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Buttler L, Velázquez-Ramírez DA, Tiede A, Conradi AM, Woltemate S, Geffers R, Bremer B, Spielmann V, Kahlhöfer J, Kraft AR, Schlüter D, Wedemeyer H, Cornberg M, Falk C, Vital M, Maasoumy B. Distinct clusters of bacterial and fungal microbiota in end-stage liver cirrhosis correlate with antibiotic treatment, intestinal barrier impairment, and systemic inflammation. Gut Microbes 2025; 17:2487209. [PMID: 40255076 PMCID: PMC12054929 DOI: 10.1080/19490976.2025.2487209] [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: 11/08/2024] [Revised: 01/22/2025] [Accepted: 03/25/2025] [Indexed: 04/22/2025] Open
Abstract
Decompensated liver cirrhosis (dLC) is associated with intestinal dysbiosis, however, underlying reasons and clinical consequences remain largely unexplored. We investigated bacterial and fungal microbiota, their relation with gut barrier integrity, inflammation, and cirrhosis-specific complications in dLC-patients. Competing-risk analyses were performed to investigate clinical outcomes within 90 days. Samples were prospectively collected from 95 dLC-patients between 2017 and 2022. Quantitative metagenomic analyses clustered patients into three groups (G1-G3) showing distinct microbial patterns. G1 (n = 39) displayed lowest diversity and highest Enterococcus abundance, G2 (n = 24) was dominated by Bifidobacteria, G3 (n = 29) was most diverse and clustered most closely with healthy controls (HC). Of note, bacterial concentrations were significantly lower in cirrhosis compared with HC, especially for G1 that also showed the lowest capacity to produce short chain fatty acids and secondary bile acids. Consequently, fungal overgrowth, dominated by Candida spp. (51.63%), was observed in G1. Moreover, G1-patients most frequently received antibiotics (n = 33; 86.8%), had highest plasma-levels of Zonulin (p = 0.044) and a proinflammatory cytokine profile along with numerically higher incidences of subsequent infections (p = 0.09). In conclusion, distinct bacterial clusters were observed at qualitative and quantitative levels and correlated with fungal abundances. Antibiotic treatment significantly contributed to dysbiosis, which translated into intestinal barrier impairment and systemic inflammation.
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Affiliation(s)
- Laura Buttler
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - David A. Velázquez-Ramírez
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Anja Tiede
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Anna M. Conradi
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Sabrina Woltemate
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
| | - Robert Geffers
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Genome Analytics Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Birgit Bremer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Vera Spielmann
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infectious Disease Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Julia Kahlhöfer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infectious Disease Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany
| | - Anke R.M Kraft
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
- Centre for Experimental and Clinical Infection Research, A Joint Venture Between Helmholtz-Centre for Infection Research and Hannover Medical School, TWINCORE, Hannover, Germany
- Center for Individualized Infection Medicine (CiiM), Hannover, Germany
| | - Dirk Schlüter
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
- Centre for Experimental and Clinical Infection Research, A Joint Venture Between Helmholtz-Centre for Infection Research and Hannover Medical School, TWINCORE, Hannover, Germany
- Center for Individualized Infection Medicine (CiiM), Hannover, Germany
| | - Christine Falk
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
- Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany
| | - Marius Vital
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
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Li X, Cui Y, Gao S, Zhang Q, Dai Y, Wang S, Wu J, Li G, Song J. Development and validation of a score model for predicting the risk of first esophagogastric variceal hemorrhage and mortality in patients with hepatocellular carcinoma. Ann Med 2025; 57:2490210. [PMID: 40210586 PMCID: PMC11986866 DOI: 10.1080/07853890.2025.2490210] [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: 11/14/2024] [Revised: 02/14/2025] [Accepted: 04/02/2025] [Indexed: 04/12/2025] Open
Abstract
AIMS Esophagogastric variceal bleeding, especially first variceal hemorrhage, represents a challenging complication in the management of patients with hepatocellular carcinoma (HCC), and its presence significantly herald poor patient prognosis. The stratification system for the risk of first variceal hemorrhage and mortality has not been validated in patients with HCC. We aimed to develop and validate a simple score for the prediction of initial variceal bleeding and mortality in patients with HCC. METHODS This multicenter retrospective-prospective study included HCC patients at three tertiary hospitals in China from January 2016 to December 2023. The bleeding following endoscopy for hepatocellular carcinoma (BFE-HCC) score was constructed by the least absolute contraction and selection operator (LASSO) regression combined with multivariate logistic regression analysis. The performance of the score model was evaluated using the receiver operating characteristic (ROC) curve, the calibration curve, and the decision curve analysis (DCA). Finally, the of the results was further verified in an independent external cohort. RESULTS We recruited 351 patients from three centers (median age 56 years, 85.5% male and 83.5% with cirrhosis), 56.6% patients presented high-risk (HR) varices, and 35% patients experienced variceal bleeding. Multivariate logistic analysis revealed that the presence of cirrhosis, a history of acute variceal bleeding (AVB), Child-Pugh score, ALBI score, tumor size and portal vein tumor thrombosis (PVTT) Vp4 were independent predictors of HR varices. The BFE-HCC is composed of six variables: white blood cell count, HR varices, Child-Pugh score, HCC therapy modality, Vp4, and tumor stage. The area under the curve (AUC) of BFE-HCC was 0.82, and the calibration plots and decision curve analysis exhibited outstanding performance compared with the MELD, ALBI, and Child-Pugh scores. In addition, Patients with BFE-HCC ≥ 4 were at increased risk of mortality (P<0.01). CONCLUSIONS The BFE-HCC score is hopeful to predict initial variceal bleeding and mortality in patients with HCC, offering a promising tool for prognostic assessment and treatment decisions.
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Affiliation(s)
- Xueyan Li
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yajie Cui
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shan Gao
- Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
| | - Qingqing Zhang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Dai
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shaotong Wang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiandi Wu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gangping Li
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Song
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Guo H, Fang F, Lin L, Guo Z, Lai L, Shi Y, Chen T, Lai R, Ou Q, Fu Y. Novel prognostic scoring models for hepatitis B virus-related acute-on-chronic liver failure: A comparison with classical models. Virulence 2025; 16:2500490. [PMID: 40376958 PMCID: PMC12087482 DOI: 10.1080/21505594.2025.2500490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 04/21/2025] [Accepted: 04/23/2025] [Indexed: 05/18/2025] Open
Abstract
Early diagnosis and accurate prognostic evaluation are important for guiding clinical treatment and reducing mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). The present study established novel prognostic scoring models to guide the clinical treatment of patients with HBV-ACLF. We performed a retrospective analysis of clinical data from two cohorts of patients diagnosed with HBV-ACLF. By comparing differences in baseline characteristics and clinical indicators between the survival (n = 102) and dead (n = 64) groups in the derivation cohort(n = 166), four laboratory indicators (age, INR, TBIL, and HBeAg status) and three clinical signs (extrahepatic infection, ascites, and hepatic encephalopathy) were identified as independent risk factors. Logistic regression and nomogram models were used to construct three novel predictive models. By comparing the death and survival groups, we found that the three new models had higher predictions for AUROC (average of 0.856) than the three old models (average of 0.773). Model 1 had the strongest predictive power for the short-term survival rate of HBV-ACLF patients. Finally, we verified the predictive value of the new models for HBV-ACLF in a validation cohort (n = 42), and the Model 2 demonstrated good predictive accuracy for the 30-day survival rate of patients. The novel model based on seven predictors could accurately predict short-term mortality in patients with HBV-ACLF, which is promising for guiding clinical management and addressing the aetiological differences in Asian populations.
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Affiliation(s)
- Hongyan Guo
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- The School of Public Health, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Fengling Fang
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Lin Lin
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Zhaopei Guo
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Lu Lai
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yue Shi
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Tianbin Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Ruimin Lai
- Department of the Center of Liver Diseases, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Qishui Ou
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Ya Fu
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Gene Diagnosis Research Center, Fujian Medical University, Fuzhou, China
- Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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Batallas D, Gallego JJ, Casanova-Ferrer F, López-Gramaje A, Rivas-Diaz P, Megías J, Escudero-García D, Durbán L, Benlloch S, Urios A, Hidalgo V, Salvador A, Montoliu C. Sex differences in the mediating role of brain-derived neurotrophic factor between inflammation and memory in cirrhotic patients with minimal hepatic encephalopathy. Brain Behav Immun Health 2025; 46:100998. [PMID: 40343108 PMCID: PMC12060516 DOI: 10.1016/j.bbih.2025.100998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/12/2025] [Accepted: 04/21/2025] [Indexed: 05/11/2025] Open
Abstract
Minimal hepatic encephalopathy (MHE) affects attention, visuo-motor coordination, and visual perception, with mixed evidence on its impact on memory. Brain-derived neurotrophic factor (BDNF) is associated with memory dysfunction, and plays a crucial role in modulating neuroplasticity. This study investigates the mediating role of BDNF in the relationship between pro-inflammatory cytokines (IL-6, IL-15, IL-18), and declarative memory performance, and the moderating effects of sex. Sixty-eight cirrhotic patients and 22 healthy volunteers performed the Psychometric Hepatic Encephalopathy Score for MHE diagnosis and logical memory subtest (Wechsler Memory Scale-III). Moderated mediation analysis using bias-corrected bootstrapping and multiple regression was performed. Results showed that increased levels of IL-18 and IL-15 were significantly associated with lower BDNF levels (p = 0.03 and p = 0.02 respectively). However, no direct effect was observed between IL-18 and IL-15 and memory. The conditional effects of BDNF on memory were significant only for women with and without MHE, and lower BDNF levels were associated with lower memory performance (without MHE: p = 0.002; MHE: p = 0.001). Moreover, BDNF mediated indirectly the relationship between pro-inflammatory cytokines and memory. IL-18 and IL-15 impacted memory through reduced BDNF levels only in women with and without MHE, whereas IL-6 showed no significant effect on BDNF or memory across groups. These findings underscore the important role of BDNF in memory in cirrhotic patients, especially women with MHE, by mediating the IL-18 and IL-15 effects. The study highlights the role of IL-18 and IL-15 cytokines in neuroplasticity-related memory decline, positioning BDNF as a key biomarker for inflammation-associated cognitive impairment in this population.
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Affiliation(s)
- Daniela Batallas
- Laboratory of Social Cognitive Neuroscience, Department of Psychobiology and IDOCAL, University of Valencia, 46010, Valencia, Spain
| | - Juan José Gallego
- Fundación Investigación Hospital Clínico Universitario de Valencia. INCLIVA, 46010, Valencia, Spain
- Department of Pathology. University of Valencia, 46010, Valencia, Spain
| | - Franc Casanova-Ferrer
- Fundación Investigación Hospital Clínico Universitario de Valencia. INCLIVA, 46010, Valencia, Spain
| | - Adriá López-Gramaje
- Fundación Investigación Hospital Clínico Universitario de Valencia. INCLIVA, 46010, Valencia, Spain
- Department of Pathology. University of Valencia, 46010, Valencia, Spain
| | - Pablo Rivas-Diaz
- Laboratory of Social Cognitive Neuroscience, Department of Psychobiology and IDOCAL, University of Valencia, 46010, Valencia, Spain
| | - Javier Megías
- Department of Pathology. University of Valencia, 46010, Valencia, Spain
| | - Desamparados Escudero-García
- Servicio de Medicina Digestiva, Hospital Clínico Universitario de Valencia, Spain
- Departamento de Medicina. University of Valencia, 46010 Valencia, Spain
| | - Lucía Durbán
- Servicio de Medicina Digestiva, Hospital Arnau de Vilanova, 46015, Valencia, Spain
| | - Salvador Benlloch
- Servicio de Medicina Digestiva, Hospital Arnau de Vilanova, 46015, Valencia, Spain
- CIBERehd, Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Amparo Urios
- Fundación Investigación Hospital Clínico Universitario de Valencia. INCLIVA, 46010, Valencia, Spain
| | - Vanesa Hidalgo
- Laboratory of Social Cognitive Neuroscience, Department of Psychobiology and IDOCAL, University of Valencia, 46010, Valencia, Spain
- Department of Psychology and Sociology, Area of Psychobiology, University of Zaragoza, Teruel, Spain
| | - Alicia Salvador
- Laboratory of Social Cognitive Neuroscience, Department of Psychobiology and IDOCAL, University of Valencia, 46010, Valencia, Spain
- Spanish National Network for Research in Mental Health CIBERSAM, 28029, Madrid, Spain
| | - Carmina Montoliu
- Fundación Investigación Hospital Clínico Universitario de Valencia. INCLIVA, 46010, Valencia, Spain
- Department of Pathology. University of Valencia, 46010, Valencia, Spain
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Saleh RO, Hamad HA, Najim MA, Menon SV, Kaur M, Sivaprasad GV, Abohassan M, Juan WT, Husseen B, Mustafa YF. Exosome-mediated Transfer of lncRNA in Liver Associated Diseases; Uncovered Truths. Cell Biochem Biophys 2025; 83:1465-1481. [PMID: 39567423 DOI: 10.1007/s12013-024-01617-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2024] [Indexed: 11/22/2024]
Abstract
Exosomes are extracellular vesicles with a diameter ranging from 40 to 160 nm. They are produced by hepatocytes, cholangiocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs) and Kupffer cells in liver tissue. The secretion of exosomes might vary in quantity and composition in reaction to multiple triggers and various stages of disease. They transport various payloads, such as proteins, DNAs, and RNAs, and enable cell interaction to regulate myriad physiological and pathological processes in liver tissue. Long non-coding RNAs (lncRNAs) are a crucial component of exosomes with an excellent capability to regulate multiple cellular activities such as differentiation, development, metabolism, proliferation, apoptosis, and activation. With the advancements in transcriptomic and genomic study methods and database management technology, the functions and mechanisms of exosomal lncRNAs in liver diseases have been well-studied. This article delves into the detailed role of exosomal lncRNAs in liver disease onset and progression, ranging from hepatocellular carcinoma (HCC) to liver fibrosis drug-induced liver damage (DILI) and steatotic liver diseases.
