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Wu S, Li L, Xi H, Wu X, He Y, Sun X, Wu L. Bibliometrics and knowledge mapping of the pathogenesis of hepatic encephalopathy in patients with liver cirrhosis. Heliyon 2024; 10:e34330. [PMID: 39145014 PMCID: PMC11320160 DOI: 10.1016/j.heliyon.2024.e34330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 07/06/2024] [Accepted: 07/08/2024] [Indexed: 08/16/2024] Open
Abstract
Background Hepatic encephalopathy is a common and serious complication of decompensated cirrhosis. It can considerably contribute to economic burden and impaired quality of life. However, its pathogenesis remains unclear. Method In this study, we aimed to visually analyse the research status and development trends in hepatic encephalopathy pathogenesis using bibliometrics and knowledge mapping. Information regarding publications between 1978 and 2022 were obtained from the Web of Science Core Collection. CiteSpace was used to analyse and present data by year, author, institution, country, journal, reference, and keyword. Results A total of 1578 publications on hepatic encephalopathy pathogenesis in patients with cirrhosis were retrieved from Web of Science Core Collection. A gradual increasing trend in annual publications has occurred. The collaborative network analysis results suggest the United States of America, the University of London, and Bajaj, Jasmohan S as the most influential country, institution, and author, respectively, in this research field. Notably, China appeariiuis to be the most promising country. Research on 'hepatology' garners the most significant papers in the field. Combined with reference co-citation and keyword co-occurrence analyses, we found that ammonia metabolism, gut microbiota, sarcopenia, and trace elements will become future research frontiers that are likely to be explored for a considerable length of time. Conclusion Future research directions in HE pathogenesis may target modulating the ammonia metabolism, the gut microbiota, sarcopenia, and trace elements.
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Affiliation(s)
- Shiyan Wu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China
- Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610031, Sichuan Province, China
| | - Lu Li
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China
- Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610031, Sichuan Province, China
| | - Heng Xi
- Department of Pharmacy, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610031, Sichuan Province, China
| | - Xiaoping Wu
- Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610031, Sichuan Province, China
| | - Yumei He
- North Sichuan Medical College, Nanchong, 623300, Sichuan Province, China
| | - Xiaobin Sun
- Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610031, Sichuan Province, China
| | - Liping Wu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China
- Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610031, Sichuan Province, China
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Ehrenbauer AF, Egge JFM, Gabriel MM, Tiede A, Dirks M, Witt J, Wedemeyer H, Maasoumy B, Weissenborn K. Comparison of 6 tests for diagnosing minimal hepatic encephalopathy and predicting clinical outcome: A prospective, observational study. Hepatology 2024; 80:389-402. [PMID: 38349709 DOI: 10.1097/hep.0000000000000770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 01/10/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND AND AIMS Current guidelines recommend the assessment for minimal HE in patients with liver cirrhosis. Various efforts were made to find tools that simplify the diagnosis. Here, we compare the 6 most frequently used tests for their validity and their predictive value for overt hepatic encephalopathy (oHE), rehospitalization, and death. APPROACH AND RESULTS One hundred thirty-two patients with cirrhosis underwent the Portosystemic Encephalopathy-Syndrome-Test yielding the psychometric hepatic encephalopathy score (PHES), Animal Naming Test (ANT), Critical Flicker Frequency (CFF), Inhibitory Control Test (ICT), EncephalApp (Stroop), and Continuous Reaction Time Test (CRT). Patients were monitored for 365 days regarding oHE development, rehospitalization, and death. Twenty-three patients showed clinical signs of HE grade 1-2 at baseline. Of the remaining 109 neurologically unimpaired patients, 35.8% had abnormal PHES and 44% abnormal CRT. Percentage of abnormal Stroop (79.8% vs. 52.3%), ANT (19.3% vs. 51.4%), ICT (28.4% vs. 36.7%), and CFF results (18.3% vs. 25.7%) changed significantly when adjusted norms were used for evaluation instead of fixed cutoffs. All test results correlated significantly with each other ( p <0.05), except for CFF. During follow-up, 24 patients developed oHE, 58 were readmitted to the hospital, and 20 died. Abnormal PHES results were linked to oHE development in the multivariable model. No other adjusted test demonstrated predictive value for any of the investigated endpoints. CONCLUSIONS Where applicable, the diagnosis of minimal HE should be made based on adjusted norm values for the tests, exclusively. The minimal HE tests cannot be equated with one another and have an overall limited value in predicting clinical outcomes.
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Affiliation(s)
- Alena F Ehrenbauer
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Julius F M Egge
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Maria M Gabriel
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Anja Tiede
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Meike Dirks
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Jennifer Witt
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
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Li X, Liu S, Guo Y, Zu H, Xiang H, Yang S, Zhang X, Meng F, Bianba Y, Li J, Liu F, Lei C, Lv J, Yang Q, Fu W, Ye W, Chen J, Gao Y, Wu C, Wang N, Zheng Q, Wang F, Yu J, Wang J, Yang X, Wang X, Liu Y, Zhao X, Wu C, Gou W, Bajaj JS, Wang F, Fu J, Qi X. Detection of minimal hepatic encephalopathy in patients with cirrhosis based on the Stroop-CN model (NCRCID-CHESS 2106): a prospective multicenter study. MedComm (Beijing) 2024; 5:e627. [PMID: 39015557 PMCID: PMC11247336 DOI: 10.1002/mco2.627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 07/18/2024] Open
Abstract
Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.
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Affiliation(s)
- Xiaoyan Li
- Medical School of Chinese PLABeijingChina
- Senior Department of Infectious DiseasesThe Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesBeijingChina
| | - Shanghao Liu
- Center of Portal HypertensionDepartment of RadiologyZhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University)NanjingChina
- Basic Medicine Research and Innovation Center of Ministry of EducationZhongda HospitalSoutheast UniversityNanjingChina
- State Key Laboratory of Digital Medical EngineeringNanjingChina
| | - Ying Guo
- Department of HepatologyThe Third People's Hospital of TaiyuanTaiyuanChina
| | - Hongmei Zu
- Department of GastroenterologyThe Fourth People's Hospital of Qinghai ProvinceXiningChina
| | - Huiling Xiang
- Department of Gastroenterology and HepatologyTianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary DiseaseTianjinChina
| | - Shaoqi Yang
- Department of GastroenterologyThe General Hospital of Ningxia Medical UniversityYinchuanChina
| | - Xiaoning Zhang
- Senior Department of Infectious DiseasesThe Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesBeijingChina
| | - Fanping Meng
- Senior Department of Infectious DiseasesThe Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesBeijingChina
| | - Yangzhen Bianba
- Department of HepatologyThe Third People's Hospital of Tibet Autonomous RegionLhasaChina
| | - Jie Li
- Department of Infectious DiseasesNanjing Drum Tower Hospital, The Affiliated Hospital of Medical SchoolNanjing UniversityNanjingChina
| | - Fei Liu
- Department of Infectious DiseasesHunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangshaChina
| | - Chuang Lei
- Department of Infectious DiseasesThe First People's Hospital of Changde CityChangdeChina
| | - Jiaojian Lv
- Department of Infectious DiseaseLishui City People's HospitalLishuiChina
| | - Qiao‐hua Yang
- Hepatology Department of Infectious Diseases CenterThe First People's Hospital of HuaihuaHuaihuaChina
| | - Wei Fu
- Department of HepatologyShenyang 739 HospitalShenyangChina
| | - Wei Ye
- Liver Cirrhosis Treatment CenterNanjing Hospital Affiliated to Nanjing University of Traditional Chinese MedicineNanjingChina
| | - Jiafang Chen
- Department of GastroenterologyDatong City Fourth People's HospitalDatongChina
| | - Yanjing Gao
- Department of GastroenterologyQilu Hospital of Shandong UniversityJinanChina
| | - Caiyun Wu
- Department of HepatologyThird People′s Hospital of Linfen CityLinfenChina
| | - Ningning Wang
- Department of GastroenterologyThe First Hospital of China Medical UniversityShenyangChina
| | - Qi Zheng
- Department of HepatologyHepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouChina
| | - Fang Wang
- Department of HepatologyShenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease, The Second Affiliated Hospital, School of Medicine, Southern University of Science and TechnologyShenzhenChina
| | - Jiali Yu
- Department of GastroenterologyThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Jing Wang
- Department of GastroenterologyThe Second Affiliated Hospital of Baotou Medical CollegeBaotouChina
| | - Xiaoting Yang
- Department of GastroenterologyWuzhong People's HospitalWuzhongChina
| | - Xiangmei Wang
- Department of Severe HepatologyMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouChina
| | - Yayuan Liu
- Department of GastroenterologyCentral hospital of DandongDandongChina
| | - Xuelan Zhao
- Department of Gastroenterology Liver DiseasesChongqing Public Health Medical CenterChongqingChina
| | - Chenxi Wu
- Liver Disease Diagnosis and Treatment CenterYiyang Fourth People's HospitalYiyangChina
| | - Wei Gou
- Qingdao Sixth People's HospitalQingdaoChina
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVirginiaUSA
| | - Fu‐Sheng Wang
- Medical School of Chinese PLABeijingChina
- Senior Department of Infectious DiseasesThe Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesBeijingChina
| | - Junliang Fu
- Medical School of Chinese PLABeijingChina
- Senior Department of Infectious DiseasesThe Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious DiseasesBeijingChina
| | - Xiaolong Qi
- Center of Portal HypertensionDepartment of RadiologyZhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University)NanjingChina
- Basic Medicine Research and Innovation Center of Ministry of EducationZhongda HospitalSoutheast UniversityNanjingChina
- State Key Laboratory of Digital Medical EngineeringNanjingChina
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Neye RM, Kircheis G, Stratmann D, Hilger N, Lüth S. Assessment of Cirrhotic Patients by the EncephalApp Fails to Predict Low-Grade Hepatic Encephalopathy. Dig Dis 2024; 42:567-575. [PMID: 38865987 DOI: 10.1159/000538924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 04/13/2024] [Indexed: 06/14/2024]
Abstract
INTRODUCTION An early detection of low-grade hepatic encephalopathy (HE) is of high importance. The aim of the study was to compare a neuropsychological with a psychophysical test on the basis of the psychometric hepatic encephalopathy score (PHES) regarding effectiveness in diagnosing minimal HE (MHE). METHODS In our prospective controlled observational study, we examined a total of 103 patients with liver cirrhosis for HE. The PHES, CFF, and EncephalApp were performed in all patients. Graduation was based on the result of the PHES. Patients without evidence for HE 1&2 according to the mental state (West-Haven criteria) with a PHES <-4 value points and no clinical symptoms were defined as having MHE. Patients were considered as HE0 when in the PHES none of the psychometric subtest results was abnormal or with a PHES ≥-4 value points. Patients with clinical symptoms were considered HE 1&2 patients. Different cut-off values were determined, and their specificity and sensitivity were calculated. RESULTS Ninety-six of the involved patients had liver cirrhosis and 25 acted as a healthy control group. The ROC analysis for the classification resulted in an AUC of 0.806, with the highest Youden index for the cut-off time >224 s, for which the sensitivity was 82% and the specificity 75%. Cases of withdrawals were seen in 10.74% of all tested patients. CONCLUSION The EncephalApp distinguishes well between HE0 and MHE but has its limitations in grading higher forms of HE. Diagnosis using only the EncephalApp is not sufficient.
