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Elbadry M, Baki AA, bakr A, Elhamrawy EA, Abdel-Tawab H, Aish A, Nooh I, Adel A, Soliman MY, Mohammed N, Zaky S. Covert hepatic encephalopathy: a neglected topic—a narrative review. EGYPTIAN LIVER JOURNAL 2024; 14:59. [DOI: 10.1186/s43066-024-00364-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 07/03/2024] [Indexed: 01/04/2025] Open
Abstract
AbstractCovert hepatic encephalopathy (CHE) is a form of cerebral dysfunction that affects 30–40% of patients with liver cirrhosis as a grave sequel of disease progression. Although being a silent condition, yet; CHE has been reported as seriously predictive for the development of overt hepatic encephalopathy. Covert hepatic encephalopathy is said to conclude grades (0 and 1) hepatic encephalopathy in West Heaven grading of hepatic encephalopathy, hence; inferring to discrete deficits in attention, cognition, and motor control, strongly associated with poorer quality of private and social aspects of the patients’ life. Clinical recognition of cases of CHE is such a tedious task that unluckily devoid of discernment. Worthwhile; the battery of neuropsychometric tests widely known as the only tool to identify CHE can give abnormal results without specifying the cause of brain dysfunction Therefore, dedicated history-taking and clinical evaluation of liver cirrhosis patients are still the cornerstones that should unify other diagnostic tools to identify those patients at risk of developing overt hepatic encephalopathy. Diagnosis of CHE is challenging and often neglected in clinical practice, so the aim of this review is to improve our approach to CHE and begin a unified effort for the advancement of CHE through studying easy, fast, and reliable psychometric diagnostic tests to meet our clinical needs.
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Shetty A, Saab EG, Choi G. Social Impact of Hepatic Encephalopathy. Clin Liver Dis 2024; 28:273-285. [PMID: 38548439 DOI: 10.1016/j.cld.2024.01.011] [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 is a medical condition that stems from liver dysfunction, leading to the accumulation of toxins in the bloodstream. This can result in cognitive impairments, mood changes, and motor dysfunction. Its social impact includes challenges in employment, relationships, and daily functioning for affected individuals. Stigma and misunderstanding around the condition can further exacerbate the difficulties faced by both patients and their caregivers. Efforts to raise awareness, improve medical management, and provide support systems can help mitigate the social impact of hepatic encephalopathy.
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Affiliation(s)
- Akshay Shetty
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA.
| | - Elena G Saab
- School of Medicine, Wake Forest University, Winston Salem, NC, USA
| | - Gina Choi
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
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Jones BI, Jenkins CA, Murphy D, Orr J, Yeoman A, Hubbuck ER, Heywood BR, Currie CJ. Predicting hepatic encephalopathy in patients with cirrhosis: A UK population-based study and validation of risk scores. Hepatol Commun 2023; 7:e0307. [PMID: 37930150 PMCID: PMC10629733 DOI: 10.1097/hc9.0000000000000307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 08/23/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND HE is a common neurologic complication in cirrhosis associated with substantial disease and economic burden. HE symptoms are nonspecific and there are limited ways of identifying patients with cirrhosis at high risk of later developing HE. A risk score was previously developed to identify patients at risk of developing HE in a predominately male US cohort. Here, we evaluated the performance of the HE risk scores in a UK cohort study. METHODS Health care records from Clinical Practice Research Datalink and linked Hospital Episode Statistics were used to select patients with cirrhosis who were diagnosed with HE, confirmed by a diagnosis code for HE or a rifaximin-α prescription. The index date was the date of incident cirrhosis. The study period was from January 2003 to June 2019. RESULTS A total of 40,809 patients with cirrhosis were selected in the UK cohort, of whom 59% were male. A total of 1561 patients were diagnosed with HE. Applying the UK cohort to the baseline sensitivity risk cutoff (≥-11) from the US cohort provided a sensitivity of 92% and a negative predictive value of 99%. Within a longitudinal model, applying a sensitivity cutoff of ≥-3 to this cohort gave a sensitivity of 89% and a negative predictive value of 99%. CONCLUSIONS Using data from the UK, the previously developed HE risk scores were found to be reliable for selecting those most likely to progress to HE in patients with liver cirrhosis. Despite the HE risk scores originally being estimated using the data from a predominately male US cohort, the scores were validated and found to be generalizable to female patients.
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Affiliation(s)
- Bethan I. Jones
- Global Pharmacoepidemiology, Human Data Sciences, Cardiff, UK
| | | | - Daniel Murphy
- Market Access and Government Affairs, Norgine Pharmaceuticals Limited, Uxbridge, UK
| | - James Orr
- Gwent Liver Unit, Hepatology Department, University Hospitals Bristol and Weston, Bristol, UK
| | - Andrew Yeoman
- Gwent Liver Unit, Aneurin Bevan University Health Board, Royal Gwent Hospital, Newport, Wales, UK
| | | | - Ben R. Heywood
- Global Pharmacoepidemiology, Human Data Sciences, Cardiff, UK
| | - Craig J. Currie
- Global Pharmacoepidemiology, Human Data Sciences, Cardiff, UK
- Institute of Population Health, School of Medicine, Cardiff University, Cardiff, UK
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Dong QY, Lin JH, Wu Y, Cao YB, Zhou MX, Chen HJ. White matter microstructural disruption in minimal hepatic encephalopathy: a neurite orientation dispersion and density imaging (NODDI) study. Neuroradiology 2023; 65:1589-1604. [PMID: 37486421 DOI: 10.1007/s00234-023-03201-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 07/11/2023] [Indexed: 07/25/2023]
Abstract
PURPOSE To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). METHODS Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. RESULTS MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. CONCLUSION MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.
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Affiliation(s)
- Qiu-Yi Dong
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jia-Hui Lin
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Ye Wu
- School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China
| | - Yun-Bin Cao
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Min-Xiong Zhou
- College of Medical Imaging, Shang Hai University of Medicine & Health Sciences, Shanghai, 201318, China
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Muñoz L, Caparrós E, Albillos A, Francés R. The shaping of gut immunity in cirrhosis. Front Immunol 2023; 14:1139554. [PMID: 37122743 PMCID: PMC10141304 DOI: 10.3389/fimmu.2023.1139554] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 03/27/2023] [Indexed: 05/02/2023] Open
Abstract
Cirrhosis is the common end-stage of chronic liver diseases of different etiology. The altered bile acids metabolism in the cirrhotic liver and the increase in the blood-brain barrier permeability, along with the progressive dysbiosis of intestinal microbiota, contribute to gut immunity changes, from compromised antimicrobial host defense to pro-inflammatory adaptive responses. In turn, these changes elicit a disruption in the epithelial and gut vascular barriers, promoting the increased access of potential pathogenic microbial antigens to portal circulation, further aggravating liver disease. After summarizing the key aspects of gut immunity during homeostasis, this review is intended to update the contribution of liver and brain metabolites in shaping the intestinal immune status and, in turn, to understand how the loss of homeostasis in the gut-associated lymphoid tissue, as present in cirrhosis, cooperates in the advanced chronic liver disease progression. Finally, several therapeutic approaches targeting the intestinal homeostasis in cirrhosis are discussed.
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Affiliation(s)
- Leticia Muñoz
- Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Esther Caparrós
- Grupo de Inmunobiología Hepática e Intestinal, Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain
- Instituto de Investigación Sanitaria ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
| | - Agustín Albillos
- Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- *Correspondence: Agustín Albillos, ; Rubén Frances,
| | - Rubén Francés
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Grupo de Inmunobiología Hepática e Intestinal, Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain
- Instituto de Investigación Sanitaria ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
- Instituto de Investigación, Desarrollo e Innovación en Biotecnologiía Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Elche, Spain
- *Correspondence: Agustín Albillos, ; Rubén Frances,
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Acharya C, McGeorge S, Fagan A, Wade JB, Lee H, Luketic V, Sterling RK, Thacker L, Bajaj JS. Substance-use simulation impairs driving capability in patients with cirrhosis regardless of hepatic encephalopathy. Hepatol Commun 2022; 6:2867-2875. [PMID: 35842916 PMCID: PMC9512458 DOI: 10.1002/hep4.2028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/16/2022] [Accepted: 06/11/2022] [Indexed: 11/07/2022] Open
Abstract
Driving is independently affected by cirrhosis and hepatic encephalopathy (HE) and alcohol/substance use, but their concomitant impact is unclear. We aimed to determine the impact of alcohol and other substances on driving-simulator performance in cirrhosis with and without HE. Outpatients with cirrhosis and controls underwent cognitive testing and driving simulation for the following three conditions: baseline, wearing goggles simulating alcohol intoxication, and wearing goggles simulating opioid/benzodiazepine abuse. Outcomes were number of centerline crossings (CCs) and road-edge excursions (REEs). We compared controls versus patients with cirrhosis then subjects with cirrhosis with and without HE for all conditions, using generalized linear modeling (GLM). Sixty subjects (17 controls, 43 with cirrhosis [Model for End-Stage Liver Disease score, 10; 21 subjects with prior HE]) were included. Simulations showed higher CCs and REEs at baseline in patients with cirrhosis with and without HE versus controls. With alcohol- and substance abuse-impairment goggles, CCs increased but REEs decreased in cirrhosis. In the GLM, a time and group interaction was seen (p < 0.001) for CCs and REEs. Patients with cirrhosis showed higher CCs and REEs at baseline than controls (CCs, p = 0.003; REEs, p = 0.0001) and higher CCs (p = 0.03) and lower REEs (p = 0.001) with alcohol-simulating goggles. All groups were equally impaired with opioid/benzodiazepine-simulating goggles (CCs, p = 0.49; REEs, p = 0.46). Controls with alcohol-simulating goggles had similar CCs as the baseline of patients with cirrhosis (p = 0.98). conclusions: Simulating alcohol intake induces greater driving impairment in patients with cirrhosis versus controls, but similar patterns were seen with opioid/benzodiazepine-simulating goggles. At baseline, patients with cirrhosis have simulator outcomes equivalent to intoxicated controls. Driving simulation with goggles modeling substance abuse could improve insight into driving errors and enhance driving rehabilitation in patients with cirrhosis.
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Affiliation(s)
- Chathur Acharya
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Sara McGeorge
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Andrew Fagan
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - James B. Wade
- Department of PsychiatryVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Hannah Lee
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Velimir Luketic
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Richard K. Sterling
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Leroy Thacker
- Department of BiostatisticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
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Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet 2021; 398:1359-1376. [PMID: 34543610 DOI: 10.1016/s0140-6736(21)01374-x] [Citation(s) in RCA: 774] [Impact Index Per Article: 193.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/02/2021] [Accepted: 06/10/2021] [Indexed: 02/06/2023]
Abstract
Cirrhosis is widely prevalent worldwide and can be a consequence of different causes, such as obesity, non-alcoholic fatty liver disease, high alcohol consumption, hepatitis B or C infection, autoimmune diseases, cholestatic diseases, and iron or copper overload. Cirrhosis develops after a long period of inflammation that results in replacement of the healthy liver parenchyma with fibrotic tissue and regenerative nodules, leading to portal hypertension. The disease evolves from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis), the complications of which often result in hospitalisation, impaired quality of life, and high mortality. Progressive portal hypertension, systemic inflammation, and liver failure drive disease outcomes. The management of liver cirrhosis is centred on the treatment of the causes and complications, and liver transplantation can be required in some cases. In this Seminar, we discuss the disease burden, pathophysiology, and recommendations for the diagnosis and management of cirrhosis and its complications. Future challenges include better screening for early fibrosis or cirrhosis, early identification and reversal of causative factors, and prevention of complications.
