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Lapenna L, Merli M, Cilla M, Cossiga V, Floreani A, Invernizzi F, Toniutto P, Burra P. Sex differences in hepatic encephalopathy: addressing the knowledge gap. Dig Liver Dis 2025:S1590-8658(25)00322-6. [PMID: 40288916 DOI: 10.1016/j.dld.2025.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 04/02/2025] [Accepted: 04/06/2025] [Indexed: 04/29/2025]
Abstract
Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portal-systemic shunting with a significant impact on patients' quality of life and healthcare systems. This narrative review was elaborated by the Special Interest Group (SIG) "Gender in Hepatology" of the Italian Association for the Study of the Liver (AISF) and addresses the underexplored area of sex differences in HE, examining epidemiological trends, clinical manifestations and potential underlying mechanisms. Current evidence suggests that men and women may experience different prevalence rates, risk factors and disease progression due to biological and psychosocial factors. However, these differences remain poorly understood, with limited research on sex-specific outcomes, treatment adherence and psychological effects. Emerging data on body composition, gut microbiota and experimental models highlight potential mechanisms contributing to these differences. Given the evolving epidemiology of liver disease, this review highlights the need for targeted studies and sex-specific approaches in the management of HE to advance personalised medicine and improve outcomes.
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Affiliation(s)
- Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy.
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Marta Cilla
- Department of Internal Medicine and Hepatology, San Raffaele Hospital, Milan, Italy
| | - Valentina Cossiga
- Diseases of the Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | | | - Federica Invernizzi
- Department of Internal Medicine and Hepatology, San Raffaele Hospital, Milan, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Academic Hospital, University of Udine, Udine, Italy
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
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Sepehrinezhad A, Moghaddam NG, Shayan N, Sahab Negah S. Correlation of ammonia and blood laboratory parameters with hepatic encephalopathy: A systematic review and meta-analysis. PLoS One 2024; 19:e0307899. [PMID: 39226259 PMCID: PMC11371226 DOI: 10.1371/journal.pone.0307899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 07/12/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition. METHODS A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE. RESULTS This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients. CONCLUSIONS These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE.
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Affiliation(s)
- Ali Sepehrinezhad
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Navidreza Shayan
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sajad Sahab Negah
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
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3
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Acharya C, Shaw J, Duong N, Fagan A, McGeorge S, Wade JB, Thacker LR, Bajaj JS. QuickStroop, a Shortened Version of EncephalApp, Detects Covert Hepatic Encephalopathy With Similar Accuracy Within One Minute. Clin Gastroenterol Hepatol 2023; 21:136-142. [PMID: 34998992 PMCID: PMC9256863 DOI: 10.1016/j.cgh.2021.12.047] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Covert hepatic encephalopathy (CHE) is associated with poor outcomes but is often not diagnosed because of the time requirement. Psychometric hepatic encephalopathy score (PHES) is the gold standard against which EncephalApp Stroop has been validated. However, EncephalApp (5 runs each in "Off" and "On" state) can take up to 10 minutes. This study sought to define the smallest number of EncephalApp runs needed for comparable accuracy to the total EncephalApp using CHE on PHES as gold standard. METHODS A derivation and a validation cohort of outpatients with cirrhosis who underwent PHES (gold standard) and total EncephalApp was recruited. Data were analyzed for individual runs versus total EncephalApp time versus PHES-CHE. The derivation cohort (n = 398) was split into training (n = 299) and test (n = 99) sets. From the training data set a regression model was created with age, gender, education, and various sums of the "Off" settings. After this, a K-fold cross-validation on the test dataset was performed for both total EncephalApp time and individual Off runs and for the validation cohort. RESULTS In both cohorts, Off runs 1 + 2 had statistically similar area under the receiver operating curve and P value to the total EncephalApp for PHES-CHE prediction. The adjusted (age, gender, education) regression formula from the derivation cohort showed an accuracy of 84% to diagnose PHES-CHE in the validation cohort. Time for CHE diagnosis decreased from 203.7 (67.82) to 36.8 (11.25) seconds in the derivation and from 178.2 (46.19) to 32.9 (9.94) seconds in the validation cohort. CONCLUSIONS QuickStroop, which is completed within 1 minute, gives an equivalent ability to predict CHE on the gold standard compared with the entire EncephalApp time.
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Affiliation(s)
- Chathur Acharya
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia
| | - Jawaid Shaw
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia
| | - Nikki Duong
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia
| | - Andrew Fagan
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia
| | - Sara McGeorge
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia
| | - James B Wade
- Department of Psychiatry, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia
| | - Leroy R Thacker
- Department of Biostatistics, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia.