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Affiliation(s)
- Rebecca Maria Neye
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany,
- Department of Otorhinolaryngology, Head and Neck Surgery, Hospital Ernst von Bergmann Potsdam, Potsdam, Germany,
| | - Gerald Kircheis
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany
| | - Daria Stratmann
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany
| | - Norbert Hilger
- Department of Psychology, University of Bonn, Bonn, Germany
| | - Stefan Lüth
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany
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Llansola M. Preface for the Vicente Felipo Honorary Issue of Neurochemical Research. Neurochem Res 2024; 49:1421-1426. [PMID: 38641758 DOI: 10.1007/s11064-024-04139-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/21/2024]
Affiliation(s)
- Marta Llansola
- Laboratory of Neurobiology, Principe Felipe Research Center, Valencia, Spain.
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Moreno-Loro A, Giráldez Á, Jiménez F, López-Bueno I, Pérez-Ramírez A, Romero-Gómez M. Novel approaches in the medical management of compensated cirrhosis. Expert Rev Gastroenterol Hepatol 2024; 18:239-256. [PMID: 38785070 DOI: 10.1080/17474124.2024.2358149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 05/17/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics. AREAS COVERED We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms. EXPERT OPINION We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.
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Affiliation(s)
- Antonio Moreno-Loro
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Álvaro Giráldez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Fernando Jiménez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Ignacio López-Bueno
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Alberto Pérez-Ramírez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Manuel Romero-Gómez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
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Ohikere K, Wong RJ. Hepatic Encephalopathy: Clinical Manifestations. Clin Liver Dis 2024; 28:253-263. [PMID: 38548437 DOI: 10.1016/j.cld.2024.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
Hepatic encephalopathy (HE) can occur as a complication of chronic liver disease as well as acute liver failure. HE is associated with significantly increased morbidity and worse patient outcomes. The clinical manifestation of HE ranges from early less-severe presentations that may only be accurately detected on dedicated psychomotor diagnostic testing to overt alterations in cognition and mental status to the most severe form of coma. Greater awareness of the clinical manifestations of HE across the spectrum of symptom severity is critical for early identification and timely initiation of appropriate therapy to improve patient outcomes.
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Affiliation(s)
- Kabiru Ohikere
- Value Based Care Department, San Francisco Health Network / Zuckerberg San Francisco General Hospital and Trauma Center
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine; Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.
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Nadinskaia MY, Maevskaya MV, Bakulin IG, Bessonova EN, Bueverov AO, Zharkova MS, Okovityi SV, Ostrovskaya AS, Gulyaeva KA, Ivashkin VT. Diagnostic and Prognostic Value of Hyperammonemia in Patients with Liver Cirrhosis, Hepatic Encephalopathy, and Sarcopenia (Experts’ Agreement). RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2024; 34:85-100. [DOI: 10.22416/1382-4376-2024-34-1-85-100] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Introduction. In cirrhotic patients, hyperammonemia develops due to impaired ammonia detoxification and portosystemic blood shunting and is most commonly associated with hepatic encephalopathy and sarcopenia. Currently, there are questions regarding the diagnosis of hyperammonemia and the effect of ammonia-lowering therapy on disease outcomes.Materials and methods. The Russian Scientific Liver Society selected a panel of seven experts in liver cirrhosis research and management of patients with this disease to make reasoned statements and recommendations on the issue of diagnostic and prognostic value of hyperammonemia in patients with liver cirrhosis, hepatic encephalopathy and sarcopenia.Results. The Delphi panel identified the most relevant topics, in the form of PICO questions (patient or population, intervention, comparison, outcome). The Delphi panel made six questions relevant to clinical practice and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the search and critical analysis of medical literature by keywords in Englishand Russian-language databases. The formulated questions could be combined into four categories: hepatic encephalopathy, sarcopenia, hyperammonemia, and ammonia-lowering therapy.Conclusions. The results of the experts' work are directly relevant to the quality management of patients with liver cirrhosis, and their recommendations and statements can be used in clinical practice.
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Affiliation(s)
- M. Yu. Nadinskaia
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. V. Maevskaya
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - I. G. Bakulin
- North-Western State Medical University named after I.I. Mechnikov
| | | | - A. O. Bueverov
- I.M. Sechenov First Moscow State Medical University (Sechenov University);
M.F. Vladimirsky Moscow Regional Research and Clinical Institute
| | - M. S. Zharkova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - S. V. Okovityi
- Saint Petersburg State Chemical Pharmaceutical University
| | - A. S. Ostrovskaya
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. A. Gulyaeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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Hamzaoui L, Mahmoudi M, Mohamed G, Elloumi H, Laabidi A, Boubaker J, Boudabbous M, Tahri N, Jemni I, Safer L, Jomni T, Douggui H, Trad D, Gargouri D, Ayadi S, Debbeche R, Belhouchet S, Marouani R, Cheikh I, Abdelli MN. EncephalApp Stroop Test for covert hepatic encephalopathy screening in Tunisian cirrhotic patients. F1000Res 2023; 11:686. [PMID: 37767072 PMCID: PMC10521086 DOI: 10.12688/f1000research.121781.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
Background: Covert hepatic encephalopathy (CHE) is underdiagnosed and is difficult to detect. The EncephalApp Stroop test is validated for its screening. The aim of the study was to define Tunisian norms for the test based on healthy controls norms and to estimate the prevalence of CHE in cirrhotic Tunisian patients. Methods: A prospective, multicenter, cross-sectional study was conducted. Ambulatory or hospitalized cirrhotic patients aged 40 years and over were recruited at 11 centers. Healthy subjects aged 40 years and over were recruited at 8 centers. We used a translated Arabic version of the streamlined EncephalApp Stroop test. The task has two components: "Off" and "On" state depending on the discordance or concordance of the stimuli. Results: 142 patients were included. The mean age was 57.26 years [40-86]. 40 (28.17%) of cirrhotic patients who were included were diagnosed as having a minimal hepatic encephalopathy or CHE. Among the ineligible patients, 22 had overt hepatic encephalopathy. If we consider these patients, the overall prevalence rate of CHE was around 24.39% in cirrhotic patients. It was more frequent in women (34.21% vs 25.96%), and in patients whose level of school education is between 6 and 13 years. Its prevalence does not appear to be affected by gender, MELD score, etiology of cirrhosis and age group of patients, as these variables were independent with respective p according to the chi-square test 0.413; 0.736; 0.663 and 0.1. The stroop times (On / Off and On + Off) correlated significantly with each other, are associated significantly and positively with age (respective Pearson coefficients: 0.578; 0.567 and 0.6). The more the age increases, the more the stroop response times increases (p > 10 -3). Conclusions: EncephalApp Stroop test was an efficient screening tool for CHE in Tunisian cirrhotic patients.
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Affiliation(s)
- Lamine Hamzaoui
- Gastroenterology, Mohamed Taher Maamouri Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Nabeul, Tunisia
| | - Moufida Mahmoudi
- Gastroenterology, Mohamed Taher Maamouri Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Nabeul, Tunisia
| | - Ghanem Mohamed
- Gastroenterology, Military Hospital of Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Hanene Elloumi
- Gastroenterology, Habib Bougatfa Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Bizerte, Tunisia
| | - Asma Laabidi
- Gastroenterology, La Rabta Hospital A, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Jalel Boubaker
- Gastroenterology, La Rabta Hospital A, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Mona Boudabbous
- Gastroenterology, Hedi Chaker Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Nabil Tahri
- Gastroenterology, Hedi Chaker Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Imen Jemni
- Gastroenterology, Fattouma Bourguiba University Hospital, Monastir, Monastir, Tunisia
| | - Leila Safer
- Gastroenterology, Fattouma Bourguiba University Hospital, Monastir, Monastir, Tunisia
| | - Taieb Jomni
- Gastroenterology, La Marsa Internal Security Forces Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Hedi Douggui
- Gastroenterology, La Marsa Internal Security Forces Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Dorra Trad
- Gastroenterology, Habib Thameur Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Dalila Gargouri
- Gastroenterology, Habib Thameur Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Shema Ayadi
- Gastroenterology, Hospital Charles Nicolle, Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Radhouane Debbeche
- Gastroenterology, Hospital Charles Nicolle, Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | | | - Ridha Marouani
- Gastroenterology, Kasserine Hospital, Kasserine, Tunisia
| | - Imed Cheikh
- Gastroenterology, Habib Bougatfa Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Bizerte, Tunisia
| | - Mohamed Nabil Abdelli
- Gastroenterology, Military Hospital of Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
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10
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Ripoll C, Greinert R, Reuken P, Reichert MC, Weber SN, Hupfer Y, Staltner R, Meier Clinien M, Lammert F, Bruns T, Zipprich A. Influence of NOD2 risk variants on hepatic encephalopathy and association with inflammation, bacterial translocation and immune activation. Liver Int 2023; 43:1793-1802. [PMID: 37249050 DOI: 10.1111/liv.15627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/21/2023] [Accepted: 05/18/2023] [Indexed: 05/31/2023]
Abstract
BACKGROUND Nucleotide-binding oligomerization domain containing 2 (NOD2) risk variants lead to impaired mucosal barrier function, increased bacterial translocation (BT), and systemic inflammation. AIM To evaluate the association between the presence of NOD2 risk variants, BT, inflammation, and hepatic encephalopathy (HE). PATIENTS AND METHODS This prospective multicenter study included patients with cirrhosis and testing for NOD2 risk variants (p.R702W, p.G908R, c.3020insC, N289S, and c.-958T>C). Patients were evaluated for covert (C) and overt (O) HE. Markers of systemic inflammation (leukocytes, CRP, IL-6, LBP) and immune activation (soluble CD14) as well as bacterial endotoxin (hTRL4 activation) were determined in serum. RESULTS Overall, 172 patients (70% men; median age 60 [IQR 54-66] years; MELD 12 [IQR 9-16]; 72% ascites) were included, of whom 53 (31%) carried a NOD2 risk variant. In this cohort, 11% presented with OHE and 27% and CHE. Presence and severity of HE and surrogates of inflammation, BT, and immune activation did not differ between patients with and without a NOD2 risk variant, also not after adjustment for MELD. HE was associated with increased ammonia and systemic inflammation, as indicated by elevated CRP (w/o HE: 7.2 [2.7-16.7]; with HE 12.6 [4.5-29.7] mg/dL; p < 0.001) and elevated soluble CD14 (w/o HE 2592 [2275-3033]; with HE 2755 [2410-3456] ng/mL; p = 0.025). CONCLUSIONS The presence of NOD2 risk variants in patients with cirrhosis is not associated with HE and has no marked impact on inflammation, BT, or immune activation. In contrast, the presence of HE was linked to ammonia, the acute phase response, and myeloid cell activation.
