encephalopathy Associated with Advanced Liver Disease. Clin Drug Investig 2022; 42:5-13. [PMID: 35536537 PMCID: PMC9205788 DOI: 10.1007/s40261-022-01146-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/24/2022] [Indexed: 12/11/2022]
Abstract
Hepatic encephalopathy (HE) is a very prevalent condition in patients with advanced liver disease and has a high recurrence rate. The pathophysiology has a multifactorial origin where hyperammonaemia and inflammation become particularly relevant. There are no HE-specific diagnostic tests, and diagnosis is usually made by taking into account the presence of suggestive and compatible clinical symptoms, the existence of a predisposing liver condition and ruling out other causes with similar clinical manifestations. Once the diagnosis of HE is established, it is essential to carry out an adequate classification based on the underlying liver disease, the intensity of clinical manifestations, the temporal course of the disease and the presence or absence of precipitating factors. Treatment should be aimed at decreasing the duration, intensity and consequences of episodes, preventing recurrence and limiting the impact of the disease in patients and their relatives.
Collapse
Affiliation(s)
- Rita García-Martínez
- Department of Internal Medicine, Gregorio Marañon University General Hospital, 28007, Madrid, Spain.
- School of Medicine, Complutense University Madrid, Madrid, Spain.
- Online Center for Biomedical Research of Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain.
- Instituto de Investigación Sanitaria Gregorio Marañón, Calle del Doctor Esquerdo, 46, 28007, Madrid, Spain.
| | - Raquel Diaz-Ruiz
- Department of Digestive Diseases, Gregorio Marañon University General Hospital, 28007, Madrid, Spain
| | - Marta Poncela
- Department of Digestive Diseases, Gregorio Marañon University General Hospital, 28007, Madrid, Spain
| |
Collapse
|
|
36
|
Jain A, Sharma BC, Mahajan B, Srivastava S, Kumar A, Sachdeva S, Sonika U, Dalal A. L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial. Hepatology 2022; 75:1194-1203. [PMID: 34822189 DOI: 10.1002/hep.32255] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 11/13/2021] [Accepted: 11/18/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Data on the use of intravenous L-ornithine L-aspartate (LOLA) in the treatment of overt HE (OHE) is limited. We evaluated the role of intravenous LOLA in patients of cirrhosis with OHE grade III-IV. APPROACH AND RESULTS In a double-blind randomized placebo-controlled trial, 140 patients were randomized to a combination of LOLA, lactulose, and rifaximin (n = 70) or placebo, lactulose, and rifaximin (n = 70). LOLA was given as continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF-α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the grade of HE at day 5. Higher rates of improvement in grade of HE (92.5% vs. 66%, p < 0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p = 0.03), and lower 28-day mortality (16.4% vs. 41.8%, p = 0.001) were seen in the LOLA group as compared with placebo. Levels of inflammatory markers were reduced in both groups. Significantly higher reductions in levels of blood ammonia, IL-6, and TNF-α were seen in the LOLA group. CONCLUSIONS Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28-day mortality.
Collapse
Affiliation(s)
- Arpan Jain
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
| | | | - Bhawna Mahajan
- Department of BiochemistryGB Pant HospitalNew DelhiIndia
| | | | - Ajay Kumar
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
| | | | - Ujjwal Sonika
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
| | - Ashok Dalal
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
| |
Collapse
|
|
37
|
Liu YB, Chen MK. The impact of proton pump inhibitors in liver diseases and the effects on the liver. J Dig Dis 2022; 23:196-208. [PMID: 35357775 DOI: 10.1111/1751-2980.13093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 03/09/2022] [Accepted: 03/29/2022] [Indexed: 12/11/2022]
Abstract
In this systematic and comprehensive overview, we aimed to evaluate the impact of proton pump inhibitors (PPIs) on chronic liver diseases, especially on cirrhosis. A manual and comprehensive search of the PubMed database was conducted to obtain relevant literatures. PPIs altered the composition and function of the intestinal microflora and might lead to small intestinal bacterial overgrowth and bacterial translocation, which were associated with adverse effects in liver diseases. They might increase the risk of hepatic encephalopathy, spontaneous bacterial peritonitis, infections, and are related to an increased mortality in cirrhosis. PPIs might lead to an increased risk of hepatocellular carcinoma, although the mechanism is unknown, and the results are controversial. PPIs also had an impact on the direct-acting antiviral regimen in patients with chronic hepatitis C. They were associated with an increased risk of liver abscess and increased mortality. Additionally, PPIs might lead to metabolic risk events, such as liver steatosis and weight gain. PPIs are associated with several adverse outcomes in liver diseases. Cautious use of PPIs is recommended and clinicians should be aware of the indications for their use in patients with liver diseases.