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Hansen MKG, Kjærgaard K, Eriksen LL, Grønkjær LL, Mikkelsen ACD, Sandahl TD, Vilstrup H, Thomsen KL, Lauridsen MME. Psychometric methods for diagnosing and monitoring minimal hepatic encephalopathy -current validation level and practical use. Metab Brain Dis 2022; 37:589-605. [PMID: 35102491 DOI: 10.1007/s11011-022-00913-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/14/2022] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is cerebral dysfunction caused by liver failure and inflicts 30-40% of patients with liver cirrhosis during their disease course. Clinically manifest HE is often preceded by minimal HE (MHE) - a clinically undetectable cognitive disturbance closely associated with loss of quality of life. Accordingly, detecting and treating MHE improve the patients' daily functioning and prevent HE-related hospital admissions. The scope of this review article is to create an overview of the validation level and usage of psychometric tests used to detect MHE: Portosystemic hepatic encephalopathy test, continuous reaction time test, Stroop EncephalApp, animal naming test, critical flicker frequency test, and inhibitory control test. Our work is aimed at the clinician or scientist who is about to decide on which psychometric test would fit best in their clinic, cohort, or study. First, we outline psychometric test validation obstacles and requirements. Then, we systematically approach the literature on each test and select well-conducted studies to answer the following questions:• Which percentage of patients with cirrhosis does the test deem as having MHE?• Is the test able to predict clinically manifest HE?• Is there a well-known test-retest variation and inter-observer variation?• Is the test able to detect a treatment response?• Is the test result affected by age, educational level, gender, or comorbidities?
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Affiliation(s)
- Mads Kingo Guldberg Hansen
- Department of Gastroenterology and Hepatology, University Hospital South Denmark, Finsensgade 35, 6700, Esbjerg, Denmark.
| | - Kristoffer Kjærgaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark
| | - Lotte Lindgreen Eriksen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark
| | - Lea Ladegaard Grønkjær
- Department of Gastroenterology and Hepatology, University Hospital South Denmark, Finsensgade 35, 6700, Esbjerg, Denmark
| | - Anne Catrine Daugaard Mikkelsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark
| | - Thomas Damgaard Sandahl
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark
| | - Karen Louise Thomsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark
| | - Mette Munk Enok Lauridsen
- Department of Gastroenterology and Hepatology, University Hospital South Denmark, Finsensgade 35, 6700, Esbjerg, Denmark
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Özbaş B, Keskin O, Hecker H, Karahan I, Özbaş C, Kalkan Ç, Kartal A, Önder FO, Öncü BK, Gençdal G, Akyildiz M, Günşar F, Idilman R, Weissenborn K, Özütemiz Ö, Yurdaydin C. Determination of Turkish norms of psychometric tests for diagnosing minimal hepatic encephalopathy and proposal of a high sensitive screening test battery. Hepatol Int 2021; 15:1442-1455. [PMID: 34085147 DOI: 10.1007/s12072-021-10207-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 04/30/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Psychometric hepatic encephalopathy score (PHES) needs local standardization. AIMS This study aimed at standardizing PHES for Turkish patients and compare them with German norms; to determine minimal hepatic encephalopathy (mHE) prevalence with two different methods [PHES battery and Critical Flicker Frequency (CFF)] and to assess whether sub-tests of the battery can be used for screening for mHE. METHODS Healthy volunteers (n = 816; 400 male) and cirrhotics (n = 124; 58 male) were included. For mHE diagnosis PHES score threshold was set at ≤ - 5 points and that of CFF at < 39 Hz. For comparing German and Turkish norms, datasets were combined. Multiple backward procedure was applied to assess effects of age, sex and education on single tests of the battery. Receiver operating characteristic (ROC) curves were created for assessing diagnostic capabilities of subtests of the battery. RESULTS PHES norms for Turks were developed. MHE prevalence in compensated cirrhotics was 29.8% and 27.4% with PHES and CFF tests, respectively, with low compatibility (kappa coefficient 0.389); mHE prevalence decreased to 16% when both tests were combined. Turks performed worse vs Germans in the digit symbol (DS) and serial dotting (SD) subtests but performed better in other subtests. In ROC analyzes of subtests, the combination of DS + SD tests achieved an AUROC of 0.974 versus PHES. CONCLUSIONS Use of two methods for diagnosing mHE is important for research purposes. From a clinical perspective, sensitivity with acceptable specificity may suffice for screening instruments for mHE. Combined use of DS and SD subtests of the PHES battery appears suitable for this purpose.