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Affiliation(s)
- Pere Ginès
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institute of Biomedical Investigation August Pi I Sunyer, Barcelona, Spain; Hepatic and Digestive Diseases Biomedical Investigation Center, Madrid, Spain.
| | - Aleksander Krag
- Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Elsa Solà
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA
| | - Núria Fabrellas
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institute of Biomedical Investigation August Pi I Sunyer, Barcelona, Spain; Hepatic and Digestive Diseases Biomedical Investigation Center, Madrid, Spain
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Characterization of brain microstructural abnormalities in cirrhotic patients without overt hepatic encephalopathy using diffusion kurtosis imaging. Brain Imaging Behav 2021; 14:627-638. [PMID: 31538276 PMCID: PMC7160080 DOI: 10.1007/s11682-019-00141-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cirrhosis is a major public health concern. However, little is known about the neurobiological mechanisms underlying brain microstructure alterations in cirrhotic patients. The purpose of this prospective study was to investigate brain microstructural alterations in cirrhosis with or without minimal hepatic encephalopathy (MHE) and their relationship with patients’ neurocognitive performance and disease duration using voxel-based analysis of diffusion kurtosis imaging (DKI). DKI data were acquired from 30 cirrhotic patients with MHE, 31 patients without MHE (NMHE) and 59 healthy controls. All DKI-derived parametric maps were compared across the three groups to investigate their group differences. Correlation analyses were further performed to assess relationships between altered imaging parameters and clinical data. Voxel-based analysis of DKI data results showed that MHE/NMHE patients had increased radial diffusivity, axial diffusivity (AD) and mean diffusivity in addition to decreased axial kurtosis (AK) and fractional anisotropy of kurtosis in several regions. Compared to controls, these regions were primarily the cingulum, temporal and frontal cortices. The DKI metrics (i.e., AK and AD) were correlated with clinical variables in the two patient groups. In conclusion, DKI is useful for detecting brain microstructural abnormalities in MHE and NMHE patients. Abnormal DKI parameters suggest alterations in brain microstructural complexity in cirrhotic patients, which may contribute to the neurobiological basis of neurocognitive impairment. These results may provide additional information on the pathophysiology of cirrhosis.
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Luo M, Mu R, Liu JF, Bai FH. Novel computerized psychometric tests as primary screening tools for the diagnosis of minimal hepatic encephalopathy. World J Clin Cases 2020; 8:3377-3389. [PMID: 32913845 PMCID: PMC7457114 DOI: 10.12998/wjcc.v8.i16.3377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/05/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting, which results in a wide range of cognitive deficits including impairments in working attention, psychomotor speed, and executive function. Current guidelines have recommended paper-and-pencil psychometric tests for the diagnosis of MHE. Most high-risk cirrhotic patients are required to be examined; however, paper-and-pencil psychometric tests are neither convenient nor rapid to perform in the clinic. Recently, novel computerized psychometric tests, including the inhibitory control test, EncephalApp Stroop App, and critical flicker frequency, have been proven to be rapid, effective, and convenient methods for screening MHE in clinical practice and for identifying high-risk cirrhotic patients for further validation using rigid neuropsychometric examinations. However, diagnostic accuracy of these tests is influenced by educational background, age, and cultural differences. This review summarizes clinical evidence of the application of novel computerized psychometric tests for screening MHE.
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Affiliation(s)
- Ming Luo
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Rui Mu
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Jian-Fang Liu
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Fei-Hu Bai
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
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Impaired brain function improved by L-carnitine in patients with cirrhosis: evaluation using near-infrared spectroscopy. Sci Rep 2020; 10:13566. [PMID: 32782294 PMCID: PMC7419306 DOI: 10.1038/s41598-020-70585-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 07/20/2020] [Indexed: 02/07/2023] Open
Abstract
To evaluate the effects of l-carnitine on impaired brain function in patients with liver cirrhosis. We conducted a retrospective cohort study that included sequential 80 liver cirrhosis patients with impaired brain function evaluated using near-infrared spectroscopy (NIRS). Among them, l-carnitine was administered to 48 patients. The NIRS data and blood ammonia level at baseline and after 8 weeks of treatment were compared between patients administered with l-carnitine (l-carnitine group) and those who were not (control group). The NIRS data at baseline were similar between the l-carnitine and control groups (0.04 ± 0.04 vs. 0.04 ± 0.05 mMmm, p = n.s), whereas those in the l-carnitine group (n = 48) were significantly better than that of the control group at 8 weeks of treatment (n = 32) (0.103 ± 0.081 vs. 0.040 ± 0.048 mMmm, p < 0.001). In the l-carnitine group, 35.4% (17/48) of patients had hyperammonemia. The NIRS data of the l-carnitine group at 8 weeks of treatment were significantly improved than that of the control group, irrespective of baseline ammonia levels (0.11 ± 0.09 vs. 0.04 ± 0.05 mMmm, p = 0.005, and 0.10 ± 0.06 vs. 0.02 ± 0.03 mMmm, p = 0.003, for normal baseline ammonia and elevated ammonia levels, respectively). In the multivariate analysis, l-carnitine administration (odds ratio [OR] 3.51, 95% confidence interval [CI] 1.23–9.99, p = 0.019) and baseline NIRS data of ≤ 0.07 mMmm (OR 5.21, 95% CI 1.69–16.0, p = 0.0041) were found as independent significant factors. l-carnitine improves impaired brain function in patients with liver cirrhosis.
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11
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Animal Naming Test - a simple and accurate test for diagnosis of minimal hepatic encephalopathy and prediction of overt hepatic encephalopathy. Clin Exp Hepatol 2020; 6:116-124. [PMID: 32728628 PMCID: PMC7380476 DOI: 10.5114/ceh.2019.95105] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 03/05/2020] [Indexed: 01/02/2023] Open
Abstract
Aim of the study Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encepha-lopathy (HE). We compared the usefulness of the Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) for the diagnosis of MHE and the prediction of the development of overt episodes of HE. Material and methods 103 consecutive patients with liver cirrhosis without overt HE were subjected to PHES and ANT evaluation. The receiver-operating characteristic curve was used to determine the optimum cut-off of the ANT value for the diagnosis of MHE. Results Thirty-seven (35.9%) patients had MHE as assessed by altered PHES. ANT (< 14) was positive in 36 (34.95%) patients with MHE with a sensitivity of 89.19% and specificity of 95.7%, positive predictive value (PPV) of 91.67%, negative predictive value (NPV) of 94.03% and diagnostic accuracy of 93.20%. The area under the curve for diagnosis of MHE was 0.978 (95% CI: 0.954-1.0). MHE patients had significantly lower ANT as compared to non-MHE patients and controls (10.81 ±0.324 vs. 15.27 ±0.147 vs. 15.78 ±0.192, respectively, p = 0.01). ANT correlated with PHES (r = 0.752, p = 0.001) and also with Child-Pugh (r = –0.408, p = 0.001) and MELD (r = –0.318, p = 0.001) scores. During follow-up, 14 patients in the MHE group and 4 in the non-MHE group developed overt episodes of HE (p = 0.001). Conclusions ANT is simple and accurate for the diagnosis of MHE and prediction of overt episodes of HE in patients with cirrhosis and correlates well with the Child-Pugh and MELD scores.
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Abstract
Hepatic encephalopathy (HE) is a multifaceted disorder, with effects stretching far beyond office visits and hospitalizations. Patients with HE suffer from varying degrees of altered consciousness, intellectual disability, and personality changes. A large social impact exists for patients with HE. Quality of life and activities of daily living, such as work capacity, driving ability, and sleep quality, have been shown to be affected. Additionally, caregiver and financial burdens are highly prevalent. Multiple tools exist to assess quality of life, including the CLD-Q questionnaire. Common treatments for HE, including rifaximin and lactulose, have been shown to improve overall quality of life.
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Affiliation(s)
- Mishal Reja
- Department of Medicine, Rutgers Robert Wood Johnson University Hospital, Clinical Academic Building (CAB), 125 Paterson Street, Suite 5100B, New Brunswick, NJ 08901, USA.
| | - Lauren Pioppo Phelan
- Department of Medicine, Rutgers Robert Wood Johnson University Hospital, Clinical Academic Building (CAB), 125 Paterson Street, Suite 5100B, New Brunswick, NJ 08901, USA
| | - Frank Senatore
- Department of Gastroenterology, Rutgers Robert Wood Johnson University Hospital, Clinical Academic Building, 125 Paterson Street, Suite 5100B, New Brunswick, NJ 08901, USA
| | - Vinod K Rustgi
- Center for Liver Diseases and Masses, Robert Wood Johnson Medical School, Clinical Academic Building (CAB), 125 Paterson Street, Suite 5100B, New Brunswick, NJ 08901, USA.
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Pawar VB, Surude RG, Sonthalia N, Zanwar V, Jain S, Contractor Q, Rathi PM. Minimal Hepatic Encephalopathy in Indians: Psychometric Hepatic Encephalopathy Score and Inhibitory Control Test for Diagnosis and Rifaximin or Lactulose for Its Reversal. J Clin Transl Hepatol 2019; 7:304-312. [PMID: 31915599 PMCID: PMC6943207 DOI: 10.14218/jcth.2017.00037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Revised: 05/28/2018] [Accepted: 02/14/2019] [Indexed: 12/15/2022] Open
Abstract
Background and Aims: Psychometric hepatic encephalopathy score (PHES) is used widely for diagnosis of minimal hepatic encephalopathy (MHE). This prospective study aimed to determine the utility of the inhibitory control test (ICT) for the diagnosis of MHE. Additionally, the efficacy of rifaximin and lactulose for reversal of MHE was evaluated. Methods: A total of 180 eligible cirrhotic patients underwent testing for MHE. When PHES was ≤ -5 and ICT lures were ≥ 14, MHE was diagnosed. The 108 patients with MHE were randomized to three groups for treatment with either lactulose, rifaximin, or placebo. Treatment outcomes were measured at the end of 3 months. Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%. The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients, by abnormal ICT and normal PHES in 37 patients, and by abnormal PHES and normal ICT in 15 patients. For diagnosis of MHE, ICT had sensitivity of 78.87%, specificity of 66.06% with 60.22% positive predictive value and 82.76% negative predictive value. An area under the curve value of 0.724 (95% CI: 0.653-0.788) was obtained for diagnosis of MHE. Reversal of MHE was seen in 71.42%, 70.27% and 11.11% of patients in the rifaximin, lactulose and placebo arms (p < 0.001). Rifaximin showed better tolerability compared to lactulose. Conclusions: For the diagnosis of MHE, ICT is a simple tool but has lower sensitivity and better specificity than PHES. Rifaximin is as efficacious as lactulose in the treatment of MHE and better tolerated.