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Affiliation(s)
- Raed Obaid Saleh
- Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al Maarif, Anbar, Iraq.
| | - Hamad Ali Hamad
- Department of Pathological Analysis, Collage of Applied Sciences, University of Fallujah, Fallujah, Iraq
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang, Malaysia
| | | | - Soumya V Menon
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Mandeep Kaur
- Department of Sciences, Vivekananda Global University, Jaipur, Rajasthan, India
| | - G V Sivaprasad
- Department of Basic Science & Humanities, Raghu Engineering College, Visakhapatnam, India
| | - Mohammad Abohassan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Wen-Tau Juan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Beneen Husseen
- Medical Laboratory Technique college, The Islamic University, Najaf, Iraq
- Medical Laboratory Technique college, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- Medical Laboratory Technique college, The Islamic University of Babylon, Babylon, Iraq
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, Iraq
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Bloom PP, Fisher CJ, Tedesco N, Kamdar N, Garrido-Trevino L, Robin J, Asrani SK, Lok AS. HEAR-MHE study: Automated speech analysis identifies minimal hepatic encephalopathy and may predict future overt hepatic encephalopathy. Hepatology 2025; 81:1740-1752. [PMID: 39264936 DOI: 10.1097/hep.0000000000001086] [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: 06/27/2024] [Accepted: 08/16/2024] [Indexed: 09/14/2024]
Abstract
BACKGROUND AND AIMS HE is a major cause of poor quality of life in patients with cirrhosis. A simple diagnostic test to identify minimal hepatic encephalopathy (MHE) and predict future overt HE (OHE) is lacking. We aimed to evaluate if analysis of speech patterns using a modern speech platform (1) correlates with validated HE tests, (2) correlates with MHE, and (3) predicts future OHE. APPROACH AND RESULTS In a two-center prospective cohort study of 200 outpatients with cirrhosis and 50 controls, patients underwent baseline speech recording and validated HE diagnostic testing with psychometric HE score. Patients were followed for 6 months to identify episodes of OHE. Seven hundred fifty-two speech variables were extracted using an automated speech analysis platform, reflecting the acoustic, lexical, and semantic aspects of speech. Patients with cirrhosis were median 63 years old (IQR 54, 68), 49.5% (99) were female. Over 100 speech variables were significantly associated with psychometric HE score ( p <0.05 with false discovery rate adjustment). A three-variable speech model (2 acoustic, 1 speech tempo variable) was similar to animal naming test in predicting MHE (AUC 0.76 vs. 0.69; p =0.11). Adding age and MELD-Na improved the accuracy of the speech model (AUC: 0.82). A combined clinical-speech model ("HEAR-MHE model") predicted time to OHE with a concordance of 0.74 ( p =0.06). CONCLUSIONS Automated speech analysis is highly correlated with validated HE tests, associated with MHE, and may predict future OHE. Future research is needed to validate this tool and to understand how it can be implemented in clinical practice.
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Affiliation(s)
- Patricia P Bloom
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Caitlyn J Fisher
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Nicholas Tedesco
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Neil Kamdar
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Stanford University, Stanford, California, USA
| | | | | | - Sumeet K Asrani
- Department of Medicine, Baylor University Medical Center, Dallas, Texas, USA
| | - Anna S Lok
- Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
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Jesudian A, Gagnon-Sanschagrin P, Maitland J, Yokoji K, Guérin A, Heimanson Z, Samson A, Olujohungbe O, Bumpass B. Assessment of Access Barriers to Rifaximin Among Patients with Hepatic Encephalopathy Using Adjudicated Claims Data. Adv Ther 2025; 42:2739-2753. [PMID: 40192964 PMCID: PMC12085396 DOI: 10.1007/s12325-025-03145-3] [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] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 02/12/2025] [Indexed: 05/18/2025]
Abstract
INTRODUCTION Continuous treatment with rifaximin 550 mg (hereafter rifaximin) is associated with lower hospitalization rates in patients with hepatic encephalopathy (HE); however, access barriers may exist. This study assessed gaps in rifaximin access and the impact of treatment gaps, particularly those resulting from claim rejections, on hospitalizations and healthcare costs among patients with HE in the United States. METHODS The IQVIA PharMetrics® Plus database linked with Longitudinal Access and Adjudicated Data (2015-2022) were used to identify adults with HE who had ≥ 1 paid rifaximin prescription fill. Rifaximin treatment gaps were assessed during the 12-month period from the first observed attempt at receiving rifaximin (index date). Adjusted number of overt HE (OHE) hospitalizations and healthcare costs were compared over the 6 months following the index date between Cohort 1, who had no gap due to claim rejection and had < 7 days of treatment gap due to other reasons, and Cohort 2, who had ≥ 1 rejection gap or had ≥ 7 days of non-rejection gap. RESULTS During the year following the index date, 94.7% of the 1711 patients experienced a treatment gap, including 34.8% with initiation gaps from first attempt at receiving rifaximin to first paid claim (77.7% of initiation gaps due to rejected claims) and 72.0% with gaps in access during active treatment (14.8% of active treatment gaps due to rejected claims). Compared with Cohort 1 (n = 432; mean age 56.3 years), Cohort 2 (n = 679; mean age 54.8 years) had 1.55 times the incidence rate of OHE hospitalizations [adjusted incidence rate ratio: 1.55 (95% confidence interval: 1.10-2.20)] and incurred US$1579 more in healthcare-associated costs per-patient-per-month (all p < 0.05). CONCLUSION Prescription claim rejections frequently led to delays in rifaximin initiation and gaps in access during active treatment. Access barriers to rifaximin were associated with increased hospitalizations and healthcare costs in patients with HE.
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Affiliation(s)
- Arun Jesudian
- Weill Cornell Medicine, 1283 York Avenue, New York, NY, 10065, USA
| | - Patrick Gagnon-Sanschagrin
- Analysis Group, Inc., 1190 Avenue des Canadiens-de-Montréal, Tour Deloitte, Suite 1500, Montréal, QC, H3B 0G7, Canada
| | - Jessica Maitland
- Analysis Group, Inc., 1190 Avenue des Canadiens-de-Montréal, Tour Deloitte, Suite 1500, Montréal, QC, H3B 0G7, Canada.
| | - Kana Yokoji
- Analysis Group, Inc., 1190 Avenue des Canadiens-de-Montréal, Tour Deloitte, Suite 1500, Montréal, QC, H3B 0G7, Canada
| | - Annie Guérin
- Analysis Group, Inc., 1190 Avenue des Canadiens-de-Montréal, Tour Deloitte, Suite 1500, Montréal, QC, H3B 0G7, Canada
| | - Zeev Heimanson
- Salix Pharmaceuticals, 400 Somerset Corporate Blvd, Bridgewater, NJ, 08807, USA
| | - Aaron Samson
- Bausch Health, 400 Somerset Corporate Blvd, Bridgewater, NJ, 08807, USA
| | | | - Brock Bumpass
- Bausch Health, 400 Somerset Corporate Blvd, Bridgewater, NJ, 08807, USA
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8
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Hanami Y, Kimura S, Suga T, Okamoto T, Ogawa E, Ashina K, Nakamura N, Kai S, Okajima H, Hatano E, Egi M, Takita J. Postoperative fluid balance and outcomes in pediatric living-donor liver transplant recipients: a retrospective cohort study. J Anesth 2025:10.1007/s00540-025-03515-9. [PMID: 40411562 DOI: 10.1007/s00540-025-03515-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Accepted: 05/06/2025] [Indexed: 05/26/2025]
Abstract
PURPOSE This study aimed to investigate the relationship between postoperative fluid balance (FB) and clinical outcomes in pediatric living-donor liver transplant (LDLT) recipients. METHODS This retrospective study was conducted at a tertiary care center. Patients aged ≤ 18 years who underwent LDLT between January 2010 and September 2023 were included. Postoperative FB was calculated as [(total fluid intake-total fluid output) / body weight] × 100 for 48 h. Patients were categorized into four groups: < 5%, 5-10%, 10-15%, and ≥ 15% FB. The primary outcome was ventilator-free days (VFD) within 30 days post-transplantation. Secondary outcomes included acute kidney injury (AKI), reintubation, hepatic arterial thrombosis, acute rejection, primary graft dysfunction, intensive care unit (ICU) length of stay (LOS), and mortality. RESULTS The study included 200 patients with a median weight of 9.0 (interquartile range [IQR]: 6.9-19.3) kg. Median VFD did not significantly differ across the FB groups: < 5% FB, 29.3 (IQR, 28.3-29.4) days; 5-10% FB, 29.3 (IQR, 28.3-29.4) days; 10-15% FB, 29.3 (IQR, 28.3-29.4) days; and ≥ 15% FB, 27.4 (IQR, 23.3-29.4) days (p = 0.27). However, multivariable analysis showed ≥ 15% FB was associated with 4.59 days shorter VFD (p = 0.004) and higher AKI incidence (odds ratio: 6.60, p = 0.012). Thrombosis occurred in 7 patients (3.5%) with no significant differences among groups (p = 0.61). Other secondary outcomes showed no significant differences. CONCLUSION Excessive postoperative FB (≥ 15%) in pediatric LDLT recipients was significantly associated with reduced VFD and increased AKI incidence, whereas other adverse outcomes were not significantly affected.
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Affiliation(s)
- Yotaro Hanami
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Kimura
- Department of Anesthesiology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Takenori Suga
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tatsuya Okamoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Eri Ogawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kazushige Ashina
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Natsumi Nakamura
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinichi Kai
- Department of Anesthesiology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hideaki Okajima
- Department of Pediatric Surgery, Kanazawa Medical University, Ishikawa, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Moritoki Egi
- Department of Anesthesiology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Junko Takita
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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9
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Fonseca A, Ramos R, Coimbra É, Caetano A, Neves T, Pereira R, Vasco IC, Alves M, Bilhim T. Controlled expansion stent grafts versus legacy stent grafts for transjugular intrahepatic portosystemic shunt: a single-centre retrospective study on the incidence of hepatic encephalopathy. CVIR Endovasc 2025; 8:48. [PMID: 40411691 PMCID: PMC12103397 DOI: 10.1186/s42155-025-00557-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 04/28/2025] [Indexed: 05/26/2025] Open
Abstract
PURPOSE Assess incidence of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients treated with 8-10 mm Controlled Expansion diameter VIATORR® (VCX) versus 10 mm diameter first-generation VIATORR® (Legacy) stent-grafts. MATERIALS AND METHODS Single-centre retrospective study (January 2015 to March 2024), including 132 adult patients with cirrhosis treated with TIPS due to complications of portal hypertension. Outcomes included post-TIPS new onset overt HE, ascites response, re-bleeding, mortality and portal pressure gradient (PPG) before and after TIPS. Comparisons used Chi square and Fisher´s exact test for categorical variables and Student´s t test or Mann-Whitney test for quantitative variables. RESULTS Indication for TIPS was refractory ascites (n = 82) and variceal bleeding (n = 50). The VCX group (n = 85) and the Legacy group (n = 47) had similar new onset overt HE: 37% (31/85) vs 43% (20/47), respectively (p = 0.31); mortality rates (34% [29/85]) vs 39% [18/47], respectively, p = 0.57) and re-bleeding (17% [6/35] vs 20% [3/15], respectively, p = 1.00). Median PPG reduction after TIPS was 10 mmHg (7 - 13) in the VCX group and 12 mmHg (9 - 15) in the Legacy group (p = 0.02). Subgroup analysis revealed post TIPS overt HE rate of 38% (19/50) in the VCX group vs 53% (17/32) in the Legacy group (p = 0.13), with refractory ascites as an indication. Shunt dysfunction rate was 7% (6/85) in the VCX group (stent thrombosis n = 6, stenosis or malpositioning n = 0) and 0% (0/47) in the Legacy group (p = 0.09). CONCLUSION VCX stent grafts induce an immediate lower PPG reduction, which might lead to more stent dysfunctions, but also to a reduction in post-TIPS HE.
