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Li XQ, Cao W, Yin TT, Lu R, Li Y, Sha YY. A Qualitative Study on Cryptogenic Hepatic Encephalopathy Screening Cognition Among Hepatology Medical Care Personnel. J Multidiscip Healthc 2025; 18:1539-1547. [PMID: 40110531 PMCID: PMC11921800 DOI: 10.2147/jmdh.s508992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 03/07/2025] [Indexed: 03/22/2025] Open
Abstract
Objective In this study, we focused on gaining an in-depth understanding on the attitudes and perceptions of hepatology healthcare professionals toward screening for cryptogenic hepatic encephalopathy (CHE), with the goal of providing references for the scientific and standardized implementation of CHE screening. Study Methods Based on the phenomenological research method, semi-structured in-depth interviews with nine medical professionals were conducted in March 2023 at the department of hepatology of a tertiary hospital in Taizhou city. The collected data was then integrated and analyzed using the Colaizzi seven-step method. Results Three main themes and seven sub-themes were identified: Inadequate knowledge of relevant information (inadequate knowledge of CHE, inadequate knowledge of neuropsychological test tools for CHE); positive attitudes toward screening for cirrhosis CHE; and screening factors (limited human resources, lack of stringent rules from the management, inability to properly use neuropsychological test tools, lack of cooperation from patients and their families, and lack of auxiliary means of screening). Conclusion Hepatology medical care personnel had a favorable outlook on CHE screening, however there is room for improvement in both their level of knowledge and clinical work. As a result the administrative departments of hospitals should focus on the factors affecting the clinical work of hepatology medical care personnel and formulate corresponding countermeasures. Emphasis should be placed on the screening and management of CHE for early recognition, early intervention, improvement of quality of life, and effective prevention of hepatic encephalopathy.
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Affiliation(s)
- Xiao-Qin Li
- Department of Infectious Disease, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, People's Republic of China
| | - Wen Cao
- Department of Infectious Disease, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, People's Republic of China
| | - Tian-Tian Yin
- Department of Infectious Disease, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, People's Republic of China
| | - Rui Lu
- Department of Infectious Disease, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, People's Republic of China
| | - Yang Li
- Department of Infectious Disease, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, People's Republic of China
| | - Ya-Yun Sha
- Department of Infectious Disease, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, People's Republic of China
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Labenz C, Gairing SJ, Kaps L, Ehrenbauer AF, Schleicher EM, Mengel S, Egge JF, Gabriel MM, Galle PR, Wedemeyer H, Zipprich A, Ripoll C, Greinert R, Maasoumy B. QuickStroop for screening for minimal hepatic encephalopathy in patients with cirrhosis. JHEP Rep 2025; 7:101298. [PMID: 40170910 PMCID: PMC11959648 DOI: 10.1016/j.jhepr.2024.101298] [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: 10/05/2024] [Revised: 11/26/2024] [Accepted: 12/05/2024] [Indexed: 04/03/2025] Open
Abstract
Background & Aims QuickStroop, a shortened version of the Stroop EncephalApp, has recently been proposed for screening for minimal hepatic encephalopathy (MHE) in patients with cirrhosis in the USA. At present, there are no data on its clinical utility for MHE screening in patients in Europe, and only limited data are available regarding its comparison to the Animal Naming Test (ANT). Methods In total, 242 patients with cirrhosis without signs of hepatic encephalopathy (HE) ≥ grade 1 and no history of overt HE were included as the development cohort. Another independent cohort comprising 104 patients with cirrhosis from a different center served as a validation set. MHE was defined using the psychometric hepatic encephalopathy score (PHES) (PHES-MHE). All patients were tested with the complete EncephalApp Stroop. A subset was also tested with the ANT. Regression formulas were fitted for patients above and below the age of 60 years, including the first two off-state runs, age, and school education (QuickStroop). Results PHES-MHE was detected in 76 (31%) patients. The first two off-state runs of the EncephalApp demonstrated a comparable discriminative ability to the complete Stroop test in distinguishing between patients with and without PHES-MHE. QuickStroop had a better discriminative ability in patients below than above the age of 60 years. The discriminative ability of QuickStroop (total cohort: AUC 0.88) was superior to ANT (AUC 0.70). QuickStroop predicted PHES-MHE with a sensitivity of 74% and a specificity of 89%, and took a median of only 34.5 s to complete. The acceptable discriminative ability of QuickStroop was confirmed in the validation cohort (AUC 0.81). Conclusion QuickStroop is a rapid screening tool to identify patients at risk for PHES-MHE, especially in patients below 60 years of age. Impact and implications QuickStroop, a shortened version of the Stroop EncephalApp, has recently been proposed for screening for MHE in patients with cirrhosis in the USA. In this study, we validated QuickStroop for patients in Germany with cirrhosis and demonstrate a good diagnostic accuracy for detecting MHE, especially in patients below 60 years of age. Additionally, QuickStroop might be superior to the ANT in patients below 60 years of age. The use of QuickStroop in clinical practice could facilitate screening for MHE.