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Affiliation(s)
- Vinay B. Pawar
- Correspondence to: Vinay B. Pawar, Department of Gastroenterology, Topiwala National Medical College and BYL Ch Hospital, Dr. A.L Nair Road, Mumbai, Maharashtra 400008, India. Tel: +22-23021639, E-mail:
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Lin W, Chen X, Gao YQ, Yang ZT, Yang W, Chen HJ. Hippocampal atrophy and functional connectivity disruption in cirrhotic patients with minimal hepatic encephalopathy. Metab Brain Dis 2019; 34:1519-1529. [PMID: 31363985 DOI: 10.1007/s11011-019-00457-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 07/03/2019] [Indexed: 12/21/2022]
Abstract
The hippocampus is a crucial pathological node for minimal hepatic encephalopathy (MHE) and it is associated with various cognitive impairments. Investigations on alterations involving hippocampal morphology and functional connectivity (FC) in MHE are limited. This study aimed to simultaneously evaluate hippocampal volume and FC alterations and their association with cognitive decline in MHE. Twenty-two cirrhotic patients with MHE, 31 cirrhotic patients without MHE (NHE), and 43 healthy controls underwent high-resolution T1-weighted imaging, resting-state functional magnetic resonance imaging, and cognition assessment based on Psychometric Hepatic Encephalopathy Score (PHES). The structural images were preprocessed using a voxel-based morphometry method, during which hippocampal volume was measured. The hippocampal connectivity network was identified using seed-based correlation analysis. Hippocampal volume and FC strength were compared across the three groups and correlated against the PHES results of the cirrhotic patients. Compared to the controls, MHE patients exhibited a significantly lower bilateral hippocampal volume. A slight decrease in hippocampal volume was obtained from NHE to MHE, but it did not reach statistically significance. In addition, the average FC strength of the bilateral hippocampal connectivity network was significantly lower in the MHE patients. In particular, the MHE patients showed a decrease in FC involving the left hippocampus to bilateral posterior cingulate gyrus and left angular gyrus. The MHE patients also showed FC reduction between the right hippocampus and bilateral medial frontal cortex. A progressive reduction in hippocampal FC from NHE to MHE was also observed. The bilateral hippocampal FC strength (but not hippocampal volume) was positively correlated with the PHES results of the cirrhotic patients. Our assessment of MHE patients revealed decreased hippocampal volume, which suggests regional atrophy, and reduced hippocampal connectivity with regions that are primarily involved in the default-mode network, thereby suggesting a functional disconnection syndrome. These alterations reveal the mechanisms underlying cognitive deterioration with disease progression.
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Affiliation(s)
- Weiwen Lin
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Xuhui Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | | | - Zhe-Ting Yang
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Weizhu Yang
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Awad MMED, El-Deib AERM, Attia FM, Negm M, Soliman MHM, Omar WH. Role of minimal hepatic encephalopathy in road traffic accidents. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2019. [DOI: 10.1186/s41983-019-0055-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Shiha G, Mousa N. Minimal Hepatic Encephalopathy: Silent Tragedy. LIVER DISEASE AND SURGERY [WORKING TITLE] 2019. [DOI: 10.5772/intechopen.88231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
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Nardelli S, Gioia S, Faccioli J, Riggio O, Ridola L. Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy. World J Gastroenterol 2019; 25:5257-5265. [PMID: 31558871 PMCID: PMC6761233 DOI: 10.3748/wjg.v25.i35.5257] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 08/08/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). MHE is considered as a preclinical stage of HE and is part of a wide spectrum of typical neurocognitive alterations characteristic of patients with liver cirrhosis, particularly involving the areas of attention, alertness, response inhibition, and executive functions. MHE can be detected by testing the patients' psychometric performance, attention, working memory, psychomotor speed, and visuospatial ability, as well as by means of electrophysiological and other functional brain measures. MHE is very frequent, affecting from 20% up to 80% of patients tested, depending of the diagnostic tools used. Although subclinical, MHE is considered to be clinically relevant. In fact, MHE has been related to the patients' falls, fitness to drive, and working ability. As a consequence, MHE affects the patients and caregivers lives by altering their quality of life and even their socioeconomic status. Recently sarcopenia, a very common condition in patients with advanced liver disease, has been shown to be strictly related to both minimal and overt HE. Aim of this review is to summarize the most recently published evidences about the emerging relationship between sarcopenia and cognitive impairment in cirrhotic patients and provide suggestions for future research.
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Affiliation(s)
- Silvia Nardelli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Jessica Faccioli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
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Shen YC, Chang YH, Fang CJ, Lin YS. Zinc supplementation in patients with cirrhosis and hepatic encephalopathy: a systematic review and meta-analysis. Nutr J 2019; 18:34. [PMID: 31279342 PMCID: PMC6612144 DOI: 10.1186/s12937-019-0461-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 06/25/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Low serum zinc level is associated with hepatic encephalopathy (HE), but the efficacy of zinc supplementation remains uncertain. This study aimed to investigate the effects of zinc supplementation on HE treatment in patients with cirrhosis. METHODS We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane CENTRAL) and Scopus from inception to December 2018; without publication date or language restrictions. Randomized controlled trials of zinc supplementation versus placebo or other treatment for the management of HE in adult patients with cirrhosis were selected. The primary outcome was the degree of HE as assessed by clinical signs or specialized psychometric tests. The secondary outcomes included serum ammonia levels, adverse events, or the length of hospital stay and costs. We carried out a meta-analysis with random effects model and summarized continuous outcomes using standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (95% CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence for each outcome was evaluated with the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS Four trials with 247 patients were included. In patients with cirrhosis who had mild HE (≤ grade II), the available evidence suggested that the combination treatment of zinc supplementation and lactulose over 3 to 6 months significantly improved performance in the number connection test (SMD: -0.97; 95% CI: - 1.75 to - 0.19; P = 0.01; moderate certainty), reported in three trials (n = 227). However, compared with lactulose therapy alone, additional zinc supplementation demonstrated no significant difference in the digit symbol test (SMD: 0.44; 95% CI: - 0.12 to 1.00; P = 0.12; very low certainty) or serum ammonia levels (MD: -10.86; 95% CI: - 25.73 to 4.01; P = 0.15; very low certainty), reported in two trials (n = 137). None of the included trials reported adverse events or effects on hospitalization. CONCLUSIONS In conclusion, a combination of zinc supplementation and lactulose over 3 to 6 months may improve the number connection test in cirrhotic patients with low grade HE, compared with lactulose only. TRIAL REGISTRATION PROSPERO: CRD42017080955 . Registered 23 November 2017.
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Affiliation(s)
- Ying-Chi Shen
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
| | - Ya-Hui Chang
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- Department of Pharmacy, MacKay Memorial Hospital, Taipei, Taiwan
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Ching-Ju Fang
- Medical Library, National Cheng Kung University, Tainan, Taiwan
- Department of Secretariat, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yang-Sheng Lin
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Evidence-Based Medicine Center, MacKay Memorial Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Deputy Director, Evidence-Based Medicine Center, MacKay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Rd., Zhongshan Dist., Taipei City, 104 Taiwan, Republic of China
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Zarantonello L, Turco M, Formentin C, Izquierdo-Altarejos P, Vuerich A, Barcenas Jimenez MJ, Montoliu C, Felipo V, Angeli P, Amodio P, Montagnese S. The influence of HE history, HE status and neuropsychological test type on learning ability in patients with cirrhosis. Liver Int 2019; 39:861-870. [PMID: 30658006 DOI: 10.1111/liv.14046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/06/2018] [Accepted: 01/11/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS Learning ability may be impaired in patients with a history of overt hepatic encephalopathy (OHE). The aim of this study was to compare performance on the first/second attempt at a series of tests. METHODS Two hundred and fourteen patients with cirrhosis were enrolled. On the day of study, 41% were classed as unimpaired, 38% as having minimal HE and 21% as having mild OHE; 58% had a history of OHE. Performance was compared between two versions of the trail-making test A (TMT-A), and between the first/second half of a simple/choice reaction time (sRT and cRT), and a working memory test (ScanRT). RESULTS Both patients with and without OHE history improved in TMT-A, sRT and ScanRT. Only patients with no OHE history improved in cRT. All patients, regardless of their HE status on the day of study, improved in TMT-A and sRT. Only patients with mild OHE on the day of study improved in cRT. Only unimpaired patients improved in ScanRT. When OHE history and HE status on the day of study were tested together, only HE status had an effect. The same held true when age, the Model for End Stage Liver Disease (MELD) and educational attainment were adjusted for. CONCLUSIONS HE status on the day of study and the type of neuropsychological test had an effect on learning ability in a well-characterized group of patients with cirrhosis.
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Affiliation(s)
| | - Matteo Turco
- Department of Medicine, University of Padova, Padova, Italy
| | | | - Paula Izquierdo-Altarejos
- Department of Medicine, University of Padova, Padova, Italy.,Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, Valencia, Spain
| | - Anna Vuerich
- Department of Medicine, University of Padova, Padova, Italy
| | | | - Carmina Montoliu
- Fundación Investigación Hospital Clínico, Instituto Investigación Sanitaria-INCLIVA, Valencia, Spain
| | - Vicente Felipo
- Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, Valencia, Spain
| | - Paolo Angeli
- Department of Medicine, University of Padova, Padova, Italy
| | - Piero Amodio
- Department of Medicine, University of Padova, Padova, Italy
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Tapper EB, Romero-Gómez M, Bajaj JS. Hepatic encephalopathy and traffic accidents: Vigilance is needed! J Hepatol 2019; 70:590-592. [PMID: 30765121 DOI: 10.1016/j.jhep.2019.01.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/17/2022]
Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA; Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
| | - Manuel Romero-Gómez
- UCM Digestive Diseases and Ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA; GI Section, Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA
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Subnetwork mining on functional connectivity network for classification of minimal hepatic encephalopathy. Brain Imaging Behav 2019; 12:901-911. [PMID: 28717971 DOI: 10.1007/s11682-017-9753-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Hepatic encephalopathy (HE), as a complication of cirrhosis, is a serious brain disease, which may lead to death. Accurate diagnosis of HE and its intermediate stage, i.e., minimal HE (MHE), is very important for possibly early diagnosis and treatment. Brain connectivity network, as a simple representation of brain interaction, has been widely used for the brain disease (e.g., HE and MHE) analysis. However, those studies mainly focus on finding disease-related abnormal connectivity between brain regions, although a large number of studies have indicated that some brain diseases are usually related to local structure of brain connectivity network (i.e., subnetwork), rather than solely on some single brain regions or connectivities. Also, mining such disease-related subnetwork is a challenging task because of the complexity of brain network. To address this problem, we proposed a novel frequent-subnetwork-based method to mine disease-related subnetworks for MHE classification. Specifically, we first mine frequent subnetworks from both groups, i.e., MHE patients and non-HE (NHE) patients, respectively. Then we used the graph-kernel based method to select the most discriminative subnetworks for subsequent classification. We evaluate our proposed method on a MHE dataset with 77 cirrhosis patients, including 38 MHE patients and 39 NHE patients. The results demonstrate that our proposed method can not only obtain the improved classification performance in comparison with state-of-the-art network-based methods, but also identify disease-related subnetworks which can help us better understand the pathology of the brain diseases.