Collapse
Affiliation(s)
- Yuan Bin Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Ming Kai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| |
Collapse
|
|
38
|
The Effect of TGF-β1 Reduced Functionality on the Expression of Selected Synaptic Proteins and Electrophysiological Parameters: Implications of Changes Observed in Acute Hepatic Encephalopathy. Int J Mol Sci 2022; 23:ijms23031081. [PMID: 35163004 PMCID: PMC8835518 DOI: 10.3390/ijms23031081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/11/2022] [Accepted: 01/14/2022] [Indexed: 12/10/2022] Open
Abstract
Decreased platelet count represents a feature of acute liver failure (ALF) pathogenesis. Platelets are the reservoir of transforming growth factor 1 (TGF-β1), a multipotent cytokine involved in the maintenance of, i.a., central nervous system homeostasis. Here, we analyzed the effect of a decrease in TGF-β1 active form on synaptic proteins levels, and brain electrophysiology, in mice after intraperitoneal (ip) administration of TGF-β1 antibody (anti-TGF-β1; 1 mg/mL). Next, we correlated it with a thrombocytopenia-induced TGF-β1 decrease, documented in an azoxymethane-induced (AOM; 100 mM ip) model of ALF, and clarified the impact of TGF-β1 decrease on blood–brain barrier functionality. The increase of both synaptophysin and synaptotagmin in the cytosolic fraction, and its reduction in a membrane fraction, were confirmed in the AOM mice brains. Both proteins’ decrease in analyzed fractions occurred in anti-TGF-β1 mice. In turn, an increase in postsynaptic (NR1 subunit of N-methyl-D-aspartate receptor, postsynaptic density protein 95, gephyrin) proteins in the AOM brain cortex, but a selective compensatory increase of NR1 subunit in anti-TGF-β mice, was observed. The alterations of synaptic proteins levels were not translated on electrophysiological parameters in the anti-TGF-β1 model. The results suggest the impairment of synaptic vesicles docking to the postsynaptic membrane in the AOM model. Nevertheless, changes in synaptic protein level in the anti-TGF-β1 mice do not affect neurotransmission and may not contribute to neurologic deficits in AOM mice.
Collapse
|
|
39
|
Li X, Partovi S, Coronado WM, Gadani S, Martin C, Thompson D, Levitin A, Kapoor B. Hepatic Encephalopathy After TIPS Placement: Predictive Factors, Prevention Strategies, and Management. Cardiovasc Intervent Radiol 2022; 45:570-577. [PMID: 34981195 DOI: 10.1007/s00270-021-03045-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 12/08/2021] [Indexed: 12/19/2022]
Abstract
Hepatic encephalopathy (HE) is a challenging complication after transjugular intrahepatic portosystemic shunt (TIPS) placement. Despite recent advances, much is still uncertain regarding risk factors, preventative measures, and the management of HE after TIPS placement. Appropriate patient selection and pre-procedural risk stratification remain areas of focus. In this manuscript, we discuss the current state of research related to HE after TIPS placement, including information regarding risk stratification, complication prevention, and treatment options.
Collapse
Affiliation(s)
- Xin Li
- Department of Radiology, Hospital of The University of Pennsylvania, Philadelphia, PA, USA
| | - Sasan Partovi
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, OH, USA.