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Affiliation(s)
- Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Simon J. Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Leonard Kaps
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Alena F. Ehrenbauer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Eva M. Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Sophie Mengel
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Julius F.M. Egge
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Maria M. Gabriel
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Peter R. Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Alexander Zipprich
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
- Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Cristina Ripoll
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
- Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Robin Greinert
- First Department of Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
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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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Gairing SJ, Mangini C, Zarantonello L, Gioia S, Nielsen EJ, Danneberg S, Lok AS, Sultanik P, Galle PR, Labenz J, Thabut D, Marquardt JU, Bloom PP, Lauridsen MM, Montagnese S, Nardelli S, Labenz C. Minimal hepatic encephalopathy is associated with a higher risk of overt hepatic encephalopathy and poorer survival. J Intern Med 2024; 295:331-345. [PMID: 37983845 DOI: 10.1111/joim.13747] [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] [Indexed: 11/22/2023]
Abstract
BACKGROUND AND AIMS Minimal hepatic encephalopathy (MHE) is a frequent complication in patients with liver cirrhosis. Its impact on predicting the development of overt hepatic encephalopathy (OHE) and survival has not been studied in large multicenter studies. METHODS Data from patients recruited at eight centers across Europe and the United States were analyzed. MHE was detected using the psychometric hepatic encephalopathy score (PHES). A subset was also tested with the simplified animal naming test (S-ANT1). Patients were followed for OHE development and death/liver transplantation (LTx). RESULTS A total of 1462 patients with a median model of end-stage liver disease of 11 were included (Child-Pugh (CP) stages: A 47%/B 41%/C 12%). Median follow-up time was 19 months, during which 336 (23%) patients developed an OHE episode and 464 (32%) reached the composite end point of death/LTx (369 deaths, 95 LTx). In multivariable analyses, MHE (defined by PHES) was associated with the development of OHE (subdistribution hazard ratio 1.74, p < 0.001) and poorer LTx-free survival (hazard ratio 1.53, p < 0.001) in the total cohort as well as in the subgroup of patients without a history of OHE. In subgroup analyses, MHE (defined by PHES) was associated with OHE development in patients with CP B, whereas there was no association in patients with CP A or C. In the subgroup of patients with available S-ANT1, MHE (defined by S-ANT1) was independently associated with OHE development. Combined testing (PHES+S-ANT1) was superior to single testing for predicting OHE and poorer LTx-free survival. CONCLUSIONS This large multicenter study demonstrates that screening for MHE is a useful tool for predicting OHE and poorer survival.