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Affiliation(s)
- Afonso Fonseca
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal
| | - Rui Ramos
- Interventional Radiology Unit, Unidade Local de Saúde Trás-Os-Montes E Alto Douro, Vila Real, Vila Real, Portugal
| | - Élia Coimbra
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal
| | - António Caetano
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal
| | - Teresa Neves
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal
| | - Rafaela Pereira
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal
| | - Inês Conde Vasco
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal
| | - Marta Alves
- Epidemiology and Statistics Unit, Research Center, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal
- Nova Medical School|Faculdade de Ciências Médicas da UNL, and Centro de Estatística E Aplicações da Universidade de Lisboa (CEAUL), Lisbon, Portugal
| | - Tiago Bilhim
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, Portugal.
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10
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Wu PS, Lee PC, Chang TE, Hsieh YC, Huang CW, Lin CH, Huang YL, Lin YT, Huo TI, Schnabl B, Lee KC, Hou MC. Fecal carriage of multidrug-resistant organisms increases the risk of hepatic encephalopathy in patients with cirrhosis: insights from gut microbiota and metabolite features. Gut Pathog 2025; 17:30. [PMID: 40380209 PMCID: PMC12085042 DOI: 10.1186/s13099-025-00706-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 04/27/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND The impact of the fecal multidrug-resistant organism (MDRO) carriage on the gut microbiota, metabolite alterations, and cirrhosis-related complications remains unclear. METHODS Eighty-eight patients with cirrhosis and 22 healthy volunteers were analyzed for plasma metabolites, fecal MDROs, and microbiota composition. The fecal bacterial and fungal composition was assessed using 16S ribosomal RNA and internal transcribed spacer sequencing, whereas plasma metabolomic analysis was evaluated via untargeted liquid chromatography-mass spectrometry. Predictors of cirrhosis-related outcomes, risk factors for MDRO carriage, and microbiota-metabolite correlations were analyzed. RESULTS Fecal MDRO carriage was detected in 33% of patients with cirrhosis. MDRO carriers had a higher risk of hepatic encephalopathy (HE) compared to non-carriers (20.7% vs. 3.2%, p = 0.008). Patients carrying MDROs had higher plasma lipopolysaccharide (LPS) levels, and both elevated LPS and MDRO carriage independently predicted HE occurrence within 1 year. Compared with non-carriers, MDRO carriers had higher fecal bacterial and fungal burdens and exhibited different gut microbiota compositions, characterized by increased Streptococcus salivarius and enrichment of Saccharomycetes and Candida albicans. Thirty-one metabolites differed significantly among healthy controls, and patients with cirrhosis, with and without MDRO carriage. Six metabolites were significantly correlated with specific microbial taxa in MDRO carriers. Isoaustin, a fungal-derived metabolite, was significantly elevated in MDRO carriers with HE. CONCLUSIONS Fecal MDRO carriage was associated with endotoxemia, altered gut microbiota, metabolic changes, and a higher risk of HE. It's worthy to monitor fecal MDRO colonization in cirrhosis.
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Affiliation(s)
- Pei-Shan Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Pei-Chang Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tien-En Chang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yun-Cheng Hsieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | | | - Chao-Hsiung Lin
- Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Long Huang
- Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Tsung Lin
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Kuei-Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan.
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan.
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan.
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan.
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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11
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Feng Y, Gao C, Peng X, Chen B, Ding M, Du D, Rong J, Lv Q, Wilson DA, Tu Y, Peng F. Chemotactic Zn micromotor for treatment of high blood ammonia-associated hepatic encephalopathy. Nat Commun 2025; 16:4525. [PMID: 40374637 PMCID: PMC12081644 DOI: 10.1038/s41467-025-59650-0] [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] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 04/28/2025] [Indexed: 05/17/2025] Open
Abstract
Hepatic fibrosis involves hepatocyte damage, causing blood ammonia accumulation, which exacerbates liver pathology and crosses the blood-brain barrier, inducing hepatic encephalopathy. It is meaningful to construct a therapeutic platform for targeted ammonia clearance. In this work, a biocompatible water-powered Zn micromotor is constructed as an ammonia chemotaxis platform, which can be actuated by the water splitting reaction and the self-generated Zn2+ gradient. It can propel towards NH3·H2O source through the formation of complex ions [Zn(NH3)1](OH)+ and [Zn(NH3)2](OH)+, representing a generalizable chemotaxis strategy via coordination reaction. In vivo, biomimetic collective behavior allows precise navigation and reduction of the intrahepatic ammonia level, reshaping the pathological microenvironment. This mechanism, operating in a green, zero-waste manner, facilitates integration of these micromotors into the domain of biological regulation. Such environment environment-adaptive platform is favorable for targeted treatment of hepatic fibrosis and hepatic encephalopathy caused by hyperammonemia, which is expected to provide inspiration for future personalized and precision medicine.
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Affiliation(s)
- Ye Feng
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China
| | - Chao Gao
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China
| | - Xiuyun Peng
- Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, Lishui People's Hospital, Lishui, China
| | - Bin Chen
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China
| | - Miaomiao Ding
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China
| | - Dailing Du
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China
| | - Jinghui Rong
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China
| | - Qi Lv
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China
| | - Daniela A Wilson
- Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands
| | - Yingfeng Tu
- Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
| | - Fei Peng
- School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, China.
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12
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Hjorth M, Forsberg A. Predictive factors for limited health literacy among persons with cirrhosis: A Swedish explorative cross-sectional study. PLoS One 2025; 20:e0321780. [PMID: 40333942 PMCID: PMC12058021 DOI: 10.1371/journal.pone.0321780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 03/11/2025] [Indexed: 05/09/2025] Open
Abstract
INTRODUCTION Fatigue and altered cognitive capacity are common symptoms following cirrhosis. Patients consider information about cirrhosis difficult to understand. Health literacy levels vary among persons with chronic illnesses, which can hamper participation in and adaptation to treatment, potential restrictions and recommendations. Limited health literacy might also lead to decreased autonomy. PURPOSE The aim was to explore predictors of limited health literacy among adults with cirrhosis. MATERIALS AND METHODS This cross-sectional study explored health literacy among 167 Swedish adults with cirrhosis, 94 men and 73 women with a median age of 65 years using the 'Newest Vital Sign' instrument. Predictors of limited health literacy were examined in relation to patient characteristics and cirrhosis disease events. The study is reported following the STROBE guidelines. RESULTS The prevalence of limited health literacy was 58%. Low education and covert hepatic encephalopathy were associated with limited health literacy (p < 0.05). CONCLUSION Limited health literacy is common among Swedish adults with cirrhosis. Both covert hepatic encephalopathy and low education might be predictors of limited health literacy. Healthcare providers should tailor their patient education based on the patient's literacy level to facilitate understanding, learning and self-management.
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Affiliation(s)
- Maria Hjorth
- Centre for Clinical Research in Dalarna, Falun, Sweden
- Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
| | - Anna Forsberg
- Institute of Health Sciences at Lund University, Lund, Sweden
- Department of Cardiothoracic Surgery, Skåne University Hospital, Lund, Sweden
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13
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Sikerwar S, Yao L, Elfarra Y, Jesudian A. Optimal Management of the Inpatient With Decompensated Cirrhosis. J Clin Gastroenterol 2025; 59:420-432. [PMID: 39889207 DOI: 10.1097/mcg.0000000000002143] [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: 08/21/2024] [Accepted: 01/14/2025] [Indexed: 02/02/2025]
Abstract
Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.
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Affiliation(s)
- Sandeep Sikerwar
- NewYork-Presbyterian Hospital/Columbia University Medical Center
| | - Leah Yao
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Yasmine Elfarra
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
| | - Arun Jesudian
- NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
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14
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Wong RJ, Gagnon-Sanschagrin P, Heimanson Z, Maitland J, Bellefleur R, Guérin A, Samson A, Olujohungbe O, Bumpass B. Real-World Trends and Future Projections of the Prevalence of Cirrhosis and Hepatic Encephalopathy Among Commercially and Medicare-Insured Adults in the United States. Clin Transl Gastroenterol 2025; 16:e00823. [PMID: 39835684 PMCID: PMC12101919 DOI: 10.14309/ctg.0000000000000823] [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: 11/13/2024] [Accepted: 01/11/2025] [Indexed: 01/22/2025] Open
Abstract
INTRODUCTION Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using healthcare claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated healthcare resource utilization among commercially and Medicare-insured adults in the United States. METHODS Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020). Annual prevalence of cirrhosis, HE, overt HE (OHE) hospitalizations, and rifaximin ± lactulose use, and costs per hospitalization per year were calculated. Average year-over-year changes in prevalence of cirrhosis, and HE were estimated. Trends were extrapolated to 2030 using ordinary least-squares regression. RESULTS From 2007 to 2020, the prevalence of cirrhosis increased by an average of 4.6% year-over-year in the Commercial population and 8.1% in the Medicare population; the prevalence of HE increased by 4.3% and 2.5%, respectively. Rates of OHE hospitalizations decreased from 27.5% to 5.5% (Commercial) and from 26.2% to 9.5% (Medicare), and rates of liver transplantation increased. Average payer costs (Commercial) and provider charges (Medicare) per OHE hospitalization increased (from $40,881 to $77,699 and from $45,913 to $74,894, respectively). Use of rifaximin ± lactulose showed an increasing trend during the observation period, whereas lactulose use declined steadily. DISCUSSION The healthcare burden of cirrhosis and HE in the United States is increasing. Trends are projected to continue unless action is taken, such as improving medication access and developing policies addressing the contributing factors.
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Affiliation(s)
- Robert J. Wong
- Gastroenterology and Hepatology Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
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15
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Singal AK, Wong RJ, Dasarathy S, Abdelmalek MF, Neuschwander-Tetri BA, Limketkai BN, Petrey J, McClain CJ. ACG Clinical Guideline: Malnutrition and Nutritional Recommendations in Liver Disease. Am J Gastroenterol 2025; 120:950-972. [PMID: 40314389 DOI: 10.14309/ajg.0000000000003379] [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: 01/31/2024] [Accepted: 01/29/2025] [Indexed: 05/03/2025]
Abstract
Malnutrition, defined as deficiency, excess, or imbalance of nutrients, is a common complication in patients with liver disease, especially those with cirrhosis. Malnutrition may present as an isolated micronutrient deficiency, such as zinc deficiency, and it commonly presents as frailty and/or sarcopenia in patients with advanced liver disease. Patients with cirrhosis and/or alcohol-associated hepatitis should be assessed for malnutrition because it adversely affects patient outcomes including mortality, as well as waitlist and posttransplant outcomes among liver transplant candidates. The prevalence of malnutrition varies based on the method of assessment and disease severity, being higher in those with advanced liver disease. Among stable outpatients with cirrhosis, counseling should be done to eat small frequent meals, a night-time snack between 7 PM and 10 PM, and 2 or more cups of coffee daily. In selected patients with metabolic dysfunction-associated steatohepatitis, vitamin E 800 IU/d should be provided. Among hospitalized patients with cirrhosis, nutritional supplementation preferably by enteral route should be implemented in those with poor oral intake of daily requirements of proteins and/or calories. Protein intake should not be restricted including patients with decompensated cirrhosis and hepatic encephalopathy. A vegetable source of protein seems to be better tolerated than an animal source of protein in patients with hepatic encephalopathy. Branched chain amino acids augment the efficacy of lactulose and rifaximin in the treatment of hepatic encephalopathy. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the auspices of the American College of Gastroenterology Practice Parameters Committee.
