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Wongtrakul W, Bandidniyamanon W, Charatcharoenwitthaya P. Relationship between Sarcopenia and minimal hepatic encephalopathy in patients with cirrhosis: a prospective observational study. BMC Gastroenterol 2025; 25:88. [PMID: 39962372 PMCID: PMC11834310 DOI: 10.1186/s12876-025-03674-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 02/10/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Sarcopenia, characterized by loss of muscle mass and function, has gained importance in the evaluation of cirrhotic patients. Evidence suggests its role in adverse clinical outcomes, including minimal hepatic encephalopathy (MHE). This study aimed to investigate the association between sarcopenia and MHE in patients with cirrhosis. METHODS We prospectively enrolled outpatients with cirrhosis to assess sarcopenia using the 2019 criteria from the Asian Working Group for Sarcopenia. MHE was diagnosed through the Psychometric Hepatic Encephalopathy Score. RESULTS Of the 210 cirrhotic patients (57.1% male, mean age 62.7 ± 9.6 years), 54 (25.7%) had sarcopenia, with 26 (12.3%) classified as severe. Thirty-seven patients (17.6%) were diagnosed with MHE. Sarcopenia prevalence was significantly higher in patients with MHE compared to those without MHE (45.9% vs. 21.4%). MHE was significantly associated with age, education level, Mini-Mental State Examination score, and a history of hepatic decompensation. No significant associations were found regarding gender, body mass index, comorbidities, sleep quality, and the etiology of cirrhosis. Multivariable logistic regression showed that MHE was significantly associated with age (adjusted odds ratio [aOR] 1.08, 95% CI 1.02-1.13), sarcopenia (aOR 3.29, 95% CI 1.44-7.50), history of overt hepatic encephalopathy (aOR 7.40, 95% CI 1.20-45.56), and variceal bleeding (aOR 3.13, 95% CI 1.38-7.10). Severe sarcopenia was also independently associated with MHE (aOR 3.64, 95% CI 1.32-10.05). CONCLUSIONS Sarcopenia is prevalent in cirrhotic patients and is associated with an increased risk of MHE. Our findings emphasize the importance of assessing sarcopenia to potentially mitigate MHE risk in managing patients with cirrhosis.
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Affiliation(s)
- Wasit Wongtrakul
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Wimolrak Bandidniyamanon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Centre for Liver and Digestive Diseases (CIBERehd). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502208. [PMID: 39756832 DOI: 10.1016/j.gastrohep.2024.502208] [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: 03/19/2024] [Revised: 04/07/2024] [Accepted: 04/09/2024] [Indexed: 01/07/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Universidad Complutense, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España.
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Albillos A, Bañares R, Hernández-Gea V. Portal hypertension: recommendations for diagnosis and treatment. Consensus document sponsored by the Spanish Association for the Study of the Liver (AEEH) and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd). REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117:14-57. [PMID: 39350672 DOI: 10.17235/reed.2024.10805/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, España
| | - Rafael Bañares
- Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Marañón
| | - Virginia Hernández-Gea
- Servicio de Hepatología, Hospital Clínic. Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
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Jiang TT, Liu XL, Yu H, Sun YX, Zhou JY, Yang ZY, Chen G. External validation of EncephalApp Stroop test to screen minimal hepatic encephalopathy patients with nonalcoholic cirrhosis. World J Hepatol 2024; 16:1450-1457. [DOI: 10.4254/wjh.v16.i12.1450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/29/2024] [Accepted: 09/11/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Neurocognitive impairment, including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, is one of the most common complications of all types of primary liver diseases, such as hepatitis B, biliary cholangitis, and autoimmune hepatitis. The EncephalApp Stroop test is a smartphone application-based test that is time-saving for MHE screening. However, neurocognitive impairment is different between alcoholic cirrhosis patients and nonalcoholic cirrhosis patients, so the cutoff value for MHE diagnosis might be inflated.
AIM To validate the Stroop test in nonalcoholic cirrhosis patients.
METHODS This external validation was performed at the National Center for Infectious Diseases (Beijing). Liver cirrhosis patients aged between 18 and 65 years who voluntarily enrolled in the study and provided signed informed consent were included. The Psychometric Hepatic Encephalopathy Score (PHES) test was used as the standard diagnostic criterion for MHE. The EncephalApp Stroop test was then performed on the iPad, including two sessions of tests (“off” and “on”) to measure patients’ ability to differentiate between numbers and letters. We assessed the performance of the EncephalApp Stroop test in terms of the area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value, with the PHES as the standard criterion.
RESULTS A total of 160 nonalcoholic cirrhosis patients were included in this validation study, including 87 (54.4%) patients without MHE and 73 (45.6%) patients with MHE. Taking the PHES as the gold standard, the EncephalApp Stroop test performed well for nonalcoholic liver cirrhosis patients in terms of “off” time [AUC: 0.85, 95% confidence interval (CI): 0.79-0.91] and “on + off” time (AUC: 0.85, 95%CI: 0.80-0.91); however, total runs of “off” session (AUC: 0.61, 95%CI: 0.52-0.69), total runs of “on” session (AUC: 0.57, 95%CI: 0.48-0.65), and “on – off” time (AUC: 0.54, 95%CI: 0.44-0.63) were comparatively low. The optimal cutoff points were “off” time > 101.93 seconds and “on + off” time > 205.86 seconds, with sensitivities of 0.84 and 0.90, specificities of 0.77 and 0.71, positive predictive values of 0.75 and 0.72, and false-positive values of 0.85 and 0.89, respectively.
CONCLUSION Our results suggest that different cutoffs should be used for the EncephalApp Stroop tool for MHE screening between alcoholic and nonalcoholic living patients, which is a critical check before generalization to screen for neurocognitive impairment among the whole population of chronic liver diseases.
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Affiliation(s)
- Ting-Ting Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing 100015, China
| | - Xiao-Li Liu
- Center of Integrative Medicine, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing 100015, China
| | - Hao Yu
- Center of Integrative Medicine, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing 100015, China
| | - Ya-Xuan Sun
- T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, United States
| | - Jia-Yan Zhou
- School of Medicine, Stanford University, Stanford, CA 94305, United States
| | - Zhi-Yun Yang
- Center of Integrative Medicine, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing 100015, China
| | - Guang Chen
- LKS Faculty of Medicine, University of Hong Kong, Hong Kong 999077, 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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Wolpert BM, Rothgerber DJ, Rosner AK, Brunier M, Kuchen R, Schramm P, Griemert EV. Evaluation of dynamic cerebrovascular autoregulation during liver transplantation. PLoS One 2024; 19:e0305658. [PMID: 39058695 PMCID: PMC11280153 DOI: 10.1371/journal.pone.0305658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 06/03/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Cerebrovascular autoregulation in patients with acute and chronic liver failure is often impaired, yet an intact autoregulation is essential for the demand-driven supply of oxygenated blood to the brain. It is unclear, whether there is a connection between cerebrovascular autoregulation during liver transplantation (LTX) and the underlying disease, and if perioperative anesthesiologic consequences can result from this. METHODS In this prospective observational pilot study, data of twenty patients (35% female) undergoing LTX were analyzed. Cerebral blood velocity was measured using transcranial doppler sonography and was correlated with arterial blood pressure. The integrity of dynamic cerebrovascular autoregulation (dCA) was evaluated in the frequency domain through transfer function analysis (TFA). Standard clinical parameters were recorded. Mixed one-way ANOVA and generalized estimating equations were fitted to data involving repeated measurements on the same patient. For all other correlation analyses, Spearman's rank correlation coefficient (Spearman's-Rho) was used. RESULTS Indications of impaired dCA are seen in frequency domain during different phases of LTX. No correlation was found between various parameter of dCA and primary disease, delirium, laboratory values, length of ICU or hospital stay, mortality or surgical technique. CONCLUSIONS Although in most cases the dCA has been impaired during LTX, the heterogeneity of the underlying diseases seems to be too diverse to draw valid conclusions from this observational pilot study.
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Affiliation(s)
- Bente Marei Wolpert
- Department of Anesthesiology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
| | - David Jonas Rothgerber
- Department of Anesthesiology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
| | - Ann Kristin Rosner
- Department of Anesthesiology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
| | - Malte Brunier
- Department of Anesthesiology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
| | - Robert Kuchen
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
| | - Patrick Schramm
- Department of Neurology, University Hospital of the Justus-Liebig-University Giessen, Giessen, Germany
| | - Eva-Verena Griemert
- Department of Anesthesiology, University Medical Centre of the Johannes-Gutenberg University Mainz, Mainz, Germany
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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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He Q, Mao C, Chen Z, Zeng Y, Deng Y, Hu R. Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials. Arab J Gastroenterol 2024; 25:84-92. [PMID: 38403493 DOI: 10.1016/j.ajg.2024.01.006] [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: 06/13/2023] [Revised: 11/12/2023] [Accepted: 01/06/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND AND STUDY AIMS Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE) and is highly prevalent. The efficacy of L-ornithine L-aspartate (LOLA) for the treatment of HE is well known but its role in MHE remains uncertain. The objectives of the current study were to evaluate the efficacy of LOLA for the treatment of MHE in patients with cirrhosis. METHODS The Cochrane Library, PubMed, EMBASE, Web of Science and Ovid databases were searched. Only randomized controlled trials (RCTs) that compared the efficacy of LOLA with placebo or no intervention for the treatment of MHE in patients with cirrhosis were included from inception to January 2023. The primary outcomes were reversal of MHE and development of overt hepatic encephalopathy (OHE). RESULTS Overall, six RCTs comprising 292 patients were included. Compared with placebo or no intervention, LOLA was more effective in reversing MHE (RR = 2.264, 95 % CI = 1.528, 3.352, P = 0.000, I2 = 0.0 %) and preventing progression of OHE (RR = 0.220, 95 % CI = 0.076, 0.637, P = 0.005, I2 = 0.0 %). Based on subgroup analyses, oral LOLA treatment appeared more likely to reverse MHE (RR = 2.648, 95 % CI = 1.593, 4.402, P = 0.000, I2 = 0.0 %), intravenous LOLA treatment yielded a similar probability of reversing MHE (RR = 1.669, 95 % CI = 0.904, 3.084, P = 0.102, I2 = 0.0 %). LOLA did not show a superior possibility in reducing mortality (RR = 0.422, 95 % CI = 0.064, 2.768, P = 0.368, I2 = 0.0 %) and ammonia levels (SMD = 0.044, 95 % CI = -0.290, 0.379, P = 0.795, I2 = 0.0 %) compared with placebo or no intervention. CONCLUSIONS LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.