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22
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Ridola L, Nardelli S, Gioia S, Riggio O. Quality of life in patients with minimal hepatic encephalopathy. World J Gastroenterol 2018; 24:5446-5453. [PMID: 30622374 PMCID: PMC6319138 DOI: 10.3748/wjg.v24.i48.5446] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 11/08/2018] [Accepted: 11/09/2018] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). This condition alters the performance of psychometric tests by impairing attention, working memory, psychomotor speed, and visuospatial ability, as well as electrophysiological and other functional brain measures. MHE is a frequent complication of liver disease, affecting up to 80% of tested patients, depending of the diagnostic tools used for the diagnosis. MHE is related to falls, to an impairment in fitness to drive and the development of overt HE, MHE severely affects the lives of patients and caregivers by altering their quality of life (QoL) and their socioeconomic status. MHE is detected in clinically asymptomatic patients through appropriate psychometric tests and neurophysiological methods which highlight neuropsychological alterations such as video-spatial orientation deficits, attention disorders, memory, reaction times, electroencephalogram slowing, prolongation of latency evoked cognitive potentials and reduction in the critical flicker frequency. Several treatments have been proposed for MHE treatment such as non-absorbable disaccharides, poorly absorbable antibiotics such rifaximin, probiotics and branched chain amino acids. However, because of the multiple diagnosis methods, the various endpoints of treatment trials and the variety of agents used in trials, to date the treatment of MHE is not routinely recommended apart from on a case-by-case basis. Aim of this review is analyze the burden of MHE on QoL of patients and provide a brief summary of therapeutic approaches.
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Affiliation(s)
- Lorenzo Ridola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina 04100, Italy
| | - Silvia Nardelli
- Department of Clinical Medicine, Sapienza University of Rome, Rome 00185, Italy
| | - Stefania Gioia
- Department of Clinical Medicine, Sapienza University of Rome, Rome 00185, Italy
| | - Oliviero Riggio
- Department of Clinical Medicine, Sapienza University of Rome, Rome 00185, Italy
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Tapper EB, Parikh ND, Sengupta N, Mellinger J, Ratz D, Lok ASF, Su GL. A risk score to predict the development of hepatic encephalopathy in a population-based cohort of patients with cirrhosis. Hepatology 2018; 68:1498-1507. [PMID: 29091289 DOI: 10.1002/hep.29628] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 09/18/2017] [Accepted: 10/30/2017] [Indexed: 12/25/2022]
Abstract
UNLABELLED Over 40% of patients with cirrhosis will develop hepatic encephalopathy (HE). HE is associated with decreased survival, falls, motor vehicle accidents, and frequent hospitalization. Accordingly, we aimed to develop a tool to risk-stratify patients for HE development. We studied a population-based cohort of all patients with cirrhosis without baseline HE (n = 1,979) from the Veterans Administration from Michigan, Indiana, and Ohio (January 1, 2005-December 31, 2010) using demographic, clinical, laboratory, and pharmacy data. The primary outcome was the development of HE. Risk scores were constructed with both baseline and longitudinal data (annually updated parameters) and validated using bootstrapping. The cohort had a mean age of 58.0 ± 8.3 years, 36% had hepatitis C, and 17% had ascites. Opiates, benzodiazepines, statins, and nonselective beta-blockers were taken at baseline by 24%, 13%, 17%, and 12%, respectively. Overall, 863 (43.7%) developed HE within 5 years. In multivariable models, risk factors (hazard ratio, 95% confidence interval) for HE included higher bilirubin (1.07, 1.05-1.09) and nonselective beta-blocker use (1.34, 1.09-1.64), while higher albumin (0.54, 0.48-0.59) and statin use (0.80, 0.65-0.98) were protective. Other clinical factors, including opiate and benzodiazepine use, were not predictive. The areas under the receiver operating characteristics curve for HE using the four significant variables in baseline and longitudinal models were 0.68 (0.66-0.70) and 0.73 (0.71-0.75), respectively. Model effects were validated and converted into a risk score. A score ≤0 in our longitudinal model assigns a 6% 1-year probability of HE, while a score >20 assigns a 38% 1-year risk. CONCLUSION Patients with cirrhosis can be stratified by a simple risk score for HE that accounts for changing clinical data; our data also highlight a role for statins in reducing cirrhosis complications including HE. (Hepatology 2017).
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI
| | - Neil Sengupta
- Section of Gastroenterology, University of Chicago, Chicago, IL
| | | | - David Ratz
- VA Center for Clinical Management Research, Ann Arbor, MI
| | - Anna S-F Lok
- Division of Gastroenterology and Hepatology, University of Michigan
| | - Grace L Su
- Division of Gastroenterology and Hepatology, University of Michigan.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI
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Barone M, Shahini E, Iannone A, Viggiani MT, Corvace V, Principi M, Di Leo A. Critical flicker frequency test predicts overt hepatic encephalopathy and survival in patients with liver cirrhosis. Dig Liver Dis 2018; 50:496-500. [PMID: 29530628 DOI: 10.1016/j.dld.2018.01.133] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 01/16/2018] [Accepted: 01/17/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND A critical flicker frequency (CFF) ≤39 Hz identifies cirrhotic patients with minimal hepatic encephalopathy (mHE) and predicts the risk of both overt hepatic encephalopathy (oHE) and mortality in patients with previous episodes of decompensation and/or oHE. AIMS Herein, we evaluated the effectiveness of CFF in predicting the first episode of oHE and survival in cirrhotics who had never experienced an episode of oHE. METHODS Our cohort study of 134 patients and 150 healthy subjects were examined. A CFF > 39 Hz was considered normal and pathological when ≤39 Hz. The median follow up was 36 months. RESULTS At baseline, all controls had CFF > 39 Hz. Ninety-three patients had a CFF > 39 Hz and 41 had a CFF ≤ 39 Hz. The prevalence of CFF ≤ 39 Hz significantly increased with the progression of the Child-Pugh class (p = 0.003). Moreover, the risk of oHE was increased by CFF ≤ 39 (p < 0.001, by log-rank test) [HR = 7.57; CI(3.27-17.50); p < 0.0001, by Cox model] and ammonia [HR = 1.02 CI(1.01-1.03), p = 0.0009]. Both a CFF value ≤ 39 Hz and Child-Pugh class were independent predictors of mortality by Cox model [HR = 1.97; CI(1.01-3.95), p = 0.049; HR = 3.85 CI(1.68-8.83), p = 0.003]. CONCLUSIONS CFF predicts the first episode of oHE in cirrhotics that had never experienced oHE, and predicts mortality risk. These findings suggest that cirrhotic patients should be routinely screened by CFF.
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Affiliation(s)
- Michele Barone
- Gastroenterology Unit, Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Italy
| | - Endrit Shahini
- Gastroenterology Unit, Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Italy
| | - Andrea Iannone
- Gastroenterology Unit, Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Italy
| | - Maria Teresa Viggiani
- Gastroenterology Unit, Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Italy
| | | | - Mariabeatrice Principi
- Gastroenterology Unit, Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Italy
| | - Alfredo Di Leo
- Gastroenterology Unit, Dept. of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Italy.
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Abstract
OBJECTIVES Minimal hepatic encephalopathy (HE) is common, characterized by deficits in reaction time and executive function, and strongly associated with disability and mortality. Point-of-care diagnostics performed without specialized skills or equipment are now available, albeit with limited data regarding their generalizability. METHODS We systematically reviewed MEDLINE, EMBASE, Cochrane Library, and Scopus for diagnostic studies of MHE using broad search terms including HE and minimal, covert, or the names of published diagnostic modalities. We included tests that provide results during clinical visits without requiring neuropsychologists to administer and/or special equipment. These include the Inhibitory Control Test (ICT, n=16), EncephalApp Stroop (n=3), an algorithm based on the Sickness Impact Profile (n=2), and the Animal Naming Test (ANT, n=1). RESULTS The populations enrolled in the included study were highly selected, excluding patients with recent (6-months) alcohol or psychoactive medications use. Cutoffs for MHE for each test varied widely. For the ICT, the optimal cutoffs for MHE varied by 300%, whereas healthy control performance varied >400%. The optimal cutoffs for the EncephalApp also varied (by 50%). The gold standards for MHE varied substantially between studies, and clinical outcomes were never used to develop test cutoffs. Data comparing the performance of each modality are lacking. Longitudinal data are limited but suggest that good performance on the ICT, EncephalApp or ANT is associated with reduced risk of developing overt HE. CONCLUSION The point-of-care tests for MHE are promising tools. However, additional longitudinal studies are needed in clinically representative populations of at-risk patients with cutoffs validated based on the development of clinical outcomes.
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Ridola L, Cardinale V, Riggio O. The burden of minimal hepatic encephalopathy: from diagnosis to therapeutic strategies. Ann Gastroenterol 2018; 31:151-164. [PMID: 29507462 PMCID: PMC5825945 DOI: 10.20524/aog.2018.0232] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 11/29/2017] [Indexed: 12/12/2022] Open
Abstract
Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE). It affects the performance of psychometric tests focused on attention, working memory, psychomotor speed, and visuospatial ability, as well as electrophysiological and other functional brain measures. MHE is a frequent complication of liver disease, affecting up to 80% of tested patients. By being related to falls, an impairment in fitness to drive and the development of overt HE, MHE severely affects the lives of patients and caregivers by altering their quality of life and their socioeconomic status. MHE is detected in clinically asymptomatic patients using appropriate psychometric tests and neurophysiological methods that highlight neuropsychological alterations, such as video-spatial orientation deficits, attention disorders, memory, reaction times, electroencephalogram slowing, prolongation of latency-evoked cognitive potentials, and reduction in the critical flicker frequency. Several treatments have been proposed for MHE treatment, including non-absorbable disaccharides, poorly absorbable antibiotics such as rifaximin, probiotics and branched-chain amino acids. However, because of the multiple diagnosis methods, the various endpoints of treatment trials and the variety of agents used in trials, the treatment of MHE is not currently recommended as routine, but only on a case-by-case basis.