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Affiliation(s)
- Burak Özbaş
- Department of Internal Medicine, Ankara University Medical School, Ankara, Turkey
| | - Onur Keskin
- Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey
| | - Hartmut Hecker
- Department of Biometrics, Hannover Medical School, Hannover, Germany
| | - Irfan Karahan
- Department of Internal Medicine, Ankara University Medical School, Ankara, Turkey
| | - Cansu Özbaş
- Department of Public Health, Gazi University Medical School, Ankara, Turkey
| | - Çağdaş Kalkan
- Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey
| | - Aysun Kartal
- Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey
| | - Fatih Oğuz Önder
- Department of Internal Medicine, Ankara University Medical School, Ankara, Turkey
| | - Burcu Kahveci Öncü
- Department of Psychiatry, Ankara University Medical School, Ankara, Turkey
| | - Genco Gençdal
- Department of Gastroenterology and Hepatology, Koç University Medical School, Istanbul, Turkey
| | - Murat Akyildiz
- Department of Gastroenterology and Hepatology, Koç University Medical School, Istanbul, Turkey
| | - Fulya Günşar
- Department of Gastroenterology, Ege University Medical School, Izmir, Turkey
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey
| | | | - Ömer Özütemiz
- Department of Gastroenterology, Ege University Medical School, Izmir, Turkey
| | - Cihan Yurdaydin
- Department of Gastroenterology, Ankara University Medical School, Ankara, Turkey.
- Department of Gastroenterology and Hepatology, Koç University Medical School, Istanbul, Turkey.
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Kim YK, Song J. Therapeutic Applications of Resveratrol in Hepatic Encephalopathy through Its Regulation of the Microbiota, Brain Edema, and Inflammation. J Clin Med 2021; 10:jcm10173819. [PMID: 34501267 PMCID: PMC8432232 DOI: 10.3390/jcm10173819] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/22/2021] [Accepted: 08/24/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatic encephalopathy is a common complication in patients with liver cirrhosis and portosystemic shunting. Patients with hepatic encephalopathy present a variety of clinical features, including neuropsychiatric manifestations, cognitive dysfunction, impaired gut barrier function, hyperammonemia, and chronic neuroinflammation. These pathogeneses have been linked to various factors, including ammonia-induced oxidative stress, neuronal cell death, alterations in the gut microbiome, astrocyte swelling, and blood-brain barrier disruptions. Many researchers have focused on identifying novel therapeutics and prebiotics in the hope of improving the treatment of these conditions. Resveratrol is a natural polyphenic compound and is known to exert several pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Recent studies suggest that resveratrol contributes to improving the neuropathogenic effects of liver failure. Here, we review the current evidence describing resveratrol's effects in neuropathogenesis and its impact on the gut-liver axis relating to hepatic encephalopathy. We highlight the hypothesis that resveratrol exerts diverse effects in hepatic encephalopathy and suggest that these effects are likely mediated by changes to the gut microbiota, brain edema, and neuroinflammation.
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Affiliation(s)
- Young-Kook Kim
- Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Korea;
| | - Juhyun Song
- Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Korea
- Correspondence: ; Tel.: +82-61-379-2706; Fax: +82-61-375-5834
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Le H, Thukral S, Devane AM, Saddekni S, Varma RK. Endovascular Management of Hepatic Encephalopathy. JOURNAL OF CLINICAL INTERVENTIONAL RADIOLOGY ISVIR 2021. [DOI: 10.1055/s-0041-1730869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
AbstractTransjugular intrahepatic portosystemic shunt (TIPS) and spontaneous portosystemic shunts (SPSS) may lead to new or worsening hepatic encephalopathy (HE), especially in patients with chronic liver disease. Patients with medically refractory HE (rHE) may benefit from endovascular interventions. In this review, we briefly describe the post-TIPS and SPSS vascular anatomy, pathophysiology, classification, factors associated with HE, and the medical management of HE. In addition, we will discuss current endovascular techniques for HE management, their advantages, disadvantages, and review of the current literature.
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Affiliation(s)
- Hieu Le
- University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
| | - Siddhant Thukral
- Department – School of Medicine, University of Missouri – Kansas City School of Medicine, Kansas City, Missouri, United States
| | - A. Michael Devane
- University of South Carolina School of Medicine Greenville, Prisma Health, Greenville, South Carolina, United States
| | - Souheil Saddekni
- Department of Radiology, Division of Interventional Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
| | - Rakesh K. Varma
- Department of Radiology, Division of Interventional Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
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Zeng X, Zhang LY, Liu Q, Lu CH, Wei J, Shi ZW, Huang WR, Qu LH, Xu F, Wang XH, Shi PM, Tan Y, Tan W, Yuan ZL, Xia CY, Liu YL, Xie WF. Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy. Clin Gastroenterol Hepatol 2020; 18:1618-1625.e7. [PMID: 31712074 DOI: 10.1016/j.cgh.2019.11.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). METHODS We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. RESULTS We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. CONCLUSION Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.