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Affiliation(s)
- Cristina Ripoll
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Robin Greinert
- Internal Medicine I, Martin Luther University Halle-Wittenberg, Halle, Germany
| | - Philipp Reuken
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | | | - Susanne N Weber
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Yvonne Hupfer
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Raphaela Staltner
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
| | - Magdalena Meier Clinien
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | | | - Tony Bruns
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
- Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Alexander Zipprich
- Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany
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11
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Thornburg B. Hepatic Encephalopathy following Transjugular Intrahepatic Portosystemic Shunt Placement. Semin Intervent Radiol 2023; 40:262-268. [PMID: 37484451 PMCID: PMC10359131 DOI: 10.1055/s-0043-1769770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
Hepatic encephalopathy (HE) is a complex condition that arises as a complication of chronic liver disease and portosystemic shunting. Its pathophysiology involves several factors, including impaired ammonia metabolism, portosystemic shunting, sarcopenia, and systemic inflammation. The symptoms of HE can vary significantly, with manifestations ranging from subclinical signs to a comatose state. The West Haven classification system is most commonly used to grade the severity of HE. There is a broad differential for the presenting symptomatology of HE and other causes of altered mental status must be excluded during the workup. HE is a well-known complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. Even though newer stent designs help reduce the risk of HE with smaller diameter shunts, it is essential that patients are counseled regarding this potential risk prior to the procedure. Once a diagnosis of HE has been confirmed, the mainstay of therapy is lactulose and rifaximin. In cases where a patient has received a TIPS placement and continues to experience refractory HE despite medical therapy, it may be necessary to consider shunt reduction or closure.
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Affiliation(s)
- Bartley Thornburg
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, Illinois
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12
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Thabut D, Bouzbib C, Meunier L, Haas M, Weiss N, Louvet A, Imbert-Bismut F, Mochel F, Nadjar Y, Santiago A, Thevenot T, Duhalde V, Oberti F, Francoz C, Coilly A, Hilleret MN, Lebray P, Liou-Schischmanoff A, Barbier L, Duvoux C, Pageaux GP, Bismuth M, Galanaud D, Broucker TD, Cadranel JF, Leroy V, Di Martino V, Larrey D, Camus C, Scatton O, De Ledinghen V, Mallat A, Rudler M, Bureau C. Diagnosis and management of hepatic encephalopathy: The French recommendations. Liver Int 2023; 43:750-762. [PMID: 36625084 DOI: 10.1111/liv.15510] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 11/27/2022] [Accepted: 12/31/2022] [Indexed: 01/11/2023]
Abstract
Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease with poor patient outcomes. However, it is a poorly understood complication, with no consensus for diagnosis. Therefore, HE is often underdiagnosed. Differential diagnosis may be cumbersome because of non-specific symptoms, such as confusion, cognitive disorders, the aetiological factors of cirrhosis and comorbidities, which are often observed in cirrhotic patients. Therefore, an overt or covert form of HE should be systematically investigated. Advice is provided to drive patient work-up. Effective treatments are available to prevent or treat HE bouts, but the issue of single or combination therapy has not been resolved. Transjugular intrahepatic portosystemic shunt (TIPS) placement largely improved the prognosis of cirrhotic patients, but HE occurrence of HE is often a fear, even when post-TIPS HE can be avoided by a careful selection of patients and preventive treatment. HE is an indication of liver transplantation. However, its reversibility post-transplantation and the consequences of transplantation in patients with other causes of neurological disorders remain controversial, which supports the performance of an extensive work-up in expert centres for this subset of patients. The present guidelines assist clinicians in the diagnosis of the overt or covert form of HE to implement curative and preventive treatments and clarify which patients require referral to expert centres for consideration for liver transplantation. These guidelines are very clinically oriented and address different frequent clinical issues to help physicians make bedside decisions.
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Affiliation(s)
- Dominique Thabut
- APHP-Sorbonne Université, Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière. INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN). Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Charlotte Bouzbib
- APHP-Sorbonne Université, Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière. INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN). Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Lucy Meunier
- Service d'hépato-gastroentérologie A et Transplantation, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France
| | - Manon Haas
- APHP-Paris Saclay, Centre Hépato-Biliaire, Hôpital Paul Brousse, Université Paris-saclay, Villejuif, France
| | - Nicolas Weiss
- APHP-Sorbonne Université, Service de réanimation neurologique, Hôpital Pitié-Salpêtrière. INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN). Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Alexandre Louvet
- Services des maladies de l'appareil digestif, CHRU de Lille, Lille, France
| | - Francois Imbert-Bismut
- APHP-Sorbonne Université, Service de biochimie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Fanny Mochel
- APHP-Sorbonne Université, Service de génétique, Hôpital Pitié-Salpêtrière, Paris, France
| | - Yann Nadjar
- APHP-Sorbonne Université, Service de neurologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Antoine Santiago
- APHP-Sorbonne Université, Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière. INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN). Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Thierry Thevenot
- Service d'hépatologie, Hôpital Jean Minjoz, CHU de Besançon, Besançon, France
| | - Véronique Duhalde
- Service de pharmacie, Hôpital Rangueil, CHU de Toulouse, Toulouse, France
| | - Frédéric Oberti
- Laboratoire HIFIH, UPRES-EA2170, Faculté de Médecine, Service d'hépato-gastroentérologie, CHU ANGERS, Angers, France
| | - Claire Francoz
- APHP-Hôpital Beaujon, Service d'hépatologie, Clichy, France
| | - Audrey Coilly
- APHP-Paris Saclay, Centre Hépato-Biliaire, Hôpital Paul Brousse, Université Paris-saclay, Villejuif, France
| | | | - Pascal Lebray
- APHP-Sorbonne Université, Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière. INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN). Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | | | - Louise Barbier
- Service de chirurgie hépatique et transplantation, CHU de Tours, Tours, France
| | | | - Georges-Philippe Pageaux
- Service d'hépato-gastroentérologie A et Transplantation, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France
| | - Michael Bismuth
- Service d'hépato-gastroentérologie B, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France
| | - Damien Galanaud
- APHP-Sorbonne Université, Service de neuro-radiologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Thomas De Broucker
- Service de Neurologie Hôpital Pierre Delafontaine, Centre Hospitalier de Saint-Denis, Saint-Denis, France
| | - Jean-François Cadranel
- Service d'hépato-gastroentérologie de nutrition et d'Alcoologie-GHPSO site de Creil, Creil, France
| | - Vincent Leroy
- APHP Hôpital Henri-Mondor, Service d'hépatologie, Créteil, France
| | - Vincent Di Martino
- Service d'hépatologie, Hôpital Jean Minjoz, CHU de Besançon, Besançon, France
| | - Dominique Larrey
- Service d'hépato-gastroentérologie A et Transplantation, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France
| | - Christophe Camus
- Service de réanimation Médicale, Hôpital Pontchaillou, CHU de Rennes, Rennes, France
| | - Olivier Scatton
- APHP-Sorbonne Université, Service de chirurgie et transplantation hépatique, Hôpital Pitié-Salpêtrière, Paris, France
| | - Victor De Ledinghen
- Service d'hépato-gastroentérologie, Hôpital du Haut-Lévêque, CHU de Bordeaux, Bordeaux, France
| | - Ariane Mallat
- APHP Hôpital Henri-Mondor, Service d'hépatologie, Créteil, France
| | - Marika Rudler
- APHP-Sorbonne Université, Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière. INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN). Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Christophe Bureau
- Service d'hépatologie, Hôpital Rangueil, CHU de Toulouse, Toulouse, France
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13
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Thanapirom K, Wongwandee M, Suksawatamnuay S, Thaimai P, Siripon N, Makhasen W, Treeprasertsuk S, Komolmit P. Psychometric Hepatic Encephalopathy Score for the Diagnosis of Minimal Hepatic Encephalopathy in Thai Cirrhotic Patients. J Clin Med 2023; 12:519. [PMID: 36675448 PMCID: PMC9864758 DOI: 10.3390/jcm12020519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 12/17/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
The psychometric hepatic encephalopathy score (PHES) is the gold standard for diagnosing minimal hepatic encephalopathy (MHE). Screening for MHE is frequently overlooked in clinical practice due to time constraints. Furthermore, the simplified animal naming test (S-ANT1) is a new simple tool for evaluating MHE in cirrhotic patients. The purpose of this study was to standardize the PHES in a healthy Thai population, assess the prevalence of MHE, and validate the S-ANT1 in detecting MHE in patients with cirrhosis. The study included 194 healthy controls and 203 cirrhotic patients without overt HE. Psychometric tests and the S-ANT1 were administered to all participants. Multiple linear regression was used to analyze factors related to PHES results, and formulas were developed to predict the results for each PHES subtest. In healthy controls, age and education were predictors of all five subtests. The PHES of the control group was −0.26 ± 2.28 points, and the threshold for detecting MHE was set at ≤ −5 points. The cirrhotic group had PHES values of −2.6 ± 3.1 points. Moreover, MHE was found to be present in 26.6% of cirrhotic patients. S-ANT1 had a moderate positive correlation with PHES (r = 0.44, p < 0.001). S-ANT1 < 22 named animals detected MHE with a sensitivity of 71.2%, specificity of 65%, and area under the receiver operating curve of 0.68 (p < 0.001). In conclusion, Thai PHES normative data have been developed to detect MHE in cirrhotic patients who do not have overt HE. The optimal cutoff for detecting MHE in Thai cirrhotic patients was PHES ≤ −5 points and S-ANT1 < 22 named.