| | | | - Sameer Gadani
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, OH, USA
| | - Charles Martin
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, OH, USA
| | - Dustin Thompson
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, OH, USA
| | - Abraham Levitin
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, OH, USA
| | - Baljendra Kapoor
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic Main Campus, Cleveland, OH, USA
| |
Collapse
|
|
40
|
Bayat M, Khalili A, Bayat G, Akbari S, Yousefi Nejad A, Borhani Haghighi A, Haghani M. Effects of platelet-rich plasma on the memory impairment, apoptosis, and hippocampal synaptic plasticity in a rat model of hepatic encephalopathy. Brain Behav 2022; 12:e2447. [PMID: 34855284 PMCID: PMC8785608 DOI: 10.1002/brb3.2447] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/22/2021] [Accepted: 10/30/2021] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES In the present study, we aimed to determine whether intraperitoneal injection of platelet-rich plasma (PRP) could have a neuroprotective effect on learning, memory, and synaptic plasticity impairment as well as hippocampal apoptosis in rats with hepatic encephalopathy induced by bile duct ligated (BDL). METHODS The rats were divided into four groups: the control, sham, BDL+ V (vehicle), and BDL+ PRP. The BDL rats were treated with PRP immediately after the surgery, and the injection was done every 3 days for 30 days. The passive avoidance and Morris water maze tests were used for the evaluation of learning and memory. The long-term potentiation (LTP), basal-synaptic transmission, and paired-pulse ratio, as an index for measurement of neurotransmitter release probability, were evaluated by field-potential recording. After taking a blood sample for assessment of the liver enzymes, the animals were sacrificed and their hippocampus was removed for evaluation of cleaved caspase-3 by Western blot. RESULTS Serological assessment of the liver function showed that BDL severely impaired the liver function. Also, PRP treatment could partially improve the liver dysfunction along with recovery in fear memory and spatial learning memory performance, LTP, basal-synaptic transmission, and neurotransmitter release probability. PRP-treated rats also showed a significant reduction in neuronal apoptosis in the CA1 area. CONCLUSIONS The results of this study suggest that PRP improves cognitive performance and synaptic plasticity in BDL rats via direct neuroprotective property and/or indirectly by improvement of hepatic dysfunction.
Collapse
Affiliation(s)
- Mahnaz Bayat
- Clinical Neurology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Azadeh Khalili
- Department of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Gholamreza Bayat
- Department of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.,Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Somayeh Akbari
- Department of Physiology, The Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirhossein Yousefi Nejad
- Faculty of Veterinary Medicine, Department of Veterinary Medicine, Islamic Azad University of Kazeroon, Shiraz, Iran
| | | | - Masoud Haghani
- Department of Physiology, The Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.,Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
41
|
Shahgond L, Patel C, Thakur K, Sarkar D, Acharya S, Patel P. Therapeutic potential of probiotics - Lactobacillus plantarum UBLP40 and Bacillus clausii UBBC07 on thioacetamide-induced acute hepatic encephalopathy in rats. Metab Brain Dis 2022; 37:185-195. [PMID: 34731397 DOI: 10.1007/s11011-021-00862-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 10/23/2021] [Indexed: 01/18/2023]
Abstract
PURPOSE Hepatic encephalopathy (HE) or hepatic coma is a demanding, not utterly understood complication of acute and chronic liver dysfunction and portosystemic shunting. In HE, hyperammonemia and inflammatory responses are believed to act in synergism. Probiotics, Lactobacillus plantarum UBLP40 and Bacillus clausii UBBC07 reduce small intestinal bacterial overgrowth and hyperammonemia, thereby preventing HE development. METHODS The effect of probiotics-Lactobacillus plantarum UBLP40 (107 CFU/day, 14 days) and Bacillus clausii UBBC07 (107 CFU/day, 14 days) combination and standard drug-lactulose (2.5 ml/kg in 3 divided doses, 14 days) was studied in thioacetamide (250 mg/kg for three days) induced acute HE in rats by measuring behavioural parameters, biochemical parameters (serum AST, ALT, ALP and ammonia level), neurochemical parameters and histopathology study in brain and liver. RESULTS In contrast to only thioacetamide treated rats, probiotics treatment substantially (p < 0.001) reduced liver function parameters, i.e. serum AST, ALT, ALP, and ammonia, improved behaviour parameters, i.e. decreased motor disruption, improved memory impairment. Probiotics treated rats have also shown a substantial improvement in oxidative stress parameters i.e. reduced lipid peroxidation and increased glutathione level in brain tissue and ameliorated the histopathological changes induced by thioacetamide in the brain and liver. CONCLUSIONS It can be concluded based on the findings that the combination therapy of Lactobacillus plantarum UBLP40 and Bacillus clausiiUBBC07 proves to be effective in acute hepatic encephalopathy in the preclinical stage, and further studies are required to assess this therapy potential in the clinical setting.