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Affiliation(s)
- Qiufeng He
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Chuangjie Mao
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Zhili Chen
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Yilan Zeng
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Yang Deng
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China
| | - Rong Hu
- Department of Hepatology, Public Health Clinical Center of Chengdu, N0.377, Jing Ming Road, Jin Jiang District, Chengdu, Sichuan, China.
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Ravindranath A, Yachha SK. An Approach to Investigations of Chronic Liver Disease. Indian J Pediatr 2024; 91:262-269. [PMID: 37702974 DOI: 10.1007/s12098-023-04751-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 06/23/2023] [Indexed: 09/14/2023]
Abstract
Chronic liver disease (CLD) in children is more diverse compared to adults with respect to the etiology, progression and response to therapy. After history and clinical examination, the first step is to confirm the presence of CLD with basic blood investigations and ultrasonography. Markers of portal hypertension are splenomegaly, increased portal vein diameter, thrombocytopenia and presence of varices on endoscopy. The next step is to evaluate the etiology of CLD which will depend on the age of the child and needs targeted investigations as metabolic and inherited causes predominate in early childhood. CLD progression ought to be monitored regularly and several non-invasive markers are available but they have to be evaluated further in children. Since CLD progresses, complications have to be detected early not only to initiate appropriate treatment but also to prognosticate.
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Affiliation(s)
- Aathira Ravindranath
- Department of Pediatric Gastroenterology, Institute of Gastrointestinal Sciences, Apollo BGS Hospitals, Kuvempunagar, Mysore, Karnataka, 570023, India
| | - Surender Kumar Yachha
- Department of Pediatric Gastroenterology, Hepatology and Liver Transplantation, Sakra World Hospital, Bengaluru, Karnataka, 560103, India.
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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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11
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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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12
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Ji J, Liu YY, Wu GW, Hu YL, Liang CH, Wang XD. Changes in dynamic and static brain fluctuation distinguish minimal hepatic encephalopathy and cirrhosis patients and predict the severity of liver damage. Front Neurosci 2023; 17:1077808. [PMID: 37056312 PMCID: PMC10086246 DOI: 10.3389/fnins.2023.1077808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 03/13/2023] [Indexed: 03/30/2023] Open
Abstract
PurposeMinimal hepatic encephalopathy (MHE) is characterized by mild neuropsychological and neurophysiological alterations that are not detectable by routine clinical examination. Abnormal brain activity (in terms of the amplitude of low-frequency fluctuation (ALFF) has been observed in MHE patients. However, little is known concerning temporal dynamics of intrinsic brain activity. The present study aimed to investigate the abnormal dynamics of brain activity (dynamic ALFF; dALFF) and static measures [static ALFF; (sALFF)] in MHE patients and to strive for a reliable imaging neuromarkers for distinguishing MHE patients from cirrhosis patients. In addition, the present study also investigated whether intrinsic brain activity predicted the severity of liver damage.MethodsThirty-four cirrhosis patients with MHE, 28 cirrhosis patients without MHE, and 33 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI). dALFF was estimated by combining the ALFF method with the sliding-window method, in which temporal variability was quantized over the whole-scan timepoints and then compared among the three groups. Additionally, dALFF, sALFF and both two features were utilized as classification features in a support vector machine (SVM) to distinguish MHE patients from cirrhosis patients. The severity of liver damage was reflected by the Child–Pugh score. dALFF, sALFF and both two features were used to predict Child–Pugh scores in MHE patients using a general linear model.ResultsCompared with HCs, MHE patients showed significantly increased dALFF in the left inferior occipital gyrus, right middle occipital gyrus, and right insula; increased dALFF was also observed in the right posterior lobe of the cerebellum (CPL) and right thalamus. Compared with HCs, noMHE patients exhibited decreased dALFF in the right precuneus. In contrast, compared with noMHE patients, MHE patients showed increased dALFF in the right precuneus, right superior frontal gyrus, and right superior occipital gyrus. Furthermore, the increased dALFF values in the left precuneus were positively associated with poor digit-symbol test (DST) scores (r = 0.356, p = 0.038); however, dALFF in the right inferior temporal gyrus (ITG) was negatively associated with the number connection test–A (NCT-A) scores (r = -0.784, p = 0.000). A significant positive correlation was found between dALFF in the left inferior occipital gyrus (IOG) and high blood ammonia levels (r = 0.424, p = 0.012). Notably, dALFF values yielded a higher classification accuracy than sALFF values in distinguishing MHE patients from cirrhosis patients. Importantly, the dALFF values predicted the Child–Pugh score (r = 0.140, p = 0.030), whereas sALFF values did not in the current dataset. Combining two features had high accuracy in classification in distinguishing MHE patients from cirrhotic patients and yielded prediction in the severity of liver damage.ConclusionThese findings suggest that combining dALFF and sALFF features is a useful neuromarkers for distinguishing MHE patients from cirrhosis patients and highlights the important role of dALFF feature in predicting the severity of liver damage in MHE.
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Affiliation(s)
- Jiang Ji
- Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China
- Department of Radiology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Yi-yang Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guo-Wei Wu
- Chinese Institute for Brain Research, Beijing, China
| | - Yan-Long Hu
- Department of Radiology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Chang-Hua Liang
- Department of Radiology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
- *Correspondence: Chang-Hua Liang,
| | - Xiao-dong Wang
- Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China
- Xiao-dong Wang,
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13
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Mangini C, Zarantonello L, Formentin C, Giusti G, Angeli P, Montagnese S. Evolution of hepatic encephalopathy over time: ecological data from a tertiary referral centre for hepatology. Dig Liver Dis 2023; 55:93-98. [PMID: 35725551 DOI: 10.1016/j.dld.2022.06.003] [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: 04/26/2022] [Revised: 05/27/2022] [Accepted: 06/01/2022] [Indexed: 12/31/2022]
Abstract
OBJECTIVES Few data on hepatic encephalopathy (HE) over time are available, thus our aim was to study its evolution in patients with varying degree of HE on first assessment. METHODS Eighty-six patients with cirrhosis (age = 58 ± 11 years; males = 72) were evaluated 2-10 times for liver transplantation selection purposes, differential diagnosis or treatment optimization. The presence/severity of HE was assessed by clinical and neuropsychiatric indices [ Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalography (EEG)] and the severity of liver disease by the Model for End-Stage Liver Disease (MELD) score. Treatment was instituted/modified after each evaluation. RESULTS Amongst 23 unimpaired patients, 56/6% remained unimpaired, 35/3% developed covert HE, 9/0% developed overt HE on second/third evaluation. Amongst 32 patients with covert HE, 25/10% became unimpaired, 44/19% remained covert, 31/13% developed overt HE. Finally, amongst 32 patients with overt HE, 19/16% became unimpaired, 25/13 % became covert and 56/25% remained overt. PHES results improved in patients with overt HE and EEG worsened over time (despite remaining normal) in unimpaired patients. In patients with multiple evaluations, HE evolution was manifold and difficult to predict. CONCLUSIONS HE evolution over time is variable and largely dependent on HE history/management. These data support the concept that HE is an essentially reversible condition.
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Affiliation(s)
- C Mangini
- Department of Medicine, University of Padova, Via Giustiniani 2, Padova 35128, Italy
| | - L Zarantonello
- Department of Medicine, University of Padova, Via Giustiniani 2, Padova 35128, Italy
| | - C Formentin
- Department of Medicine, University of Padova, Via Giustiniani 2, Padova 35128, Italy
| | - G Giusti
- Department of Medicine, University of Padova, Via Giustiniani 2, Padova 35128, Italy
| | - P Angeli
- Department of Medicine, University of Padova, Via Giustiniani 2, Padova 35128, Italy
| | - S Montagnese
- Department of Medicine, University of Padova, Via Giustiniani 2, Padova 35128, Italy.