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Affiliation(s)
- Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Chiara Mangini
- Department of Medicine, University of Padova, Padova, Italy
| | | | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Elise Jonasson Nielsen
- Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Esbjerg, Denmark
| | - Sven Danneberg
- Department of Medicine I, University Hospital Schleswig-Holstein, Lübeck, Germany
| | - Anna S Lok
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Philippe Sultanik
- Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - Peter Robert Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Joachim Labenz
- Department of Medicine, Diakonie Hospital Jung-Stilling, Siegen, Germany
| | - Dominique Thabut
- Service d'hépato-gastroentérologie, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - Jens Uwe Marquardt
- Department of Medicine I, University Hospital Schleswig-Holstein, Lübeck, Germany
| | - Patricia P Bloom
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Mette Munk Lauridsen
- Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Esbjerg, Denmark
| | - Sara Montagnese
- Department of Medicine, University of Padova, Padova, Italy
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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Bajaj JS, O'Leary JG, Jakab SS, Fagan A, Sikaroodi M, Gillevet PM. Gut microbiome profiles to exclude the diagnosis of hepatic encephalopathy in patients with cirrhosis. Gut Microbes 2024; 16:2392880. [PMID: 39189586 PMCID: PMC11352695 DOI: 10.1080/19490976.2024.2392880] [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: 05/28/2024] [Revised: 07/15/2024] [Accepted: 08/12/2024] [Indexed: 08/28/2024] Open
Abstract
Patients with cirrhosis who have cognitive complaints are presumed to have hepatic encephalopathy (HE), which leads to unwarranted medications while ignoring the underlying disease process causing these complaints. Since neuropsychological testing, the current gold standard for HE diagnosis, is not readily available, an orderable test is needed. We aimed to develop and validate a rapid gut microbiota test to exclude HE and determine stakeholder input on this approach. Stool was collected from two cohorts: a two-center training cohort (n = 305, on/not on HE-related therapy) and a multicenter validation cohort (n = 30, on HE treatment). Stool microbiota was analyzed rapidly using nanopore analysis. Stakeholder (patients and clinicians) needs assessment was evaluated using semi-quantitative questionnaires. In the training cohort, machine learning using neural network identified a 20-species signature that differentiated HE vs no-HE with 84% specificity compared to the gold standard neuropsychological testing. This high specificity persisted regardless of whether patients were on HE-related therapy or not. In the validation cohort, application of this profile led to reevaluation of the HE diagnosis and treatment in > 40% of the patients. This approach was acceptable to patients (Veterans in the validation cohort) and clinician (n = 40 nationwide) stakeholders. We conclude that a machine learning stool signature based on 20 microbial species developed in a training set and validated in a separate multicenter prospective cohort differentiated those with vs. without HE, identified patients misdiagnosed with HE, and was acceptable to patients and clinician stakeholders.
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Affiliation(s)
- Jasmohan S Bajaj
- Department of Medicine, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, VA, USA
| | - Jacqueline G O'Leary
- Department of Medicine, North Texas VA Medical Center and UT Southwestern Medical Center, Dallas, TX, USA
| | - Sofia S Jakab
- Department of Medicine, West Haven VA Medical Center and Yale University School of Medicine, West Haven, CT, USA
| | - Andrew Fagan
- Department of Medicine, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, VA, USA
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Gairing SJ, Mangini C, Zarantonello L, Gioia S, Nielsen EJ, Danneberg S, Gabriel M, Ehrenbauer AF, Bloom PP, Ripoll C, Sultanik P, Galle PR, Labenz J, Thabut D, Zipprich A, Lok AS, Weissenborn K, Marquardt JU, Lauridsen MM, Nardelli S, Montagnese S, Labenz C. Prevalence of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Multicenter Study. Am J Gastroenterol 2023; 118:2191-2200. [PMID: 36940426 DOI: 10.14309/ajg.0000000000002251] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 03/01/2023] [Indexed: 03/22/2023]
Abstract