Collapse
Affiliation(s)
- Lalita Shahgond
- Department of Pharmacology, S.S.R. College of Pharmacy, Silvassa, Dadra and Nagar Haveli, India, 396230
| | - Chirag Patel
- Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, 380009, India.
| | - Khushboo Thakur
- Department of Pharmacology, S.S.R. College of Pharmacy, Silvassa, Dadra and Nagar Haveli, India, 396230
| | - Dipta Sarkar
- Department of Pharmacology, S.S.R. College of Pharmacy, Silvassa, Dadra and Nagar Haveli, India, 396230
| | - Sanjeev Acharya
- Department of Pharmacology, S.S.R. College of Pharmacy, Silvassa, Dadra and Nagar Haveli, India, 396230
| | - Priyanshi Patel
- Department of Pharmacology, S.S.R. College of Pharmacy, Silvassa, Dadra and Nagar Haveli, India, 396230
| |
Collapse
|
|
42
|
Devabhaktuni S, Patkar P, Pooja V, Dhamija S, Gupta N, Chaudhury S, Saldanha D. Differentiation of hepatic encephalopathy from delirium tremens: A case series and review. Ind Psychiatry J 2021; 30:S214-S220. [PMID: 34908693 PMCID: PMC8611582 DOI: 10.4103/0972-6748.328865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/18/2021] [Accepted: 06/03/2021] [Indexed: 11/04/2022] Open
Abstract
Hepatic encephalopathy (HE) is an important and potentially life threatening complication in alcoholic patients with decompensated liver function that develop even as they continue drinking. Delirium tremens, on the other hand, is an acute condition resulting from alcohol abstinence in a person dependent on alcohol, making it a life threatening diagnosis that requires intensive care and successful management of the withdrawal. Often in medical wards, these two conditions are mistaken and so is the management plan confused with each other. Making the right diagnosis early on during the hospital course is extremely important in these critical conditions so as to make an appropriate schedule for treatment and a better outcome for the same. A case series of patients who presented with a diagnostic dilemma is reported. Clinical examinations, diagnostic tools to measure the levels of ammonia and liver function tests and hemogram, West Haven criteria and Child-Pugh grading, and clinical scales of these patients are reported. Increased levels of ammonia were present in all the cases. The subtle similarities in the presentation of the two conditions often make it confusing for the clinician to distinguish between them. Using a simple test of measuring ammonia levels in the blood helps in such situations. The detection of raised levels of ammonia in cases of chronic liver disease helps in not just the diagnosis but also is an important prognostic indicator for development of HE.
Collapse
Affiliation(s)
- Spandana Devabhaktuni
- Department of Psychiatry, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Prajakta Patkar
- Department of Psychiatry, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - V Pooja
- Department of Psychiatry, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Sana Dhamija
- Department of Psychiatry, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Nishtha Gupta
- Department of Psychiatry, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Suprakash Chaudhury
- Department of Psychiatry, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Daniel Saldanha
- Department of Psychiatry, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| |
Collapse
|
|
43
|
Li Y, Liu H, Chen K, Wu X, Wu J, Yang Z, Yao L, Wen G, Zhang C, Chen X, Chen X, Tang D, Wang X, Liu J. Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy. Front Med (Lausanne) 2021; 8:706407. [PMID: 34527681 PMCID: PMC8435674 DOI: 10.3389/fmed.2021.706407] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 08/10/2021] [Indexed: 11/27/2022] Open
Abstract
Background and Aim: Hepatic encephalopathy (HE) is a neurological disease caused by severe liver disease. Early identification of the risk factor is beneficial to the prevention and treatment of HE. Free bilirubin has always been considered to be the culprit of neonatal kernicterus, but there is no research to explore its role in HE. In this study, we aim to study the clinical significance of the indirect bilirubin-albumin ratio in HE. Methods: A retrospective case-control study of 204 patients with liver failure was conducted. Human serum albumin (HSA) or heme oxygenase-1 (HO-1) inhibitor SnPP (Tin protoporphyrin IX dichloride) was injected intraperitoneally into Ugt1−/− mice to establish a treatment model for endogenous hyperbilirubinemia. Results: IBil/albumin ratio (OR = 1.626, 95% CI1.323–2.000, P < 0.001), white blood cell (WBC) (OR = 1.128, 95% CI 1.009–1.262, P = 0.035), ammonia (OR = 1.010, 95% CI 1.001–1.019, P = 0.027), platelet (OR=1.008, 95% CI 1.001–1.016, P = 0.022), Hb (OR = 0.977, 95% CI 0.961–0.994, P = 0.007), and PTA (OR = 0.960, 95% CI 0.933–0.987, P = 0.005) were independent factors of HE. Patients with a history of liver cirrhosis and severe HE (OR = 12.323, 95% CI 3.278–47.076, P < 0.001) were more likely to die during hospitalization. HSA or SnPP treatment improved cerebellum development and reduced apoptosis of cerebellum cells. Conclusion: The IBil/albumin ratio constitutes the most powerful risk factor in the occurrence of HE, and reducing free bilirubin may be a new strategy for HE treatment.