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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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Minimal Hepatic Encephalopathy Affects Daily Life of Cirrhotic Patients: A Viewpoint on Clinical Consequences and Therapeutic Opportunities. J Clin Med 2022; 11:jcm11237246. [PMID: 36498820 PMCID: PMC9736966 DOI: 10.3390/jcm11237246] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/21/2022] [Accepted: 11/27/2022] [Indexed: 12/12/2022] Open
Abstract
Minimal hepatic encephalopathy (MHE) is a frequent complication of hepatic encephalopathy (HE) and can affect up to 80% of patients with liver cirrhosis. It is characterized by the lack of obvious clinical signs and the presence of alterations detectable using psychometric or electrophysiological testing focused on attention, working memory, psychomotor speed and visuospatial ability. Ideally, each patient should be tested for this condition because, despite the absence of symptoms, it has severe repercussions on daily life activities. It may be responsible for an inability to drive, sleep disturbances, risk of falls and inability to work. Some studies have highlighted its prognostically unfavorable role on mortality and risk of "overt" HE (OHE). Finally, MHE severely affects the lives of patients and caregivers, altering their quality of life and their socioeconomic status. Several treatments have been proposed for MHE treatment, including non-absorbable disaccharides, poorly absorbable antibiotics, such as rifaximin, probiotics and branched-chain amino acids, with promising results. For this reason, early diagnosis and intervention with appropriate measures is essential, with the aim of improving both performance on psychometric tests, as well as clinical aspects related to this condition.
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16
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Gairing SJ, Anders J, Kaps L, Nagel M, Michel M, Kremer WM, Hilscher M, Galle PR, Schattenberg JM, Wörns MA, Labenz C. Evaluation of IL-6 for Stepwise Diagnosis of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis. Hepatol Commun 2022; 6:1113-1122. [PMID: 35032100 PMCID: PMC9035565 DOI: 10.1002/hep4.1883] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 11/28/2021] [Accepted: 12/06/2021] [Indexed: 11/10/2022] Open
Abstract
Diagnosis of minimal hepatic encephalopathy (MHE) requires psychometric testing, which is time-consuming and often neglected in clinical practice. Elevated Interleukin-6 (IL-6) serum levels have been linked to MHE. The aim of this study was to investigate the usefulness of IL-6 as a biomarker in a stepwise diagnostic algorithm to detect MHE in patients with liver cirrhosis. A total of 197 prospectively recruited patients without clinical signs of hepatic encephalopathy (HE) served as the development cohort. Another independent cohort consisting of 52 patients served for validation purposes. Psychometric Hepatic Encephalopathy Score (PHES) was applied for the diagnosis of MHE. Fifty (25.4%) patients of the development cohort presented with MHE. Median IL-6 levels were more than twice as high in patients with MHE than in patients without HE (16 vs. 7 pg/mL; P < 0.001). On multivariable logistic regression analysis, higher IL-6 levels (odds ratio 1.036; 95% confidence interval [CI] 1.009-1.064; P = 0.008) remained independently associated with the presence of MHE. IL-6 levels ≥ 8pg/mL discriminated best between patients with and without MHE in receiver operating characteristic (ROC) analysis (area under the ROC 0.751). With a cutoff value of ≥7 pg/mL, further elaborate testing with PHES could be avoided in 38% of all patients with a sensitivity of 90% (95% CI 77%-96%) and a negative predictive value (NPV) of 93% (95% CI 84%-98%). This diagnostic accuracy was confirmed in the validation cohort (sensitivity 94%; NPV 93%). Conclusion: Using IL-6 serum levels as a biomarker in a stepwise diagnostic algorithm to detect MHE could substantially reduce the number of patients requiring testing with PHES and in turn the workload. IL-6 may have especially helped in patients who are unable to perform other screening tests.
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Affiliation(s)
- Simon Johannes Gairing
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Julian Anders
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany
| | - Leonard Kaps
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Michael Nagel
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Maurice Michel
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Wolfgang Maximilian Kremer
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Max Hilscher
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Peter Robert Galle
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Jörn M Schattenberg
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Metabolic Liver Research ProgramUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
| | - Marcus-Alexander Wörns
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany.,Department of Gastroenterology, Hematology, Oncology and EndocrinologyKlinikum Dortmund GmbHDortmundGermany
| | - Christian Labenz
- Department of Internal Medicine IUniversity Medical Center of the Johannes Gutenberg-UniversityMainzGermany.,Cirrhosis Center MainzUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
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17
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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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18
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Gupta P, Vyas S, Salan T, Jain C, Taneja S, Dhiman RK, Singh P, Ahuja CK, Ray N, Govind V. Whole brain atlas-based diffusion kurtosis imaging parameters for evaluation of minimal hepatic encephalopathy. Neuroradiol J 2022; 35:67-76. [PMID: 34187242 PMCID: PMC8826285 DOI: 10.1177/19714009211026924] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND AND PURPOSES Minimal hepatic encephalopathy (MHE) has no recognizable clinical symptoms, but patients have cognitive and psychomotor deficits. Hyperammonemia along with neuroinflammation lead to microstructural changes in cerebral parenchyma. Changes at conventional imaging are detected usually at the overt clinical stage, but microstructural alterations by advanced magnetic resonance imaging techniques can be detected at an early stage. MATERIALS AND METHODS Whole brain diffusion kurtosis imaging (DKI) data acquired at 3T was analyzed to investigate microstructural parenchymal changes in 15 patients with MHE and compared with 15 age- and sex-matched controls. DKI parametric maps, namely kurtosis fractional anisotropy (kFA), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK), were evaluated at 64 white matter (WM) and gray matter (GM) regions of interest (ROIs) in the whole brain and correlated with the psychometric hepatic encephalopathy score (PHES). RESULTS The MHE group showed a decrease in kFA and AK across the whole brain, whereas MK and RK decreased in WM ROIs but increased in several cortical and deep GM ROIs. These alterations were consistent with brain regions involved in cognitive function. Significant moderate to strong correlations (-0.52 to -0.66; 0.56) between RK, MK and kFA kurtosis metrics and PHES were observed. CONCLUSION DKI parameters show extensive microstructural brain abnormalities in MHE with minor correlation between the severity of tissue damage and psychometric scores.
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Affiliation(s)
- Prateek Gupta
- Department of Radiodiagnosis and
Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh,
India
| | - Sameer Vyas
- Department of Radiodiagnosis and
Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh,
India,Sameer Vyas, Department of Radiodiagnosis
and Imaging, Postgraduate Institute of Medical Education and Research,
Chandigarh, India.
| | - Teddy Salan
- Department of Radiology, University
of Miami, USA
| | - Chirag Jain
- Department of Radiodiagnosis and
Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh,
India
| | - Sunil Taneja
- Department of Hepatology,
Postgraduate Institute of Medical Education and Research, Chandigarh,
India
| | - RK Dhiman
- Department of Hepatology,
Postgraduate Institute of Medical Education and Research, Chandigarh,
India
| | - Paramjeet Singh
- Department of Radiodiagnosis and
Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh,
India
| | - Chirag K Ahuja
- Department of Radiodiagnosis and
Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh,
India
| | - Nirmalya Ray
- Department of Radiodiagnosis and
Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh,
India
| | - Varan Govind
- Department of Radiology, University
of Miami, USA
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Ibáñez-Samaniego L, Bañares R. Evaluation of the Role of Minimal Perihepatic Ascites, Minimal Hepatic Encephalopathy, and Bleeding Due to Portal Hypertensive Gastroenteropathy in the Definition of Decompensation. PORTAL HYPERTENSION VII 2022:363-392. [DOI: 10.1007/978-3-031-08552-9_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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20
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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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Gazda J, Drotar P, Drazilova S, Gazda J, Gazda M, Janicko M, Jarcuska P. Artificial Intelligence and Its Application to Minimal Hepatic Encephalopathy Diagnosis. J Pers Med 2021; 11:1090. [PMID: 34834442 PMCID: PMC8626051 DOI: 10.3390/jpm11111090] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunting. HE manifests as a spectrum of neurological or psychiatric abnormalities. Diagnosis of overt HE (OHE) is based on the typical clinical manifestation, but covert HE (CHE) has only very subtle clinical signs and minimal HE (MHE) is detected only by specialized time-consuming psychometric tests, for which there is still no universally accepted gold standard. Significant progress has been made in artificial intelligence and its application to medicine. In this review, we introduce how artificial intelligence has been used to diagnose minimal hepatic encephalopathy thus far, and we discuss its further potential in analyzing speech and handwriting data, which are probably the most accessible data for evaluating the cognitive state of the patient.
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Affiliation(s)
- Jakub Gazda
- 2nd Department of Internal Medicine, PJ Safarik University and Louis Pasteur University Hospital, 040 11 Kosice, Slovakia; (J.G.); (S.D.); (P.J.)
| | - Peter Drotar
- Intelligent Information Systems Lab, Faculty of Electrical Engineering and Informatics, Technical University of Kosice, 040 01 Kosice, Slovakia; (P.D.); (J.G.); (M.G.)
| | - Sylvia Drazilova
- 2nd Department of Internal Medicine, PJ Safarik University and Louis Pasteur University Hospital, 040 11 Kosice, Slovakia; (J.G.); (S.D.); (P.J.)
| | - Juraj Gazda
- Intelligent Information Systems Lab, Faculty of Electrical Engineering and Informatics, Technical University of Kosice, 040 01 Kosice, Slovakia; (P.D.); (J.G.); (M.G.)
| | - Matej Gazda
- Intelligent Information Systems Lab, Faculty of Electrical Engineering and Informatics, Technical University of Kosice, 040 01 Kosice, Slovakia; (P.D.); (J.G.); (M.G.)
| | - Martin Janicko
- 2nd Department of Internal Medicine, PJ Safarik University and Louis Pasteur University Hospital, 040 11 Kosice, Slovakia; (J.G.); (S.D.); (P.J.)
| | - Peter Jarcuska
- 2nd Department of Internal Medicine, PJ Safarik University and Louis Pasteur University Hospital, 040 11 Kosice, Slovakia; (J.G.); (S.D.); (P.J.)