INTRODUCTION The prevalence of minimal hepatic encephalopathy (MHE), in particular in different subgroups, remains unknown. This study aimed to analyze the prevalence of MHE in different subgroups to identify patients at high risk and to pave the way for personalized screening approaches. METHODS In this study, data of patients recruited at 10 centers across Europe and the United States were analyzed. Only patients without clinical signs of hepatic encephalopathy were included. MHE was detected using the Psychometric Hepatic Encephalopathy Score (PHES, cut-off < or ≤-4 depending on local norms). Clinical and demographic characteristics of the patients were assessed and analyzed. RESULTS In total, 1,868 patients with cirrhosis with a median model for end-stage liver disease (MELD) of 11 were analyzed (Child-Pugh [CP] stages: A 46%, B 42%, and C 12%). In the total cohort, MHE was detected by PHES in 650 patients (35%). After excluding patients with a history of overt hepatic encephalopathy, the prevalence of MHE was 29%. In subgroup analyses, the prevalence of MHE in patients with CP A was low (25%), whereas it was high in CP B or C (42% and 52%). In patients with a MELD score <10, the prevalence of MHE was only 25%, but it was 48% in patients with a MELD score ≥20. Standardized ammonia levels (ammonia level/upper limit of normal of each center) correlated significantly, albeit weakly with PHES (Spearman ρ = -0.16, P < 0.001). DISCUSSION The prevalence of MHE in patients with cirrhosis was high but varied substantially between diseases stages. These data may pave the way for more individualized MHE screening approaches.
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Affiliation(s)
- Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Chiara Mangini
- Department of Medicine, University of Padova, Padova, Italy
| | | | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Elise Jonasson Nielsen
- Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Esbjerg, Denmark
| | - Sven Danneberg
- Department of Medicine I, University Hospital Schleswig-Holstein, Lübeck, Germany
| | - Maria Gabriel
- Clinic for Neurology, Hannover Medical School, Hannover, Germany
| | | | - Patricia P Bloom
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Cristina Ripoll
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
- First Department of Internal Medicine, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | - Philippe Sultanik
- Service d'hépato-gastroentérologie, Sorbonne Université, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Paris, France
| | - Peter Robert Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Joachim Labenz
- Department of Medicine, Diakonie Hospital Jung-Stilling, Siegen, Germany
| | - Dominique Thabut
- Service d'hépato-gastroentérologie, Sorbonne Université, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Paris, France
| | - Alexander Zipprich
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
- First Department of Internal Medicine, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | - Anna S Lok
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Jens Uwe Marquardt
- Department of Medicine I, University Hospital Schleswig-Holstein, Lübeck, Germany
| | - Mette Munk Lauridsen
- Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Esbjerg, Denmark
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Sara Montagnese
- Department of Medicine, University of Padova, Padova, Italy
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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Ismond KP, Spiers JA, Tandon P. Identifying opportunities for hepatic encephalopathy self-management: A mixed methods systematic review and synthesis. CANADIAN LIVER JOURNAL 2023; 6:215-233. [PMID: 37503524 PMCID: PMC10370725 DOI: 10.3138/canlivj-2022-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 08/20/2022] [Indexed: 07/29/2023]
Abstract
Background Hepatic encephalopathy (HE) in cirrhosis is an extremely challenging complication for patients and care partners. To identify potentially modifiable factors to enhance HE self-management strategies, we conducted a synthesis of quantitative and qualitative research about real-world HE behaviours, knowledge, and experiences. Methods Using the EPPI-Centre's mixed methods synthesis procedure, a systematic literature search in five databases was completed; methods of selected articles underwent critical appraisal followed by descriptive analysis and coded line-by-line of content. Through refutational translation, the findings from the quantitative and qualitative syntheses were juxtaposed to highlight congruencies, incongruencies, or gaps. These findings informed generation of cross-analytical themes that were transformed into action statements. Results The quantitative narrative review of synthesis (n = 17) generated four themes (patients had low awareness of HE and low treatment adherence rates, physicians had a non-uniform approach to non-pharmaceutical therapies). Meta-aggregation of qualitative data from six articles yielded three themes (patients and care partners had low levels of HE awareness, were unfamiliar with HE self-management, and were adherent to treatments). Comparison of findings revealed three congruencies, two gaps, and one incongruency. The combined synthesis yielded two self-management themes: universal patient-oriented cirrhosis HE education and ensuring each health care encounter systematically addresses HE to guarantee health care is continuously modified to meet their needs. Conclusions By drawing on elements of Bloom's Taxonomy and distributed knowledge networks, deliberate patient-oriented HE messaging at all health care encounters is greatly needed to improve health outcomes and reduce care burdens related to HE.