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Affiliation(s)
- Lorenzo Ridola
- Department of Medico-Surgical Sciences and Biotechnologies (Lorenzo Ridola, Vincenzo Cardinale), Sapienza University of Rome, Italy
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies (Lorenzo Ridola, Vincenzo Cardinale), Sapienza University of Rome, Italy
| | - Oliviero Riggio
- Department of Clinical Medicine (Oliviero Riggio), Sapienza University of Rome, Italy
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Jiao Y, Wang XH, Chen R, Tang TY, Zhu XQ, Teng GJ. Predictive models of minimal hepatic encephalopathy for cirrhotic patients based on large-scale brain intrinsic connectivity networks. Sci Rep 2017; 7:11512. [PMID: 28912425 PMCID: PMC5599725 DOI: 10.1038/s41598-017-11196-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Accepted: 08/18/2017] [Indexed: 01/09/2023] Open
Abstract
We aimed to find the most representative connectivity patterns for minimal hepatic encephalopathy (MHE) using large-scale intrinsic connectivity networks (ICNs) and machine learning methods. Resting-state fMRI was administered to 33 cirrhotic patients with MHE and 43 cirrhotic patients without MHE (NMHE). The connectivity maps of 20 ICNs for each participant were obtained by dual regression. A Bayesian machine learning technique, called Graphical Model-based Multivariate Analysis, was applied to determine ICN regions that characterized group differences. The most representative ICNs were evaluated by the performance of three machine learning methods (support vector machines (SVMs), multilayer perceptrons (MLP), and C4.5). The clinical significance of these potential biomarkers was further tested. The temporal lobe network (TLN), and subcortical network (SCN), and sensorimotor network (SMN) were selected as representative ICNs. The distinct functional integration patterns of the representative ICNs were significantly correlated with behavior criteria and Child-Pugh scores. Our findings suggest the representative ICNs based on GAMMA can distinguish MHE from NMHE and provide supplementary information to current MHE diagnostic criteria.
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Affiliation(s)
- Yun Jiao
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Xun-Heng Wang
- College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou, 310018, China
| | - Rong Chen
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, School of Medicine, Baltimore, MD, 21201, USA
| | - Tian-Yu Tang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Xi-Qi Zhu
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China.,Department of Radiology, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing, 210003, China
| | - Gao-Jun Teng
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China.
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Amodio P, Montagnese S, Spinelli G, Schiff S, Mapelli D. Cognitive reserve is a resilience factor for cognitive dysfunction in hepatic encephalopathy. Metab Brain Dis 2017; 32:1287-1293. [PMID: 28573602 DOI: 10.1007/s11011-017-0032-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Accepted: 05/11/2017] [Indexed: 12/11/2022]
Abstract
Cognitive Reserve (CR) modulates symptoms of brain disease. The aim of this study was: to evaluate the effect of CR on cognition in cirrhosis and on the mismatch between cognitive and neurophysiologic assessment of hepatic encephalopathy (HE). Eighty-two outpatient patients with cirrhosis without overt HE were studied [73% males; age: 62 (54-68) (median, interq. range) yrs.; education: 8 (6-13) yrs.]. The Psychometric Hepatic Encephalopathy Score (PHES) was used as cognitive measure of HE. The spectral analysis of the electroencephalogram (EEG) was used as neurophysiologic measure of HE. The CR was assessed by the CR Index (CRI), which was measured by the CRI questionnaire (CRIq) ( http://cri.psy.unipd.it ). The PHES was altered in 28% of patients and the EEG in 41%. Altered PHES was related to the severity of cirrhosis as assessed by Child-Pugh classification (R = 0.31, p < 0.005). Patients with maintained PHES had higher CRI than those with altered PHES (CRI = 100 ± 20 vs. 88 ± 12 vs., p < 0.01), but not the ones with normal EEG compared to those with abnormal EEG (CRI = 96 ± 17 vs. 98 ± 17 vs. p: n.s.).The PHES, but not the EEG, was found to be related to the CRI (r = 0.35, p < 0.01). The mismatch between cognitive and neurophysiologic evaluation of non-overt HE (the ratio between PHES and the mean dominant frequency -MDF- of the EEG i.e., cognitive performance normalized by EEG speed) was found to be correlated to the CRI (r = 0.36, p < 0.005). CR is a resilience factor for cognitive dysfunction in cirrhosis, and is easily measurable by CRIq.
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Affiliation(s)
- Piero Amodio
- Department of Medicine-DIMED- & CIRMANMEC, University of Padua, Padova, Italy.
- Clinica Medica 5, via Giustinini 2, 35128, Padova, Italy.
| | - Sara Montagnese
- Department of Medicine-DIMED- & CIRMANMEC, University of Padua, Padova, Italy
- Clinica Medica 5, via Giustinini 2, 35128, Padova, Italy
| | | | - Sami Schiff
- Department of Medicine-DIMED- & CIRMANMEC, University of Padua, Padova, Italy
- Clinica Medica 5, via Giustinini 2, 35128, Padova, Italy
| | - Daniela Mapelli
- Department of General Psychology & CIRMANMEC, University of Padua, Padova, Italy
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Abstract
Liver cirrhosis is a public health problem and hepatic encephalopathy is one of its main complications, which can be either overt meaning thereby evident and readily diagnosed, or covert/minimal (covert hepatic encephalopathy-CHE) needing psychometric testing for diagnosis. Patients with CHE hepatic encephalopathy have deficits in multiple domains including visuospatial assessment, attention, response inhibition, working memory, along with psychomotor speed to name a few areas. These patients have poor navigational skills, get fatigued easily, and demonstrate poor insight into their driving deficits. The combination of all these leads them to have poor driving skills leading to traffic violations and crashes as demonstrated not only on the simulation testing but also in real-life driving events. There are multiple psychometric tests for CHE testing but these are not easily available and there is no uniform consensus on the gold standard testing as of yet. It does not automatically connote that all patients who test positive on driving simulation testing are unfit to drive. The physicians are encouraged to take driving history from the patient and the caregivers on every encounter and focus their counseling efforts more on patients with recent history of traffic crashes, with abnormal simulation studies and history of alcohol cessation within last year. As physicians are not trained to determine fitness to drive, their approach toward CHE patients in regards to driving restrictions should be driven by ethical principles while as respecting the local laws.
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Affiliation(s)
- Jawaid Shaw
- Department of Medicine, McGuire VA Medical Center, Richmond, Virginia, 23249. Tel: 804-675-5000 Ext 3535; Fax: 804-675-6473
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
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Moratalla A, Ampuero J, Bellot P, Gallego-Durán R, Zapater P, Roger M, Figueruela B, Martínez-Moreno B, González-Navajas JM, Such J, Romero-Gómez M, Francés R. Lactulose reduces bacterial DNA translocation, which worsens neurocognitive shape in cirrhotic patients with minimal hepatic encephalopathy. Liver Int 2017; 37:212-223. [PMID: 27388776 DOI: 10.1111/liv.13200] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 07/02/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Minimal hepatic encephalopathy is associated with poor prognosis and mortality in patients with cirrhosis. We aimed at investigating whether bacterial-DNA translocation affects hyperammonaemia and neurocognitive scores in patients with mHE according to the use of lactulose. METHODS Observational study including 72 mHE cirrhotic patients, as defined by a psychometric hepatic encephalopathy score (PHES)<-4 and/or a critical flicker frequency (CFF)<39 Hz. Bacterial-DNA, serum ammonia, pro-inflammatory cytokines and nitric oxide levels were evaluated. A second cohort of 40 lactulose-untreated patients were evaluated before and 6-month after lactulose administration (30-60 mL/d). RESULTS In the first cohort, bacterial-DNA rate was significantly higher in patients without lactulose (39% vs 23%, P=.03). Serum ammonia and inflammatory markers were significantly increased in patients with bacterial-DNA, regardless the use of lactulose, and correlated with the amount of amplified bacterial-DNA. Neurocognitive scores were significantly worse in bacterial-DNA positive vs negative patients (PHES -7.6±1.1 vs -5.5±1.0; CFF 32.5±2.6 vs 36.2±2.8, P=.01). Lactulose was associated with improved neurocognitive scores in patients without bacterial-DNA. Serum ammonia levels inversely correlated with neurocognitive scores in patients with bacterial-DNA (PHES r=-.84; CFF r=-.72, P=.001). In the second cohort, lactulose reduced bacterial-DNA translocation (36%-16%, P=.02). Neurocognitive scores were significantly improved in bacterial-DNA positive patients who cleared bacterial-DNA during the period on lactulose. Serum ammonia levels correlated with both neurocognitive scores in patients with bacterial-DNA, either before or after lactulose. CONCLUSION Bacterial-DNA translocation worsens neurocognitive scores in mHE patients and it is reduced by lactulose, enhancing the relevance of controlling bacterial antigen translocation in these patients.
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Affiliation(s)
- Alba Moratalla
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain
| | - Javier Ampuero
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain
| | - Pablo Bellot
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain
| | - Rocío Gallego-Durán
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain
| | - Pedro Zapater
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Servicio de Farmacología Clinica, Hospital General Universitario de Alicante, Alicante, Spain
| | - Manuela Roger
- Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain
| | - Blanca Figueruela
- Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain
| | - Belén Martínez-Moreno
- Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain
| | - José M González-Navajas
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain
| | - José Such
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Manuel Romero-Gómez
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Unit for the Clinical Management of Digestive Diseases, Hospital Universitario Valme de Sevilla, Sevilla, Spain
| | - Rubén Francés
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-Fundación FISABIO), Alicante, Spain.,Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain
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Abstract
Health-related quality of life (HRQOL) has become an important outcome for patients with liver cirrhosis as the number of transplantation candidates increases by the progression of treatment strategies. Falls and fall-related injuries are common in patients with liver cirrhosis and negatively affect HRQOL. Many factors increase the risk for falls such as minimal hepatic encephalopathy, psychoactive drugs, muscle strength, autonomic dysfunction, hyponatremia, and sleep problems. It is important to understand the underlying mechanisms for falls in cirrhotic patients to prevent severe injuries such as fractures, decrease healthcare costs, and improve HRQOL. Healthcare professionals, including physiotherapists and nurses, should be aware of the higher risk for falls in this population and therapeutic interventions must be designed for patients, especially those waiting on the transplant list.