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Coubard OA, Ober KM, Gaumet M, Urbanski M, Amato JN, Chapron V, Weiss N, Kinugawa K, Weissenborn K, Thabut D. Standardization of the psychometric hepatic encephalopathy score in a French population. PLoS One 2021; 16:e0257136. [PMID: 34506569 PMCID: PMC8432843 DOI: 10.1371/journal.pone.0257136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 08/24/2021] [Indexed: 01/18/2023] Open
Abstract
The Psychometric Hepatic Encephalopathy Score (PHES) has previously been standardized in thirteen countries on three continents, confirming its status of gold standard test to detect minimal hepatic encephalopathy (MHE). In the meantime, performance has also been shown to vary with variables such as age, education, and barely sex. The present study aimed at standardizing the PHES in a French population. One hundred and ninety-six French healthy participants completed a French version of the paper-and-pencil PHES, involving five tests and six measures. Importantly, the balance was perfect between all levels of the three controlled factors, which were sex, age (seven decade-levels from 20–29 to 80–89 years), and education (two levels below or above 12 years of education). Raw measures were transformed to fit the normal distribution. ANOVAs on transformed variables showed no effect of sex, but an effect of age on all measures, and of education on five measures. Multiple or simple regressions were completed to build up normograms. Thorough analysis of variability within each test failed to find outliers that may bias the results. Comparison between French and seminal German data showed that they highly fitted though cultural and cognitive style specificities could be observed. This is the first study to standardize the PHES in a French population and to extensively explore the effects of sex, age and education using perfectly balanced samples. Subtle differences between countries of the same continent emphasize the need to build up normative data in each country to get accurate PHES in patients.
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Affiliation(s)
| | - Kinga M. Ober
- The Neuropsychological Laboratory, CNS-Fed, Paris, France
| | - Marie Gaumet
- The Neuropsychological Laboratory, CNS-Fed, Paris, France
| | - Marika Urbanski
- Service de Médecine et de Réadaptation Gériatrique et Neurologique, Hôpitaux de Saint-Maurice, Saint-Maurice, France
| | | | | | - Nicolas Weiss
- Department of Neurology & Institut de Cardiométabolisme et Nutrition, Neurological Intensive Care Unit, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
- Centre de Recherche Saint-Antoine, UMR_S 938 INSERM-Sorbonne Université, Paris, France
| | - Kiyoka Kinugawa
- Functional Explorations and Sleep Investigation Unit for Older Patients, AP-HP, Ivry-sur-Seine, France
- Biological Adaptation and Aging, UMR 8256, CNRS-Sorbonne Université, Paris, France
| | | | - Dominique Thabut
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
- Centre de Recherche Saint-Antoine, UMR_S 938 INSERM-Sorbonne Université, Paris, France
- Service d’Hépato-gastro-entérologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
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Pessidjo Djomatcho L, Kowo MP, Ndam AN, Njonnou SRS, Kenfack GU, Andoulo FA, Bagnaka SFE, Bekolo WT, Malongue A, Babagna ID, Sida MB, Luma H, Njoya O. Normalisation of the psychometric encephalopathy score within the Cameroonian population. BMC Gastroenterol 2021; 21:287. [PMID: 34247589 PMCID: PMC8273953 DOI: 10.1186/s12876-021-01858-7] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 06/28/2021] [Indexed: 12/15/2022] Open
Abstract
Background Minimal hepatic encephalopathy (MHE) is the presence of neuropsychological abnormalities detectable by psychometric tests. Psychometric Hepatic Encephalopathy Score (PHES) is a gold standard test for the early diagnosis of MHE in cirrhotic patients. The aim of this study was to standardize the PHES in a healthy Cameroonian population and to evaluate the prevalence of MHE among cirrhotic patients.
Methods This was a prospective, multicentric study from 1 December 2018 to 31 July 2019 in two groups: healthy volunteers and cirrhotic patients without clinical signs of hepatic encephalopathy. The results of the number connection test-A, number connection test-B, serial dotting test, line tracing test were expressed in seconds and those of the digit symbol test in points. Results A total of 102 healthy volunteers (54 men, 48 women) and 50 cirrhotic patients (29 men, 31 women) were included. The mean age was 38.1 ± 12.55 years in healthy volunteers and 49.3 ± 15.6 years in cirrhotic patients. The mean years of education level was 11.63 ± 4.20 years in healthy volunteers and 9.62 ± 3.9 years in cirrhotic patients. The PHES of the healthy volunteer group was − 0.08 ± 1.28 and the cut-off between normal and pathological values was set at − 3 points. PHES of the cirrhotic patients was − 7.66 ± 5.62 points and significantly lower than that of volunteers (p < 0.001). Prevalence of MHE was 74% among cirrhotic patients. Age and education level were associated with MHE.
Conclusion PHES cut-off value in Cameroonians is − 3, with MHE prevalence of 74% among cirrhotic patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01858-7.
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Affiliation(s)
| | - Mathurin Pierre Kowo
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon. .,University Teaching Hospital Yaounde, Yaoundé, Cameroon.
| | - Antonin Ndjitoyap Ndam
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.,Yaounde General Hospital, Yaoundé, Cameroon
| | | | - Gabin Ulrich Kenfack
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Firmin Ankouane Andoulo
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.,Yaounde Central Hospital, Yaoundé, Cameroon
| | - Servais Fiacre Eloumou Bagnaka
- Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.,Gynaeco-Obstetric and Paediatric Hospital Douala, Douala, Cameroon
| | - Winnie Tatiana Bekolo
- Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon.,Gynaeco-Obstetric and Paediatric Hospital Douala, Douala, Cameroon
| | | | | | - Magloire Biwolé Sida
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Henry Luma
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.,Douala General Hospital, Douala, Cameroon
| | - Oudou Njoya
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.,University Teaching Hospital Yaounde, Yaoundé, Cameroon
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Minimal Hepatic Encephalopathy and Biejia-Ruangan Are Associated with First Hospital Readmission in Nonalcoholic Cirrhosis Patients. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6652858. [PMID: 34055016 PMCID: PMC8123979 DOI: 10.1155/2021/6652858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 04/06/2021] [Accepted: 04/19/2021] [Indexed: 11/17/2022]
Abstract
Introductionand Aim. Patients with cirrhosis are often hospitalized repeatedly for a variety of complications. This retrospective study aimed to assess the effects of minimal hepatic encephalopathy (MHE) and Biejia-Ruangan (BR) on first hospital readmission in nonalcoholic cirrhosis patients without previous overt hepatic encephalopathy (OHE) or hepatocellular carcinoma (HCC). Materials and Methods. A total of 176 hospitalized patients with nonalcoholic cirrhosis were included in this retrospective study. Patients who were first admitted to Beijing Ditan Hospital of Capital Medical University from January 2017 to September 2019 were enrolled. The primary endpoint was their first liver-related hospital readmission. The risk factors for readmission were analyzed by Cox proportional hazard regression analysis. Results. A total of 176 nonalcoholic cirrhosis patients without previous OHE or HCC were included; 57 patients (32.4%) were diagnosed with MHE, and 63 patients (35.8%) were administered BR (2 g, three times a day). Multivariate analysis revealed that nonalcoholic cirrhosis patients with MHE (HR, 5.805; 95% CI, 3.007-11.206; x, P < 0.001) and a higher Model for End-Stage Liver Disease (MELD) score (HR, 1.145; 95% CI, 1.068-1.227; P < 0.001) had an increased risk of first hospital readmission, and patients treated with BR (HR, 0.318; 95% CI, 0.151-0.670; P=0.003) had a decreased risk of first hospital readmission. Conclusion. MHE increased the risk of hospital readmission in nonalcoholic cirrhosis patients without previous OHE or HCC, and this risk was decreased by BR administration.
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Formentin C, Zarantonello L, Mangini C, Frigo AC, Montagnese S, Merkel C. Clinical, neuropsychological and neurophysiological indices and predictors of hepatic encephalopathy (HE). Liver Int 2021; 41:1070-1082. [PMID: 33411388 DOI: 10.1111/liv.14785] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/30/2020] [Accepted: 01/01/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The occurrence of overt hepatic encephalopathy (HE) marks a significant progression in the natural history of liver disease. The aims of the present study were to: 1) describe a large cohort of patients with cirrhosis in terms of neuropsychological or neurophysiological HE indices, and 2) test if the severity of liver disease and/or any such indices [Psychometric Hepatic Encephalopathy Score (PHES), Scan test, electroencephalography (EEG)] predicted mortality/HE risk in a subgroup of such cohort. METHOD Four hundred and sixty-one patients with cirrhosis (59 ± 10 years; 345 males) were included; information on previous overt HE episodes was available in 407. Follow-up information on mortality/HE-related hospitalization in 134/127 respectively. Information on previous overt HE episodes and both mortality and HE-related hospitalization over the follow-up in 124. RESULTS Patients with a history of overt HE (60%) had poorer liver function, worse neuropsychiatric indices, higher ammonia levels and higher prevalence of portal-systemic shunt. The risk of HE-related hospitalization over the follow-up was higher in patients with higher MELD score and worse Scan performance. Mortality was higher in those with higher MELD. Among patients without a history of overt HE, those with worse PHES had higher HE risk. Among patients with a history, those with higher MELD, better PHES and worse Scan performance had higher HE risk. CONCLUSIONS In patients without previous overt HE episodes, neuropsychological and neurophysiological tests predict HE, while in those with previous overt HE episodes, HE development largely depends on the severity of liver dysfunction.