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Affiliation(s)
- Kathleen P Ismond
- Division of Gastroenterology, Liver Unit, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Jude A Spiers
- Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada
| | - Puneeta Tandon
- Division of Gastroenterology, Liver Unit, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
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Gairing SJ, Schleicher EM, Galle PR, Labenz C. Prediction and prevention of the first episode of overt hepatic encephalopathy in patients with cirrhosis. Hepatol Commun 2023; 7:02009842-202304010-00007. [PMID: 36930868 PMCID: PMC10027066 DOI: 10.1097/hc9.0000000000000096] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 12/13/2022] [Indexed: 03/19/2023] Open
Abstract
Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients' quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.
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Affiliation(s)
- Simon J Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Eva M Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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9
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Gairing SJ, Müller L, Kloeckner R, Galle PR, Labenz C. Review article: post-TIPSS hepatic encephalopathy-current knowledge and future perspectives. Aliment Pharmacol Ther 2022; 55:1265-1276. [PMID: 35181894 DOI: 10.1111/apt.16825] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/23/2022] [Accepted: 02/02/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND In light of the global rise in the burden of chronic liver diseases and liver cirrhosis, the number of patients suffering from decompensation events is expected to increase. Transjugular intrahepatic portosystemic shunts (TIPSS) provide effective long-term symptom control and may prolong transplant-free survival in portal hypertension-driven recurrent ascites and variceal bleeding. New-onset or recurrent hepatic encephalopathy (HE) after TIPSS insertion (post-TIPSS HE) represents the most severe post-interventional complication. AIMS To provide insight into the epidemiology and risk factors for post-TIPSS HE and scrutinize the current state of the art in treatment and drug therapy options. METHODS We conducted a literature search on post-TIPSS HE in patients with liver cirrhosis. RESULTS Post-TIPSS HE occurs in up to 54.5% of cases and particularly early recurrent HE is associated with a dismal prognosis. In recent years, several risk factors for the development of post-TIPSS HE have been identified. These include not only parameters reflecting liver function (model for end-stage liver disease score/Child-Pugh score) as well as cognitive dysfunction caused by minimal HE but also extrahepatic factors such as sarcopenia and common medications such as proton pump inhibitors. In addition, new data on the benefit of rifaximin and of smaller stent grafts emerged and may improve the prevention of post-TIPSS HE. CONCLUSIONS Careful selection of TIPSS candidates is of utmost importance to reduce the risk of post-TIPSS HE. In this narrative review, we provide a concise overview of the current epidemiology and risk factors of the treatment options for post-TIPSS HE.