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Affiliation(s)
- Ashwani K Singal
- Department of Medicine, University of Louisville, Louisville, Kentucky, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Srinivasan Dasarathy
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, Ohio, USA
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Brent A Neuschwander-Tetri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA
| | - Berkeley N Limketkai
- Divisions of Digestive Diseases and Clinical Nutrition, UCLA School of Medicine, Los Angeles, California, USA
| | - Jessica Petrey
- Kornhauser Health Sciences Library, University of Louisville, Louisville, Kentucky, USA; and
| | - Craig J McClain
- Departments of Medicine and Pharmacology & Toxicology, Chief of Research Affairs, Division of Gastroenterology, Hepatology and Nutrition, Associate Vice President for Health Affairs/Research, Associate Vice President for Translational Research, Louisville, Kentucky, USA
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16
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Moraru MV, Bucurica S, Proske BNA, Stoleru S, Zugravu A, Coman OA, Fulga I. Endoscopy Sedation Challenges in Patients With Hepatic Encephalopathy: A Focused Review on Propofol and Selective Use of Benzodiazepines. Am J Ther 2025; 32:e247-e255. [PMID: 40338682 DOI: 10.1097/mjt.0000000000001926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
BACKGROUND Hepatic encephalopathy (HE) presents a significant challenge in gastrointestinal endoscopy sedation due to impaired liver function, which alters drug metabolism and increases the risk of adverse effects. In the absence of clear guidelines and specific biomarkers for diagnosis and assessment of HE, there is insufficient evidence to formulate standardized protocols for management, diagnosis, and sedation during endoscopy. AREAS OF UNCERTAINTY Rigid protocols for sedation are difficult to implement due to wide variation in patient age, comorbidities, and disease severity, which creates a "gray zone." This leaves decisions heavily reliant on the clinician's preference or experience, patient characteristics, and institutional protocols. This review highlights the strengths and limitations of propofol, midazolam, and remimazolam in efforts to improve sedation strategies for endoscopic procedures in patients with HE. DATA SOURCES A review was conducted using PubMed and Scopus databases, keeping in view recent publications. Only primary research studies were considered for this review. Inclusion was based on the relevance of patient side effects, sedation outcomes, and safety profiles, with a particular focus on gastrointestinal endoscopy procedures and their implications in HE. RESULTS Propofol remains preferred in patients with HE, demonstrating manageable cardiovascular and respiratory events without worsening encephalopathy. However, its safety requires careful consideration in this high-risk population. The combination of propofol with adjuncts, such as esketamine, has shown potential in mitigating adverse effects and optimizing sedation protocols in challenging cases. Midazolam, though historically used, is not recommended in HE due to exacerbation of encephalopathy and unfavorable safety profiles. While remimazolam shows promise, no evidence in HE populations precludes definitive conclusions about its efficacy and safety. CONCLUSIONS Future research should focus on optimizing sedation protocols according to the needs of HE patients, including tools for risk stratification and guidelines considering individual patient profiles. Furthermore, studies must be performed to evaluate remimazolam's outcomes and safety profiles, both as a standalone sedative and in combination with other agents.
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Affiliation(s)
- Miruna V Moraru
- Department of Geriatrics and Gerontology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Sandica Bucurica
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- University Emergency Central Military Hospital "Dr. Carol Davila," Bucharest, Romania
| | - Benjamin N A Proske
- General Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania ; and
| | - Smaranda Stoleru
- Department of Pharmacology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Aurelian Zugravu
- Department of Pharmacology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Oana A Coman
- Department of Pharmacology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Ion Fulga
- Department of Pharmacology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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17
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Lauridsen MM, Bajaj JS. Hepatic encephalopathy as an indication or contraindication to liver transplant? Metab Brain Dis 2025; 40:181. [PMID: 40232524 PMCID: PMC12000178 DOI: 10.1007/s11011-025-01614-w] [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: 04/01/2024] [Accepted: 04/11/2025] [Indexed: 04/16/2025]
Abstract
Hepatic encephalopathy (HE) presents a significant challenge in liver transplantation (LT). On the one hand, LT can provide a curative treatment for HE by addressing its underlying cause, suggesting HE should be a strong indication for LT. Conversely, the severity of HE may reflect advanced liver disease and significant neurocognitive impairment, potentially complicating post-transplant outcomes and raising concerns about its suitability as an indication. This review will provide helpful insight to the hepatologist deciding whether HE should be considered an indication or a contraindication to liver transplantation in their patient. It gives an overview of the burden of HE pretransplant, HE's current status in the transplant listing process, and pre- and post-transplant cognitive issues to be mindful of. The main take-away messages are that pre-transplant HE should be managed aggressively, that neurodegenerative disorders and other differential diagnoses to HE should be thoroughly excluded, and that immunosuppressants can cause new onset cognitive issues post-transplant and should be monitored closely. In the future, objective measures of HE severity should be included in the MELD score to enhance the fairness and efficacy of transplant listings, ensuring those with cirrhosis complicated by HE receive timely and appropriate treatment.
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Affiliation(s)
- Mette Munk Lauridsen
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, VA, USA
- Department of Gastroenterology, University Hospital of South Denmark, Finsensgade 35, Esbjerg, 6700, Denmark
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, VA, USA.
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18
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Dobbermann H, Schlüter R, Lyubchenko Y, Beder J, Danneberg S, Mitzlaff K, Engelbart I, Jessberger J, Braun F, Becker T, Labenz C, Janneck M, Matthies D, Sayk F, Marquardt JU. Minimal Hepatic Encephalopathy in Cirrhotic Patients: A New Simple and Fast Digital Screening Method. United European Gastroenterol J 2025. [PMID: 40235140 DOI: 10.1002/ueg2.70004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 12/18/2024] [Accepted: 12/31/2024] [Indexed: 04/17/2025] Open
Abstract
BACKROUND Minimal hepatic encephalopathy is a common and prognostically severe complication of cirrhosis with a significant impact on the quality of life. Detailed diagnostic work-up of minimal hepatic encephalopathy is time-consuming and difficult to integrate into daily clinical routine. OBJECTIVE We aimed to develop a new, simple, and easy-applicable smartphone-based self-assessment method for screening of minimal hepatic encephalopathy. METHODS 92 patients with cirrhosis and 20 healthy controls were recruited to perform 3 different short digital tests on smartphones (Tip test (TT), number connection test (dNCT) and modified Stroop test (ST)). Results were correlated with the Psychometric Hepatic Encephalopathy Score (PHES) as the presumed gold standard for minimal hepatic encephalopathy. The impact of age, gender, education, CHILD and MELD scores was further investigated. RESULTS All 3 digital tests showed good correlation with PHES (TT r = -0.76, dNCT r = -0.58, and ST r = -0.65; all p < 0.001). Digital tests were performed significantly faster (TT median 41s (IQR 36-51s); dNCT median 21s (IQR 8-16s); ST median 76s (IQR 55-99s) than PHES (median 322s; IQR 261-434s); There were significant differences between age groups and different levels of education (p < 0.05). AUC for TT was 0.835 (95% confidence interval 0.747-0.922, p < 0.001) and highest among all digital tests. CONCLUSION All 3 digital tests proved to be suitable for screening of minimal hepatic encephalopathy. TT showed the highest correlation with reference PHES and was not affected by language skills or color blindness, and, thus, might represent a new and fast method for minimal hepatic encephalopathy detection. Intra-individually adjusted smartphone-based thresholds might further eliminate the influence of age, gender, educational level or training, to refine early app-based alerts in case of cognitive deterioration in cirrhotic patients.
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Affiliation(s)
- Henrike Dobbermann
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Raffael Schlüter
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Yevgeniy Lyubchenko
- Department of Electrical Engineering and Computer Science, Technische Hochschule Lübeck, University of Applied Sciences, Lübeck, Germany
| | - Johanna Beder
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Sven Danneberg
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Katharina Mitzlaff
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Iris Engelbart
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Jakob Jessberger
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Felix Braun
- Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany
| | - Thomas Becker
- Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, University Medical Centre Schleswig-Holstein (UKSH), Kiel, 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
| | - Monique Janneck
- Department of Electrical Engineering and Computer Science, Technische Hochschule Lübeck, University of Applied Sciences, Lübeck, Germany
| | - Denys Matthies
- Department of Electrical Engineering and Computer Science, Technische Hochschule Lübeck, University of Applied Sciences, Lübeck, Germany
| | - Friedhelm Sayk
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Jens U Marquardt
- Department of Medicine I, University Medical Center Schleswig-Holstein, Lübeck, Germany
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19
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Broca F, Dufrenoy M, Martin M. [Management of hepatic encephalopathy: A general review]. Rev Med Interne 2025; 46:211-219. [PMID: 39516076 DOI: 10.1016/j.revmed.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/13/2024] [Accepted: 10/05/2024] [Indexed: 11/16/2024]
Abstract
Hepatic encephalopathy is a severe complication with high mortality in patients with hepatopathy and/or portosystemic shunts, partly due to the presence of hyperammonemia because of defective hepatic detoxification. Diagnosis is essentially clinical, characterized by various neuropsychiatric symptoms, possibly associated with hyperammonemia. Complementary tests, such as electroencephalogram to identify metabolic encephalopathy, or specific abnormalities on cerebral magnetic resonance imagery, may also support the diagnosis. Management is essentially based on treatment of triggering factors such as ionic disorders or sepsis, and symptomatic therapy with non-absorbable disaccharides (notably lactulose) or polyethylene glycol, possibly combined with rifaximin. Progression varies according to the initial severity and management of hepatic encephalopathy, but this condition is potentially reversible with treatment.
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Affiliation(s)
- Florent Broca
- Service de médecine interne, CHU La Milétrie, Poitiers, France; Faculté de médecine et de pharmacie, université de Poitiers, Poitiers, France.
| | - Mylène Dufrenoy
- Service de médecine interne, CHU La Milétrie, Poitiers, France; Faculté de médecine et de pharmacie, université de Poitiers, Poitiers, France.
| | - Mickaël Martin
- Service de médecine interne, CHU La Milétrie, Poitiers, France; Faculté de médecine et de pharmacie, université de Poitiers, Poitiers, France; Inserm U1313, université de Poitiers, Poitiers, France.
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20
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Higaki A, Yamamoto A, Okada T, Ueno T, Tomiyama Y, Ito K, Tamada T. 4D Flow MRI Reflects Physiological Hemodynamics for the Diagnosis and Management of Portosystemic Shunts. Magn Reson Med Sci 2025; 24:149-154. [PMID: 38417875 PMCID: PMC11996251 DOI: 10.2463/mrms.ici.2023-0161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/11/2024] [Indexed: 03/01/2024] Open
Abstract
A woman in her sixties with portosystemic shunt and hepatic encephalopathy underwent open mesenteric vein ligation, resulting in improved portal flow and blood ammonia. In this case, 4D flow MRI was a valuable diagnostic and follow-up tool, visualizing and quantifying physiological portal hemodynamics with features distinct from those of contrast-enhanced CT and digital subtraction angiography. Our case study highlights the value of 4D flow MRI for managing portosystemic shunts.