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Affiliation(s)
- Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Monton Wongwandee
- Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Nakhon Nayok 26120, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Napaporn Siripon
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Wanwisar Makhasen
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
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14
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Tan W, Wang J, Shi PM, Feng LM, Shi J, Ning BF, Yuan ZL, Zeng X, Xie WF. Effects of Low-dose and High-dose Rifaximin in the Treatment of Covert Hepatic Encephalopathy. J Clin Transl Hepatol 2022; 10:1099-1106. [PMID: 36381088 PMCID: PMC9634763 DOI: 10.14218/jcth.2021.00457] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Rifaximin is effective in preventing and treating hepatic encephalopathy (HE). This study aimed to investigate the efficacy and safety of different dosages of rifaximin in the treatment of cirrhotic patients with covert HE (CHE). METHODS In this single-center, randomized, controlled, open-label study, CHE was diagnosed using a combination of the psychometric HE score and the EncephalApp Stroop test. Cirrhotic patients with CHE were recruited and randomly assigned to low-dose rifaximin 800 mg/day, high-dose rifaximin (1,200 mg/day), and control groups, and were treated for 8 weeks. The sickness impact profile (SIP) scale was used to evaluate the health-related quality of life (HRQOL) of patients. Forty patients were included in the study, 12 were assigned to the low-dose group, 14 to the high-dose group, and 14 patients to the control group. RESULTS The percentage of patients with CHE reversal was significantly higher in both the low-dose (41.67%, 5/12) and high-dose (57.14%, 8/14) groups than in the control group (7.14%, 1/14) at 8 weeks (p=0.037 and p=0.005, respectively). In addition, both doses of rifaximin resulted in significant improvement of the total SIP score compared with the control group. There were no significant differences in the CHE reversal rate, total SIP score improvement, and incidence of adverse event between the low-dose and high-dose groups (p>0.05). CONCLUSIONS Low-dose rifaximin reverses CHE and improves HRQOL in cirrhotic patients with comparable effects and safety to high-dose rifaximin.
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Affiliation(s)
- Wei Tan
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Jian Wang
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Pei-Mei Shi
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Ling-Mei Feng
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Jian Shi
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Bei-Fang Ning
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Zong-Li Yuan
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Xin Zeng
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Correspondence to: Xin Zeng, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. Tel/Fax: +86-21-38804518, E-mail: ; Wei-Fen Xie, Department of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China. Tel: +86-21-81885341, Fax: +86-21-81886924, E-mail:
| | - Wei-Fen Xie
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Correspondence to: Xin Zeng, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. Tel/Fax: +86-21-38804518, E-mail: ; Wei-Fen Xie, Department of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China. Tel: +86-21-81885341, Fax: +86-21-81886924, E-mail:
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15
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Aspinall RJ, Hudson M, Ryder SD, Richardson P, Farrington E, Wright M, Przemioslo RT, Perez F, Kent M, Henrar R, Hickey J, Shawcross DL. Real-world evidence of long-term survival and healthcare resource use in patients with hepatic encephalopathy receiving rifaximin-α treatment: a retrospective observational extension study with long-term follow-up (IMPRESS II). Frontline Gastroenterol 2022; 14:228-235. [PMID: 37056320 PMCID: PMC10086718 DOI: 10.1136/flgastro-2022-102221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 10/02/2022] [Indexed: 11/12/2022] Open
Abstract
Objective To describe survival of patients with hepatic encephalopathy (HE), up to 5 years after initiation of rifaximin-α (RFX) treatment. Design/Method A retrospective, observational extension study within 9 National Health Service secondary/tertiary UK care centres. All patients had a clinical diagnosis of HE, were being treated with RFX and were included in the previous IMPRESS study which reported the 1-year experience. Demographics, clinical outcomes, selected cirrhosis-related complications, hospital admissions and attendances up to 5 years from RFX initiation were extracted from patient medical records and hospital electronic databases. The primary outcome measure was survival at 5 years post-initiation of RFX treatment. Results The study included 138 patients. The survival rate at 5 years post-initiation of RFX was 35% (95% CI 28.2% to 44.4%) overall and 36% (95% CI 26.1% to 45.4%) for patients with alcohol-related liver disease. Median survival from RFX initiation was 2.8 years (95% CI 2.0 to 3.8; n=136). Among 48 patients alive at 5 years, 69% remained on RFX treatment at the end of the observation period, 74% reported no cirrhosis-related complications and 24% (9/37) had received a liver transplant. Between 1 and 5 years post-initiation, total numbers of liver-related emergency department visits, inpatient admissions, intensive care unit admissions and outpatient visits were 84, 194, 3 and 709, respectively; the liver-related 30-day readmission rate was 37%. Conclusion Within UK clinical practice, RFX use in HE was associated with a 35% survival rate with high treatment adherence, 76% transplant-free survival rate, minimal healthcare resource and low rates of complications at 5 years post-initiation.
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Affiliation(s)
- Richard J Aspinall
- Department of Gastroenterology & Hepatology, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Mark Hudson
- Formerly Liver Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Stephen D Ryder
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Paul Richardson
- Department of Gastroenterology and Hepatology, Royal Liverpool & Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Elizabeth Farrington
- Department of Gastroenterology & Hepatology, Royal Cornwall Hospital, Cornwall, UK
| | - Mark Wright
- Department of Hepatology, University Hospital Southampton, Southampton, UK
| | | | - Francisco Perez
- Department of Gastroenterology, University Hospital of North Durham, Durham, UK
| | - Melanie Kent
- Department of Gastroenterology, University Hospital of North Durham, Durham, UK
| | | | | | - Debbie L Shawcross
- Institute of Liver Studies, Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK
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16
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Efecto de la erradicación del VHC sobre la frecuencia crítica de parpadeo en pacientes coinfectados por VIH/VHC con cirrosis avanzada. Rev Clin Esp 2022. [DOI: 10.1016/j.rce.2022.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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17
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Häussinger D, Dhiman RK, Felipo V, Görg B, Jalan R, Kircheis G, Merli M, Montagnese S, Romero-Gomez M, Schnitzler A, Taylor-Robinson SD, Vilstrup H. Hepatic encephalopathy. Nat Rev Dis Primers 2022; 8:43. [PMID: 35739133 DOI: 10.1038/s41572-022-00366-6] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/12/2022] [Indexed: 01/18/2023]
Abstract
Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging.
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Affiliation(s)
- Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | - Radha K Dhiman
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (Uttar Pradesh), India
| | - Vicente Felipo
- Laboratory of Neurobiology, Centro de Investigación Principe Felipe, Valencia, Spain
| | - Boris Görg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Rajiv Jalan
- Liver Failure Group ILDH, Division of Medicine, UCL Medical School, Royal Free Campus, London, UK.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Gerald Kircheis
- Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg an der Havel, Brandenburg Medical School, Brandenburg an der Havel, Germany
| | - Manuela Merli
- Department of Translational and Precision Medicine, Universita' degli Studi di Roma - Sapienza, Roma, Italy
| | | | - Manuel Romero-Gomez
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, St. Mary's Hospital Campus, Imperial College London, London, UK
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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Analysis of Gut Microbiome Structure Based on GMPR+Spectrum. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12125895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The gut microbiome is related to many major human diseases, and it is of great significance to study the structure of the gut microbiome under different conditions. Multivariate statistics or pattern recognition methods were often used to identify different structural patterns in gut microbiome data. However, these methods have some limitations. Minimal hepatic encephalopathy (MHE) datasets were taken as an example. Due to the physical lack or insufficient sampling of the gut microbiome in the sequencing process, the microbiome data contains many zeros. Therefore, the geometric mean of pairwise ratios (GMPR) was used to normalize gut microbiome data, then Spectrum was used to analyze the structure of the gut microbiome, and lastly, the structure of core microflora was compared with Network analysis. GMPR calculates the Intraclass correlation coefficient (ICC), whose reproducibility was significantly better than other normalization methods. In addition, running-time, Normalized Mutual Information (NMI), Davies-Boulding Index (DBI), and Calinski-Harabasz index (CH) of GMPR+Spectrum were far superior to other clustering algorithms such as M3C, iClusterPlus. GMPR+Spectrum can not only perform better but also effectively identify the structural differences of intestinal microbiota in different patients and excavate the unique critical bacteria such as Akkermansia, and Lactobacillus in MHE patients, which may provide a new reference for the study of the gut microbiome in disease.
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Hontañón V, González-García J, Rubio-Martín R, Díez C, Serrano-Morago L, Berenguer J. Effect of HCV eradication on critical flicker frequency in HIV/HCV coinfected patients with advanced cirrhosis. Rev Clin Esp 2022; 222:479-485. [DOI: 10.1016/j.rceng.2022.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 02/16/2022] [Indexed: 10/18/2022]
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20
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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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21
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Attia MS, Youssef AO, Abdel-Sattar NA, Amin MA, Alharthi S, Mohamed EH, Mahmoud SA, Abou-Omar MN. A highly selective and sensitive spectrofluorimetric method for the assessment of 3-nitrotyrosine in serum using (Eu(TTA) 3Phen) photo probe. RSC Adv 2022; 12:4536-4542. [PMID: 35425515 PMCID: PMC8981050 DOI: 10.1039/d1ra07351f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 01/22/2022] [Indexed: 11/21/2022] Open
Abstract
A simple, accurate and fast method was developed for the assessment of 3-nitrotyrosine as a biomarker for the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) using a (Eu(TTA)3Phen) photo probe. 3-Nitrotyrosine can remarkably quench the luminescence intensity of the (Eu(TTA)3Phen) complex in DMSO at pH = 9 and λem = 617 nm. The quenching of the luminescence intensity of (Eu(TTA)3Phen) complex particularly the electrical emission band at λem = 617 nm is used for the assessment of 3-nitrotyrosine in different serum samples of patients with liver cirrhosis. A simple, accurate and fast method was developed for the assessment of 3-nitrotyrosine as a biomarker for the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) using a (Eu(TTA)3Phen) photo probe.![]()
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Affiliation(s)
- Mohmed S Attia
- Chemistry Department, Faculty of Science, Ain Shams University Cairo 11566 Egypt
| | - Ahmed O Youssef
- Chemistry Department, Faculty of Science, Ain Shams University Cairo 11566 Egypt
| | - Nour A Abdel-Sattar
- Chemistry Department, Faculty of Science, Ain Shams University Cairo 11566 Egypt
| | - Mohammed A Amin
- Department of Chemistry, College of Science, Taif University P.O. Box 11099 Taif 21944 Saudi Arabia
| | - Sarah Alharthi
- Department of Chemistry, College of Science, Taif University P.O. Box 11099 Taif 21944 Saudi Arabia
| | - Ekram H Mohamed
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt El Sherouk City Cairo Egypt
| | - Safwat A Mahmoud
- Physics Department, Faculty of Science, Northern Border University Arar Saudi Arabia
| | - Mona N Abou-Omar
- Department of Chemistry, Faculty of Women for Arts, Science and Education, Ain Shams University Cairo Egypt
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22
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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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Han X, Luo Z, Wang W, Zheng P, Li T, Mei Z, Wang J. Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy. Front Pharmacol 2021; 12:696065. [PMID: 34690751 PMCID: PMC8533823 DOI: 10.3389/fphar.2021.696065] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 09/21/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE. Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE. Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02-1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12-2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18-1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54-1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54-0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients. Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.