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Cabrera-Pastor A, Hernandez-Rabaza V, Taoro-Gonzalez L, Balzano T, Llansola M, Felipo V. In vivo administration of extracellular cGMP normalizes TNF-α and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1β, NMDA receptors in membrane and working memory in hyperammonemic rats. Brain Behav Immun 2016; 57:360-370. [PMID: 27189036 DOI: 10.1016/j.bbi.2016.05.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/13/2016] [Accepted: 05/13/2016] [Indexed: 12/20/2022] Open
Abstract
Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The underlying mechanisms remain unknown. It also remains unknown whether extracellular cGMP improves neuroinflammation or restores spatial learning in hyperammonemic rats and if it affects differently reference and working memory. The aims of this work were: Spatial working and reference memory were assessed using the radial and Morris water mazes and neuroinflammation by immunohistochemistry and Western blot. Membrane expression of NMDA and AMPA receptor subunits was analyzed using the BS3 crosslinker. Extracellular cGMP was administered intracerebrally using osmotic minipumps. Chronic hyperammonemia induces neuroinflammation in hippocampus, with astrocytes activation and increased IL-1β, which are associated with increased NMDA receptors membrane expression and impaired working memory. This process is not affected by extracellular cGMP. Hyperammonemia also activates microglia and increases TNF-α, alters membrane expression of AMPA receptor subunits (increased GluA1 and reduced GluA2) and impairs reference memory. All these changes are reversed by extracellular cGMP. These results show that extracellular cGMP modulates spatial reference memory but not working memory. This would be mediated by modulation of TNF-α levels and of membrane expression of GluA1 and GluA2 subunits of AMPA receptors.
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Affiliation(s)
- Andrea Cabrera-Pastor
- Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Spain
| | | | - Lucas Taoro-Gonzalez
- Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Spain
| | - Tiziano Balzano
- Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Spain
| | - Marta Llansola
- Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Spain
| | - Vicente Felipo
- Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Spain.
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Subasinghe SKCE, Nandamuni Y, Ranasinghe S, Niriella MA, Miththinda JKND, Dassanayake A, de Silva AP, de Silva HJ. Association between road accidents and low-grade hepatic encephalopathy among Sri Lankan drivers with cirrhosis: a prospective case control study. BMC Res Notes 2016; 9:303. [PMID: 27296988 PMCID: PMC4907045 DOI: 10.1186/s13104-016-2106-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 05/31/2016] [Indexed: 01/18/2023] Open
Abstract
Background Low-grade hepatic encephalopathy (LGHE) comprises minimal hepatic encephalopathy (MHE) and grade 1 hepatic encephalopathy. LGHE has no or minimal recognizable symptoms but has mild cognitive and psychomotor deficits. Studies in Western countries have demonstrated increased road accidents (RA) among patients with MHE. Our objective was to investigate the association between Sri Lankan LGHE phenotype and RA. Study design and methods A prospective, case–control study was conducted in the University Medical Unit, North Colombo Teaching Hospital, Ragama Sri Lanka. Patients with cirrhosis of any aetiology, without OHE, who had been driving during previous 1 month were included. A similar number of age matched, healthy control drivers were also enrolled. Both groups were subjected to five pencil-paper based psychometric tests used to detect LGHE in cirrhotics. Self-reported RA during the previous 1 month were recorded: categorized as ‘major’ when resulted in hospitalization of the involved, ‘minor’ when there were injuries, but not serious enough for hospitalization of the involved and ‘other’ when limited to damages to vehicle or environment without injuries. Results Among 55 drivers with cirrhosis and LGHE [males, median age 53 years (range 30–60)], 7 (12.7 %) reported RA compared to 6 (10.9 %) among 55 controls [males; median age 51 years (range 30–60)]. There were no ‘major’ accidents in either group. 2/55 (3.6 %) cases and 2/55 (3.6 %) controls reported ‘minor’ accidents. Conclusion There was no increased frequency of RA among Sri Lankan drivers with LGHE compared to healthy controls. This is with the limitation of the study based only on self reported RA.
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Affiliation(s)
- S K C E Subasinghe
- Professorial Medical Unit, North Colombo Teaching Hospital, Ragama, Sri Lanka
| | - Y Nandamuni
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Thalagolla Road, PO Box 6, Ragama, GQ 11010, Sri Lanka
| | - S Ranasinghe
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Thalagolla Road, PO Box 6, Ragama, GQ 11010, Sri Lanka
| | - M A Niriella
- Professorial Medical Unit, North Colombo Teaching Hospital, Ragama, Sri Lanka. .,Department of Medicine, Faculty of Medicine, University of Kelaniya, Thalagolla Road, PO Box 6, Ragama, GQ 11010, Sri Lanka.
| | - J K N D Miththinda
- Professorial Medical Unit, North Colombo Teaching Hospital, Ragama, Sri Lanka
| | - A Dassanayake
- Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
| | - A P de Silva
- Professorial Medical Unit, North Colombo Teaching Hospital, Ragama, Sri Lanka.,Department of Medicine, Faculty of Medicine, University of Kelaniya, Thalagolla Road, PO Box 6, Ragama, GQ 11010, Sri Lanka
| | - H J de Silva
- Professorial Medical Unit, North Colombo Teaching Hospital, Ragama, Sri Lanka.,Department of Medicine, Faculty of Medicine, University of Kelaniya, Thalagolla Road, PO Box 6, Ragama, GQ 11010, Sri Lanka
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Nardone R, Taylor AC, Höller Y, Brigo F, Lochner P, Trinka E. Minimal hepatic encephalopathy: A review. Neurosci Res 2016; 111:1-12. [PMID: 27153746 DOI: 10.1016/j.neures.2016.04.009] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 04/02/2016] [Accepted: 04/23/2016] [Indexed: 02/07/2023]
Abstract
Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of patients with liver cirrhosis. By definition, MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, but obvious clinical manifestation are lacking. MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis can be achieved through neuropsychological testing, recently developed computerized psychometric tests, such as the critical flicker frequency and the inhibitory control tests, as well as neurophysiological procedures. Event related potentials can reveal subtle changes in patients with normal neuropsychological performances. Spectral analysis of electroencephalography (EEG) and quantitative analysis of sleep EEG provide early markers of cerebral dysfunction in cirrhotic patients with MHE. Neuroimaging, in particular MRI, also increasingly reveals diffuse abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. Medical treatment for MHE to date has been focused on reducing serum ammonia levels and includes non-absorbable disaccharides, probiotics or rifaximin. Liver transplantation may not reverse the cognitive deficits associated with MHE. We performed here an updated review on epidemiology, burden and quality of life, neuropsychological testing, neuroimaging, neurophysiology and therapy in subjects with MHE.
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Affiliation(s)
- Raffaele Nardone
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria; Department of Neurology, Franz Tappeiner Hospital, Italy.
| | - Alexandra C Taylor
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
| | - Yvonne Höller
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
| | - Francesco Brigo
- Department of Neurology, Franz Tappeiner Hospital, Italy; Department of Neurological and Movement Sciences, Section of Clinical Neurology, University of Verona, Italy
| | - Piergiorgio Lochner
- Department of Neurology, Saarland University Medical Center, Homburg, Germany
| | - Eugen Trinka
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
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Lauridsen MM, Thacker LR, White MB, Unser A, Sterling RK, Stravitz RT, Matherly S, Puri P, Sanyal AJ, Gavis EA, Luketic V, Siddiqui MS, Heuman DM, Fuchs M, Bajaj JS. In Patients With Cirrhosis, Driving Simulator Performance Is Associated With Real-life Driving. Clin Gastroenterol Hepatol 2016; 14:747-52. [PMID: 26601613 PMCID: PMC4836981 DOI: 10.1016/j.cgh.2015.11.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 10/13/2015] [Accepted: 11/09/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) has been linked to higher real-life rates of automobile crashes and poor performance in driving simulation studies, but the link between driving simulator performance and real-life automobile crashes has not been clearly established. Furthermore, not all patients with MHE are unsafe drivers, but it is unclear how to distinguish them from unsafe drivers. We investigated the link between performance on driving simulators and real-life automobile accidents and traffic violations. We also aimed to identify features of unsafe drivers with cirrhosis and evaluated changes in simulated driving skills and MHE status after 1 year. METHODS We performed a study of outpatients with cirrhosis (n = 205; median 55 years old; median model for end-stage liver disease score, 9.5; none with overt hepatic encephalopathy or alcohol or illicit drug use within previous 6 months) seen at the Virginia Commonwealth University and McGuire Veterans Administration Medical Center, from November 2008 through April 2014. All participants were given paper-pencil tests to diagnose MHE (98 had MHE; 48%), and 163 patients completed a standardized driving simulation. Data were collected on traffic violations and automobile accidents from the Virginia Department of Motor Vehicles and from participants' self-assessments when they entered the study, and from 73 participants 1 year later. Participants also completed a questionnaire about alcohol use and cessation patterns. The driving simulator measured crashes, run-time, road center and edge excursions, and illegal turns during navigation; before and after each driving simulation session, patients were asked to rate their overall driving skills. Drivers were classified as safe or unsafe based on crashes and violations reported on official driving records; simulation results were compared with real-life driving records. Multivariable regression analyses of real-life crashes and violations was performed using data on demographics, cirrhosis details, MHE status, and alcohol cessation patterns, at baseline and at 1 year. RESULTS Drivers categorized as unsafe had more crashes and made more illegal turns on the driving simulator than drivers categorized as safe; a higher proportion of subjects with MHE were categorized as unsafe drivers at baseline (16%) than subjects without MHE (7%; P = .02), and at 1-year follow-up (18% vs 0%; P = .02). Alcohol cessation within <1 year and illegal turns during simulator navigation tasks were associated with real-life automobile crashes and MHE in regression analysis; road edge excursions in the simulator were associated with real-life traffic violations. Personal assessment of driving skills improved after each simulation episode. CONCLUSIONS In a study of 205 patients with cirrhosis, we associated results from driving simulation tests with real-life driving records and MHE. Traffic safety counseling should focus on patients with cirrhosis who recently quit consuming alcohol and perform poorly on driving simulation.
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Affiliation(s)
- Mette M Lauridsen
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Leroy R Thacker
- Division of Biostatistics, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Melanie B White
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Ariel Unser
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Richard K Sterling
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Richard T Stravitz
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Scott Matherly
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Puneet Puri
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Edith A Gavis
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Velimir Luketic
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Muhammad S Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Douglas M Heuman
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Michael Fuchs
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Administration Medical Center, Richmond, Virginia.
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Thuluvath PJ, Nuthalapati A, Price J, Maheshwari A. Driving Performance Among Patients with Cirrhosis Who Drove to Their Outpatient Hepatology Clinic Appointments. J Clin Exp Hepatol 2016; 6:3-9. [PMID: 27194889 PMCID: PMC4862017 DOI: 10.1016/j.jceh.2015.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 09/18/2015] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Minimal hepatic encephalopathy (MHE) may adversely affect driving skills. AIMS To compare the driving performance of cirrhotic patients with and without prior HE as well as controls using a driving stimulator and to correlate psychometric testing with driving performance. METHODS Adult patients with cirrhosis, who drove to the outpatient clinic for their routine appointments underwent a battery of driving and psychometric tests including number connection tests A & B (NCT-A and NCT-B), digit symbol test (DST) and critical flicker and fusion frequency (CFF) testing. RESULTS Cirrhotics had significantly higher NCT-A (39.3 s vs. 31.2 s, P = 0.006) and DST scores (317 s vs. 245 s, P = 0.012), and lower CFF scores Fusion (33 vs. 36 Hz, P = 0.05), Flicker (35 vs. 42 Hz, P = 0.007) than controls. There was no difference in NCT-A, DST and CFF scores between patients with and without HE. Ten (22%) patients, 7 (27%) with prior HE and 3 (15%) without prior HE, had abnormal NCT-A scores (i.e. >control mean ± 2SD), and 12% of patients with prior HE had one or more driving test accidents, while controls and patients without prior HE had none. Patients with cirrhosis were more likely to hit pedestrians compared to controls (P = 0.05). There was no correlation between CFF, DST and NCTB scores with driving performance test results. CONCLUSIONS Unlike previous reports, no significant differences were noted between the patients with and without prior HE on psychometric testing, and on the driving simulator, but driving accidents were seen in only those with previous history of HE.