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Affiliation(s)
- Atsushi Higaki
- Department of Radiology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Akira Yamamoto
- Department of Radiology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Toshimasa Okada
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Tomio Ueno
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Yasuyuki Tomiyama
- Department of Nutrition, Kurashiki Sakuyo University, Kurashiki, Okayama, Japan
- Department of Gastroenterology and Hepatology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Kosuke Ito
- Department of Radiology, Kawasaki Medical School, Kurashiki, Okayama, Japan
| | - Tsutomu Tamada
- Department of Radiology, Kawasaki Medical School, Kurashiki, Okayama, Japan
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21
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Song J, Lu W, Yang S, Wu F, Zhao Z, Ji J. Effects of shunt embolization on hepatic encephalopathy recurrence in patients with major portosystemic shunts: A systematic review and meta‑analysis. Biomed Rep 2025; 22:72. [PMID: 40083600 PMCID: PMC11904764 DOI: 10.3892/br.2025.1950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 09/06/2024] [Indexed: 03/16/2025] Open
Abstract
This study addresses the effects of shunt embolization on the recurrence of hepatic encephalopathy (HE) in patients with major portosystemic shunts. MEDLINE via PubMed, Google Scholar, and Scopus was searched to find the relevant full-text articles published from inception until August 2024. The primary outcome was the degree of HE or mental state change determined by the West-Heaven classification system. Dichotomous data were compared using odds ratios (OR). 95% confidence (CI) intervals were provided for each outcome in the report. The random-effects model was used to analyze the data. Trim and fill, Egger's regression and funnel plot were employed to evaluate publication bias in this body of literature. A total of 7 articles and 254 patients were included in the present meta-analysis. It was found that shunt embolization significantly reduced the recurrence of HE in patients with portosystemic shunts due to liver cirrhosis. Overall analysis showed that the pooled OR was 0.253 and the overall heterogeneity of the data was substantial (95% CI: 0.117-0.550, I 2=60.52% and P=0.001). The funnel plot was reasonably symmetrical and no study was trimmed to either side of the mean. Begg's (P=0.229) and Egger's tests (P=0.273) showed no significant risk of publication bias. Quality assessment showed that the majority of the included studies were of low quality. In conclusion, the present meta-analysis indicates that shunt embolization after portosystemic shunt significantly reduces the recurrence of HE in patients with liver cirrhosis. However, the findings should be interpreted with caution due to the low quality and low number of the included studies. Future research should prioritize higher-quality trials to validate these results and explore long-term outcomes.
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Affiliation(s)
- Jingjing Song
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Cancer Center of The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 32300, P.R. China
| | - Weiye Lu
- Ultrasound Department, The Fifth Affiliated Hospital of Wenzhou Medical University. Lishui, Zhejiang 32300, P.R. China
| | - Shengli Yang
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Cancer Center of The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 32300, P.R. China
| | - Fazong Wu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Cancer Center of The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 32300, P.R. China
| | - Zhongwei Zhao
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Cancer Center of The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 32300, P.R. China
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Cancer Center of The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 32300, P.R. China
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22
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Xiang Y, Tie J, Wang G, Zhuge Y, Wu H, Zhu X, Xue H, Liu S, Yang L, Xu J, Zhang F, Zhang M, Wei B, Li P, Wang Z, Wu W, Chen C, Yang S, Han Y, Tang C, Qi X, Zhang C. Post-TIPS Overt Hepatic Encephalopathy Increases Long-Term but Not Short-Term Mortality in Cirrhotic Patients With Variceal Bleeding: A Large-Scale, Multicenter Real-World Study. Aliment Pharmacol Ther 2025; 61:1183-1196. [PMID: 39962750 DOI: 10.1111/apt.18509] [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: 11/06/2024] [Revised: 11/24/2024] [Accepted: 01/06/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) is an established procedure for managing portal hypertension in cirrhotic patients, but the impact of post-TIPS overt hepatic encephalopathy (OHE) on survival remains controversial. While its effect on short-term survival is well-documented, its long-term implications remain unclear. AIMS This study aims to investigate the long-term impact of post-TIPS OHE on mortality in cirrhotic patients for variceal bleeding, focusing on the timing and predictive value of OHE beyond the first year post-TIPS. METHODS A multicenter, retrospective cohort study was conducted involving 3262 cirrhotic patients who underwent TIPS for variceal bleeding at seven Chinese tertiary centers between January 2010 and June 2020. Clinical data, including demographics, procedure details, post-TIPS complications and survival outcomes, were collected. The primary endpoints were all-cause mortality and OHE, with follow-up until death, liver transplantation or 60 months. Propensity score matching minimised confounding effects, and multivariate Fine-Grey competing risk models identified independent mortality predictors. RESULTS During a median follow-up of 1077 days, 33.2% developed post-TIPS OHE, associated with higher MELD and Child-Pugh scores. Among these, 19.3% died, with a median time from OHE onset to death of 947 days. Post-TIPS OHE was not linked to early survival (within 12 months) but emerged as an independent predictor of long-term mortality beyond 24 months, consistent across various clinical scenarios. CONCLUSION Post-TIPS OHE does not affect short-term survival but significantly increases long-term mortality risk. These findings highlight the need for continuous monitoring and tailored interventions to improve long-term outcomes in post-TIPS patients.
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Affiliation(s)
- Yi Xiang
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging and Interventional Radiology, Nanjing, Jiangsu, China
| | - Jun Tie
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi, China
| | - Guangchuan Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Hao Wu
- Department of Gastroenterology and Hepatology, West China Hospital, Chengdu, Sichuan, China
| | - Xiaoli Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Hui Xue
- Gastroenterology of the First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Shanghao Liu
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging and Interventional Radiology, Nanjing, Jiangsu, China
| | - Ling Yang
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging and Interventional Radiology, Nanjing, Jiangsu, China
| | - Jiao Xu
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi, China
| | - Feng Zhang
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Mingyan Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Bo Wei
- Department of Gastroenterology and Hepatology, West China Hospital, Chengdu, Sichuan, China
| | - Peijie Li
- Gastroenterology of the First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Ze Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wei Wu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chao Chen
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shifeng Yang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Yicheng Han
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Chengwei Tang
- Department of Gastroenterology and Hepatology, West China Hospital, Chengdu, Sichuan, China
| | - Xiaolong Qi
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging and Interventional Radiology, Nanjing, Jiangsu, China
| | - Chunqing Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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Yakut A. Gut microbiota in the development and progression of chronic liver diseases: Gut microbiota-liver axis. World J Hepatol 2025; 17:104167. [PMID: 40177197 PMCID: PMC11959663 DOI: 10.4254/wjh.v17.i3.104167] [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: 12/12/2024] [Revised: 01/28/2025] [Accepted: 02/25/2025] [Indexed: 03/26/2025] Open
Abstract
The gut microbiota (GM) is a highly dynamic ecology whose density and composition can be influenced by a wide range of internal and external factors. Thus, "How do GM, which can have commensal, pathological, and mutualistic relationships with us, affect human health?" has become the most popular research issue in recent years. Numerous studies have demonstrated that the trillions of microorganisms that inhabit the human body can alter host physiology in a variety of systems, such as metabolism, immunology, cardiovascular health, and neurons. The GM may have a role in the development of a number of clinical disorders by producing bioactive peptides, including neurotransmitters, short-chain fatty acids, branched-chain amino acids, intestinal hormones, and secondary bile acid conversion. These bioactive peptides enter the portal circulatory system through the gut-liver axis and play a role in the development of chronic liver diseases, cirrhosis, and hepatic encephalopathy. This procedure is still unclear and quite complex. In this study, we aim to discuss the contribution of GM to the development of liver diseases, its effects on the progression of existing chronic liver disease, and to address the basic mechanisms of the intestinal microbiota-liver axis in the light of recent publications that may inspire the future.
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Affiliation(s)
- Aysun Yakut
- Department of Gastroenterology, İstanbul Medipol University Sefakoy Health Practice Research Center, İstanbul 38000, Türkiye.
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Masuzaki R, Kogure H. Smartphone-based Stroop Test, EncephalApp: What is the optimal cutoff for diagnosing minimal hepatic encephalopathy? World J Hepatol 2025; 17:101649. [PMID: 40177203 PMCID: PMC11959658 DOI: 10.4254/wjh.v17.i3.101649] [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: 09/23/2024] [Revised: 02/04/2025] [Accepted: 02/13/2025] [Indexed: 03/26/2025] Open
Abstract
Jiang et al explored the diagnostic capabilities of EncephalApp, a smartphone-based Stroop Test, in patients with nonalcoholic liver disease. The study included 160 patients with nonalcoholic cirrhosis and utilized the psychometric hepatic encephalopathy score as a benchmark for diagnosing minimal encephalopathy. The identified optimal cutoff times were > 101.93 seconds for the "off" time and > 205.86 seconds for the combined "on + off" time, demonstrating sensitivities of 0.84 and 0.90, and specificities of 0.77 and 0.71, respectively. The findings suggest the necessity of employing different cutoffs for patients with alcoholic vs nonalcoholic liver cirrhosis, reflecting the distinct pathophysiologies underlying each condition. Additionally, alcohol consumption itself may influence Stroop test outcomes. Therefore, it is reasonable to establish separate benchmarks for alcoholic and nonalcoholic cirrhotic patients. Further validation in larger patient cohorts with clinical outcomes is essential. The demand for noninvasive liver disease assessments remains high in clinical practice.
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Affiliation(s)
- Ryota Masuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo 176-8610, Japan.
| | - Hirofumi Kogure
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo 176-8610, Japan
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Xia Y, Tie J, Wang G, Wu H, Zhuge Y, Yuan X, Huang G, Li Z, Liu X, Chen A, Zhang L, Cai Z, Tang C, Zhang C. Benefits of TIPS for Patients With Large Ascites Preceding Recurrent or Refractory ascites: A Multicenter Cohort Study. J Gastroenterol Hepatol 2025. [PMID: 40135340 DOI: 10.1111/jgh.16948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 02/27/2025] [Accepted: 03/16/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND AND AIM Patients with recurrent or refractory ascites can benefit from transjugular intrahepatic portosystemic shunt (TIPS). However, the value of TIPS for patients with large ascites remains unclear. METHODS This retrospective multicenter study included patients who underwent TIPS or medicine plus large-volume paracentesis (medicine + LVP) for ascites between January 2014 and December 2022 at five centers. The primary endpoint was recurrence or worsening of ascites. The secondary endpoints were liver-related death, all-cause hemorrhage, overt hepatic encephalopathy (OHE), and shunt dysfunction. RESULTS Overall, 724 patients were evaluated, including 373 patients with large ascites preceding recurrent or refractory ascites received TIPS (the LA-TIPS group), 282 patients with recurrent and refractory ascites received TIPS (the RA-TIPS group), and 69 patients with large ascites preceding recurrent or refractory ascites received medicine + LVP (the LA-M group). Patients in the LA-TIPS group had significantly lower incidences of recurrence or worsening of ascites (37.4% vs. 45.3%, p < 0.001), liver-related death (44.8% vs. 62.0%, p < 0.001), and OHE (47.3% vs. 60.3%, p < 0.001) than those in the RA-TIPS group. Meanwhile, patients in the LA-TIPS group had significantly lower incidences of recurrence or worsening of ascites (37.4% vs. 44.6%, p = 0.006) and hemorrhage (38.3% vs. 47.2%, p = 0.042), but a higher incidence of OHE (34.2% vs. 4.5%, p < 0.001) than those in the LA-M group. CONCLUSIONS In terms of controlling ascites, the benefit of TIPS was greater in patients with large ascites preceding recurrent or refractory ascites, suggesting that TIPS might be considered in patients with large ascites before they progress to recurrent or refractory stages.
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Affiliation(s)
- Yifu Xia
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jun Tie
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi, China
| | - Guangchuan Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Hao Wu
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xulong Yuan
- National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, Shaanxi, China
| | - Guangjun Huang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Zhen Li
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xu Liu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Anbang Chen
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Linhao Zhang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zihao Cai
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Chengwei Tang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chunqing Zhang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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Shin S, Roberts SB, Sachar Y, Verma AA, Razak F, Brahmania M. Clinical impact of Choosing Wisely Canada hepatology recommendations: an interrupted time-series analysis using data from GEMINI. BMJ Open Qual 2025; 14:e003142. [PMID: 40122575 PMCID: PMC11934363 DOI: 10.1136/bmjoq-2024-003142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 03/04/2025] [Indexed: 03/25/2025] Open
Abstract
INTRODUCTION Choosing Wisely Canada (CWC) Hepatology published recommendations in 2017 aiming to reduce low-value care and testing, including serum ammonia tests for hepatic encephalopathy (HE) and transfusion of blood products for minor invasive procedures. We explored the impact of these recommendations in reducing rates of low-value testing and care. METHODS We included all medicine inpatients from 23 hospitals in Ontario, Canada from the GEMINI database between April 2015 and March 2022. Weekly rates of low-value care were measured before and after the CWC Hepatology recommendations (19 July 2017). Interrupted time-series regression models were used to assess time trends for rates of low-value care. Subgroup analysis was completed on hospitalisations under hepatology or gastroenterology services. RESULTS Of 59 155 patients identified with liver disease, 17 906 developed HE and 11 676 cirrhosis patients underwent minor invasive procedures. In the HE cohort, there was no immediate change in the rate of ammonia tests with recommendations, but the overall rate decreased by 0.002 tests per hospitalisation per week (95% CI -0.00413 to -0.000009). With recommendations, we observed an increase in the rate of 0.242 (95% CI 0.010 to 0.474 transfusions/hospitalisation), but no significant difference in the rate change nor in the rate of platelet and vitamin K transfusions. There was no significant change in the rate of platelet and vitamin K transfusions. Hospitalisations under hepatology or gastroenterology services also did not have a change in rates of low-value care overall, except for ammonia tests where the rate decreased by 0.012 tests (95% CI -0.0177 to -0.00626 tests/hospitalisation) per week after recommendations. CONCLUSIONS The CWC recommendations were associated with a reduction in the rate of serum ammonia tests, but not with transfusion of blood products. Thus, there remains an opportunity to reduce low-value care and application of clinical guidelines.