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Affiliation(s)
- Xianghui Han
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhanyang Luo
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wenyi Wang
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peiyong Zheng
- Institute of Digestive Diseases, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Anorectal Disease Institute of Shuguang Hospital, Shanghai, China
| | - Jianyi Wang
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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24
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Salman T, Elsabaawy M, Omar M, Afify M, Elezawy H, Ghanem S, Abdelraouf O, Rewisha E, Shebl N. Evaluation of different diagnostic modalities of minimal hepatic encephalopathy in cirrhotic patients: case-control study. Clin Exp Hepatol 2021; 7:312-319. [PMID: 34712834 PMCID: PMC8527340 DOI: 10.5114/ceh.2021.109292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/13/2021] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Minimal hepatic encephalopathy (MHE) represents one of the most overlooked complications of liver cirrhosis. AIM OF THE STUDY To compare the utility and efficacy of different MHE diagnostic modalities. MATERIAL AND METHODS This case-control study was conducted on hepatitis C virus (HCV)-related compensated cirrhotic patients. The Psychometric Hepatic Encephalopathy Score (PHES) was used to assign patients to MHE and controls. All patients were subjected to plasma ammonia, serum 3-nitrotyrosine (3-NT), critical flicker frequency (CFF), and the modified inhibitory control test (ICT). RESULTS CFF was significantly lower in the control group (38.5, 40 Hz, p = 0.003). The unweighted lures on ICT were 8.7, 4.9 in MHE and controls (p < 0.001). Moreover, ammonia was higher in the MHE group (89, 61.5 µmol/l, p < 0.001). 3-NT was also higher in the MHE group (31.5, 13.7 nmol/l, p < 0.001) respectively. CFF at cutoff < 39 Hz had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 57.5%, 77.5%, 71.9% and 64.6%, respectively; in modified ICT, at cutoff > 5 unweighted lures the values were 87.5%, 80%, 81.4% and 86.5%, respectively; in ammonia, at cutoff ≥ 76.45 µmol/l the values were 65%, 72.5%, 70.3% and 67.4%, respectively; for 3-NT at cutoff ≥ 14.15 nmol/l the values were 85%, 82.5%, 82.9% and 84.6%, respectively. The accuracy for MHE diagnosis was 67.5%, 83.3%, 68.8%, 83.8% relying on CFF, 3-NT, ammonia, and ICT respectively. On multivariate analysis, CFF < 39 Hz (OR = 10.2, p = 0.04), modified ICT > 5 unweighted lures (OR = 43.2, p = 0.002), and serum 3-NT levels ≥ 14.15 nmol/l (OR = 50.4, p < 0.001) were independent predictors of MHE. CONCLUSIONS 3-NT and ICT are advantageous to reveal MHE in compensated liver cirrhosis, while CFF can be only used as adjuncts, with humble merits of ammonia.
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Affiliation(s)
- Tary Salman
- National Liver Institute, Menoufia University, Egypt
| | | | - Mahmoud Omar
- National Liver Institute, Menoufia University, Egypt
| | - Mohamed Afify
- National Liver Institute, Menoufia University, Egypt
| | | | - Samar Ghanem
- National Liver Institute, Menoufia University, Egypt
| | - Osama Abdelraouf
- Faculty of Computers and Information, Menoufia University, Egypt
| | - Eman Rewisha
- National Liver Institute, Menoufia University, Egypt
| | - Nashwa Shebl
- National Liver Institute, Menoufia University, Egypt
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25
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Häussinger D, Butz M, Schnitzler A, Görg B. Pathomechanisms in hepatic encephalopathy. Biol Chem 2021; 402:1087-1102. [PMID: 34049427 DOI: 10.1515/hsz-2021-0168] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 05/12/2021] [Indexed: 02/06/2023]
Abstract
Hepatic encephalopathy (HE) is a frequent neuropsychiatric complication in patients with acute or chronic liver failure. Symptoms of HE in particular include disturbances of sensory and motor functions and cognition. HE is triggered by heterogeneous factors such as ammonia being a main toxin, benzodiazepines, proinflammatory cytokines and hyponatremia. HE in patients with liver cirrhosis is triggered by a low-grade cerebral edema and cerebral oxidative/nitrosative stress which bring about a number of functionally relevant alterations including posttranslational protein modifications, oxidation of RNA, gene expression changes and senescence. These alterations are suggested to impair astrocyte/neuronal functions and communication. On the system level, a global slowing of oscillatory brain activity and networks can be observed paralleling behavioral perceptual and motor impairments. Moreover, these changes are related to increased cerebral ammonia, alterations in neurometabolite and neurotransmitter concentrations and cortical excitability in HE patients.
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Affiliation(s)
- Dieter Häussinger
- Clinic for Gastroenterology, Hepatology, and Infectious Diseases, Heinrich Heine University, Moorenstr. 5, D-40225 Düsseldorf, Germany
| | - Markus Butz
- Department of Neurology/Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Moorenstr. 5, D-40225 Düsseldorf, Germany
| | - Alfons Schnitzler
- Department of Neurology/Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Moorenstr. 5, D-40225 Düsseldorf, Germany
| | - Boris Görg
- Clinic for Gastroenterology, Hepatology, and Infectious Diseases, Heinrich Heine University, Moorenstr. 5, D-40225 Düsseldorf, Germany
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26
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Barone M, Suppressa P, Viggiani MT, Lenato GM, Scardapane A, Chiumarulo L, Ambrosini N, Leo AD, Sabbà C. Minimal portosystemic encephalopathy: A new nosological entity in patients with hereditary haemorrhagic telangiectasia. Eur J Intern Med 2021; 90:43-48. [PMID: 34020869 DOI: 10.1016/j.ejim.2021.04.026] [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: 01/18/2021] [Revised: 04/24/2021] [Accepted: 04/26/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Portosystemic shunts in Hereditary Haemorrhagic Telangiectasia (HHT) are often overlooked by conventional imaging although they could reduce hepatic clearance of gut-derived toxins. AIMS To evaluate, the presence of subclinical neurological alterations (SNAs), that we named "minimal portosystemic encephalopathy" (mPSE) in HHT patients without advanced liver disease (ALD). METHODS In this cross sectional study, consecutive HHT outpatients were firstly screened by critical flicker frequency (CFF) test (abnormal ≤39Hz), and the simplified animal naming test (S-ANT1) (abnormal <15) was used to confirm the diagnosis of mPSE. Furthermore, we evaluated the effect of lactulose administration on mPSE. Multi-slice CT, cerebral dynamic magnetic resonance, laboratory analyses and transient elastography were also used. RESULTS None of the 37 enrolled patients showed portosystemic shunts at imaging techniques. However, 33 patients had normal CFF values (CFF-) and 4 displayed CFF alterations (37.0±0.7Hz, CFF+). The S-ANT1 confirmed an impaired neurological performance (10.2±2.8) in CFF+ patients thus confirming the presence of mPSE. Noteworthy, lactulose administration determined a CFF increase (39.1±0.4Hz) and S-ANT1 normalization in these patients. Neither mPSE- nor mPSE+ patients had ALD and showed similar demographic, clinical and laboratory parameters. Finally, no mPSE+ patient showed radiologically-detectable brain vascular malformations or other brain abnormalities at imaging. CONCLUSIONS HHT patients represent a human model of mPSE secondary to portosystemic shunts escaping radiological detection. mPSE evaluation should be incorporated in HHT surveillance protocols since it can affect both health-related/social aspects and pharmacokinetics of orally administered drugs with a narrow therapeutic index and high hepatic first-pass uptake.
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Affiliation(s)
- Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, (D.E.T.O.), University of Bari Aldo Moro, Policlinico University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy.
| | - Patrizia Suppressa
- "Frugoni" Internal Medicine Unit, Centre for Rare Diseases, Interdepartmental Centre for Hereditary Haemorrhagic Telangiectasia, Interdisciplinary Department of Medicine (D.I.M.), VascERN HHT Reference Centre, University of Bari Aldo Moro, Policlinico University Hospital, Bari, Italy
| | - Maria Teresa Viggiani
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, (D.E.T.O.), University of Bari Aldo Moro, Policlinico University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy
| | - Gennaro Mariano Lenato
- "Frugoni" Internal Medicine Unit, Centre for Rare Diseases, Interdepartmental Centre for Hereditary Haemorrhagic Telangiectasia, Interdisciplinary Department of Medicine (D.I.M.), VascERN HHT Reference Centre, University of Bari Aldo Moro, Policlinico University Hospital, Bari, Italy
| | - Arnaldo Scardapane
- Interdisciplinary Department of Medicine-Radiology Unit, University of Bari Aldo Moro, Policlinico University Hospital, Bari, Italy
| | - Luigi Chiumarulo
- Neuroradiology Unit, Policlinico University Hospital, Bari, Italy
| | - Nicola Ambrosini
- "Frugoni" Internal Medicine Unit, Centre for Rare Diseases, Interdepartmental Centre for Hereditary Haemorrhagic Telangiectasia, Interdisciplinary Department of Medicine (D.I.M.), VascERN HHT Reference Centre, University of Bari Aldo Moro, Policlinico University Hospital, Bari, Italy
| | - Alfredo Di Leo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, (D.E.T.O.), University of Bari Aldo Moro, Policlinico University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy
| | - Carlo Sabbà
- "Frugoni" Internal Medicine Unit, Centre for Rare Diseases, Interdepartmental Centre for Hereditary Haemorrhagic Telangiectasia, Interdisciplinary Department of Medicine (D.I.M.), VascERN HHT Reference Centre, University of Bari Aldo Moro, Policlinico University Hospital, Bari, Italy
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27
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Giménez-Garzó C, Fiorillo A, Ballester-Ferré MP, Gallego JJ, Casanova-Ferrer F, Urios A, Benlloch S, Martí-Aguado D, San-Miguel T, Tosca J, Ríos MP, Montón C, Durbán L, Escudero-García D, Aparicio L, Felipo V, Montoliu C. A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease. J Clin Med 2021; 10:2806. [PMID: 34202269 PMCID: PMC8268962 DOI: 10.3390/jcm10132806] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/21/2021] [Accepted: 06/24/2021] [Indexed: 01/10/2023] Open
Abstract
Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The neurological functions affected remain unclear. The aims were to: (1) Characterize the neuropsychological alterations in NAFLD patients; (2) assess the prevalence of impairment of neurological functions evaluated; (3) develop a new score for sensitive and rapid MCI detection in NAFLD; (4) assess differences in MCI features between patients with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); and (5) compare neuropsychological alterations in NAFLD patients with cirrhotic patients with MCI. Fifty-nine NAFLD patients and 53 controls performed psychometric tests assessing different neurological functions: PHES (Psychometric Hepatic Encephalopathy Score) battery, d2, Stroop, Oral SDMT (Symbol Digit Modalities Test), Digit Span, number-letter test, and bimanual and visual-motor coordination tests. NAFLD patients show impairment in attention, mental concentration, psychomotor speed, cognitive flexibility, inhibitory mental control, and working memory. We developed a new, rapid, and sensitive score based on the most affected parameters in NAFLD patients, unveiling that 32% of NAFLD show MCI. Prevalence was similar in NAFL (36%) or NASH (27%) patients, but lower in NAFLD than in cirrhosis (65%). MCI prevalence is significant in NAFLD patients. Psychometric testing is warranted in these patients to unveil MCI and take appropriate measures to reverse and prevent its progression.