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Affiliation(s)
- Xin Zeng
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Li-Yuan Zhang
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Qing Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
| | - Cui-Hua Lu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Jue Wei
- Department of Gastroenterology, Tong Ren hospital, Jiaotong University, Shanghai, China
| | - Zhi-Wen Shi
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Rong Huang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Li-Hong Qu
- Department of Infectious Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fei Xu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiao-Hang Wang
- Department of Endoscopy, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Pei-Mei Shi
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yu Tan
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei Tan
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zong-Li Yuan
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Chun-Yan Xia
- Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Lan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
| | - Wei-Fen Xie
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
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Abstract
Minimal hepatic encephalopathy, previously called subclinical hepatic encephalopathy, represents the earliest and mildest form of hepatic encephalopathy. It is the most under-recognized and underdiagnosed form of hepatic encephalopathy. Although there is no diagnostic gold standard, validated testing modalities have been devised to detect this neurocognitive complication. The newest developments include medically related apps for smartphones or tablets that can be easily used to diagnose and monitor minimal hepatic encephalopathy. Although recognition of this neurocognitive impairment can be challenging, early detection is paramount with the discovery of an association with worse clinical outcomes in patients diagnosed with minimal hepatic encephalopathy.
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Affiliation(s)
- Briette Verken Karanfilian
- Department of Internal Medicine, Rutgers- Robert Wood Johnson Medical School, 125 Paterson Street, CAB 7302, New Brunswick, NJ 08901, USA
| | - Taeyang Park
- Department of Internal Medicine, Rutgers- Robert Wood Johnson Medical School, 125 Paterson Street, CAB 7302, New Brunswick, NJ 08901, USA.
| | - Frank Senatore
- Department of Gastroenterology and Hepatology, Rutgers- Robert Wood Johnson Medical School, 125 Paterson Street, CAB 7302, 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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Luo M, Ma P, Li L, Cao WK. Advances in psychometric tests for screening minimal hepatic encephalopathy: From paper-and-pencil to computer-aided assessment. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:398-407. [PMID: 31060994 DOI: 10.5152/tjg.2019.18226] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Minimal hepatic encephalopathy (MHE) is a major neuropsychiatric complication of liver cirrhosis and portosystemic shunting. Although MHE produces a spectrum of cognitive impairments in the domains of short-term attention, working memory, and executive function, it generally does not present with obvious clinical manifestation on conventional assessments. Paper-and-pencil psychometric tests, such as the psychometric hepatic encephalopathy score and the repeatable battery for the assessment of neuropsychological status, are recommended to diagnose MHE. However, these tests are neither rapid nor convenient to use in practice. To facilitate repeated testing in clinic and follow-up, computer-aided psychometric tests, such as the scan test, Cognitive Drug Research assessment battery, inhibitory control test, EncephalApp Stroop App, and critical flicker frequency, have been used to screen for MHE among patients with liver cirrhosis. The aim of this review was to describe the progression from the utility of paper-and-pencil to computer-aided psychometric tests for MHE screening in clinical practice.
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Affiliation(s)
- Ming Luo
- Department of Gastroenterology, Ningxia People's Hospital, Ningxia, China
| | - Ping Ma
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Lei Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Wu-Kui Cao
- Tianjin Liver Disease Institute, Tianjin Second People's Hospital, Tianjin, China
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11
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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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12
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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: 26] [Impact Index Per Article: 3.7] [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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Cook NA, Kim JU, Pasha Y, Crossey MM, Schembri AJ, Harel BT, Kimhofer T, Taylor-Robinson SD. A pilot evaluation of a computer-based psychometric test battery designed to detect impairment in patients with cirrhosis. Int J Gen Med 2017; 10:281-289. [PMID: 28919805 PMCID: PMC5593417 DOI: 10.2147/ijgm.s140197] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Psychometric testing is used to identify patients with cirrhosis who have developed hepatic encephalopathy (HE). Most batteries consist of a series of paper-and-pencil tests, which are cumbersome for most clinicians. A modern, easy-to-use, computer-based battery would be a helpful clinical tool, given that in its minimal form, HE has an impact on both patients' quality of life and the ability to drive and operate machinery (with societal consequences). AIM We compared the Cogstate™ computer battery testing with the Psychometric Hepatic Encephalopathy Score (PHES) tests, with a view to simplify the diagnosis. METHODS This was a prospective study of 27 patients with histologically proven cirrhosis. An analysis of psychometric testing was performed using accuracy of task performance and speed of completion as primary variables to create a correlation matrix. A stepwise linear regression analysis was performed with backward elimination, using analysis of variance. RESULTS Strong correlations were found between the international shopping list, international shopping list delayed recall of Cogstate and the PHES digit symbol test. The Shopping List Tasks were the only tasks that consistently had P values of <0.05 in the linear regression analysis. CONCLUSION Subtests of the Cogstate battery correlated very strongly with the digit symbol component of PHES in discriminating severity of HE. These findings would indicate that components of the current PHES battery with the international shopping list tasks of Cogstate would be discriminant and have the potential to be used easily in clinical practice.