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Affiliation(s)
- Paul J. Thuluvath
- University of Maryland School of Medicine & Mercy Medical Center, Medicine, 301 Saint Paul Place, Baltimore, MD 21202, United States,Address for correspondence: Paul J. Thuluvath, University of Maryland School of Medicine & Mercy Medical Center, Medicine, 301 Saint Paul Place, Baltimore, MD 21202, United States.
| | | | - Jennifer Price
- Department of Medicine, University of San Francisco School of Medicine, San Francisco, CA, United States
| | - Anurag Maheshwari
- University of Maryland School of Medicine & Mercy Medical Center, Medicine, 301 Saint Paul Place, Baltimore, MD 21202, United States
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Taneja S, Dhiman RK. Can Testing the Impact of Minimal Hepatic Encephalopathy on Driving Skills be Prolific to Translate Research to Real Life Clinical Medicine? J Clin Exp Hepatol 2016; 6:1-2. [PMID: 27194888 PMCID: PMC4862144 DOI: 10.1016/j.jceh.2016.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Affiliation(s)
- Sunil Taneja
- Address for correspondence: Sunil Taneja, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.Department of Hepatology, Postgraduate Institute of Medical Education and ResearchChandigarh160012India
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Lauridsen MM, Wade JB, Bajaj JS. What Is the ethical (Not Legal) responsibility of a physician to treat minimal hepatic encephalopathy and advise patients not to drive? Clin Liver Dis (Hoboken) 2015; 6:86-89. [PMID: 31040996 PMCID: PMC6490655 DOI: 10.1002/cld.501] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Mette M. Lauridsen
- Department of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and McGuire VA Medical CenterRichmondVA
| | - James B. Wade
- Department of PsychiatryVirginia Commonwealth University and McGuire VA Medical CenterRichmondVA
| | - Jasmohan S. Bajaj
- Department of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and McGuire VA Medical CenterRichmondVA
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Bajaj JS, Heuman DM, Sterling RK, Sanyal AJ, Siddiqui M, Matherly S, Luketic V, Stravitz RT, Fuchs M, Thacker LR, Gilles H, White MB, Unser A, Hovermale J, Gavis E, Noble NA, Wade JB. Validation of EncephalApp, Smartphone-Based Stroop Test, for the Diagnosis of Covert Hepatic Encephalopathy. Clin Gastroenterol Hepatol 2015; 13:1828-1835.e1. [PMID: 24846278 PMCID: PMC4234700 DOI: 10.1016/j.cgh.2014.05.011] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 04/12/2014] [Accepted: 05/07/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Detection of covert hepatic encephalopathy (CHE) is difficult, but point-of-care testing could increase rates of diagnosis. We aimed to validate the ability of the smartphone app EncephalApp, a streamlined version of Stroop App, to detect CHE. We evaluated face validity, test-retest reliability, and external validity. METHODS Patients with cirrhosis (n = 167; 38% with overt HE [OHE]; mean age, 55 years; mean Model for End-Stage Liver Disease score, 12) and controls (n = 114) were each given a paper and pencil cognitive battery (standard) along with EncephalApp. EncephalApp has Off and On states; results measured were OffTime, OnTime, OffTime+OnTime, and number of runs required to complete 5 off and on runs. Thirty-six patients with cirrhosis underwent driving simulation tests, and EncephalApp results were correlated with results. Test-retest reliability was analyzed in a subgroup of patients. The test was performed before and after transjugular intrahepatic portosystemic shunt placement, and before and after correction for hyponatremia, to determine external validity. RESULTS All patients with cirrhosis performed worse on paper and pencil and EncephalApp tests than controls. Patients with cirrhosis and OHE performed worse than those without OHE. Age-dependent EncephalApp cutoffs (younger or older than 45 years) were set. An OffTime+OnTime value of >190 seconds identified all patients with CHE with an area under the receiver operator characteristic value of 0.91; the area under the receiver operator characteristic value was 0.88 for diagnosis of CHE in those without OHE. EncephalApp times correlated with crashes and illegal turns in driving simulation tests. Test-retest reliability was high (intraclass coefficient, 0.83) among 30 patients retested 1-3 months apart. OffTime+OnTime increased significantly (206 vs 255 seconds, P = .007) among 10 patients retested 33 ± 7 days after transjugular intrahepatic portosystemic shunt placement. OffTime+OnTime decreased significantly (242 vs 225 seconds, P = .03) in 7 patients tested before and after correction for hyponatremia (126 ± 3 to 132 ± 4 meq/L, P = .01) 10 ± 5 days apart. CONCLUSIONS A smartphone app called EncephalApp has good face validity, test-retest reliability, and external validity for the diagnosis of CHE.
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Affiliation(s)
- Jasmohan S Bajaj
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia.
| | - Douglas M Heuman
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Richard K Sterling
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Arun J Sanyal
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Muhammad Siddiqui
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Scott Matherly
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Velimir Luketic
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - R Todd Stravitz
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Michael Fuchs
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Leroy R Thacker
- Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - HoChong Gilles
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Melanie B White
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Ariel Unser
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - James Hovermale
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Edith Gavis
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Nicole A Noble
- Department of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - James B Wade
- Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
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Role of local and distant functional connectivity density in the development of minimal hepatic encephalopathy. Sci Rep 2015; 5:13720. [PMID: 26329994 PMCID: PMC4556960 DOI: 10.1038/srep13720] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 07/27/2015] [Indexed: 02/07/2023] Open
Abstract
The progression of functional connectivity (FC) patterns from non-hepatic encephalopathy (non-HE) to minimal HE (MHE) is not well known. This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated the evolution of intrinsic FC patterns from non-HE to MHE. A total of 103 cirrhotic patients (MHE, n = 34 and non-HE, n = 69) and 103 healthy controls underwent rs-fMRI scanning. Maps of distant and local FC density (dFCD and lFCD, respectively) were compared among MHE, non-HE, and healthy control groups. Decreased lFCD in anterior cingulate cortex, pre- and postcentral gyri, cuneus, lingual gyrus, and putamen was observed in both MHE and non-HE patients relative to controls. There was no difference in lFCD between MHE and non-HE groups. The latter showed decreased dFCD in inferior parietal lobule, cuneus, and medial frontal cortex relative to controls; however, MHE patients showed decreased dFCD in frontal and parietal cortices as well as increased dFCD in thalamus and caudate head relative to control and non-HE groups. Abnormal FCD values in some regions correlated with MHE patients’ neuropsychological performance. In conclusion, lFCD and dFCD were perturbed in MHE. Impaired dFCD in regions within the cortico-striato-thalamic circuit may be more closely associated with the development of MHE.
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Abstract
Both covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE) impair the ability to operate machinery. The legal responsibilities of US physicians who diagnose and treat patients with hepatic encephalopathy vary among states. It is imperative that physicians know the laws regarding reporting in their state. OHE represents a neuropsychiatric impairment that meets general reporting criteria. The medical advisory boards of the states have not identified OHE as a reportable condition. In the absence of validated diagnostic guidelines, physicians are not obligated to perform tests for CHE. There is a need for explicit guidance from professional associations regarding this issue.
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Abstract
Covert hepatic encephalopathy is a common problem in cirrhosis, affecting up to 80% of patients. It is defined as test-dependent brain dysfunction with clinical consequences in the setting of cirrhosis in patients who are not disoriented. Because it is not apparent clinically, and diagnostic testing has not been standardized, the issue has often been ignored in clinical practice. Yet, the clinical consequences are notable, including impaired quality of life, diminished work productivity, and poor driving skills.
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Affiliation(s)
- Steven L Flamm
- Liver Transplantation Program, Northwestern Feinberg School of Medicine, Arkes 19-041, 676 North Saint Clair, Chicago, IL 60611, USA.
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Gupta D, Ingle M, Shah K, Phadke A, Sawant P. Prospective comparative study of inhibitory control test and psychometric hepatic encephalopathy score for diagnosis and prognosis of minimal hepatic encephalopathy in cirrhotic patients in the Indian subcontinent. J Dig Dis 2015; 16:400-7. [PMID: 25858627 DOI: 10.1111/1751-2980.12248] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE This study aimed to determine the usefulness of inhibitory control test (ICT) for diagnosing minimal hepatic encephalopathy (MHE) in the Indian subcontinent and its correlation with the severity of liver disease and to determine its prognostic significance. METHODS Two hundred patients with cirrhosis and 200 healthy controls were enrolled. Only patients were administered with psychometric hepatic encephalopathy score (PHES), while both patients and controls were subjected to ICT. MHE was diagnosed when PHES ≤ -5. ICT was considered abnormal when the numbers of ICT lures were ≥ 14. RESULTS Overall, 135 (67.5%) patients had MHE. Mean ICT lures were higher in cirrhotic patients with MHE than those without MHE (17.27, 95% confidence interval [CI] 13.9-22.3 vs 8.79, 95% CI 6.8-12.60, P < 0.001). Target accuracy was lower in patients with MHE than in those without (84.35, 95% CI 78.5-89.8 vs 95.36, 95% CI 90.1-99.2, P < 0.001). ICT had a sensitivity of 92.6% and specificity of 78.5% with the area under the receiver operating characteristic curve of 0.855 (95% CI 0.791-0.920) for MHE. ICT was correlated with Child-Turcotte-Pugh class (P < 0.001) and the model for end-stage liver disease score (P < 0.001) and predicted the development of overt hepatic encephalopathy (OHE) and probable survival with excellent test-retest reliability. CONCLUSIONS ICT is useful for diagnosing MHE in patients with cirrhosis. It is correlated with disease severity and predicts the development of OHE and probable survival with excellent test-retest reliability.
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Affiliation(s)
- Dhaval Gupta
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College & Hospital, Mumbai, India
| | - Meghraj Ingle
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College & Hospital, Mumbai, India
| | - Kaivan Shah
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College & Hospital, Mumbai, India
| | - Aniruddha Phadke
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College & Hospital, Mumbai, India
| | - Prabha Sawant
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College & Hospital, Mumbai, India
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Agrawal S, Umapathy S, Dhiman RK. Minimal hepatic encephalopathy impairs quality of life. J Clin Exp Hepatol 2015; 5:S42-8. [PMID: 26041957 PMCID: PMC4442849 DOI: 10.1016/j.jceh.2014.11.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 11/26/2014] [Indexed: 01/18/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life.