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Affiliation(s)
- Saeha Shin
- Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
- Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada
| | - Surain B Roberts
- Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Yashasavi Sachar
- Department of Medicine, Western University, London, Ontario, Canada
| | - Amol A Verma
- Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Temerty Centre for AI Research and Education in Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Fahad Razak
- Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Mayur Brahmania
- Divisions of Gastroenterology and Hepatology and Medical Transplant, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada
- O'Brien Institute of Public Health, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
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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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Koyano K, Atsukawa M, Tsubota A, Kondo C, Miwa T, Namisaki T, Hiraoka A, Toyoda H, Tada T, Kobayashi Y, Kawata K, Matsuura K, Mikami S, Kawabe N, Oikawa T, Suzuki K, Kawano T, Okubo T, Arai T, Tani J, Morishita A, Iwasa M, Ishikawa T, Ikegami T, Tanaka Y, Shimizu M, Yoshiji H, Iwakiri K. Association Between Laboratory Values and Covert Hepatic Encephalopathy in Patients with Liver Cirrhosis: A Multicenter, Retrospective Study. J Clin Med 2025; 14:1858. [PMID: 40142666 PMCID: PMC11942637 DOI: 10.3390/jcm14061858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/24/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objective: Recently, there has been an increasing need to implement the diagnosis of the presence of covert hepatic encephalopathy (CHE) in patients with cirrhosis. The aim of this study was to identify novel factors associated with CHE in clinical practice. Methods: This retrospective study enrolled a total of 402 patients with cirrhosis at 17 institutions. The Stroop test was performed to diagnose CHE at each center. Results: The patients comprised 233 males and 169 females, with a median age of 69 (IQR, 61-75) years. The median albumin and 25(OH)D3 levels were 3.9 (3.5-4.3) g/dL and 15.4 (11.0-21.0) ng/mL, respectively. This cohort included 181 patients with esophageal varices (EV). Multivariate analysis revealed that low 25(OH)D3 (p < 0.05) and EV (p < 0.05) were independent risk factors for CHE. When limited to only laboratory factors, low albumin (p < 0.01) and low 25(OH)D3 (p < 0.05) were independent factors for CHE. The optimal cut-off values of albumin and 25(OH)D3 for predicting CHE were 3.7 g/dL and 16.5 ng/mL, respectively. The prevalence of CHE was 59.2% for 25(OH)D3 < 16.5 ng/mL and EV, 53.8% for albumin < 3.7 g/dL and 25(OH)D3 < 16.5 ng/mL, and 66.7% for albumin < 3.7 g/dL, EV, and 25(OH)D3 < 16.5 ng/mL. Conclusions: Low 25(OH)D3 and albumin levels, and the EV were positively associated with CHE in patients with cirrhosis. Specifically, the prevalence of CHE increased with a decrease in 25(OH)D3 levels. Patients with such risk factors should be actively and carefully examined for the presence of CHE.
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Affiliation(s)
- Kaori Koyano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (A.T.); (T.O.)
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan (M.S.)
| | - Tadashi Namisaki
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan; (T.N.); (H.Y.)
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama 790-0024, Japan;
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Gifu 503-8502, Japan;
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji 670-8540, Japan;
| | - Yuji Kobayashi
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan; (Y.K.); (T.I.)
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu 431-3125, Japan;
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 464-0083, Japan;
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda 278-0005, Japan;
| | - Naoto Kawabe
- Department of Gastroenterology and Hepatology, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan;
| | - Tsunekazu Oikawa
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (A.T.); (T.O.)
| | - Kenta Suzuki
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Tadamichi Kawano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Tomomi Okubo
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai 270-1694, Japan;
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Joji Tani
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa 761-0793, Japan; (J.T.); (A.M.)
| | - Asahiro Morishita
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa 761-0793, Japan; (J.T.); (A.M.)
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu 514-8507, Japan;
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan; (Y.K.); (T.I.)
| | - Tadashi Ikegami
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki 300-0332, Japan;
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8555, Japan;
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan (M.S.)
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan; (T.N.); (H.Y.)
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
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Kerbert AJC, Engelmann C, Habtesion A, Kumar P, Hassan M, Qi T, Volkert I, Otto T, Hall A, Khetan VU, Olde Damink S, Aguilar F, Chollet C, Brunet L, Clària J, Moreau R, Arroyo V, Coenraad MJ, Mehta G, Castelli F, Trautwein C, Fenaille F, Andreola F, Jalan R. Hyperammonemia induces programmed liver cell death. SCIENCE ADVANCES 2025; 11:eado1648. [PMID: 40053595 PMCID: PMC11887801 DOI: 10.1126/sciadv.ado1648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 01/31/2025] [Indexed: 03/09/2025]
Abstract
Hyperammonemia is common in liver cirrhosis and causally associated with hepatic encephalopathy development. Little is known about its hepatotoxic effects, which we aimed to characterize in this study. In a mouse model of chronic hyperammonemia without preexisting liver disease, we observed development of liver fibrogenesis and necroptotic cell death. Hyperammonemia also induced dysregulation of its main metabolic pathway, the urea cycle, as reflected by down-regulation of urea cycle enzyme protein expression and accumulation of its metabolites. Inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and its upstream inducer Toll-like receptor 4 (TLR4) protected against liver injury and further hyperammonemia. In clinically relevant rodent models of hyperammonemia (genetic ornithine transcarbamylase deficiency and bile duct ligation-induced cirrhosis), TLR4 inhibition reduced circulating ammonia. In conclusion, hyperammonemia induces liver fibrogenesis and RIPK1-mediated cell death, which is associated with urea cycle dysfunction. Inhibition of RIPK1 and TLR4 protects against hyperammonemia-induced liver injury and are potential therapeutic targets for hyperammonemia and chronic liver disease progression.
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Affiliation(s)
- Annarein J. C. Kerbert
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | - Cornelius Engelmann
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- Medical Department, Division of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charite - Universitätsmedizin Berlin, Berlin, Germany
| | - Abeba Habtesion
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
| | - Pavitra Kumar
- Medical Department, Division of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charite - Universitätsmedizin Berlin, Berlin, Germany
| | - Mohsin Hassan
- Medical Department, Division of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charite - Universitätsmedizin Berlin, Berlin, Germany
- Department of CardioMetabolic Disease Research, Boehringer Ingelheim, Biberach, Germany
| | - Tingting Qi
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ines Volkert
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Tobias Otto
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Andrew Hall
- The Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK
- Department of Cellular Pathology, Royal Free Hospital, London, UK
| | - Varun U. Khetan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
| | - Steven Olde Damink
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Ferran Aguilar
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Céline Chollet
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB-IDF, 91191 Gif-sur-Yvette, France
| | - Ludovic Brunet
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB-IDF, 91191 Gif-sur-Yvette, France
| | - Joan Clària
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
- Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
- Inserm and Université de Paris, Centre de Recherche sur l’Inflammation (CRI), UMRS1149 Paris, France
- Service d’Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Minneke J. Coenraad
- Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | - Gautam Mehta
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK
| | - Florence Castelli
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB-IDF, 91191 Gif-sur-Yvette, France
| | - Christian Trautwein
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
- IFADO, Department of Toxicology, TU Dortmund, Dortmund, Germany
| | - François Fenaille
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), MetaboHUB-IDF, 91191 Gif-sur-Yvette, France
| | - Fausto Andreola
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
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Xu X, Zhu T, Jing C, Jiang M, Fu Y, Xie F, Meng Q, Li J. Hepatic encephalopathy treatment after transjugular intrahepatic portosystemic shunt: a new perspective on the gut microbiota. Front Med (Lausanne) 2025; 12:1423780. [PMID: 40124683 PMCID: PMC11926149 DOI: 10.3389/fmed.2025.1423780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) placement alleviates portal hypertension symptoms. Hepatic encephalopathy (HE) is a common complication of TIPS, impacting patient quality of life and the healthcare burden. Post-TIPS HE is associated with portosystemic shunting, elevated blood ammonia levels, and inflammation. Increasing attention has been given to the liver and intestinal circulation in recent years. An imbalance in intestinal microecology plays a role in the occurrence of HE and may be a new target for treatment. This review discusses the causes, diagnosis, and treatment strategies for post-TIPS HE and focuses on exploring treatment strategies and their relationships with the gut microbiota, suggesting an innovative approach to address this complication.
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Affiliation(s)
- Xiaotong Xu
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Tong Zhu
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Changyou Jing
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Minjie Jiang
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yunlai Fu
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Fang Xie
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jianjun Li
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
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31
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Verma N, Kaur P, Garg P, Ranjan V, Ralmilay S, Rathi S, De A, Premkumar M, Taneja S, Roy A, Goenka M, Duseja A, Jalan R. Clinical and pathophysiological characteristics of non-acute decompensation of cirrhosis. J Hepatol 2025:S0168-8278(25)00137-0. [PMID: 40056937 DOI: 10.1016/j.jhep.2025.02.028] [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: 10/28/2024] [Revised: 02/07/2025] [Accepted: 02/11/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND & AIMS The heterogenous presentation patterns in decompensated cirrhosis confer variable outcomes. While acute decompensation (AD) is well-characterized, the presentation patterns and outcomes of non-acute decompensation (NAD) remain unclear. The aim of this study was to characterize clinical and pathophysiological features of NAD and identify predictors of progression in NAD. METHODS In this prospective study, patients across the cirrhosis spectrum were enrolled from two centers in India between 2020-2023: compensated cirrhosis (CC; n = 29), NAD (n = 311), AD (n = 201), and healthy controls (n = 10). Clinical and laboratory parameters, cytokine levels (IL-6, TNF, IL-10, MCP-1) and cell death markers (M30, M65, Gasdermin-D, RIPK3, MLKL) were assessed at baseline. Twelve-month overall survival was assessed in all patients. The predictors of progression to AD and mortality were evaluated in patients with NAD. RESULTS Survival was lower in patients with NAD (81.7%) than in those with CC (100%), but higher than in those with AD (31.2%) (p <0.001). Despite no significant systemic inflammation, patients with NAD exhibited elevated levels of cell death markers, particularly Gasdermin-D and RIPK3, compared to healthy controls and patients with CC. Both inflammatory and cell death markers were most pronounced in AD. Over 12 months, the cumulative incidence of progression to AD among those with NAD was 55.1%, significantly reducing their survival (68.2% vs. 95.3%, p <0.001). Predictors of such progression to AD included severe ascites, lower IGF-1, albumin, BMI, and higher bilirubin, Gasdermin-D, and RIPK3 levels, as well as higher CTP and MELD scores. CONCLUSIONS NAD represents a clinically, prognostically and pathophysiologically distinct entity in cirrhosis. Patients with NAD express elevated cell death markers and remain at risk of progression to AD and mortality. Identifying such high-risk patients should prompt interventions to prevent progression. Modulation of cell death is a potentially disease-modifying target in cirrhosis. IMPACT AND IMPLICATIONS This study highlights non-acute decompensation as a clinically, prognostically and pathophysiologically distinct subset of cirrhosis, underscoring the importance of understanding its progression dynamics. Identifying key predictors of acute decompensation, including ascites severity, low IGF-1 levels, and elevated cell death markers, such as Gasdermin-D and RIPK3, potentially uncovers new therapeutic avenues. These findings are crucial for helping hepatologists and researchers to risk stratify patients and optimize transplant candidacy. Interventions targeting necroptosis and pyroptosis pathways may improve outcomes, providing a significant shift towards precision medicine in cirrhosis care.
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Affiliation(s)
- Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India.
| | - Parminder Kaur
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Pratibha Garg
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Vivek Ranjan
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispecialty Hospitals, Kolkata, India
| | - Samonee Ralmilay
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Sahaj Rathi
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Akash Roy
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispecialty Hospitals, Kolkata, India
| | - Mahesh Goenka
- Institute of Gastrosciences and Liver Transplantation, Apollo Multispecialty Hospitals, Kolkata, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, United Kingdom.