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Affiliation(s)
- Nicola A Cook
- Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Jin Un Kim
- Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Yasmin Pasha
- Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Mary Me Crossey
- Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Adrian J Schembri
- Cogstate, Inc., New Haven, CT, USA.,Department of Psychology, Royal Melbourne Institute of Technology University, Melbourne, VIC, Australia
| | - Brian T Harel
- Cogstate, Inc., New Haven, CT, USA.,Child Study Center, Yale University, New Haven, CT, USA
| | - Torben Kimhofer
- Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK
| | - Simon D Taylor-Robinson
- Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, London, UK
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Morgan MY, Amodio P, Cook NA, Jackson CD, Kircheis G, Lauridsen MM, Montagnese S, Schiff S, Weissenborn K. Qualifying and quantifying minimal hepatic encephalopathy. Metab Brain Dis 2016; 31:1217-1229. [PMID: 26412229 DOI: 10.1007/s11011-015-9726-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2015] [Accepted: 09/01/2015] [Indexed: 12/11/2022]
Abstract
Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is no gold standard for the diagnosis of this syndrome. As these patients have, by definition, no recognizable clinical features of brain dysfunction, the primary prerequisite for the diagnosis is careful exclusion of clinical symptoms and signs. A large number of psychometric tests/test systems have been evaluated in this patient group. Of these the best known and validated is the Portal Systemic Hepatic Encephalopathy Score (PHES) derived from a test battery of five paper and pencil tests; normative reference data are available in several countries. The electroencephalogram (EEG) has been used to diagnose hepatic encephalopathy since the 1950s but, once popular, the technology is not as accessible now as it once was. The performance characteristics of the EEG are critically dependent on the type of analysis undertaken; spectral analysis has better performance characteristics than visual analysis; evolving analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test together with one of the validated alternative techniques or the EEG. Minimal hepatic encephalopathy has a detrimental effect on the well-being of patients and their care-givers. It responds well to treatment with resolution of test abnormalities and the associated detrimental effects on quality of life, liver-related mortality and morbidity. Patients will only benefit in this way if they can be effectively diagnosed. Corporate efforts and consensus agreements are needed to develop effective diagnostic algorithms.
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Affiliation(s)
- Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, Rowland Hill Street, London, NW32PF, UK.
| | - Piero Amodio
- Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy
| | - Nicola A Cook
- Department of Medicine, St Mary's Hospital Campus, Imperial College, London, W2 1NY, UK
| | - Clive D Jackson
- Department of Neurophysiology, Royal Free Hospital, Royal Free London NHS Foundation Trust, Pond Street, London, Hampstead, NW3 2QG, UK
| | - Gerald Kircheis
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Mette M Lauridsen
- Department of Gastroenterology, Hospital of South West Jutland, Finsensgade 35, 6700, Esbjerg, Denmark
| | - Sara Montagnese
- Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy
| | - Sami Schiff
- Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy
| | - Karin Weissenborn
- Department of Neurology, Hannover Medical School, 30623, Hannover, Germany
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Osman MA, Sayed MM, Mansour KA, Saleh SA, Ibrahim WA, Abdelhakam SM, Bahaa M, Yousry WA, Elbaz HS, Mikhail RN, Hassan AM, Elsayed EH, Mahmoud DA. Reversibility of minimal hepatic encephalopathy following liver transplantation in Egyptian cirrhotic patients. World J Hepatol 2016; 8:1279-1286. [PMID: 27843538 PMCID: PMC5084057 DOI: 10.4254/wjh.v8.i30.1279] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Accepted: 09/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the reversibility of minimal hepatic encephalopathy (MHE) following liver transplantation (LT) in Egyptian cirrhotic patients.