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Affiliation(s)
- Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Lukas Müller
- Department of Radiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Roman Kloeckner
- Department of Radiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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10
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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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11
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Kaps L, Hildebrand K, Nagel M, Michel M, Kremer WM, Hilscher M, Galle PR, Schattenberg JM, Wörns MA, Labenz C. Validation of EncephalApp_Stroop as screening tool for the detection of minimal hepatic encephalopathy in German patients with liver cirrhosis. Clin Res Hepatol Gastroenterol 2022; 46:101873. [PMID: 35124289 DOI: 10.1016/j.clinre.2022.101873] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 12/14/2021] [Accepted: 01/17/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND In contrast to overt hepatic encephalopathy (OHE), the diagnosis of minimal HE (MHE) is challenging in patients with cirrhosis requiring elaborate, specialized testing. The EncephalApp_Stroop is a smartphone-based application established as screening tool for the diagnosis of MHE but has not yet been validated in a German cohort and country specific cut-offs are currently missing. METHODS 93 patients with cirrhosis were enroled into this study. Psychometric hepatic encephalopathy score (PHES) was used to detect MHE, and a subset of the patients was tested with critical flicker frequency (CFF). All patients underwent testing with EncephalApp_Stroop. Cut-off thresholds for EncephalApp_Stroop were calculated according to Youden's Index and a separate cut-off was determined with focus on sensitivity. RESULTS 24 (26%) patients had MHE according to PHES. EncephalApp_Stroop had a strong correlation with PHES (r=-0.76, p<0.001), while there was only a modest correlation with CFF (r=-0.51, <0.001). On time as well as on+off time discriminated best between patients with and without MHE with AUROCS of 0.87 for both measures. According to Youden's index, a cut-off of >224.7 s (sec) (on+off time) discriminated best between patients with and without MHE with a sensitivity of 71% and a specificity of 88%. The adjusted cut-off value for on+off time with focus on sensitivity (sensitivity:specificity weighed 2:1) was 185.1 s, yielding an optimized sensitivity of 92% and a negative predictive value of 96%. By using this cut-off as a pre-screening test in a stepwise diagnosis algorithm, elaborate testing with PHES could have been avoided in 49% of all patients. CONCLUSION EncephalApp_Stroop may be useful in a stepwise diagnosis algorithm or even as a stand-alone screening tool to detect MHE in German patients with cirrhosis.
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Affiliation(s)
- Leonard Kaps
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.
| | - Katharina Hildebrand
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Michael Nagel
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Maurice Michel
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Wolfgang Maximilian Kremer
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Max Hilscher
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Jörn M Schattenberg
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Marcus-Alexander Wörns
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Department of Gastroenterology, Hematology, Oncology and Endocrinology, Klinikum Dortmund, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.
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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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Yu X, Jin Y, Zhou W, Xiao T, Wu Z, Su J, Gao H, Shen P, Zheng B, Luo Q, Li L, Xiao Y. Rifaximin Modulates the Gut Microbiota to Prevent Hepatic Encephalopathy in Liver Cirrhosis Without Impacting the Resistome. Front Cell Infect Microbiol 2022; 11:761192. [PMID: 35118004 PMCID: PMC8804384 DOI: 10.3389/fcimb.2021.761192] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 12/22/2021] [Indexed: 12/21/2022] Open
Abstract
The gut microbiota has an important role in the pathogenesis of hepatic encephalopathy(HE). Rifaximin, an intestinal non-absorbable antibacterial agent, is effective in the treatment of HE. However, whether long-term prophylactic use induces antibacterial resistance and its mechanism for treating HE remains unclear. This prospective study assessed the impact of 12 weeks rifaximin administration on the gut microbiota and resistome in cirrhotic patients. Fecal sampling was conducted 1 day before the first rifaximin administration and at Weeks 1, 2, 4, 6, 8, 10, 12 of the study. Thirty cirrhotic patients who were in remission from recurrent HE was enrolled to receive rifaximin (400mg TID for 12 weeks). Rifaximin improved hyperammonemia and cognitive function in the 21 patients who completed rifaximin treatment. The dynamic observations showed the gut microbiota diversity, composition and the number of resistance genes, plasmids, insertion sequences did not change significantly during the period(P>0.05). Metabolic pathways such as aromatic amino acids, tryptophan synthesis, urea cycle, and LPS synthesis reduced. No new antimicrobial resistance genes was emergenced. However, the number of aminoglycosides, rifamycin and phenolic resistance genes increased, whereas tetracycline, fosfomycin and cephamycin decreased (P<0.05). Changes in the abundance of E. coli, K. pneumoniae, and B. longum strains correlated with changes of resistance genes. Prophylactic use of rifaximin for 12 weeks improved hyperammonemia and neurophysiological function, maintained gut microbiota diversity, composition and did not change the overall resistome. Rifaximin altered expression of HE-related metabolic pathways. All of these effects could play a key role in preventing HE. Clinical Trial Registration: ChiCTR1900022234 (registered at the Chinese Clinical Trial Registry).