Collapse
Affiliation(s)
- Yanling Li
- The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Huiyuan Liu
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Keng Chen
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xueheng Wu
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Jiawen Wu
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Zhenjun Yang
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Leyi Yao
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.,Institute of Digestive Disease of Guangzhou Medical University, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| | - Guanmei Wen
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Change Zhang
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Xin Chen
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Xiaohui Chen
- The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, United States
| | - Xuejun Wang
- Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, SD, United States
| | - Jinbao Liu
- Guangzhou Municipal and Guangdong Provincial Key Lab of Protein Modification and Degradation Lab, State Key Lab of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.,Institute of Digestive Disease of Guangzhou Medical University, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China
| |
Collapse
|
|
44
|
Tarnacka B, Jopowicz A, Maślińska M. Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions. Int J Mol Sci 2021; 22:ijms22157820. [PMID: 34360586 PMCID: PMC8346158 DOI: 10.3390/ijms22157820] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/12/2021] [Accepted: 07/20/2021] [Indexed: 12/18/2022] Open
Abstract
Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. An imbalance in the levels of these metals weakens the structural, regulatory, and catalytic roles of different enzymes, proteins, receptors, and transporters and is known to provoke the development of various neurological conditions through different mechanisms, such as via induction of oxidative stress, increased α-synuclein aggregation and fibril formation, and stimulation of microglial cells, thus resulting in inflammation and reduced production of metalloproteins. In the present review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. In our review, we described diseases related to these metals, such as aceruloplasminaemia, neuroferritinopathy, pantothenate kinase-associated neurodegeneration (PKAN) and other very rare classical NBIA forms, manganism, attention-deficit/hyperactivity disorder (ADHD), ephedrone encephalopathy, HMNDYT1-SLC30A10 deficiency (HMNDYT1), HMNDYT2-SLC39A14 deficiency, CDG2N-SLC39A8 deficiency, hepatic encephalopathy, prion disease and “prion-like disease”, amyotrophic lateral sclerosis, Huntington’s disease, Friedreich’s ataxia, and depression.
Collapse
Affiliation(s)
- Beata Tarnacka
- Department of Rehabilitation Medicine, Faculty of Medicine, Warsaw Medical University, Spartańska 1, 02-637 Warsaw, Poland
- Correspondence: ; Tel.: +48-603944804
| | - Anna Jopowicz
- Department of Rehabilitation, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland;
| | - Maria Maślińska
- Department of Early Arthritis, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland;
| |
Collapse
|
|
45
|
Milewski K, Czarnecka AM, Albrecht J, Zielińska M. Decreased Expression and Uncoupling of Endothelial Nitric Oxide Synthase in the Cerebral Cortex of Rats with Thioacetamide-Induced Acute Liver Failure. Int J Mol Sci 2021; 22:6662. [PMID: 34206365 PMCID: PMC8268495 DOI: 10.3390/ijms22136662] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/16/2021] [Accepted: 06/18/2021] [Indexed: 02/04/2023] Open
Abstract
Acute liver failure (ALF) is associated with deregulated nitric oxide (NO) signaling in the brain, which is one of the key molecular abnormalities leading to the neuropsychiatric disorder called hepatic encephalopathy (HE). This study focuses on the effect of ALF on the relatively unexplored endothelial NOS isoform (eNOS). The cerebral prefrontal cortices of rats with thioacetamide (TAA)-induced ALF showed decreased eNOS expression, which resulted in an overall reduction of NOS activity. ALF also decreased the content of the NOS cofactor, tetrahydro-L-biopterin (BH4), and evoked eNOS uncoupling (reduction of the eNOS dimer/monomer ratio). The addition of the NO precursor L-arginine in the absence of BH4 potentiated ROS accumulation, whereas nonspecific NOS inhibitor L-NAME or EDTA attenuated ROS increase. The ALF-induced decrease of eNOS content and its uncoupling concurred with, and was likely causally related to, both increased brain content of reactive oxidative species (ROS) and decreased cerebral cortical blood flow (CBF) in the same model.