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Affiliation(s)
- Chiara Formentin
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Lisa Zarantonello
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Chiara Mangini
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Anna C Frigo
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Sara Montagnese
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Carlo Merkel
- Department of Medicine, and Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy
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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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Theodorakopoulos T, Kalafateli M, Kalambokis GN, Samonakis DN, Aggeletopoulou I, Tsolias C, Mantaka A, Tselekouni P, Vourli G, Assimakopoulos SF, Gogos C, Thomopoulos K, Milionis H, Triantos C. Natural history of grade 1 ascites in patients with liver cirrhosis. Ann Gastroenterol 2020; 34:93-103. [PMID: 33414628 PMCID: PMC7774664 DOI: 10.20524/aog.2020.0553] [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: 05/15/2020] [Accepted: 09/02/2020] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND No evidence is available on the natural history of grade 1 ascites and its progression to grade 2/3 in patients with liver cirrhosis. The aim of the current study was to address this issue, to assess the development of main comorbid disorders closely related to ascites progression, and to identify the predictive factors for survival in this setting. METHODS Consecutive Caucasian cirrhotic patients with grade 1 ascites were retrospectively analyzed. None of patients was under treatment with diuretics at diagnosis. Control groups consisted of 145 cirrhotics with grade 2/3 ascites and 175 cirrhotics without ascites. RESULTS Diuretics were initiated in 58 patients with grade 1 ascites at baseline by the attending physician. At the last follow up, 29 patients had no ascites, 33 patients had grade 1 and 38 patients had grade 2/3 ascites. No variable was found to be an independent predictor of grade 2/3 ascites. Seven patients developed spontaneous bacterial peritonitis while under treatment with diuretics; at that time only 1 patient had grade 1 ascites. The mortality rate was similar among all examined groups. CONCLUSIONS This study suggests that the presence of grade 1 ascites does not constitute a precursor of grade 2/3 ascites in patients with cirrhosis. Thus, patients with grade 1 ascites do not require specific treatment with diuretics.
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Affiliation(s)
- Theodoros Theodorakopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras (Theodoros Theodorakopoulos, Maria Kalafateli, Ioanna Aggeletopoulou, Chrysostomos Tsolias, Paraskevi Tselekouni, Konstantinos Thomopoulos, Christos Triantos)
| | - Maria Kalafateli
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras (Theodoros Theodorakopoulos, Maria Kalafateli, Ioanna Aggeletopoulou, Chrysostomos Tsolias, Paraskevi Tselekouni, Konstantinos Thomopoulos, Christos Triantos)
| | - Georgios N. Kalambokis
- Division of Internal Medicine, First Division of Internal Medicine and Liver Unit, Medical School, University of Ioannina, Ioannina (Georgios N. Kalambokis, Haralampos Milionis)
| | - Dimitrios N. Samonakis
- Division of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete (Dimitrios N. Samonakis, Aikaterini Mantaka)
| | - Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras (Theodoros Theodorakopoulos, Maria Kalafateli, Ioanna Aggeletopoulou, Chrysostomos Tsolias, Paraskevi Tselekouni, Konstantinos Thomopoulos, Christos Triantos)
| | - Chrysostomos Tsolias
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras (Theodoros Theodorakopoulos, Maria Kalafateli, Ioanna Aggeletopoulou, Chrysostomos Tsolias, Paraskevi Tselekouni, Konstantinos Thomopoulos, Christos Triantos)
| | - Aikaterini Mantaka
- Division of Gastroenterology and Hepatology, University Hospital of Crete, Heraklion, Crete (Dimitrios N. Samonakis, Aikaterini Mantaka)
| | - Paraskevi Tselekouni
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras (Theodoros Theodorakopoulos, Maria Kalafateli, Ioanna Aggeletopoulou, Chrysostomos Tsolias, Paraskevi Tselekouni, Konstantinos Thomopoulos, Christos Triantos)
| | - Georgia Vourli
- Division of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens (Georgia Vourli)
| | - Stelios F. Assimakopoulos
- Division of Internal Medicine, University Hospital of Patras (Stelios F. Assimakopoulos, Charalampos Gogos), Greece
| | - Charalampos Gogos
- Division of Internal Medicine, University Hospital of Patras (Stelios F. Assimakopoulos, Charalampos Gogos), Greece
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras (Theodoros Theodorakopoulos, Maria Kalafateli, Ioanna Aggeletopoulou, Chrysostomos Tsolias, Paraskevi Tselekouni, Konstantinos Thomopoulos, Christos Triantos)
| | - Haralampos Milionis
- Division of Internal Medicine, First Division of Internal Medicine and Liver Unit, Medical School, University of Ioannina, Ioannina (Georgios N. Kalambokis, Haralampos Milionis)
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras (Theodoros Theodorakopoulos, Maria Kalafateli, Ioanna Aggeletopoulou, Chrysostomos Tsolias, Paraskevi Tselekouni, Konstantinos Thomopoulos, Christos Triantos)
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Aberrant dynamic functional network connectivity in cirrhotic patients without overt hepatic encephalopathy. Eur J Radiol 2020; 132:109324. [PMID: 33038576 DOI: 10.1016/j.ejrad.2020.109324] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/16/2020] [Accepted: 09/25/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE Neurocognitive impairment is a common complication in cirrhosis and is associated with alterations in static functional network connectivity (FNC) between distinct brain systems. However, accumulating evidence suggests temporal variability in FNC even at rest. This study aimed to explore dynamic FNC (dFNC) differences and to elucidate their association with neurocognitive changes in cirrhotic patients. METHODS Fifty-four cirrhotic patients and 42 controls underwent resting-state functional magnetic resonance imaging. Psychometric hepatic encephalopathy score (PHES) was used to assess neurocognitive function. Independent component analysis was performed to identify the components of seven intrinsic brain networks, including sensorimotor (SMN), auditory, visual, cognitive control (CCN), default mode (DMN), subcortical (SC), and cerebellar networks. Sliding window correlation approach was employed to calculate dFNC. FNC states were determined by k-means clustering method, and then functional state analysis was conducted to measure dynamic indices. RESULTS The patients showed decreased dFNC in State 2, involving the connectivity between posterior subsystem of DMN and CCN (represented by bilateral insular cortex), and in State 3, involving the connectivity between SMN (represented by bilateral precentral gyrus) and SC (represented by bilateral putamen and caudate). The patients spent significantly longer time in State 4 that was with weakest FNC across all networks. We observed a significant correlation between PHES and fraction time/mean dwell time in State 4. CONCLUSIONS Aberrant dFNC may be the underlying mechanism of neurocognitive impairments in cirrhosis. Dynamic FNC analysis may potentially be utilized in investigating cirrhosis-related neuropathological processes.
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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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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: 84] [Impact Index Per Article: 16.8] [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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Zeng X, Zhang LY, Liu Q, Lu CH, Wei J, Shi ZW, Huang WR, Qu LH, Xu F, Wang XH, Shi PM, Tan Y, Tan W, Yuan ZL, Xia CY, Liu YL, Xie WF. Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy. Clin Gastroenterol Hepatol 2020; 18:1618-1625.e7. [PMID: 31712074 DOI: 10.1016/j.cgh.2019.11.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). METHODS We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. RESULTS We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. CONCLUSION Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.
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Affiliation(s)
- Xin Zeng
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Li-Yuan Zhang
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Qing Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
| | - Cui-Hua Lu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Jue Wei
- Department of Gastroenterology, Tong Ren hospital, Jiaotong University, Shanghai, China
| | - Zhi-Wen Shi
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Rong Huang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Li-Hong Qu
- Department of Infectious Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fei Xu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiao-Hang Wang
- Department of Endoscopy, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Pei-Mei Shi
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yu Tan
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei Tan
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zong-Li Yuan
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Chun-Yan Xia
- Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Lan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
| | - Wei-Fen Xie
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
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Bamidele OF, Olokoba AB, Bojuwoye MO, Akintayo RO, Bamidele O. Prevalence of minimal hepatic encephalopathy among patients with chronic liver disease in Ilorin, Nigeria. Ghana Med J 2020; 53:299-303. [PMID: 32116342 PMCID: PMC7036435 DOI: 10.4314/gmj.v53i4.8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Minimal Hepatic encephalopathy is the mildest form of Hepatic Encephalopathy which presents with significant cognitive impairment and affectation of activities of daily living. The literature is scanty on the prevalence of minimal hepatic encephalopathy in Nigerians with chronic liver disease. Aim This study aimed at determining the prevalence of minimal hepatic encephalopathy among patients with chronic liver disease using neuro-psychometric tests. Methods The study was a hospital-based cross-sectional study carried out at the University of Ilorin Teaching Hospital, Ilorin from February 2015 to February 2016. Chronic liver disease was diagnosed with the presence of peripheral stigmata of liver disease, liver biochemistry, prothrombin time, and sonographic findings in keeping with liver disease. Minimal hepatic encephalopathy was diagnosed using number connection tests-A and B for patients who were educated while Line tracing test and constructional dyspraxia were used for patients without any formal education. Data obtained were analysed using Statistical Package for the Social Sciences (SPSS) version 20 computer software package. Results Sixty-four patients with chronic liver disease were recruited. The mean age (SD) of the patients was 47.1±14.6 yrs, and the 30-39 and 40-49 yrs age groups each had the highest frequency of 21(32.8%). There were 54 (84.4%) males and 10 (15.6%) females. The prevalence of Minimal Hepatic Encephalopathy was 43.8%. Conclusion The prevalence of Minimal Hepatic Encephalopathy in this study was similar to previous studies. Significant number of patients with minimal HE were in Child-Pugh class B and C. Funding None.