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Miwa T, Tsuruoka M, Ueda H, Abe T, Inada H, Yukawa-Muto Y, Ohara M, Arai T, Tamai Y, Isoda H, Tadokoro T, Hanai T, Ito T, Tamaki N, Sakamaki A, Aoki Y, Tada F, Yoshio S, Takahashi H, Morishita A, Ishikawa T, Inoue J, Suda G, Ogawa C, Atsukawa M, Hiraoka A, Kuroda H, Namisaki T, Honda T, Kawaguchi T, Tanaka Y, Terai S, Ikegami T, Yoshiji H, Iwasa M, Shimizu M. Current management and future perspectives of covert hepatic encephalopathy in Japan: a nationwide survey. J Gastroenterol 2025:10.1007/s00535-025-02232-0. [PMID: 40053108 DOI: 10.1007/s00535-025-02232-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 02/16/2025] [Indexed: 04/20/2025]
Abstract
BACKGROUND Covert hepatic encephalopathy (CHE) leads to devastating outcomes in patients with cirrhosis. This study aims to elucidate the current management and future perspectives of CHE in Japan. METHODS A questionnaire-based cross-sectional study was conducted among physicians involved in managing cirrhosis in Japan. The primary aim was to elucidate the real-world management of CHE, including testing and treatment. Factors influencing the implementation of CHE testing were analyzed using a logistic regression model. Limitations and future perspectives for improving the management of CHE were also evaluated. RESULTS Of 511 physicians surveyed, 93.9% recognized CHE as a significant problem, and 86.9% agreed that it should be tested. Overall, 62.8% of physicians tested for CHE, whereas 37.2% did not. Multivariable analysis identified institutional factors and certifying board as significant determinants of CHE test implementation. The Stroop (68.2%) and neuropsychiatric tests (57.5%) were the most commonly used methods of identifying CHE. Among those who tested for CHE, 87.7% treated CHE; the most common treatments were lactulose (81.5%), rifaximin (76.3%), and branched-chain amino acids (70.4%). Among non-testers, the primary barrier was the time requirement for testing. Proposals to encourage CHE testing included the development of simple tests and integration of multidisciplinary teams. CONCLUSIONS Most physicians involved in cirrhosis care in Japan recognize CHE as a significant problem that warrants testing. However, testing for CHE remains limited by institutional factors and physician specialties. Time requirements for CHE testing are the primary barrier, and simple tests and multidisciplinary teams are recommended to enhance CHE management.
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Affiliation(s)
- Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
| | - Mio Tsuruoka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, 980-8574, Japan
| | - Hajime Ueda
- Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-Machi, Inashiki-Gun, Ibaraki, 300-3095, Japan
| | - Tamami Abe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-Cho, Shiwa-Gun, Yahaba, Iwate, 028-3694, Japan
| | - Hiroki Inada
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto University, 1-1-1, Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Yoshimi Yukawa-Muto
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-Shi, Hokkaido, 060-8638, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan
| | - Yasuyuki Tamai
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan
| | - Hiroshi Isoda
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu, Kagawa, 761-0793, Japan
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa, Nagoya, 466-8550, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1Kyonan-Cho, Musashino-Shi, Tokyo, 180-8610, Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-Ku, Niigata, 951-8510, Japan
| | - Yoshihiko Aoki
- Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, 272-8516, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-Cho, Matsuyama, Ehime, 790-0024, Japan
| | - Sachiyo Yoshio
- Department of Human Immunology and Translational Research, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu, Kagawa, 761-0793, Japan
| | - Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube-Yamaguchi, 7558505, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, 980-8574, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-Ku, Sapporo-Shi, Hokkaido, 060-8638, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, 4-1-3 Bancho, Takamatsu City, Kagawa Prefecture, 760-0017, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-Cho, Matsuyama, Ehime, 790-0024, Japan
| | - Hidekatsu Kuroda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate Medical University School of Medicine, Nishitokuta 2-1-1, Yahaba-Cho, Shiwa-Gun, Yahaba, Iwate, 028-3694, Japan
| | - Tadashi Namisaki
- Department of Gastroenterology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa, Nagoya, 466-8550, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, 830-0011, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto University, 1-1-1, Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-Ku, Niigata, 951-8510, Japan
| | - Tadashi Ikegami
- Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-Machi, Inashiki-Gun, Ibaraki, 300-3095, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
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Torre A, Córdova-Gallardo J, Martínez-Sánchez FD. Hepatic encephalopathy: risk identification and prophylaxis approaches. Metab Brain Dis 2025; 40:138. [PMID: 40053146 DOI: 10.1007/s11011-025-01531-y] [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: 08/12/2024] [Accepted: 01/08/2025] [Indexed: 03/26/2025]
Abstract
Hepatic encephalopathy (HE) is a debilitating neurological condition associated with cirrhosis, characterized by cognitive impairment ranging from minimal to overt symptoms. It significantly impacts patients' quality of life and substantially burdens healthcare systems. This review examines current prophylactic strategies for HE, focusing on established treatments, emerging therapies, and predictive tools to identify high-risk patients. Traditional treatments such as lactulose and rifaximin remain the cornerstone of HE management, effectively reducing ammonia levels and preventing recurrence. However, novel approaches like L-ornithine L-aspartate, albumin infusions, and antioxidants like resveratrol show promise in further improving outcomes by addressing underlying pathophysiological mechanisms, including systemic inflammation and gut dysbiosis. Developing predictive models, such as the AMMON-OHE score and clinical-genetic risk assessments, enhances the ability to tailor preventive interventions to individual patient profiles. These advancements are crucial in mitigating the incidence of overt HE, reducing hospital admissions, and improving patient survival rates. The future of HE management lies in personalized medicine, targeting specific inflammatory and metabolic pathways, with the potential integration of genetic manipulation. Continued research is essential to refine these strategies, ultimately aiming to improve the prognosis and quality of life for cirrhotic patients at risk of HE.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran", Vasco de Quiroga 15, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México, 14080, Mexico.
- Department of Gastroenterology, Medical Center ABC, Sur 136 116, Las Américas, Álvaro Obregón, 01120, Ciudad de México, Mexico.
| | - Jacqueline Córdova-Gallardo
- Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Escolar 411A, Copilco Universidad, Coyoacán, Ciudad de México, 04360, Mexico.
- Department of Hepatology, Hospital General "Dr. Manuel Gea González", Calz. de Tlalpan 4800, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México, 14080, Mexico.
| | - Froylan David Martínez-Sánchez
- Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Escolar 411A, Copilco Universidad, Coyoacán, Ciudad de México, 04360, Mexico
- Department of Internal Medicine, Hospital General "Dr. Manuel Gea González", 14080 Mexico City, Mexico. Calz. de Tlalpan 4800, Belisario Domínguez Secc 16, Tlalpan, 14080, Ciudad de México, Mexico
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Hanson C, Goacher EK. Hepatic encephalopathy in patients with cirrhosis: Key clinical considerations for the nurse practitioner and physician assistant. J Am Assoc Nurse Pract 2025; 37:173-181. [PMID: 39932441 DOI: 10.1097/jxx.0000000000001105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 11/07/2024] [Indexed: 03/04/2025]
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a common neurocognitive cirrhosis-related complication with a broad range of symptoms. Timely recognition and treatment of HE, including identifying precipitating factors, when possible, is critical for improving outcomes in patients with cirrhosis. Lactulose and rifaximin therapies, as appropriate, are recommended for patients with cirrhosis and a history of HE episode(s) to reduce risk of HE recurrence. OBJECTIVES To provide clinical considerations for nurse practitioners and physician assistants (PAs) on the diagnosis and management of patients with cirrhosis. DATA SOURCES A PubMed search of English-language articles published between January 1, 2008, and March 13, 2024, was performed to identify publications on the diagnosis and treatment of HE. RESULTS Important topics to address when discussing care with patients with cirrhosis and their caregivers include concomitant medication use, recent infection history, comorbid conditions (e.g., diabetes), fall and frailty risks, and sleep quality. In addition, ensuring treatment adherence is important for reducing the risk of future HE episodes and HE-related hospitalizations. Engaging and empowering caregivers helps reinforce the need for patient adherence to treatment and facilitates earlier identification of HE symptoms. CONCLUSIONS Early recognition of HE, treatment, and reduction in risk of recurrence are imperative to minimize patient morbidity and mortality. IMPLICATIONS FOR PRACTICE Nurse practitioners and PAs play an important role in supporting patients with cirrhosis who are at risk for developing HE, as well as their caregivers. Understanding and recognizing precipitating factors and clinical symptoms of HE and treating and preventing HE recurrence can improve patient outcomes.
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Affiliation(s)
| | - Elizabeth K Goacher
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
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Mikkelsen ACD, Kjærgaard K, Schapira AHV, Mookerjee RP, Thomsen KL. The liver-brain axis in metabolic dysfunction-associated steatotic liver disease. Lancet Gastroenterol Hepatol 2025; 10:248-258. [PMID: 39701123 DOI: 10.1016/s2468-1253(24)00320-0] [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: 06/24/2024] [Revised: 09/25/2024] [Accepted: 09/26/2024] [Indexed: 12/21/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population. Studies suggest that MASLD is associated with compromised brain health and cognitive dysfunction, initiating a growing interest in exploring the liver-brain axis mechanistically within MASLD pathophysiology. With the prevalence of MASLD increasing at an alarming rate, leaving a large proportion of people potentially at risk, cognitive dysfunction in MASLD is a health challenge that requires careful consideration and awareness. This Review summarises the current literature on cognitive function in people with MASLD and discusses plausible causes for its impairment. It is likely that a multifaceted spectrum of factors works collectively to affect cognition in patients with MASLD. We describe the role of inflammation, vascular disease, and brain ageing and neurodegeneration as possible key players. This Review also highlights the need for future studies to identify the optimal test for diagnosing cognitive dysfunction in patients with MASLD, to examine the correlation between MASLD progression and the severity of cognitive dysfunction, and to evaluate whether new MASLD-targeted therapies also improve brain dysfunction.
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Affiliation(s)
- Anne Catrine Daugaard Mikkelsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Kristoffer Kjærgaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Anthony H V Schapira
- Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, London, UK
| | - Rajeshwar P Mookerjee
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Institute for Liver and Digestive Health, University College London, London, UK
| | - Karen Louise Thomsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Institute for Liver and Digestive Health, University College London, London, UK.
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Meszaros M, Hilleret M, Dumortier J, D'Alteroche L, Abergel A, Latournerie M, Antonini T, Conti F, Borentain P, Dharancy S, Pageaux G. Bulevirtide in Chronic Hepatitis D Patients Awaiting Liver Transplantation Results From a French Multicentric Retrospective Study. Liver Int 2025; 45:e70033. [PMID: 39960163 PMCID: PMC11831879 DOI: 10.1111/liv.70033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/09/2025] [Accepted: 02/04/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND AND AIMS The impact of bulevirtide in patients awaiting liver transplantation (LT) for decompensated liver disease and/or hepatocellular carcinoma (HCC) is unclear. We assessed clinical, virological, and biochemical responses to bulevirtide in patients with chronic hepatitis delta virus (HDV) awaiting LT and compared outcomes with a cohort of similar untreated patients. METHODS Consecutive HDV-infected patients waiting for LT since bulevirtide approval were included. Patients receiving 2 mg of bulevirtide daily had clinical, biological, and virological data collected at baseline, Week 24, Week 48, at LT, and post-LT. Patients not receiving bulevirtide had data collected at baseline, LT, and post-LT for comparison. RESULTS Forty-one patients from nine LT centers were included. In the bulevirtide group (20 patients; mean age 52.8 ± 9.98 years; 75% male), 65%, 10% and 25% were Child-Pugh A, B and C, respectively. Fifteen completed 48 weeks of therapy. At 48 weeks, median HDV RNA decreased by 2.56 log IU/mL (p = 0.004). Virological and biochemical responses were obtained in 73.3% and 66.6% of patients. Twelve patients (60%) underwent LT. No serious adverse events occurred. Bulevirtide improved liver function, enabling one (7.1%) HCC patient to undergo chemoembolization while on the WL and leading to delisting of three (15%) other patients. In untreated patients (mean age 42.9 ± 7.9 years; 76.2% Child-Pugh C), none were delisted. Three-month transplant-free survival was 76.9% in the bulevirtide group versus 36.7% (p = 0.007) in the control group. CONCLUSIONS Bulevirtide demonstrates safety and efficacy in HDV-infected patients listed on the LT waiting list and may potentially improve pre-transplant outcomes.