METHODS This prospective study included twenty patients with biopsy-proven liver cirrhosis listed for LT and twenty age- and sex-matched healthy control subjects. All underwent neuro-psychiatric examination, laboratory investigations, radiological studies and psychometric tests including trail making test A (TMT A), TMT B, digit symbol test and serial dotting test. The psychometric hepatic encephalopathy score (PHES) was calculated for patients to diagnose MHE. Psychometric tests were repeated six months following LT in the cirrhotic patient group.
RESULTS Before LT, psychometric tests showed highly significant deficits in cirrhotic patients in comparison to controls (P < 0.001). There was a statistically significant improvement in test values in the patient group after LT; however, their values were still significantly worse than those of the controls (P < 0.001). The PHES detected MHE in 16 patients (80%) before LT with a median value of -7 ± 3.5. The median PHES value was significantly improved following LT, reaching -4.5 ± 5 (P < 0.001), and the number of patients with MHE decreased to 11 (55%). The pre-transplant model for end-stage liver disease (MELD) score ≥ 15 was significantly related to the presence of post-transplant MHE (P = 0.005). More patients in whom reversal of MHE was observed had a pre-transplant MELD score < 15.
CONCLUSION Reversal of MHE in cirrhotic patients could be achieved by LT, especially in those with a MELD score < 15.
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Lee Y, Kim C, Suk KT, Choi HC, Bang CS, Yoon JH, Baik GH, Kim DJ, Jang MU, Sohn JH. Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis. Metab Brain Dis 2016; 31:369-376. [PMID: 26563125 DOI: 10.1007/s11011-015-9761-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 11/06/2015] [Indexed: 12/11/2022]
Abstract
As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 ± 3.6 and 17.8 ± 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 ± 2.6 and 17.3 ± 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 ± 6.9 and 12.7 ± 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 ± 1.9 and 26.2 ± 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23%, 26%, and 26% and 33%, 43%, and 49% in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE.
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Affiliation(s)
- Yunhyeong Lee
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Chulho Kim
- Department of Neurology, Hallym University College of Medicine, Chuncheon, South Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
- Department of Medicine, Columbia University, New York, NY, USA
- Department in Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon,, Gyo-dong, 200-704, South Korea
| | - Hui Chul Choi
- Department of Neurology, Hallym University College of Medicine, Chuncheon, South Korea.
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Gyo-dong, 200-704, South Korea.
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Jai Hoon Yoon
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Min Uk Jang
- Department of Neurology, Hallym University College of Medicine, Chuncheon, South Korea
| | - Jong Hee Sohn
- Department of Neurology, Hallym University College of Medicine, Chuncheon, South Korea
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Liu A, Perumpail RB, Kumari R, Younossi ZM, Wong RJ, Ahmed A. Advances in cirrhosis: Optimizing the management of hepatic encephalopathy. World J Hepatol 2015; 7:2871-2879. [PMID: 26692331 PMCID: PMC4678373 DOI: 10.4254/wjh.v7.i29.2871] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 10/24/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatic encephalopathy (HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE (CHE) and overt HE (OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis.
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Weissenborn K. Diagnosis of minimal hepatic encephalopathy. J Clin Exp Hepatol 2015; 5:S54-9. [PMID: 26041959 PMCID: PMC4442856 DOI: 10.1016/j.jceh.2014.06.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Accepted: 06/05/2014] [Indexed: 12/12/2022] Open
Abstract
Minimal hepatic encephalopathy (mHE) has significant impact upon a liver patient's daily living and health related quality of life. Therefore a majority of clinicians agree that mHE should be diagnosed and treated. The optimal means for diagnosing mHE, however, is controversial. This paper describes the currently most frequently used methods-EEG, critical flicker frequency, Continuous Reaction time Test, Inhibitory Control Test, computerized test batteries such as the Cognitive Drug Research test battery, the psychometric hepatic encephalopathy score (PHES) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)-and their pros and cons.
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Key Words
- CDR, cognitive drug research
- CFF, critical flicker frequency
- CRT, continuous reaction time test
- EEG, electroencephalography
- ICT, inhibitory control test
- PHES, psychometric hepatic encephalopathy score
- PSE, portosystemic encephalopathy
- RBANS, repeatable battery for the assessment of neuropsychological status
- TA, target accuracy
- WL, weighted lures
- diagnostic means
- diagnostic use
- mHE, minimal hepatic encephalopathy
- minimal hepatic encephalopathy
- sensitivity
- specificity
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Affiliation(s)
- Karin Weissenborn
- Address for correspondence: Karin Weissenborn, Department of Neurology, Hannover Medical School, 30623 Hannover, Germany. Tel.: +49 511 532 2339; fax: +49 511 532 3115.