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Affiliation(s)
- Opeyemi F Bamidele
- Department of Medicine, University of Ilorin Teaching Hospital, Ilorin. Nigeria
| | | | - Matthew O Bojuwoye
- Department of Medicine, University of Ilorin Teaching Hospital, Ilorin. Nigeria
| | - Richard O Akintayo
- Department of Medicine, University of Ilorin Teaching Hospital, Ilorin. Nigeria
| | - Oluwakemi Bamidele
- Department of Behavioural Sciences, University of Ilorin Teaching Hospital, Ilorin. Nigeria
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Abstract
The presence of hepatic encephalopathy is often associated with worse clinical outcomes and increased mortality. Even subclinical hepatic encephalopathy has clinical impacts on daily life and has been linked to increased falls, motor vehicle accidents, and hospitalizations. The presence and degree of hepatic encephalopathy can also affect survival outcomes in cirrhosis, acute liver failure, and liver transplant recipients. Patients may have improved clinical outcomes after treatment of hepatic encephalopathy, but the long-term impact of treatment on prognosis is unclear.
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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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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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Dhiman RK, Thumburu KK, Verma N, Chopra M, Rathi S, Dutta U, Singal AK, Taneja S, Duseja A, Singh M. Comparative Efficacy of Treatment Options for Minimal Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis. Clin Gastroenterol Hepatol 2020; 18:800-812.e25. [PMID: 31476436 DOI: 10.1016/j.cgh.2019.08.047] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 08/07/2019] [Accepted: 08/09/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We aimed to synthesize evidence for most effective treatments for minimal hepatic encephalopathy (HE) and prevention of overt HE in patients with cirrhosis. METHODS We performed a systematic search of the PubMed, EMBASE, OvidSP, and Cochrane Central Register of Controlled Trials databases through July 26, 2018, for randomized controlled trials evaluating treatments for minimal HE in patients with cirrhosis, with primary outcomes of reversal of minimal HE or prevention of overt HE. We conducted a meta-analysis and then used network meta-analysis and surface under cumulated ranking (SUCRA) to pool the direct and indirect estimates and rank the different treatments. We appraised study quality using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS Our meta-analysis and network meta-analysis included 25 trials, comprising 1563 participants. Agents found to be effective in reversing minimal HE compared with placebo or no treatment included rifaximin (odds ratio [OR], 7.53; 95% predictive interval [PrI], 4.45-12.73; SUCRA, 89.2%; moderate quality), lactulose (OR, 5.39; 95% PrI, 3.60-8.0; SUCRA, 67.2%; moderate quality), the combination of probiotics and lactulose (OR, 4.66; 95% PrI, 1.90-11.39; SUCRA, 52.4%; low quality), L-ornithine L-aspartate (OR, 4.45; 95% PrI, 2.67-7.42; SUCRA, 47.2%; low moderate quality), and probiotics (OR, 3.89; 95% PrI, 2.52-6.02; SUCRA, 34.1%; low quality). Agents found to be effective in preventing episodes of overt HE compared with placebo or no treatment included L-ornithine L-aspartate (OR, 0.19; 95% PrI, 0.04-0.91; SUCRA, 75.1%; high moderate quality), lactulose (OR, 0.22; 95% PrI, 0.09-0.52; SUCRA, 73.9%; moderate quality), and probiotics (OR, 0.27; 95% PrI, 0.11-0.62; SUCRA, 59.6%; low quality). CONCLUSIONS In a meta-analysis of data from 25 trials, we found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis. L-ornithine L-aspartate and lactulose are most effective in the prevention of overt HE. Lactulose was the only agent that was effective in reversing minimal HE, preventing overt HE, reducing ammonia, and improving quality of life, with tolerable adverse effects. International prospective register of systematic reviews ID: 107003.
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Affiliation(s)
| | | | | | | | | | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | | | | | - Meenu Singh
- Department of Paediatrics, Chandigarh, India
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Chen QF, Zou TX, Yang ZT, Chen HJ. Identification of patients with and without minimal hepatic encephalopathy based on gray matter volumetry using a support vector machine learning algorithm. Sci Rep 2020; 10:2490. [PMID: 32051514 PMCID: PMC7016173 DOI: 10.1038/s41598-020-59433-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 01/29/2020] [Indexed: 12/13/2022] Open
Abstract
Minimal hepatic encephalopathy (MHE) is characterized by diffuse abnormalities in cerebral structure, such as reduced cortical thickness and altered brain parenchymal volume. This study tested the potential of gray matter (GM) volumetry to differentiate between cirrhotic patients with and without MHE using a support vector machine (SVM) learning method. High-resolution, T1-weighted magnetic resonance images were acquired from 24 cirrhotic patients with MHE and 29 cirrhotic patients without MHE (NHE). Voxel-based morphometry was conducted to evaluate the GM volume (GMV) for each subject. An SVM classifier was employed to explore the ability of the GMV measurement to diagnose MHE, and the leave-one-out cross-validation method was used to assess classification accuracy. The SVM algorithm based on GM volumetry achieved a classification accuracy of 83.02%, with a sensitivity of 83.33% and a specificity of 82.76%. The majority of the most discriminative GMVs were located in the bilateral frontal lobe, bilateral lentiform nucleus, bilateral thalamus, bilateral sensorimotor areas, bilateral visual regions, bilateral temporal lobe, bilateral cerebellum, left inferior parietal lobe, and right precuneus/posterior cingulate gyrus. Our results suggest that SVM analysis based on GM volumetry has the potential to help diagnose MHE in cirrhotic patients.
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Affiliation(s)
- Qiu-Feng Chen
- College of Computer and Information Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China
| | - Tian-Xiu Zou
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Zhe-Ting Yang
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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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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Pawar VB, Surude RG, Sonthalia N, Zanwar V, Jain S, Contractor Q, Rathi PM. Minimal Hepatic Encephalopathy in Indians: Psychometric Hepatic Encephalopathy Score and Inhibitory Control Test for Diagnosis and Rifaximin or Lactulose for Its Reversal. J Clin Transl Hepatol 2019; 7:304-312. [PMID: 31915599 PMCID: PMC6943207 DOI: 10.14218/jcth.2017.00037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Revised: 05/28/2018] [Accepted: 02/14/2019] [Indexed: 12/15/2022] Open
Abstract
Background and Aims: Psychometric hepatic encephalopathy score (PHES) is used widely for diagnosis of minimal hepatic encephalopathy (MHE). This prospective study aimed to determine the utility of the inhibitory control test (ICT) for the diagnosis of MHE. Additionally, the efficacy of rifaximin and lactulose for reversal of MHE was evaluated. Methods: A total of 180 eligible cirrhotic patients underwent testing for MHE. When PHES was ≤ -5 and ICT lures were ≥ 14, MHE was diagnosed. The 108 patients with MHE were randomized to three groups for treatment with either lactulose, rifaximin, or placebo. Treatment outcomes were measured at the end of 3 months. Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%. The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients, by abnormal ICT and normal PHES in 37 patients, and by abnormal PHES and normal ICT in 15 patients. For diagnosis of MHE, ICT had sensitivity of 78.87%, specificity of 66.06% with 60.22% positive predictive value and 82.76% negative predictive value. An area under the curve value of 0.724 (95% CI: 0.653-0.788) was obtained for diagnosis of MHE. Reversal of MHE was seen in 71.42%, 70.27% and 11.11% of patients in the rifaximin, lactulose and placebo arms (p < 0.001). Rifaximin showed better tolerability compared to lactulose. Conclusions: For the diagnosis of MHE, ICT is a simple tool but has lower sensitivity and better specificity than PHES. Rifaximin is as efficacious as lactulose in the treatment of MHE and better tolerated.
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Affiliation(s)
- Vinay B. Pawar
- Correspondence to: Vinay B. Pawar, Department of Gastroenterology, Topiwala National Medical College and BYL Ch Hospital, Dr. A.L Nair Road, Mumbai, Maharashtra 400008, India. Tel: +22-23021639, E-mail:
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Safety profile of sedative endoscopy including cognitive performance in liver cirrhosis: A double-blind randomized controlled trial. Sci Rep 2019; 9:16798. [PMID: 31727915 PMCID: PMC6856546 DOI: 10.1038/s41598-019-52897-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 10/24/2019] [Indexed: 12/13/2022] Open
Abstract
The indiscriminate use of sedative drugs during endoscopy can pose multiple risks including cognitive impairment in advanced liver cirrhosis. However, the data are scarce regarding which sedative drugs are safest in these populations. The aim of this study was to evaluate the safety profiles including cognitive performance among midazolam, propofol, and combination therapy in advanced cirrhotic patients. This double-blind randomized controlled study included 60 consecutive advanced cirrhotic patients who underwent upper gastrointestinal endoscopy. The Stroop application was used to screen for cognitive impairment. Patients were randomly assigned to one of 3 groups, midazolam, propofol, or the combination group, and underwent Stroop test before and two hours after the completion of endoscopy. Hemodynamic safety and the subjective satisfaction score were also evaluated. Patients did not show significant changes in on-time or off-time on the Stroop test before and two hours after sedatives, and there was no significant difference among the 3 treatment groups. Also, there were no significant vital sign changes after sedatives. Time-to-recovery was longest in midazolam group, and patient awakening and patient memory were highest in propofol group. However, all 3 groups showed no difference in patient satisfaction, but the combination group was more preferred in terms of subjective satisfaction by physicians. Factors affecting worsened Stroop speed after sedatives were older age, low education level and high MELD score. All sedative methods using midazolam, propofol, or combination therapy showed similar safety profile in advanced cirrhosis, and were not associated with increased risk of cognitive impairment.