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Affiliation(s)
- Carla Giménez-Garzó
- Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain; (C.G.-G.); (A.U.)
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
| | - Alessandra Fiorillo
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
| | - María-Pilar Ballester-Ferré
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
- Servicio de Medicina Digestiva, Hospital Clínico Valencia, 46010 Valencia, Spain
| | - Juan-José Gallego
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
| | - Franc Casanova-Ferrer
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
| | - Amparo Urios
- Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain; (C.G.-G.); (A.U.)
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
| | - Salvador Benlloch
- Servicio de Digestivo, Hospital Arnau de Vilanova, 46015 Valencia, Spain; (S.B.); (M.-P.R.); (L.D.)
- CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - David Martí-Aguado
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
- Servicio de Medicina Digestiva, Hospital Clínico Valencia, 46010 Valencia, Spain
| | - Teresa San-Miguel
- Departamento de Patología, Universidad Valencia, 46010 Valencia, Spain;
| | - Joan Tosca
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
- Servicio de Medicina Digestiva, Hospital Clínico Valencia, 46010 Valencia, Spain
| | - María-Pilar Ríos
- Servicio de Digestivo, Hospital Arnau de Vilanova, 46015 Valencia, Spain; (S.B.); (M.-P.R.); (L.D.)
| | - Cristina Montón
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
- Servicio de Medicina Digestiva, Hospital Clínico Valencia, 46010 Valencia, Spain
| | - Lucía Durbán
- Servicio de Digestivo, Hospital Arnau de Vilanova, 46015 Valencia, Spain; (S.B.); (M.-P.R.); (L.D.)
| | - Desamparados Escudero-García
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
- Servicio de Medicina Digestiva, Hospital Clínico Valencia, 46010 Valencia, Spain
- Departamento de Medicina, Universidad Valencia, 46010 Valencia, Spain
| | - Luis Aparicio
- Departamento de Anatomía y Embriología, Universidad Valencia, 46010 Valencia, Spain;
| | - Vicente Felipo
- Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, 46012 Valencia, Spain; (C.G.-G.); (A.U.)
| | - Carmina Montoliu
- Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, 46010 Valencia, Spain; (A.F.); (M.-P.B.-F.); (J.-J.G.); (F.C.-F.); (D.M.-A.); (J.T.); (C.M.); (D.E.-G.); (C.M.)
- Departamento de Patología, Universidad Valencia, 46010 Valencia, Spain;
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Moran S, López-Sánchez M, Milke-García MDP, Rodríguez-Leal G. Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis. World J Gastroenterol 2021; 27:3050-3063. [PMID: 34168407 PMCID: PMC8192295 DOI: 10.3748/wjg.v27.i22.3050] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/01/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.
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Affiliation(s)
- Segundo Moran
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
| | - Marlene López-Sánchez
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
| | | | - Gustavo Rodríguez-Leal
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
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Rudler M, Weiss N, Bouzbib C, Thabut D. Diagnosis and Management of Hepatic Encephalopathy. Clin Liver Dis 2021; 25:393-417. [PMID: 33838857 DOI: 10.1016/j.cld.2021.01.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatic encephalopathy (HE) is a severe complication of cirrhosis. The prevalence of overt HE (OHE) ranges from 30% to 45%, whereas the prevalence of minimal HE (MHE) is as high as 85% in some case series. Widespread use of transjugular intrahepatic portosystemic shunt to control complications related to portal hypertension is associated with an increase in HE incidence. If the diagnosis of OHE remains simple in most cases, then the diagnosis of MHE is less codified because of many differential diagnoses with different therapeutic implications. This review analyzes current knowledge about the pathophysiology, diagnosis, and different therapeutic options of HE.
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Affiliation(s)
- Marika Rudler
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Nicolas Weiss
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Neurological Intensive Care Unit, Neurology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne Université, Paris F-75005, France
| | - Charlotte Bouzbib
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Dominique Thabut
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne Université, Paris F-75005, France.
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Yazici A, Emre Yildirim A, Konduk B, Aytaç İ, Barutçu S. A novel method: can stapedial acoustic reflex have a role in the diagnosis of minimal hepatic encephalopathy? Eur J Gastroenterol Hepatol 2021; 33:717-721. [PMID: 32568804 DOI: 10.1097/meg.0000000000001781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Stapedial acoustic reflex is an easily accessible and applicable test which is also valuable for the clinical conditions which affect the various locations of the central nervous system. Searching the diagnostic value of stapedial acoustic reflex at minimal hepatic encephalopathy is the aim of this research. METHODS Diagnosis of minimal hepatic encephalopathy was conducted by mini-mental state and critical flickered frequency tests. Minimal hepatic encephalopathy diagnosed patients were established in the first group. Cirrhosis (without minimal hepatic encephalopathy or overt hepatic encephalopathy) diagnosed patients were created the control group. The stapedial acoustic reflex test was applied for minimal hepatic encephalopathy and the control group by audiologists in a soundproof room. RESULTS In total, 221 patients were screened and 97 patients meet the inclusion criterions. Out of 97 patients, 52 were the minimal hepatic encephalopathy patients and the remaining patients were the control group. Acoustic reflex tests battery includes the evaluation of two pathways called ipsilateral and contralateral. Ipsilateral way test results were found positive in all minimal hepatic encephalopathy patients and 95% positive in the control group. Contralateral acoustic reflex test results were found 36% positive in minimal hepatic encephalopathy patients and 95% positive in the control group, respectively. A comparison of ipsilateral and contralateral acoustic reflex test results was displayed a statistical significance. CONCLUSION Stapedial acoustic reflex test results of cirrhosis patients may cover additional parameters for the diagnosis of minimal hepatic encephalopathy.
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Affiliation(s)
| | - Abdullah Emre Yildirim
- Gastroenterology, University of Gaziantep Medical Faculty, Department, Gaziantep, Turkey
| | - BuğraTolga Konduk
- Gastroenterology, University of Gaziantep Medical Faculty, Department, Gaziantep, Turkey
| | | | - Sezgin Barutçu
- Gastroenterology, University of Gaziantep Medical Faculty, Department, Gaziantep, Turkey
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Sanchez-Meza F, Torre A, Castillo-Martinez L, Sanchez-Roman S, Morales-Buenrostro LE. Evaluation of cerebral dysfunction in patients with chronic kidney disease using neuropsychometric and neurophysiological tests. Ren Fail 2021; 43:577-584. [PMID: 33757399 PMCID: PMC7993379 DOI: 10.1080/0886022x.2021.1901740] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). Objective To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. Methods This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and < −4 for PHES. All participants were also screened for cognitive function and depression. Results Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy. Conclusions It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents.
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Affiliation(s)
- Fabiola Sanchez-Meza
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Tlalpan, Mexico
| | - Aldo Torre
- Liver Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Tlalpan, Mexico
| | - Lilia Castillo-Martinez
- Department of Clinical Nutrition, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Tlalpan, Mexico
| | - Sofia Sanchez-Roman
- Neurology and Psychiatry Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Tlalpan, Mexico
| | - Luis Eduardo Morales-Buenrostro
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Tlalpan, Mexico
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Brain-derived neurotrophic factor as a potential diagnostic marker in minimal hepatic encephalopathy. Clin Exp Hepatol 2021; 7:117-124. [PMID: 34027124 PMCID: PMC8122095 DOI: 10.5114/ceh.2021.103242] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 01/15/2021] [Indexed: 11/22/2022] Open
Abstract
Introduction Minimal hepatic encephalopathy (MHE) is a common complication of liver cirrhosis not only leading to a decrease in the quality of life, but also predicting development of overt encephalopathy. The diagnosis of MHE usually relies on a combination of neuropsychological tests, while robust serum biomarkers are lacking. We aimed to assess serum concentrations of brain-derived neurotrophic factor (BDNF) in MHE patients. Material and methods Serum BDNF was assessed in 78 patients with liver cirrhosis (53 male, median age 55 years) and 40 healthy individuals. 43 subjects underwent extensive evaluation for MHE by psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT) or critical flicker frequency (CFF). Results Serum BDNF was twofold lower in liver cirrhosis compared to healthy subjects [13.6 (7.8-22.6) vs. 33.0 (24.1-40.7) ng/ml, p < 0.001] and its decrease reflected a degree of liver insufficiency assessed by model for end-stage liver disease (MELD). BDNF showed a negative correlation with bilirubin (R = –0.35, p = 0.005) and international normalized ratio (INR) (R = –0.37, p = 0.003), and positive with platelets (PLT) (R = 0.36, p = 0.004), while no associations with age, sex, body mass index (BMI), waist-hip ratio (WHR), creatinine and ammonia were noted. Importantly, subjects with a diagnosis of MHE by at least two modalities showed the lowest levels of BDNF [10.9 (2.5-14.4) vs. 19.9 (9.3-29.4) ng/ml, p < 0.01]. Patients with self-reported sleep disturbances had significantly lower serum BDNF [13.0 (2.5-23.4) vs. 20.0 (8.4-31.3) ng/ml, p = 0.04]. Conclusions The lowest serum BDNF concentration was noted in patients with MHE and sleep disturbances, which suggests a role in pathophysiology of hepatic encephalopathy but also as a potential biomarker.