Collapse
Affiliation(s)
| | | | | | - Magdalena Zielińska
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str, 02-106 Warsaw, Poland; (K.M.); (A.M.C.); (J.A.)
| |
Collapse
|
|
46
|
Luo G, Xie L, He M, Jaisutti R, Zhu Z. Flexible fabric gas sensors based on reduced graphene-polyaniline nanocomposite for highly sensitive NH 3detection at room temperature. NANOTECHNOLOGY 2021; 32:305501. [PMID: 33794514 DOI: 10.1088/1361-6528/abf455] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 04/01/2021] [Indexed: 06/12/2023]
Abstract
A flexible fabric gas sensor for the detection of sub-ppm-level NH3is reported in this paper. The reduced graphene oxide (rGO)-polyaniline (PANI) nanocomposite was successfully coated on cotton thread via anin situpolymerization technique. The morphology, microstructure and composition were analyzed by field-emission scanning electron microscope, x-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy. Furthermore, we have studied the responses of the rGO-PANI nanocomposite-based flexible sensors for the detection of NH3varying from 1-100 ppm, operated at 22 °C. At the optimized concentration of rGO, the response of these sensors increased by 4-5 times in comparison with the pristine rGO and PANI. These flexible sensors exhibited fast response, remarkable long-term stability, good selectivity and a low detection limit. The sensing mechanism for the high sensing performance has been thoroughly discussed and it is mainly due to the distinctive 1D fiber structure, the formation of a p-p heterojunction between the rGO nanosheets and PANI. The rGO-PANI composite-based fabric sensor with low power consumption is a potential flexible electronic device for the detection of NH3.
Collapse
Affiliation(s)
- Guifang Luo
- School of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, 201209, People's Republic of China
| | - Lili Xie
- School of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, 201209, People's Republic of China
- Shanghai Engineering Research Center of Advanced Thermal Functional Materials, Shanghai Polytechnic University, Shanghai, 201209, People's Republic of China
| | - Meng He
- School of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, 201209, People's Republic of China
| | - Rawat Jaisutti
- Department of Physics, Faculty of Science and Technology, Thammasat University, Pathumthani, 12120, Thailand
- Research Unit in Innovative Sensor and Nanoelectronic Devices, Thammasat University, Pathumthani, 12120, Thailand
| | - Zhigang Zhu
- School of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, 201209, People's Republic of China
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People's Republic of China
| |
Collapse
|
|
47
|
Altamura C, Corbelli I, de Tommaso M, Di Lorenzo C, Di Lorenzo G, Di Renzo A, Filippi M, Jannini TB, Messina R, Parisi P, Parisi V, Pierelli F, Rainero I, Raucci U, Rubino E, Sarchielli P, Li L, Vernieri F, Vollono C, Coppola G. Pathophysiological Bases of Comorbidity in Migraine. Front Hum Neurosci 2021; 15:640574. [PMID: 33958992 PMCID: PMC8093831 DOI: 10.3389/fnhum.2021.640574] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 02/23/2021] [Indexed: 12/12/2022] Open
Abstract
Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.