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Association between Aspartate Aminotransferase-to-Platelet Ratio Index and Hepatocellular Carcinoma Risk in Patients with Chronic Hepatitis: A Meta-Analysis of Cohort Study. DISEASE MARKERS 2019; 2019:2046825. [PMID: 31814857 PMCID: PMC6877976 DOI: 10.1155/2019/2046825] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 09/11/2019] [Indexed: 02/06/2023]
Abstract
Background and Aim Aspartate aminotransferase-to-platelet ratio index (APRI) is widely used in the assessment of fibrosis and cirrhosis, especially in patients with chronic hepatitis. However, the prognostic value of APRI in patients with chronic hepatitis with regard to the prediction of hepatocellular carcinoma (HCC) occurrence remains controversial. The objective of this meta-analysis is to investigate the association between APRI and HCC risk on the basis of cohort studies. Methods We systematically reviewed PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure databases for relevant cohort studies up to May 1, 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and subgroup analyses were calculated with Stata 12.0 software for the assessment of the relationship between APRI and HCC risk. Results A total of 13 studies, involving 8897 patients, were included in the meta-analysis, of which 11 explored the association between pretreatment APRI and HCC risk and four reported the relationship between posttreatment APRI and HCC risk. Pooled results showed that an elevated level of pretreatment APRI was associated with increased HCC risk (HR = 2.56, 95% CI: 1.78–3.68). When stratified by hepatitis type, high pretreatment APRI predicted HCC development in patients with chronic hepatitis B (CHB) and C (CHC) but not in alcoholic liver cirrhosis (ALC). In the subgroup analyses of study region, cut-off value, sample size, and analysis method, the relationship between high pretreatment APRI and increased HCC risk was significant. Meanwhile, patients with a high level of posttreatment APRI suffered from high HCC risk (HR = 3.69, 95% CI: 2.52–5.42). Conclusion: Results revealed a significant association between elevated APRI and HCC development in patients with chronic hepatitis, suggesting that APRI might serve as a valuable predictor for HCC risk in patients with chronic hepatitis.
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Ponziani FR, Funaro B, Lupascu A, Ainora ME, Garcovich M, Caracciolo G, Quadarella A, Nesci A, Riccardi L, Gasbarrini A, Pompili M, Zocco MA. Minimal Hepatic Encephalopathy is Associated with Increased Cerebral Vascular Resistance. A Transcranial Doppler Ultrasound Study. Sci Rep 2019; 9:15373. [PMID: 31653939 PMCID: PMC6814853 DOI: 10.1038/s41598-019-51867-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 10/09/2019] [Indexed: 12/13/2022] Open
Abstract
Minimal hepatic encephalopathy (MHE) is a subclinical complication of liver cirrhosis with a relevant social impact. Thus, there is urgent need to implement easy to use diagnostic tools for the early identification of affected patients. The aim of this study was to investigate cerebral blood flow, systemic hemodynamics as well as endothelial function of cirrhotic patients with MHE, and to verify their change after treatment with rifaximin. Fifty cirrhotic patients with or without MHE and an equal number of healthy controls underwent transcranial Doppler ultrasound (TCD), abdominal Doppler ultrasound (US), and measurement of flow mediated dilation (FMD). In cirrhotic patients diagnosed with MHE receiving rifaximin, the tests were repeated at the end of treatment. Middle (MCA) and posterior (PCA) cerebral artery resistive (RI) and pulsatility (PI) indices were higher in cirrhotic patients than controls, as well as renal and splenic artery RI. Conversely, FMD was reduced. MCA-RI and PI were even higher in cirrhotic patients with MHE compared to those without; a MCA-RI cut-off of 0.65 showed an accuracy of 74% in discriminating the presence of MHE, with 65% sensitivity and 76% specificity. Rifaximin treatment showed no efficacy in the modulation of cerebral vascular flow. In conclusion, cirrhotic patients with MHE have significantly increased cerebral vascular resistances that are not improved by rifaximin treatment. MCA-RI measurement has a good accuracy for the diagnosis of MHE and can be useful for the early identification of this harmful complication of liver cirrhosis.
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Affiliation(s)
- Francesca Romana Ponziani
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy.
| | - Barbara Funaro
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Andrea Lupascu
- Internal Medicine, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Maria Elena Ainora
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Matteo Garcovich
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Gianluigi Caracciolo
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Alessandro Quadarella
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Nesci
- Internal Medicine, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Laura Riccardi
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Maurizio Pompili
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
| | - Maria Assunta Zocco
- Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy
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Abstract
Overt and covert hepatic encephalopathy (HE) are debilitating complications of cirrhosis. HE results in a poor quality of life for patients and their caregivers and, unless there is access to liver transplantation, the prognosis is poor. The development of overt HE is often unpredictable, and its management, particularly in the ward, remains challenging. There is an urgent need for novel approaches to treat HE. Until recently, therapies for this complication were disappointing, with frequently intolerable side effects such as diarrhoea and faecal incontinence. However, a non-absorbable antibiotic, rifaximin, * has been approved for the prevention of recurrent overt HE. It aims to reduce hospitalisation and resource use, as well as improve patients' quality of life. This article describes the practical aspects of diagnosing, classifying and managing HE. It reviews the pharmacological options for the treatment and prophylaxis of overt HE, and explores the evidence base demonstrating that rifaximin reduces the recurrence of overt HE.
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Affiliation(s)
- Debbie L Shawcross
- Reader and Honorary Consultant Hepatologist, Institute of Liver Studies, School of Immunity and Microbial Science, Faculty of Life Sciences and Medicine, King's College Hospital, London
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Shiha G, Mousa N. Minimal Hepatic Encephalopathy: Silent Tragedy. LIVER DISEASE AND SURGERY [WORKING TITLE] 2019. [DOI: 10.5772/intechopen.88231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
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Critical flickering frequency test: a diagnostic tool for minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol 2019; 31:1030-1034. [PMID: 31274595 DOI: 10.1097/meg.0000000000001375] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Minimal hepatic encephalopathy (MHE) is underestimated. It affects 30-55% of patients with liver cirrhosis and can change their daily functions. Psychometric tests are sensitive in diagnosing MHE, but interpretation is difficult. Availability of a simpler diagnostic tool for MHE is mandatory. Critical flicker frequency (CFF) is a simple diagnostic test. AIM The aim of this study was to assess the diagnostic accuracy of CFF test for MHE. PATIENTS AND METHODS A total of 86 patients with cirrhosis with negative history of overt hepatic encephalopathy were included. History, clinical examination, laboratory investigations, and abdominal ultrasonography data were collected. Arabic version of number connection test, serial dotting test, and line tracing test were done. Total psychometric hepatic encephalopathy score (PHES) was used to diagnose MHE. CFF was done for all patients with MHE diagnosis at 39 Hz. RESULTS Of the 86 patients, 45 (52.3%) had MHE with PHES. Patients with MHE had significantly older age, presentation with jaundice, ascites, lower hemoglobin level, lower serum albumin, prolonged INR, higher Child class and score (P≤0.001), and higher model of end stage liver disease score (P=0.001) than patients without MHE. In comparison with PHES, CFF has a sensitivity of 91.1±8.32%, specificity of 92.7±7.96%, positive predictive value of 93.2±7.44%, and negative predictive value of 90.4±8.91%. In receiver operating characteristic curve, CFF is excellent in diagnosis of MHE, with area under the curve 0.937 (P<0.001). CONCLUSION MHE is common among patients with liver cirrhosis. CFF is a simple, rapid, noninvasive test for diagnosis of MHE, with a very good accuracy at 39 Hz.