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Affiliation(s)
- Xiao Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Ye Jin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wangxiao Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tingting Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhongwen Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Junwei Su
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Hainv Gao
- Department of Infectious Disease, ShuLan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| | - Ping Shen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Beiwen Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Qixia Luo
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yonghong Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Yonghong Xiao,
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14
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Labenz C, Kostev K, Galle PR, Wörns MA, Schattenberg JM. Prescription rates of common medications in patients with decompensated cirrhosis in Germany. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 60:165-169. [PMID: 34820806 DOI: 10.1055/a-1676-4822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Adequate pharmacological treatment is of pivotal importance to improve prognosis in patients with decompensated liver cirrhosis. We studied the adherence to recommended pharmacological treatments as secondary prevention in cirrhotic patients following a first decompensation in German primary care. METHODS Using the Disease Analyzer Database, the current study sample included patients with liver cirrhosis who had an initial diagnosis of a first decompensation event between 2015 and 2018 (index date) and a follow-up time of at least 6 months after the index date. Pharmacological treatments following the 6 months after the index date were studied. RESULTS The study included 1538 patients with a first decompensation event. The frequency of first-time complications of cirrhosis was 60% new onset of ascites, 25% overt hepatic encephalopathy (HE), 3% spontaneous bacterial peritonitis (SBP), and 12% acute variceal bleeding. The adherence to guideline-recommended treatment following the initial decompensation was highest for ascites, with 91.3% of patients receiving diuretics. Non-selective beta-blockers following an event of variceal bleeding were prescribed in 69.1% and lactulose and/or rifaximin in 59.1% after a bout of HE. The frequency of prescriptions of antibiotics after SBP was 60.4%. Potenzially harmful prescribed medications included non-steroidal anti-inflammatory drugs in 15.5%, benzodiazepines in 12.8%, opioids in 9.5%, and proton pump inhibitors in 73.7%. CONCLUSION Our findings underline the need for intensified efforts to distribute practice guidelines for liver cirrhosis and increase awareness of over-prescribing of potentially harmful medication.
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Affiliation(s)
- Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | | | - Peter Robert Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Marcus-Alexander Wörns
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jörn M Schattenberg
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
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15
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Kaps L, Hildebrand K, Nagel M, Michel M, Kremer WM, Hilscher M, Galle PR, Schattenberg JM, Wörns MA, Labenz C. Risk factors for poorer health literacy in patients with liver cirrhosis. PLoS One 2021; 16:e0255349. [PMID: 34314445 PMCID: PMC8315548 DOI: 10.1371/journal.pone.0255349] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 07/14/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Health literacy is a concept that refers to patients' ability to manage their disease and the health system's ability to guarantee access to services. There is evidence that health literacy impacts the health outcomes of patients with chronic diseases, but detailed information on this topic in patients with liver cirrhosis is scarce. It was the aim of this study to identify risk factors for poorer health literacy in patients with liver cirrhosis. METHODS 89 patients with liver cirrhosis were enrolled in this study and health literacy was measured using the Health Literacy Questionnaire (HLQ). Covert hepatic encephalopathy (CHE) was diagnosed clinically according to the West-Haven Criteria (HE grade 1) and the PHES (minimal HE). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS). Based on the nine subscales of the HLQ, risk factors for poor health literacy were identified using linear regression models. RESULTS Normalized HLQ scores ranged between 65-76%, while appraisal of health information had lowest score (65%) and ability to actively engage with healthcare providers had highest score (76%). Multivariable regression analyses revealed an association of poorer health literacy and liver function as determined by MELD score and complications of liver cirrhosis such as a history of ascites or CHE. Additionally, we identified modifiable or preventable factors such as depressive symptoms, a history of falls, and active smoking as risk factors for poorer health literacy. CONCLUSION Multiple factors seem to impact on health literacy in patients with liver cirrhosis. Addressing modifiable and preventable factors may improve health literacy.