Collapse
Affiliation(s)
- Claudia Altamura
- Headache and Neurosonology Unit, Neurology, Campus Bio-Medico University Hospital, Rome, Italy
| | - Ilenia Corbelli
- Clinica Neurologica, Dipartimento di Medicina, Ospedale S.M. Misericordia, Università degli Studi di Perugia, Perugia, Italy
| | - Marina de Tommaso
- Applied Neurophysiology and Pain Unit, SMBNOS Department, Bari Aldo Moro University, Policlinico General Hospital, Bari, Italy
| | - Cherubino Di Lorenzo
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy
| | - Giorgio Di Lorenzo
- Laboratory of Psychophysiology and Cognitive Neuroscience, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.,IRCCS-Fondazione Santa Lucia, Rome, Italy
| | | | - Massimo Filippi
- Neuroimaging Research Unit, Division of Neuroscience, Institute of Experimental Neurology, Milan, Italy.,Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Tommaso B Jannini
- Laboratory of Psychophysiology and Cognitive Neuroscience, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Roberta Messina
- Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Vita-Salute San Raffaele University, Milan, Italy
| | - Pasquale Parisi
- Child Neurology, Department of Neuroscience, Mental Health and Sense Organs (NESMOS), Faculty of Medicine & Psychology, c/o Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | | | - Francesco Pierelli
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy.,Headache Clinic, IRCCS-Neuromed, Pozzilli, Italy
| | - Innocenzo Rainero
- Neurology I, Department of Neuroscience "Rita Levi Montalcini," University of Torino, Torino, Italy
| | - Umberto Raucci
- Department of Emergency, Acceptance and General Pediatrics, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Rome, Italy
| | - Elisa Rubino
- Neurology I, Department of Neuroscience "Rita Levi Montalcini," University of Torino, Torino, Italy
| | - Paola Sarchielli
- Clinica Neurologica, Dipartimento di Medicina, Ospedale S.M. Misericordia, Università degli Studi di Perugia, Perugia, Italy
| | - Linxin Li
- Nuffield Department of Clinical Neurosciences, Centre for Prevention of Stroke and Dementia, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Fabrizio Vernieri
- Headache and Neurosonology Unit, Neurology, Campus Bio-Medico University Hospital, Rome, Italy
| | - Catello Vollono
- Department of Neurology, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Catholic University, Rome, Italy
| | - Gianluca Coppola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy
| |
Collapse
|
|
48
|
López-Franco Ó, Morin JP, Cortés-Sol A, Molina-Jiménez T, Del Moral DI, Flores-Muñoz M, Roldán-Roldán G, Juárez-Portilla C, Zepeda RC. Cognitive Impairment After Resolution of Hepatic Encephalopathy: A Systematic Review and Meta-Analysis. Front Neurosci 2021; 15:579263. [PMID: 33790729 PMCID: PMC8006450 DOI: 10.3389/fnins.2021.579263] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 01/14/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatic encephalopathy (HE) is one of the most disabling metabolic diseases. It consists of a complication of liver disease through the action of neurotoxins, such as excessive production of ammonia from liver, resulting in impaired brain function. Its prevalence and incidence are not well known, although it has been established that up to 40% of cirrhotic patients may develop HE. Patients with HE episodes display a wide range of neurological disturbances, from subclinical alterations to coma. Recent evidence suggests that the resolution of hepatic encephalopathy does not fully restore cognitive functioning in cirrhotic patients. Therefore, the aim of this review was to evaluate the evidence supporting the presence of lingering cognitive deficits in patients with a history of HE compared to patients without HE history and how liver transplant affects such outcome in these patients. We performed two distinct meta-analysis of continuous outcomes. In both cases the results were pooled using random-effects models. Our results indicate that cirrhotic patients with a history of HE show clear cognitive deficits compared to control cirrhotic patients (Std. Mean Difference (in SDs) = −0.72 [CI 95%: −0.94, −0.50]) and that these differences are not fully restored after liver transplant (Std. Mean Difference (in SDs) = −0.48 [CI 95%: −0.77, −0.19]).
Collapse
Affiliation(s)
- Óscar López-Franco
- Laboratorio de Medicina Traslacional, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa, Mexico
| | - Jean-Pascal Morin
- Laboratorio de Neurobiología de la Conducta, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Ciudad de Mexico, Mexico
| | | | - Tania Molina-Jiménez
- Instituto Interdisciplinario de Investigaciones de la Universidad de Xalapa, Xalapa, Mexico
| | - Diana I Del Moral
- Programa de Doctorado en Ciencias Biomédicas, Universidad Veracruzana, Xalapa, Mexico
| | - Mónica Flores-Muñoz
- Laboratorio de Medicina Traslacional, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa, Mexico
| | - Gabriel Roldán-Roldán
- Laboratorio de Neurobiología de la Conducta, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Ciudad de Mexico, Mexico
| | - Claudia Juárez-Portilla
- Laboratorio de Biomedicina Integral y Salud, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Mexico
| | - Rossana C Zepeda
- Laboratorio de Biomedicina Integral y Salud, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Mexico