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Abstract
Type C hepatic encephalopathy (HE) is a brain dysfunction caused by severe hepatocellular failure or presence of portal-systemic shunts in patients with liver cirrhosis. In its subclinical form, called “minimal hepatic encephalopathy (MHE), only psychometric tests or electrophysiological evaluation can reveal alterations in attention, working memory, psychomotor speed and visuospatial ability, while clinical neurological signs are lacking. The term “covert” (CHE) has been recently used to unify MHE and Grade I HE in order to refer to a condition that is not unapparent but also non overt. “Overt” HE (OHE) is characterized by personality changes, progressive disorientation in time and space, acute confusional state, stupor and coma. Based on its time course, OHE can be divided in Episodic, Recurrent or Persistent. Episodic HE is generally triggered by one or more precipitant factors that should be found and treated. Unlike MHE, clinical examination and clinical decision are crucial for OHE diagnosis and West Haven criteria are widely used to assess the severity of neurological dysfunction. Primary prophylaxis of OHE is indicated only in the patient with gastrointestinal bleeding using non-absorbable antibiotics (Rifaximin) or non-absorbable disaccharides (Lactulose). Treatment of OHE is based on the identification and correction of precipitating factors and starting empirical ammonia-lowering treatment with Rifaximin and Lactulose (per os and enemas). The latter should be used for secondary prophylaxis, adding Rifaximin if HE becomes recurrent. In recurrent/persistent HE, the treatment options include fecal transplantation, TIPS revision and closure of eventual splenorenal shunts. Treatment of MHE should be individualized on a case-by-case basis.
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Rose CF, Amodio P, Bajaj JS, Dhiman RK, Montagnese S, Taylor-Robinson SD, Vilstrup H, Jalan R. Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol 2020; 73:1526-1547. [PMID: 33097308 DOI: 10.1016/j.jhep.2020.07.013] [Citation(s) in RCA: 266] [Impact Index Per Article: 53.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 07/01/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is a frequent and serious complication of both chronic liver disease and acute liver failure. HE manifests as a wide spectrum of neuropsychiatric abnormalities, from subclinical changes (mild cognitive impairment) to marked disorientation, confusion and coma. The clinical and economic burden of HE is considerable, and it contributes greatly to impaired quality of life, morbidity and mortality. This review will critically discuss the latest classification of HE, as well as the pathogenesis and pathophysiological pathways underlying the neurological decline in patients with end-stage liver disease. In addition, management strategies, diagnostic approaches, currently available therapeutic options and novel treatment strategies are discussed.
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Affiliation(s)
- Christopher F Rose
- Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada.
| | - Piero Amodio
- Department of Medicine, University of Padova, Padova, Italy
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Radha Krishan Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, St. Mary's Hospital Campus, Imperial College London, London, United Kingdom
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, United Kingdom; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.
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Greinert R, Zipprich A, Simón-Talero M, Stangl F, Ludwig C, Wienke A, Praktiknjo M, Höhne K, Trebicka J, Genescà J, Ripoll C. Covert hepatic encephalopathy and spontaneous portosystemic shunts increase the risk of developing overt hepatic encephalopathy. Liver Int 2020; 40:3093-3102. [PMID: 32890428 DOI: 10.1111/liv.14660] [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: 04/03/2020] [Revised: 08/14/2020] [Accepted: 08/20/2020] [Indexed: 12/13/2022]
Abstract
AIM The aim of the study was to evaluate the presence of covert hepatic encephalopathy (cHE) and its characteristics according to the presence of spontaneous portosystemic shunts (SPSS) and their influence on the development of overt hepatic encephalopathy. METHODS Secondary analysis of a multicentre study, which evaluated the association between SPSS and complications of cirrhosis. The present study population includes those patients who also underwent cHE diagnostic evaluation. Presence of SPSS was evaluated by cross-sectional imaging and quantified by total SPSS-area. Logistic and Cox-regression competing risk analyses were performed. RESULTS About 65 patients were included of age 58 (IQR 50-66), MELD 15 (IQR 10-20), with alcoholic liver disease 63%. Thirty-two patients (49%) had cHE, had higher MELD [16 (IQR 12-24) vs 13 (IQR 9-17), P = .027], a greater proportion of SPSS [n = 18 (56%) vs n = 8 (24%); P = .008] and a higher total cross-sectional SPSS-area [28.3 (0-94.2) vs 0 (0-14.1); P = .005]. On multivariate analysis MELD [OR 1.11 (95% CI 1.01-1.21)] and presence of SPSS [OR 3.95 (95% CI 1.22-12.80)] were independently associated to cHE at baseline. During follow-up cHE was an independent predictor of oHE [cHE: HR 6.93 (95% CI 2.64-18.20). The effect of cHE on the development of oHE was greater in patients with SPSS [only cHE: HR 5.66 (95% CI 1.82-17.62), cHE and SPSS: HR 8.63 (95% CI 3.15-23.65)]. CONCLUSIONS cHE is independently associated to the presence of SPSS (and total cross-sectional SPSS-area) and MELD. Furthermore, the presence of SPSS seems to increase the risk of cHE of developing of overt hepatic encephalopathy.
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Affiliation(s)
- Robin Greinert
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
| | - Alexander Zipprich
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
| | - Macarena Simón-Talero
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), CIBEREHD, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Franz Stangl
- Department of Radiology, Martin-Luther University Halle-Wittenberg, Halle, Germany
| | - Christiane Ludwig
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
| | - Andreas Wienke
- Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | | | - Kevin Höhne
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
| | - Jonel Trebicka
- Medizinische Klinik 1, Universitätsklinikum Frankfurt. Goethe Universität, Frankfurt, Germany
| | - Joan Genescà
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), CIBEREHD, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Cristina Ripoll
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
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Jo G, Kim YM, Jun DW, Jeong E. Pitch Processing Can Indicate Cognitive Alterations in Chronic Liver Disease: An fNIRS Study. Front Hum Neurosci 2020; 14:535775. [PMID: 33132872 PMCID: PMC7578697 DOI: 10.3389/fnhum.2020.535775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 08/26/2020] [Indexed: 11/13/2022] Open
Abstract
Early detection and evaluation of cognitive alteration in chronic liver disease is important for predicting the subsequent development of hepatic encephalopathy. While visuomotor tasks have been rigorously employed for cognitive evaluation in chronic liver disease, there is a paucity of auditory processing task. Here we focused on auditory perception and examined behavioral and haemodynamic responses to a melodic contour identification task (CIT) to compare cognitive abilities in patients with chronic liver disease (CLD, N = 30) and healthy controls (N = 25). Further, we used support vector machines to examine the optimal combination of channels of functional near-infrared spectroscopy that can classify cognitive alterations in CLD. Behavioral findings showed that CIT performance was significantly worse in the patient group and CIT significantly correlated with neurocognitive evaluation (i.e., number connection test, digit span test). The findings indicated that CIT can measure auditory cognitive capacity and its difference existing between patient group and healthy controls. Additionally, optimal subsets classified the 16-dimensional haemodynamic data with 78.35% classification accuracy, yielding markers of cognitive alterations in the prefrontal regions (CH6, CH7, CH10, CH13, CH14, and CH16). The results confirmed the potential use of behavioral as well as haemodynamic responses to music perception as an alternative or supplementary method for evaluating cognitive alterations in chronic liver disease.
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Affiliation(s)
- Geonsang Jo
- Daehong Communications Inc, Seoul, South Korea
| | - Young-Min Kim
- Graduate School of Technology and Innovation Management, Hanyang University, Seoul, South Korea
- College of Interdisciplinary Industrial Studies, Hanyang University, Seoul, South Korea
| | - Dae Won Jun
- Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, South Korea
- *Correspondence: Dae Won Jun
| | - Eunju Jeong
- College of Interdisciplinary Industrial Studies, Hanyang University, Seoul, South Korea
- Department of Music and Science for Clinical Practice, Hanyang University, Seoul, South Korea
- Eunju Jeong
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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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Impact of sustained viral response in the evolution of minimal hepatic encephalopathy: A prospective pilot study. Ann Hepatol 2020; 18:429-433. [PMID: 31054981 DOI: 10.1016/j.aohep.2018.07.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Revised: 07/30/2018] [Accepted: 07/31/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIMS To determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. MATERIALS AND METHODS We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. RESULTS 64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p<0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p=0.02), higher Child-Pugh scores at 24-weeks post-treatment (p=0.04), higher baseline INR levels (1.4 vs. 1.1; p<0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p=0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p=0.04). CONCLUSION We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.
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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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Bajaj JS, Lauridsen M, Tapper EB, Duarte-Rojo A, Rahimi RS, Tandon P, Shawcross DL, Thabut D, Dhiman RK, Romero-Gomez M, Sharma BC, Montagnese S. Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus. Am J Gastroenterol 2020; 115:989-1002. [PMID: 32618647 DOI: 10.14309/ajg.0000000000000603] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Management of hepatic encephalopathy (HE) remains challenging from a medical and psychosocial perspective. Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management focused on (i) driving, (ii) ammonia levels in clinical practice, (iii) testing strategies for covert or minimal HE, (iv) therapeutic options, and (v) nutrition and patient-reported outcomes. The consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice, laying the groundwork for future investigations.