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Rathi S, Chopra M, Chouduri G, Sharma P, Madan K, Chhabra M, Rai RR, Govil A, Konar A, Goenka M, Agarwal M, Mukherjee J, Thorat V, Salunkhe S, Abraham P, Nagral A, Jhaveri A, Bhat N, Varghese J, R.S. A, Ravishankar, Reddy DC, Dhiman RK. Prevalence of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Cross-Sectional, Clinicoepidemiological, Multicenter, Nationwide Study in India: The PREDICT Study. J Clin Exp Hepatol 2019; 9:476-483. [PMID: 31516264 PMCID: PMC6728606 DOI: 10.1016/j.jceh.2018.09.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 09/19/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The study aimed at assessing the prevalence and clinical profile of minimal hepatic encephalopathy (MHE) in patients with cirrhosis using neuropsychological assessment and at understanding the management practices of MHE in the Indian clinical setting. METHODS This cross-sectional, clinicoepidemiological study conducted at 20 sites enrolled liver cirrhosis patients with Grade 0 hepatic encephalopathy according to West-Haven Criteria. Patients were subjected to mini-mental state examination and those with a score of ≥24 were assessed using psychometric hepatic encephalopathy score. Short Form-36 questionnaire was administered to assess the impact on health-related quality of life. RESULTS Of the 1260 enrolled patients, 1114 were included in the analysis. The mean age was 49.5 years and majority were males (901 [81%]). The prevalence of MHE was found to be 59.7% (665/1114) based on the psychometric hepatic encephalopathy score of ≤-5. Alcohol-related liver disease was the most common etiology (482 [43.27%]) followed by viral infection (239 [21.45%]). Past smokers as well as those currently smoking were more likely to have MHE than nonsmokers. A significant association was found between tobacco chewing, smoking, alcohol consumption, diabetes, and the presence of MHE. Multivariable analysis revealed smoking as the only parameter associated with MHE. A total of 300 (26.9%) patients were on prophylaxis with lactulose/lactitol or rifaximin. These patients were less likely to have MHE as compared to those not on prophylaxis (odds ratio, 0.67; 95% confidence interval, 0.50-0.88; P = 0.005). CONCLUSION The disease burden of MHE is quite substantial in patients with cirrhosis with no apparent cognitive defect. Smoking, whether past or current, has significant association with the presence of MHE. Although MHE has been shown to adversely affect quality of life, prophylaxis for MHE is not routinely practiced in the Indian setting.The study has been registered under clinical trials registry of India (CTRI/2014/01/004306).
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Key Words
- ALD, alcohol-related liver disease
- CI, confidence interval
- DST, Digit Symbol Test
- FCT, figure connection test
- HE, hepatic encephalopathy
- HRQL, health-related quality of life
- MCS, mental component summary
- MELD, model for end-stage liver disease
- MHE, minimal hepatic encephalopathy
- MMSE, mini-mental state examination
- NCT, number connection test
- PCS, physical component summary
- PHES
- PHES, psychometric hepatic encephalopathy score
- SF-36, Short Form-36
- cirrhosis
- covert hepatic encephalopathy
- hepatic encephalopathy
- lactulose
- minimal hepatic encephalopathy
- quality of life
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Affiliation(s)
- Sahaj Rathi
- Postgraduate Institute of Medical Research, Chandigarh, India
| | - Madhu Chopra
- Postgraduate Institute of Medical Research, Chandigarh, India
| | | | | | - Kaushal Madan
- Institute of Digestive and Hepatobiliary Sciences, Medanta – The Medicity, Gurgoan, India
| | | | | | - Anurag Govil
- Santokba Durlabhji Memorial Hospital, Jaipur, India
| | | | | | | | | | | | | | - Philip Abraham
- PD Hinduja Hospital and Medical Research Centre, Mumbai, India
| | | | | | - Naresh Bhat
- Columbia Asia Referral Hospital, Bangalore, India
| | | | - Arun R.S.
- Madras Medical Mission, Chennai, India
| | | | | | - Radha K. Dhiman
- Postgraduate Institute of Medical Research, Chandigarh, India
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Yoon EL, Jun DW, Jeong JY, Kim TY, Song DS, Ahn SB, Kim HY, Jung YK, Song MJ, Kim SE, Kim HS, Jeong SW, Kim SG, Lee TH, Cho YK, Kim JK, Ryu H. Validation of the Korean Stroop Test in Diagnosis of Minimal Hepatic Encephalopathy. Sci Rep 2019; 9:8027. [PMID: 31142824 PMCID: PMC6541633 DOI: 10.1038/s41598-019-44503-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 05/15/2019] [Indexed: 12/13/2022] Open
Abstract
The burden of minimal hepatic encephalopathy (MHE) is significant, but no universal criteria for diagnosis have been established. We aimed to validate the Korean Stroop Test for MHE screening. Chronic hepatitis B-related liver cirrhosis patients were recruited prospectively from 13 centers. The Korean Stroop Test consisted of two Stroop-off states (color and word) and two Stroop-on states (inhibition and switching). Accuracy adjusted psychomotor speed (rate correct score) of these tests were analyzed. Sex- and age- adjusted rate correct scores of these tests were rated as the Korean Stroop Score (K-Stroop score). MHE was diagnosed when Portosystemic Encephalopathy Syndrome Test (PHES) scores were below -4. A total of 220 liver cirrhosis patients and 376 healthy controls were enrolled. Prevalence of MHE was 20.6% in cirrhosis patients. Rate correct scores and the K-Stroop score showed significant differences between healthy controls, cirrhosis patients without MHE, and cirrhosis patients with MHE. The rate correct score of the K-Stroop score was 0.74 (95% Confidence Interval: 0.66-0.83, P < 0.001). Female gender and the K-Stroop score were significant for MHE diagnosis. The Korean Stroop Test is simple and valid for screening of MHE.
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Affiliation(s)
- Eileen L Yoon
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, 01757, Republic of Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, 04763, Republic of Korea.
| | - Jae Yoon Jeong
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri-si, 11923, Republic of Korea
| | - Tae Yeob Kim
- Department of Internal Medicine, New Hope Internal Medicine Clinic, Seoul, 03113, Republic of Korea
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, 16247, Republic of Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, 01830, Republic of Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu-si, 11765, Republic of Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University Medical Center, Ansan-si, 02841, Republic of Korea
| | - Myeong Jun Song
- Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, 34943, Republic of Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, 14068, Republic of Korea
| | - Hyoung Su Kim
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 05355, Republic of Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul, 04401, Republic of Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon-si, 14584, Republic of Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, 35365, Republic of Korea
| | - Yong Kyun Cho
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 03181, Republic of Korea
| | - Jae-Kwan Kim
- Department of Arts & Technology, Hanyang University, Seoul, 04763, Republic of Korea
| | - Hokyoung Ryu
- Department of Arts & Technology, Hanyang University, Seoul, 04763, Republic of Korea
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Sahney A, Sharma BC, Jindal A, Anand L, Arora V, Vijayaraghavan R, Dhamija RM, Kumar G, Bhardwaj A, Sarin SK. A double-blind randomized controlled trial to assess efficacy of bromocriptine in cirrhotic patients with hepatic parkinsonism. Liver Int 2019; 39:684-693. [PMID: 30554466 DOI: 10.1111/liv.14024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 11/28/2018] [Accepted: 12/01/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Parkinsonism like features can be seen in cirrhotics, possibly related to alterations in brain dopamine metabolism, transport and receptor integrity at basal ganglia. Hepatic parkinsonism is often not suspected and only ammonia-reducing therapies are given to such patients. We investigated the efficacy and safety of bromocriptine, a dopaminergic agent, in patients with hepatic parkinsonism. PATIENTS AND METHODS Cirrhotics were screened for the presence of extrapyramidal symptoms and were diagnosed as hepatic parkinsonism if any two of tremor, bradykinesia and/or rigidity were present, supported by MRI brain showing T1 hyperintensities in basal ganglia and substantia nigra. Patients were randomized to receive placebo (Gr A, n = 22) or bromocriptine (Gr B, n = 24) for 12 weeks. Complete, partial and non-response were defined as 30%, 10%-30% and <10% reduction,respectively, in Unified Parkinson's Disease Rating Scale motor score. RESULTS Of 1016 cirrhotics, 50 (4.9%) had hepatic parkinsonism. Patients in two treatment groups were comparable for MELD score, arterial NH3 and frequency of portosystemic shunts. Bromocriptine therapy for 12 weeks resulted in improvement in rigidity, tremors, bradykinesia and gait compared to placebo with complete and partial response in seven vs none (29.1%, 0%, P < 0.01) and 12 vs one (50%, 4.5%, P < 0.01) patients. Prolonged and more severe motor symptoms were associated with non-response to bromocriptine therapy. There were no major side effects in either treatment group. CONCLUSIONS Hepatic parkinsonism is seen in ~5% cirrhotics. Bromocriptine is a safe and effective therapy for these patients and is more effective in mild to moderate hepatic parkinsonism.
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Affiliation(s)
- Amrish Sahney
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Lovkesh Anand
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Guresh Kumar
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankit Bhardwaj
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Abstract
In general, hepatic encephalopathy (HE) is defined as a brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting. This article relates to the so-called type C HE: that is, HE in patients with liver cirrhosis. It manifests as a wide spectrum of neurological or psychiatric abnormalities, ranging from subclinical alterations, detectable only by neuropsychological or neurophysiological assessment, to coma. Several scales have been developed for grading the extent of HE. The most often used is the West Haven criteria (WHC), which differentiate between four grades of clinically overt HE. Patients with liver cirrhosis without clinically overt symptoms of HE but neuropsychological or neurophysiological findings indicating brain dysfunction are considered to have minimal hepatic encephalopathy (MHE). For simplification, some experts suggest differentiating between covert HE (MHE plus grade I HE according to WHC) and overt HE (WHC grades II-IV). Diagnosis of both MHE and overt HE is hampered by the fact that none of the symptoms of HE or the findings in the various diagnostic measures applied are specific. Thus, a diagnosis of HE or MHE can only be made after exclusion of other possible causes of brain dysfunction.
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Affiliation(s)
- Karin Weissenborn
- Clinic for Neurology, Hannover Medical School, 30623, Hannover, Germany.
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