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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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Razek AAKA, Abdalla A, Ezzat A, Megahed A, Barakat T. Minimal hepatic encephalopathy in children with liver cirrhosis: diffusion-weighted MR imaging and proton MR spectroscopy of the brain. Neuroradiology 2014; 56:885-91. [PMID: 25060166 DOI: 10.1007/s00234-014-1409-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 07/16/2014] [Indexed: 01/04/2023]
Abstract
INTRODUCTION The aim of this work was to detect minimal hepatic encephalopathy (minHE) in children with diffusion-weighted MR imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) of the brain. METHODS Prospective study conducted upon 30 consecutive children (age range 6-16 years, 21 boys and 9 girls) with liver cirrhosis and 15 age- and sex-matched healthy control children. Patients with minHE (n = 17) and with no minHE (n = 13) groups and control group underwent DWI, 1H-MRS, and neuropsychological tests (NPTs). The glutamate or glutamine (Glx), myoinositol (mI), choline (Cho), and creatine (Cr) at the right ganglionic region were determined at 1H-MRS. The apparent diffusion coefficient (ADC) value and metabolic ratios of Glx/Cr, mI/Cr, and Cho/Cr were calculated. RESULTS There was elevated ADC value and Glx/Cr and decreased mI/CI and Ch/Cr in patients with minHE compared to no minHE and control group. There was significant difference between minHE, no minHE, and control group in the ADC value (P = 0.001 for all groups), GLx/Cr (P = 0.001 for all groups), mI/Cr (P = 0.004, 0.001, and 0.001, respectively), Ch/Cr (P = 0.001 for all groups), and full-scale IQ of NPT (P = 0.001, 0.001, and 0.143, respectively). The NPT of minHE had negative correlation with ADC value (r = -0.872, P = 0.001) and GLx/Cr (r = -0.812, P = 0.001) and positive correlation with mI/Cr (r = 0.732, P = 0.001). CONCLUSION DWI and 1H-MRS are imaging modalities that can detect minHE in children with liver cirrhosis and correlate well with parameters of NPT.
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Merli M, Lucidi C, Pentassuglio I, Giannelli V, Giusto M, Di Gregorio V, Pasquale C, Nardelli S, Lattanzi B, Venditti M, Riggio O. Increased risk of cognitive impairment in cirrhotic patients with bacterial infections. J Hepatol 2013; 59:243-50. [PMID: 23523580 DOI: 10.1016/j.jhep.2013.03.012] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Revised: 03/02/2013] [Accepted: 03/06/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS A causal relationship between infection, systemic inflammation, and hepatic encephalopathy (HE) has been suggested in cirrhosis. No study, however, has specifically examined, in cirrhotic patients with infection, the complete pattern of clinical and subclinical cognitive alterations and its reversibility after resolution. Our investigation was aimed at describing the characteristics of cognitive impairment in hospitalized cirrhotic patients, in comparison with patients without liver disease, with and without infection. METHODS One hundred and fifty cirrhotic patients were prospectively enrolled. Eighty-one patients without liver disease constituted the control group. Bacterial infections and sepsis were actively searched in all patients independently of their clinical evidence at entry. Neurological and psychometric assessment was performed at admission and in case of nosocomial infection. The patients were re-evaluated after the resolution of the infection and 3months later. RESULTS Cognitive impairment (overt or subclinical) was recorded in 42% of cirrhotics without infection, in 79% with infection without SIRS and in 90% with sepsis. The impairment was only subclinical in controls and occurred only in patients with sepsis (42%). Multivariate analysis selected infection as the only independent predictor of cognitive impairment (OR 9.5; 95% CI 3.5-26.2; p=0.00001) in cirrhosis. The subclinical alterations detected by psychometric tests were also strongly related to the infectious episode and reversible after its resolution. CONCLUSIONS Infections are associated with a worse cognitive impairment in cirrhotics compared to patients without liver disease. The search and treatment of infections are crucial to ameliorate both clinical and subclinical cognitive impairment of cirrhotic patients.