| |
Collapse
|
|
49
|
Avgustinovich D, Kovner A, Kashina E, Shatskaya N, Vishnivetskaya G, Bondar N, Lvova M. The pathogenic potential of the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice. Int J Parasitol 2020; 51:353-363. [PMID: 33378706 DOI: 10.1016/j.ijpara.2020.10.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 10/09/2020] [Accepted: 10/12/2020] [Indexed: 12/24/2022]
Abstract
Parasitic food-borne diseases and chronic social stress are frequent attributes of day-to-day human life. Therefore, our aim was to model the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice. Histological examination of the liver revealed inflammation sites, pronounced periductal fibrosis, and cholangiofibrosis together with proliferation of bile ducts and hepatocyte dystrophy in the infected mice, especially in the stress-exposed ones. Simultaneously with liver pathology, we detected significant structural changes in the cerebral cortex. Immunohistochemical analysis of the hippocampus indicated the highest increase in numerical density of Iba 1-, IL-6-, iNOS-, and Arg1-positive cells in mice simultaneously subjected to the two adverse factors. The number of GFAP-positive cells rose during repeated social defeat stress, most strongly in the mice subjected to both infection and stress. Real-time PCR analysis showed that the expression of genes Aif1 and Il6 differed among the analysed brain regions (hippocampus, hypothalamus, and frontal cortex) and depended on the adverse factors applied. In addition, among the brain regions, there was no consistent increase or decrease in these parameters when the two adverse treatments were combined: (i) in the hippocampus, there was upregulation of Aif1 and no change in Il6 expression; (ii) in the hypothalamus, expression levels of Aif1 and Il6 were not different from controls; and (iii) in the frontal cortex, Aif1 expression did not change while Il6 expression increased. It can be concluded that a combination of two long-lasting adverse factors, O. felineus infection and repeated social defeat stress, worsens not only the hepatic but also brain state, as evidenced behaviorally by disturbances of the startle response in mice.
Collapse
Affiliation(s)
- Damira Avgustinovich
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia; Institute of Solid State Chemistry and Mechanochemistry, SB RAS, Novosibirsk, Russia.
| | - Anna Kovner
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia
| | - Elena Kashina
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia; AO Vector-Best, Novosibirsk, Russia
| | - Natalia Shatskaya
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia
| | - Galina Vishnivetskaya
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia
| | - Natalia Bondar
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia
| | - Maria Lvova
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia
| |
Collapse
|
|
50
|
Teodorowski O, Adaszek Ł, Erman Or M, Dokuzeylül B, Ercan AM, Tarhan D, Staniec M, Winiarczyk S. Elevated serum manganese concentration in dogs as a possible predisposing factor of cerebral babesiosis in dogs. Acta Vet Hung 2020; 68:354-360. [PMID: 33372913 DOI: 10.1556/004.2020.00053] [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: 06/09/2020] [Accepted: 09/04/2020] [Indexed: 11/19/2022]
Abstract
The aim of this study was to demonstrate a relationship between the occurrence of clinical signs of brain involvement in dogs with babesiosis and the concentration of manganese (Mn) in their serum. The study included seven dogs with early babesiosis (Group 1), seven dogs with cerebral babesiosis (Group 2) and seven healthy dogs (Group 3). Haematological and biochemical blood tests were performed in all dogs, and the results were analysed statistically. The Mann-Whitney rank test was used to demonstrate the differences in Mn concentrations, as well as other haematological and biochemical parameters between groups. In dogs in Group 2 with cerebral babesiosis, as compared to dogs in Groups 1 and 3, a statistically significant increase in serum Mn concentration was shown (P = 0.002 and P = 0.029) that may have been associated with the development of anaemia and/or impairment of liver function. Given the well-established neurotoxic effects of Mn in humans, experimental rodents and primates, additional studies on the role of Mn in the pathogenesis of the cerebral form of canine babesiosis are warranted.
Collapse
Affiliation(s)
| | - Łukasz Adaszek
- 2Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka str. 30, 20-612 Lublin, Poland
| | - Mehmet Erman Or
- 3Department of Internal Medicine, Faculty of Veterinary Medicine, Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey
| | - Banu Dokuzeylül
- 3Department of Internal Medicine, Faculty of Veterinary Medicine, Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey
| | - Alev Meltem Ercan
- 4Department of Biophysics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Fatih, Istanbul, Turkey
| | - Duygu Tarhan
- 4Department of Biophysics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Fatih, Istanbul, Turkey
| | - Marta Staniec
- 2Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka str. 30, 20-612 Lublin, Poland
| | - Stanisław Winiarczyk
- 2Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka str. 30, 20-612 Lublin, Poland
| |
Collapse
|