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Affiliation(s)
| | | | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India
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Bajaj JS, Thacker LR, Leszczyszyn D, Taylor SA, Heuman DM, Raman S, Sterling RK, Siddiqui MS, Stravitz RT, Sanyal AJ, Puri P, Luketic V, Matherly S, Fuchs M, White MB, Noble NA, Unser AB, Wade JB. Effects of obstructive sleep apnea on sleep quality, cognition, and driving performance in patients with cirrhosis. Clin Gastroenterol Hepatol 2015; 13:390-397.e1. [PMID: 25158922 PMCID: PMC4339674 DOI: 10.1016/j.cgh.2014.08.028] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 07/28/2014] [Accepted: 08/06/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS In patients with cirrhosis, sleep disturbances are assumed to result from hepatic encephalopathy (HE). The effects of obstructive sleep apnea (OSA) on cognition, sleep parameters, or driving in patients with cirrhosis are unclear. METHODS We performed a cross-sectional and prospective study of 118 subjects. Subjects were assigned to 1 of 4 groups: those with OSA and cirrhosis (without hepatic encephalopathy or ascites, n = 34), those with cirrhosis only (n = 30), those with OSA only (n = 29), and those without OSA or cirrhosis (controls, n = 25). None of the OSA patients were receiving continuous positive airway pressure (CPAP) therapy. Subjects underwent cognitive testing (paper-pencil tests for psychomotor speed and attention, as well as executive function tests), sleep assessment (daytime sleepiness and night-time sleep quality), and a monotonous driving simulation (worsening lane deviations over time indicated poor performance). We also tested patients with OSA, with cirrhosis (n = 10) and without cirrhosis (n = 7), before and after CPAP therapy. RESULTS Daytime sleepiness and sleep quality were worse in subjects in the OSA groups (with or without cirrhosis) than subjects with cirrhosis alone or controls. Of subjects with only OSA, 36% had impaired psychomotor speed and attention, compared with more than 60% of subjects in both cirrhosis groups. In contrast, executive function was uniformly worse in subjects with OSA, with or without cirrhosis, than groups without OSA. Simulator performance (lane deviations) worsened over time in both OSA groups. CPAP therapy significantly increased executive function and sleep quality, and reduced simulator lane deviations and sleepiness, in OSA subjects with and without cirrhosis. After CPAP therapy, performance on the paper-pencil test improved significantly only in subjects with OSA without cirrhosis. CONCLUSIONS OSA should be considered in evaluating sleep impairment in patients with cirrhosis. In patients with cirrhosis and OSA, psychomotor speed and attention issues likely are related to cirrhosis, whereas executive function and simulator performance are affected by OSA. CPAP therapy improves executive function and simulator performance in patients with OSA, regardless of cirrhosis.
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Affiliation(s)
- Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia.
| | - Leroy R Thacker
- Department of Biostatistics, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - David Leszczyszyn
- Division of Sleep Medicine, Department of Neurology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Samuel A Taylor
- Division of Sleep Medicine, Department of Neurology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Douglas M Heuman
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Shekar Raman
- Division of Sleep Medicine, Department of Neurology, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Richard K Sterling
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Muhammad S Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - R Todd Stravitz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Puneet Puri
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Velimir Luketic
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Scott Matherly
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Michael Fuchs
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Melanie B White
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Nicole A Noble
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Ariel B Unser
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - James B Wade
- Division of Clinical Psychology, Department of Psychiatry, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, Virginia
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Galal GM, Saif-Al-Islam M, Abd Al Rahman MAAG, Ahmed NS, Abd El Rhman MM. Role of Serum Zinc Level and P300 Event Related Potential in Detection of Minimal Hepatic Encephalopathy. OPEN JOURNAL OF GASTROENTEROLOGY 2015; 05:58-65. [DOI: 10.4236/ojgas.2015.56011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Qi R, Zhang LJ, Luo S, Ke J, Kong X, Xu Q, Liu C, Lu H, Lu GM. Default mode network functional connectivity: a promising biomarker for diagnosing minimal hepatic encephalopathy: CONSORT-compliant article. Medicine (Baltimore) 2014; 93:e227. [PMID: 25501083 PMCID: PMC4602782 DOI: 10.1097/md.0000000000000227] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
To investigate the contribution of brain default mode network (DMN) in the early diagnosis of the minimal hepatic encephalopathy (MHE), the mildest form of HE from cirrhotic patients by using resting-state functional magnetic resonance imaging (rs-fMRI). This study was approved by the local ethical committee, and a written informed consent was obtained from each participant. A total of 103 cirrhotic patients (34 MHE, 69 non-HE) and 103 matched healthy controls underwent rs-fMRI scanning. The DMN correlation map was acquired by using unbiased seed-based functional connectivity analysis and compared among MHE patients, non-HE patients, and healthy controls with analysis of variance tests. Pearson correlation analysis was performed between the abnormal DMN connectivity and neuropsychological performances. Receiver operator characteristic (ROC) analysis was used to evaluate the contribution of DMN connectivity strength in the differential diagnosis between MHE and non-HE. Compared with the healthy controls, MHE and non-HE patients showed decreased DMN connectivity in medial prefrontal cortex (MPFC), left superior frontal gyrus (SFG), left temporal lobe, and bilateral middle temporal gyri (MTG). The MHE patients showed even more decreased connectivity in MPFC, left SFG, and right MTG when compared with non-HE patients. Pearson correlation analyses revealed that the decreased connectivity strength of some DMN regions correlated with patients' neuropsychological tests scores. Connectivity strength of the MPFC, right MTG, and left SFG could differentiate MHE from non-HE, of which the MPFC had the highest effectiveness (sensitivity = 81.5%, specificity = 70.4%). Cirrhotic patients had gradually reduced DMN functional connectivity from non-HE patients to MHE patients. DMN function, especially the MPFC, might be a useful imaging marker for differentiating MHE from cirrhotic patients.
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Affiliation(s)
- Rongfeng Qi
- From the Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, 210002, China (RQ, LJZ, SL, JK, XK, QX, GML); Department of Gastroenterology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, 210002, China (CL, HL)
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Patidar KR, Thacker LR, Wade JB, Sterling RK, Sanyal AJ, Siddiqui MS, Matherly SC, Stravitz RT, Puri P, Luketic VA, Fuchs M, White MB, Noble NA, Unser AB, Gilles H, Heuman DM, Bajaj JS. Covert hepatic encephalopathy is independently associated with poor survival and increased risk of hospitalization. Am J Gastroenterol 2014; 109:1757-63. [PMID: 25178701 PMCID: PMC4321782 DOI: 10.1038/ajg.2014.264] [Citation(s) in RCA: 144] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2014] [Accepted: 07/02/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Despite the high prevalence of covert hepatic encephalopathy (CHE) in cirrhotics without previous overt HE (OHE), its independent impact on predicting clinically relevant outcomes is unclear. The aim of this study was to define the impact of CHE on time to OHE, hospitalization, and death/transplant in prospectively followed up patients without previous OHE. METHODS Outpatient cirrhotics without OHE were enrolled and were administered a standard paper-pencil cognitive battery for CHE diagnosis. They were systematically followed up and time to first OHE development, hospitalization (liver-related/unrelated), and transplant/death were compared between CHE and no-CHE patients at baseline using Cox regression. RESULTS A total of 170 cirrhotic patients (55 years, 58% men, 14 years of education, Model for End-Stage Liver Disease (MELD 9), 53% hepatitis C virus (HCV), 20% nonalcoholic etiology) were included, of whom 56% had CHE. The entire population was followed up for 13.0 ± 14.6 months, during which time 30% developed their first OHE episode, 42% were hospitalized, and 19% had a composite death/transplant outcome. Age, gender, etiology, the MELD score, and CHE status were included in Cox regression models for time to first OHE episode, hospitalization, death, and composite death/transplant outcomes. On Cox regression, despite controlling for MELD, those with CHE had a higher risk of developing OHE (hazard ratio: 2.1, 95% confidence interval 1.01-4.5), hospitalization (hazard ratio: 2.5, 95% confidence interval 1.4-4.5), and death/transplant (hazard ratio: 3.4, 95% confidence interval 1.2-9.7) in the follow-up period. CONCLUSIONS Covert HE is associated with worsened survival and increased risk of hospitalization and OHE development, despite controlling for the MELD score. Strategies to detect and treat CHE may improve these risks.
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Affiliation(s)
- Kavish R. Patidar
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Leroy R. Thacker
- Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - James B. Wade
- Department of Psychiatry, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Richard K. Sterling
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Arun J. Sanyal
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Mohammad S. Siddiqui
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Scott C. Matherly
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - R. Todd Stravitz
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Puneet Puri
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Velimir A. Luketic
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Michael Fuchs
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Melanie B. White
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Nicole A. Noble
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Ariel B. Unser
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - HoChong Gilles
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Douglas M. Heuman
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
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Pu Y, Yang JH, Jing-Yang, Xu Y, Tang YM. Progress in diagnosis of minimal hepatic encephalopathy. Shijie Huaren Xiaohua Zazhi 2014; 22:3759-3765. [DOI: 10.11569/wcjd.v22.i25.3759] [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] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) is defined as HE without symptoms on clinical/neurological examination, but with deficits in some cognitive areas that can only be measured by neuropsychometric testing. MHE is associated with reduced quality of working, driving, memory, and cognitive function, and is a risk factor for the development of overt HE. Compared with non-MHE patients, MHE patients have a high mortality rate, so positive screening and intervention in patients with MHE are needed to improve the quality of life in patients with cirrhosis and reduce traffic accidents and the social burden of medical care. The current approach to the diagnosis of MHE includes mental scales (paper pencil test, computer test, or the combination of the two), electrophysiological examination, and imaging examination. Diagnosis of MHE is still a challenge now, and it is needed to establish a better clinical diagnosis standard to improve the diagnostic level.
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50
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Savlan I, Liakina V, Valantinas J. Concise review of current concepts on nomenclature and pathophysiology of hepatic encephalopathy. MEDICINA (KAUNAS, LITHUANIA) 2014; 50:75-81. [PMID: 25172600 DOI: 10.1016/j.medici.2014.06.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Accepted: 04/24/2014] [Indexed: 01/18/2023]
Abstract
Hepatic encephalopathy is a neuropsychiatric complication of liver cirrhosis the symptoms of which may vary from imperceptible to severe, invaliding, and even lethal. Minimal hepatic encephalopathy is also important because of its tendency to impair patients' cognitive functions and quality of life. The polyetiological pathogenesis of hepatic encephalopathy is intensively studied. A general consensus exists that not only excess of ammonia but also inflammatory, oxidative, and other processes are significant in the development of hepatic encephalopathy.
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Affiliation(s)
- Ilona Savlan
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Valentina Liakina
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania; Department of Biomechanics, Faculty of Mechanics, Vilnius Gediminas Technical University, Vilnius, Lithuania
| | - Jonas Valantinas
- Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
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