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Affiliation(s)
- Manuela Merli
- Gastroenterology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
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Chepkova AN, Sergeeva OA, Haas HL. Alterations of corticostriatal plasticity by ammonium and rescue by green tea polyphenols. Arch Biochem Biophys 2013; 536:176-82. [DOI: 10.1016/j.abb.2013.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 01/31/2013] [Accepted: 02/05/2013] [Indexed: 01/22/2023]
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Kappus MR, Bajaj JS. Covert hepatic encephalopathy: not as minimal as you might think. Clin Gastroenterol Hepatol 2012; 10:1208-19. [PMID: 22728384 DOI: 10.1016/j.cgh.2012.05.026] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Revised: 05/30/2012] [Accepted: 05/31/2012] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is a serious neuropsychiatric and neurocognitive complication of acute and chronic liver disease. Symptoms are often overt (confusion, disorientation, ataxia, or coma) but can also be subtle (difficulty with cognitive abilities such as executive decision-making and psychomotor speed). There is consensus that HE is characterized as a spectrum of neuropsychiatric symptoms in the absence of brain disease, ranging from overt HE (OHE) to minimal HE (MHE). The West Haven Criteria are most often used to grade HE, with scores ranging from 0-4 (4 being coma). However, it is a challenge to diagnose patients with MHE or grade 1 HE; it might be practical to combine these entities and name them covert HE for clinical use. The severity of HE is associated with the stage of liver disease. Although the pathologic mechanisms of HE are not well understood, they are believed to involve increased levels of ammonia and inflammation, which lead to low-grade cerebral edema. A diagnosis of MHE requires dedicated psychometric tests and neurophysiological techniques rather than a simple clinical assessment. Although these tests can be difficult to perform in practice, they are cost effective and important; the disorder affects patients' quality of life, socioeconomic status, and driving ability and increases their risk for falls and the development of OHE. Patients with MHE are first managed by excluding other causes of neurocognitive dysfunction. Therapy with gut-specific agents might be effective. We review management strategies and important areas of research for MHE and covert HE.
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Affiliation(s)
- Matthew R Kappus
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia 23249, USA
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Kappus MR, Bajaj JS. Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests). Clin Liver Dis 2012; 16:43-55. [PMID: 22321464 PMCID: PMC3312030 DOI: 10.1016/j.cld.2011.12.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Minimal hepatic encephalopathy (MHE) is associated with a high risk of development of overt hepatic encephalopathy, impaired quality of life, and driving accidents. The detection of MHE requires specialized testing because it cannot, by definition, be diagnosed on standard clinical examination. Psychometric and neurophysiologic techniques are often used to test for MHE. Paper-pencil psychometric batteries and computerized tests have proved useful in diagnosing MHE and predicting its outcomes. Neurophysiologic tests also provide useful information. The diagnosis of MHE is an important issue for clinicians and patients alike. Testing strategies depend on the normative data available, patient comfort, and local expertise.
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Affiliation(s)
- Matthew R Kappus
- Division of Gastroenterology, Hepatology and Nutrition, McGuire VA Medical Center, Virginia Commonwealth University, 1201 Broad Rock Boulevard, Richmond, VA 23249, USA
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Moscucci F, Nardelli S, Pentassuglio I, Pasquale C, Ridola L, Merli M, Riggio O. Previous overt hepatic encephalopathy rather than minimal hepatic encephalopathy impairs health-related quality of life in cirrhotic patients. Liver Int 2011; 31:1505-10. [PMID: 22093325 DOI: 10.1111/j.1478-3231.2011.02598.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2011] [Accepted: 06/30/2011] [Indexed: 12/24/2022]
Abstract
BACKGROUND It has been observed that overt hepatic encephalopathy (HE) is accompanied by a persistent cognitive defect, suggesting that HE may not be fully reversible. The health-related quality-of-life (HRQoL) has been shown to be impaired by cirrhosis, and, according to some reports, influenced by minimal HE. Little is known about the effect of previous HE on HRQoL. AIM To investigate the relative impact of previous HE and minimal HE on HRQoL in a group of consecutively hospitalized cirrhotic patients. PATIENTS/METHODS Seventy five consecutive cirrhotic patients were evaluated using the Psychometric HE Score (PHES) and simplified Psychometric HE Score (SPHES) to detect the presence of minimal HE and using SF-36 to assess the HRQoL, both corrected for age and education. Eighteen of them had previous bouts of overt HE. RESULTS Minimal HE was significantly more frequent in patients with previous HE than in those without (p < 0.001), independently on the method used for the diagnosis (PHES or SPHES). A deeper impairment in several domains of SF-36 was observed in patients with previous bouts of overt HE, in those with ascites, as well as in those with decompensated cirrhosis. At multivariate analysis, ascites, MELD score and previous HE were independently related to the mental-component-summary (MCS) of SF-36, whereas ascites was the only variable independently associated with the physical-component-summary (PCS) of SF-36. Minimal HE (independently on the method used for its diagnosis) impaired only one domain of SF-36. CONCLUSIONS These data suggest that previous bouts of HE, despite their complete clinical resolution, play an independent role in producing a persistent impairment in HRQoL of cirrhotics.
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Affiliation(s)
- Federica Moscucci
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
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