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Affiliation(s)
- Jasmohan S Bajaj
- Virginia Commonwealth University, McGuire VA Medical Center, Richmond, Virginia, USA
| | | | | | | | | | | | | | - Dominique Thabut
- Paris Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France
| | - Radha K Dhiman
- Postgraduate Institute of Medical Education & Research, Chandigarh, India
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Abid S, Kamran M, Abid A, Butt N, Awan S, Abbas Z. Minimal Hepatic Encephalopathy: Effect of H. pylori infection and small intestinal bacterial overgrowth treatment on clinical outcomes. Sci Rep 2020; 10:10079. [PMID: 32572109 PMCID: PMC7308324 DOI: 10.1038/s41598-020-67171-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 06/03/2020] [Indexed: 12/18/2022] Open
Abstract
The effect Helicobacter pylori (Hp) infection and small intestinal bacterial over growth (SIBO) in minimal hepatic encephalopathy (MHE) is not well understood. The aim of the study was to determine the effect of eradication of Hp infection and SIBO treatment on MHE in patients with cirrhosis. Patients with cirrhosis were enrolled and MHE was determined by psychometric tests and critical flicker frequency analysis. Hp infection and SIBO were assessed by urea breath and Hydrogen breath tests respectively in patients with cirrhosis and in healthy volunteers. Patients with Hp infection and SIBO were given appropriate treatment. At six weeks follow-up, presence of Hp infection, SIBO and MHE status was reassessed. Ninety patients with cirrhosis and equal number of healthy controls were included. 55 (61.1%) patients in the cirrhotic group were diagnosed to have underlying MHE. Among cirrhotic group, Hp infection was present in 28 with MHE (50.9%) vs. in 15 without MHE (42.8%) (p = 0.45). Similarly, SIBO was present in 17 (30.9%) vs. 11 (31.4%) (p = 0.95) in patients with and without MHE respectively. In comparison with healthy controls, patients with cirrhosis were more frequently harboring Hp and SIBO (47.7% vs. 17.7% (p < 0.001) and 31.1% vs. 4.4% (p < 0.001) respectively. On follow-up, all patients showed evidence of eradication of Hp and SIBO infection. Treatment of SIBO significantly improved the state of MHE in cirrhotics, however eradication of Hp infection did not improve MHE significantly. Additionally, patients with low Model for End-Stage Liver Disease (MELD) score and belonging to Child class B had significantly better improvement in MHE. A large number of patients with cirrhosis had either active Hp infection or SIBO with or without MHE, compared to healthy controls. Treatment of SIBO significantly improved MHE in patients with cirrhosis, whereas eradication of Hp did not affect the outcome of MHE in these patients.
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Affiliation(s)
- Shahab Abid
- Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Pakistan.
| | - Muhammad Kamran
- Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Adeel Abid
- Medical College, Aga Khan University, Karachi, Pakistan
| | - Nazish Butt
- Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Safia Awan
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Zaigham Abbas
- Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Pakistan
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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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Zarrindast MR, Issazadeh Y, Rezaei N, Khakpai F. Possible involvement of the opioidergic system in the modulation of body temperature, jumping behavior and memory process in cholestatic and addicted mice. EXCLI JOURNAL 2020; 19:311-322. [PMID: 32256271 PMCID: PMC7105937 DOI: 10.17179/excli2019-2055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 02/24/2020] [Indexed: 11/10/2022]
Abstract
Cholestasis is related to an increased plasma level of endogenous opioid levels. Naloxone-induced withdrawal syndrome has been reported in a mouse model of cholestasis. Moreover, studies revealed that the memory process is affected by cholestasis. Thus, we aimed at determining whether pharmacological manipulation of the opioidergic system is involved in signs of cholestasis disease such as hypothermia and withdrawal behaviors such as jumping behavior as well as memory process in mice. Cholestasis was induced by bile duct resection in mice and physical dependence was induced by administration of morphine and/or tramadol three times daily (8, 12 and 16 h) at the doses of 25, 50 and 75 mg/kg during three consecutive days. The memory process was assessed by a step-down passive avoidance test. Our results indicated that cholestatic mice showed hypothermia whereas cholestatic- and drug dependent mice indicated hyperthermia. Moreover, administration of morphine (50 mg/kg) and/or tramadol (50 mg/kg) on the 4th day, 2 h before naloxone injection significantly decreased latency to first jumping but increased the number of jumping and rearing behavior as well as locomotor activity in BDL-vs. sham-operated mice. In addition, the latency time of the step-down test decreased in BDL-vs. sham-operated group, showing impairment of memory in BDL mice. The results of this study support the evidence that (1) the opioidergic system involved in thermoregulation of cholestasis mice, (2) μ-opioid receptors play an important role in withdrawal behaviors, and (3) memory process is affected by cholestasis and addiction in mice.
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Affiliation(s)
- Mohammad-Reza Zarrindast
- Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.,Department of Neuroendocrinology, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Yasaman Issazadeh
- Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Niloofar Rezaei
- Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Khakpai
- Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications. Clin Mol Hepatol 2020; 26:83-127. [PMID: 31918536 PMCID: PMC7160350 DOI: 10.3350/cmh.2019.0010n] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 10/23/2019] [Indexed: 02/06/2023] Open
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Ampuero J, Gil A, Viloria MDM, Rico MC, Millán R, Camacho I, Romero-Gómez M. Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy. Liver Int 2020; 40:921-930. [PMID: 31729816 DOI: 10.1111/liv.14297] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/22/2019] [Accepted: 10/25/2019] [Indexed: 02/13/2023]
Abstract
BACKGROUND The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE. METHODS We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post-load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low-, intermediate- and high-risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow-up. RESULTS The 28.3% (56/198) of the main cohort suffered from HE during the follow-up. In the competing risk analysis, both intermediate- (subhazard ratio (sHR) 2.01 (95% CI 1.00-4.14); P = .048) and high-risk groups (sHR 4.67 (95% CI 2.19-9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high-risk group was two and four times greater than the intermediate- and low-risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high-risk group, while infections and electrolyte imbalance predominated in the rest of patients. CONCLUSION Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision-making process for the adequate management of HE.
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Affiliation(s)
- Javier Ampuero
- Hospital Universitario Virgen del Rocío, Sevilla, Spain.,Instituto de Biomedicina de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.,Universidad de Sevilla, Sevilla, Spain
| | - Antonio Gil
- Instituto de Biomedicina de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | | | - María Carmen Rico
- Instituto de Biomedicina de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Raquel Millán
- Instituto de Biomedicina de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Inés Camacho
- Hospital Universitario Virgen de Valme, Sevilla, Spain
| | - Manuel Romero-Gómez
- Hospital Universitario Virgen del Rocío, Sevilla, Spain.,Instituto de Biomedicina de Sevilla, Sevilla, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.,Universidad de Sevilla, Sevilla, Spain
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47
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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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Coronel-Castillo C, Contreras-Carmona J, Frati-Munari A, Uribe M, Méndez-Sánchez N. Efficacy of rifaximin in the different clinical scenarios of hepatic encephalopathy. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2020. [DOI: 10.1016/j.rgmxen.2019.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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49
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Coronel-Castillo CE, Contreras-Carmona J, Frati-Munari AC, Uribe M, Méndez-Sánchez N. Efficacy of rifaximin in the different clinical scenarios of hepatic encephalopathy. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2020; 85:56-68. [PMID: 31836274 DOI: 10.1016/j.rgmx.2019.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 08/21/2019] [Accepted: 09/04/2019] [Indexed: 06/10/2023]
Abstract
Hepatic encephalopathy is a frequent complication in patients with cirrhosis of the liver and is associated with a high mortality rate. Costs attributed to the management of patients with cirrhosis are especially high due to complications, such as hepatic encephalopathy, given that they increase the number of days of hospital stay. Different drugs are currently used to treat hepatic encephalopathy, and the main ones are lactulose, L-ornithine L-aspartate (LOLA), and certain antibiotics, especially rifaximin-α (RFX). Even though many of them have been shown to be effective to greater or lesser degrees, it is important to understand the differences between them, so that every patient receives individualized treatment and the best option is chosen, in accordance with the different clinical scenarios. Thus, the aim of the present study was to analyze the evidence on the advantages and disadvantages of the individual or combined use of the 3 main treatments for hepatic encephalopathy, specifically taking into consideration their different degrees of efficacy, their impact on quality of life, prophylaxis, and cost reduction.
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Affiliation(s)
- C E Coronel-Castillo
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México
| | - J Contreras-Carmona
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México
| | - A C Frati-Munari
- Departamento de Medicina Interna, Fundación Clínica Médica Sur, Ciudad de México, México
| | - M Uribe
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México
| | - N Méndez-Sánchez
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México; Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México.
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50
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Hopp AE, Dirks M, Petrusch C, Goldbecker A, Tryc AB, Barg-Hock H, Strassburg C, Klempnauer J, Weissenborn K, Pflugrad H. Hepatic Encephalopathy Is Reversible in the Long Term After Liver Transplantation. Liver Transpl 2019; 25:1661-1672. [PMID: 31437344 DOI: 10.1002/lt.25626] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 08/10/2019] [Indexed: 12/14/2022]
Abstract
Cognitive dysfunction caused by hepatic encephalopathy (HE) improves within the first year after liver transplantation (LT). However, cognitive restitution seems to be incomplete in a subset of patients and after LT a new-onset cognitive decline was described. Data about the longterm development of cognitive function after liver transplantation (LT) are sparse. This prospective study analyzed whether a history of hepatic encephalopathy (HE) before LT had an impact on the longterm outcome of cognitive function after LT and if patients who underwent LT 5 years earlier showed worse cognitive function than healthy controls. The cognitive function of 34 patients was assessed before LT and at 1 year and 5 years after LT by psychometric tests, including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the portosystemic encephalopathy syndrome test, which provides the psychometric hepatic encephalopathy score (PHES). Furthermore, patients completed surveys to assess health-related quality of life (HRQOL). An 22 additional patients were included after LT. Patients were subdivided by having a history of HE before LT. The control group consisted of 55 healthy patients adjusted for age and education. Before LT, patients performed significantly worse than controls in the psychometric tests: RBANS Total Scale (TS), mean ± standard deviation (SD), 92.6 ± 13.3 versus 99.9 ± 12.0, P = 0.01; and PHES, median (interquartile range [IQR]), 0 (-3 to 1) versus 1 (0-2), P < 0.001. At 1 year after LT, patients with a history of HE still showed cognitive impairment compared with controls: RBANS TS, mean ± SD, 89.8 ± 15.1 versus 99.9 ± 12.0, P < 0.01; and PHES, median (IQR), 0 (-2 to 1.25) versus 1 (0-2), P = 0.03. At 5 years after LT, patients with and without a history of HE showed normal cognitive function and improved HRQOL. In conclusion, HE-associated cognitive impairment seems to be reversible within 5 years after LT.
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Affiliation(s)
| | - Meike Dirks
- Department of Neurology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany
| | | | - Annemarie Goldbecker
- Department of Neurology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany
| | - Anita Blanka Tryc
- Department of Neurology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany
| | - Hannelore Barg-Hock
- Clinic for Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Christian Strassburg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Jürgen Klempnauer
- Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany.,Clinic for Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Karin Weissenborn
- Department of Neurology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany
| | - Henning Pflugrad
- Department of Neurology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany
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