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Affiliation(s)
- Leonard Kaps
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Institute of Translational Immunology, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Katharina Hildebrand
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Michael Nagel
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Maurice Michel
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Wolfgang Maximilian Kremer
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Max Hilscher
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter R. Galle
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Jörn M. Schattenberg
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Marcus-Alexander Wörns
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Centre Mainz (CCM), University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
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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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Labenz C, Schattenberg JM. Letter: proton pump inhibitor use and bone fracture risk-a mechanistic point of view. Authors' reply. Aliment Pharmacol Ther 2021; 53:673. [PMID: 33566419 DOI: 10.1111/apt.16257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Jörn M Schattenberg
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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Lauridsen MM, Jepsen P, Wernberg CW, Schaffalitzky de Muckadell OB, Bajaj JS, Vilstrup H. Validation of a Simple Quality-of-Life Score for Identification of Minimal and Prediction of Overt Hepatic Encephalopathy. Hepatol Commun 2020; 4:1353-1361. [PMID: 32923838 PMCID: PMC7471424 DOI: 10.1002/hep4.1555] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 05/07/2020] [Accepted: 05/17/2020] [Indexed: 12/28/2022] Open
Abstract
Minimal hepatic encephalopathy (MHE) is underdiagnosed because most clinics refrain from psychometric testing. Diagnostic activities need to go up so patients with MHE can get the treatment their condition requires. The sickness impact profile questionnaire for covert hepatic encephalopathy (SIPCHE) score is based on quality‐of‐life outcomes and has been proposed as a simple, patient‐administered diagnostic score for grade 1 and MHE. Validate the SIPCHE for MHE identification and overt hepatic encephalopathy (OHE) prediction. 110 patients with liver cirrhosis (age 60 years, Model for End‐Stage Liver Disease score of 11.4, 80% blue‐collar) provided information for SIPCHE scoring: gender, age, and four SIP statements: “I do not maintain balance (physically),” “I act irritable or impatient with myself,” “I am not doing any of the usual physical recreation or activities,” and “I am eating much less than usual.” MHE was diagnosed using an abnormal continuous reaction time test and/or portosystemic encephalopathy syndrome test score. Patients were followed for 2.7 years on average. SIPCHE score positivity had high sensitivity (82%) but low specificity (38%) for MHE detection. Patients with an abnormal SIPCHE had a higher incidence of OHE during follow‐up (35% vs. 14%, P = 0.05). OHE prediction sensitivity was 87% and exclusion sensitivity was 85%. The patients with an abnormal SIPCHE had twice as many subsequent episodes of OHE, and despite their high mortality, also a higher risk. An abnormal SIPCHE had a high sensitivity and low specificity for MHE identification. An abnormal SIPCHE was associated with a more than doubled risk of OHE, even with death as a competing event. SIPCHE could be used as a high‐sensitivity, low‐cost, surrogate marker of MHE in clinics without availability of psychometric tests and allow more patients to benefit from anti‐MHE treatment.
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Affiliation(s)
- Mette Munk Lauridsen
- Department of Gastroenterology and Hepatology University Hospital of South Denmark Esbjerg Denmark
| | - Peter Jepsen
- Department of Hepatology and Gastroenterology Aarhus University Hospital Aarhus Denmark
| | | | | | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University and McGuire VA Medical Center Richmond VA
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology Aarhus University Hospital Aarhus Denmark
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