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Affiliation(s)
- Magdalena Meszaros
- Liver Transplantation and Hepatogastroenterology UnitCHU Montpellier, CHU MontpellierMontpellierFrance
| | | | - Jérôme Dumortier
- Digestive Diseases FederationEdouard Herriot Hospital, Hospices Civils de Lyon, Université Claude Bernard Lyon 1LyonFrance
| | | | - Armand Abergel
- Hepatogastroenterology UnitCHU Estaing Clermont‐FerrandClermont‐FerrandFrance
| | | | | | - Filomena Conti
- Hepatology UnitPitié Salpêtrière, Assistance Publique‐Hôpitaux de ParisParisFrance
| | | | | | - Georges‐Philippe Pageaux
- Liver Transplantation and Hepatogastroenterology UnitCHU Montpellier, CHU MontpellierMontpellierFrance
- University of MontpellierMontpellierFrance
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Divyaveer S, Kashyap M, Kekan K, Yadav AK, Kaur J, Premkumar M, Gandotra A, Prajapati K, De A, Duseja AK, Verma N, Aggarwal R, Venkatasubramanian V, Tiwari V, Bagur V, Patil AN, Safiq N, Kohli HS. Comparison of Measured Glomerular Filtration Rate Versus Estimated Glomerular Filtration Rate in Indian Cirrhotic Patients: Report of a Pilot Study. J Clin Exp Hepatol 2025; 15:102464. [PMID: 39760116 PMCID: PMC11697551 DOI: 10.1016/j.jceh.2024.102464] [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: 07/16/2024] [Accepted: 11/17/2024] [Indexed: 01/07/2025] Open
Abstract
Background Renal impairment significantly affects morbidity and mortality rates of cirrhosis patients. Studies on glomerular filtration rate (eGFR) estimation did not include cirrhosis patients. These equations are erroneous and unreliable in cirrhosis due to sarcopenia. Further, the accuracy of eGFR equations varies across different ethnic groups. Measurement of GFR by iohexol clearance is a gold standard method of accurate determination of GFR. There is scarce data on iohexol GFR in cirrhosis and none in Indian population. Methodology This was prospective observational study. Consecutive adult patients with cirrhosis with stable renal function for prior 1 month were included. Iohexol weight-based dosage was given and timed blood samples were taken to measure iohexol clearance. Plasma iohexol levels was measured by high performance liquid chromatography (HPLC) and Cystatin-C was measured by ELISA in plasma samples. Results Thirty-five patients were enrolled in the study. Hepatitis B (n = 5), hepatitis C (n = 4); alcoholic liver disease (n = 20), metabolic dysfunctional associated steatotic liver disease (n = 2), others/overlap (n = 3). The average eGFR by MDRD4, MDRD6, CKD-EPI Creat, CKD EPI Cys C, CKD EPI Creat-Cys C, RFHand GRAIL formulae were 105.24(24.2),104.75(23.5),102.14(15.9),68.91(16.5),82.91(15.21), 67.27 (14.08) and 112.9 (19.5) ml/min ml/min/1.73m2, respectively. The average mGFR measured by iohexol method was 73.44 (16.8)ml/min/1.73 m2. 30% agreement with mGFR was found with eGFR by MDRD4 in 38.2% (n = 13), MDRD6 38.2% ((n = 13), CKD-EPI Creat in 35.2% (n = 12), CKD EPI Cys C in 79.41% (n = 27), CKD EPI Creat-Cys C in 76.42% (n = 26), RFH 76.4% (n = 26) and GRAIL 20.5% (n = 7). Conclusion The eGFR equations using creatinine are imprecise and less accurate in Indian patients with cirrhosis. All equations overestimate GFR. Equations especially developed for cirrhosis patients like MDRD6 are also not precise. Cystatin C based equations are better than creatinine-based equations. Further studies with large sample size are needed to establish an accurate method of GFR assessment in Indian patients with cirrhosis.
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Affiliation(s)
- Smita Divyaveer
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Madhuri Kashyap
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kushal Kekan
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashok K. Yadav
- Department of Experimental Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Jaskiran Kaur
- Department of Experimental Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Akash Gandotra
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kanchan Prajapati
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay K. Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Radhika Aggarwal
- Department of Community Medicine, School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Vaibhav Tiwari
- Department of Nephrology, Sir Gangaram Hospital, Delhi, India
| | | | - Amol N. Patil
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nusrat Safiq
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Harbir S. Kohli
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Tapper EB, Nikirk S, Evon DM, Asrani S, Bloom P, Hynes JW, Alber JM, Gill A, Mehta S, Weinberg E, Alexander NB, Althuis K, Hoelscher A, Zhao L, Chen X, Burdzy A, Serper M. LIVE-SMART: A sequential, multiple assignment randomized trial to reduce falls in cirrhosis. Hepatol Commun 2025; 9:e0626. [PMID: 39969429 PMCID: PMC11841856 DOI: 10.1097/hc9.0000000000000626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 11/04/2024] [Indexed: 02/20/2025] Open
Abstract
INTRODUCTION Falls are a major threat to the well-being of patients with cirrhosis. We are performing a clinical trial to determine whether lactulose, TeleTai-Chi, or their combination will reduce falls in HE and improve health-related quality of life (HRQOL) among patients with cirrhosis. METHODS AND ANALYSIS Patients with cirrhosis and portal hypertension without HE will be enrolled in 3 US states and followed participants for 24 weeks. In stage 1 (12 wk), participants will be randomized to receive either lactulose therapy or enhanced usual care. In stage 2 (12 wk), participants will be randomized to either TeleTai-Chi or usual care. The primary outcome is a hierarchical composite: Injurious falls, noninjurious falls, incident HE, and death/transplantation. Secondary outcomes include cognitive function, days-alive and out-of-hospital, and HRQOL. After completion of the interventions, participants will be followed for 48 weeks for health and financial outcomes. ETHICS AND DISSEMINATION Our study has a central institutional review board with individual site IRB review. Dissemination includes the publication of study findings and patient-focused educational webinars.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Samantha Nikirk
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Donna M. Evon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, USA
| | - Sumeet Asrani
- Baylor University Medical Center, Dallas, Texas, USA
| | - Patricia Bloom
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | | | - J. Mark Alber
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Anna Gill
- Baylor University Medical Center, Dallas, Texas, USA
| | | | | | - Neil B. Alexander
- Department of Veterans Affairs, Geriatric Research Education Clinical Center, Ann Arbor, USA
| | - Katie Althuis
- Department of Veterans Affairs, Geriatric Research Education Clinical Center, Ann Arbor, USA
| | - Alise Hoelscher
- Department of Veterans Affairs, Geriatric Research Education Clinical Center, Ann Arbor, USA
| | - Lili Zhao
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Xi Chen
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
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Gao W, Yin C, Zhou C, Cheng D, Chen J, Liu C, Zeng Y. Hemodynamic investigations on the portal hypertension and treatment of transjugular intrahepatic portosystemic shunt (TIPS) based on CFD simulation. J Biomech 2025; 181:112516. [PMID: 39874736 DOI: 10.1016/j.jbiomech.2025.112516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Revised: 11/25/2024] [Accepted: 01/03/2025] [Indexed: 01/30/2025]
Abstract
Hemodynamic processes from the portal vein(PV) to the inferior vena cava(IVC) were mimicked for three patients with portal hypertension(PH) and the effects of stent parameters on the outcomes of transjugular intrahepatic portosystemic shunt(TIPS) were investigated through computational fluid dynamics(CFD). The liver region was simulated with porous media model and the spatial distributions of superior mesenteric vein(SMV) and splenic vein(SV) blood were solved through the Eulerian multiphase model. The present method is able to simulate the PH flow and predict the PV pressure, the stent shunt rate and the SMV blood proportion after TIPS treatment. According to the CFD results, the stent diameter exerts dominant effects on the TIPS outcomes while the stent placement shows substantial effects on the TIPS outcomes. Energy loss of the TIPS stents and distributary effects of the PV bifurcation dominate the PV hemodynamics and the TIPS outcomes. For stents with large diameter or proper placement, the energy loss is low therefore the PV pressure reduction and stent shunt rate are high. Stents inserted on the left and right branches of the PV are able to utilize distributary effects of the PV bifurcation therefore reduce the SMV blood flowing into the IVC.
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Affiliation(s)
- Wenzhi Gao
- School of Mechanical Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China
| | - Chunzhen Yin
- School of Mechanical Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China
| | - Chunze Zhou
- Interventional Radiology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, PR China.
| | - Delei Cheng
- Interventional Radiology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, PR China
| | - Jian Chen
- School of Mechanical Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China
| | - Changhai Liu
- School of Mechanical Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China
| | - Yishan Zeng
- School of Mechanical Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
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Tapper EB, Goldberg D, Parikh ND, Terrault NA, Welch N, Sharpton S, Hameed B, Khalili M, Stolz A, Verna EC, Brown RS, Sanyal AJ, VanWagner L, Ladner DP, Moylan CA, Diehl AM, Jones PD, Loomba RC, Dasarathy S, Simonetto DA, Shah VH, Bajaj JS. The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints. Am J Gastroenterol 2025; 120:570-575. [PMID: 39018024 PMCID: PMC11739427 DOI: 10.14309/ajg.0000000000002953] [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: 03/22/2024] [Accepted: 06/12/2024] [Indexed: 07/18/2024]
Abstract
INTRODUCTION One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis. METHODS The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee. RESULTS The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified. DISCUSSION The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion. REGISTRATION NCT05740358.
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Affiliation(s)
- Elliot B. Tapper
- Division of Transplantation, Department of Surgery, Northwestern University
| | - David Goldberg
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine
| | - Neehar D. Parikh
- Division of Gastroenterology and Hepatology, University of Michigan
| | - Norah A. Terrault
- Division of Gastrointestinal and Liver Diseases, Keck Medicine of University of Southern California
| | - Nicole Welch
- Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic
| | - Suzanne Sharpton
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego
| | - Bilal Hameed
- Division of Gastroenterology and Hepatology, University of California-San Francisco
| | - Mandana Khalili
- Division of Gastroenterology and Hepatology, University of California-San Francisco
| | - Andrew Stolz
- Division of Gastrointestinal and Liver Diseases, Keck Medicine of University of Southern California
| | | | - Robert S. Brown
- Division of Gastroenterology & Hepatology, Weill Cornell Medicine
| | - Arun J. Sanyal
- Division of Gastroenterology and hepatology, Virginia Commonwealth University and Richmond VA Medical Center
| | - Lisa VanWagner
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center
| | - Daniela P. Ladner
- Division of Transplantation, Department of Surgery, Northwestern University
| | - Cynthia A. Moylan
- Division of Gastroenterology and Hepatology, Duke University School of Medicine
| | - Anna Mae Diehl
- Division of Gastroenterology and Hepatology, Duke University School of Medicine
| | - Patricia D. Jones
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine
| | - Rohit C. Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego
| | | | | | - Vijay H. Shah
- Division of Gastroenterology and hepatology, Mayo Clinic Rochester
| | - Jasmohan S Bajaj
- Division of Gastroenterology and hepatology, Virginia Commonwealth University and Richmond VA Medical Center
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Shi W, Xu W, Fan N, Li Y, Chen X, Zhao Y, Bai X, Yang Y. Body Compositions Correlate With Overt Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt: A Multicentre Cohort Study. J Clin Gastroenterol 2025; 59:262-268. [PMID: 38683235 DOI: 10.1097/mcg.0000000000002014] [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: 11/09/2023] [Accepted: 03/17/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND The relationship between body composition and the risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) needs to be investigated. METHODS Overall, 571 patients from 5 medical centers were included. To assess body compositions, we evaluated skeletal muscle indices, adipose tissue indices, sarcopenia, and myosteatosis at the third lumbar vertebral level. Univariate and Multivariate logistic regression analyses were performed to identify independent risk factors for post-TIPS OHE. An integrated score was then constructed using stepwise multiple regression analyses, with a cut-off value selected using the best Youden index. Finally, the Akaike information criterion (AIC) was performed to compare the integrated score and independent risk factors on their ability in predicting post-TIPS OHE. RESULTS Sarcopenia and all skeletal muscle indices had limited associations with post-TIPS OHE. The index of the subcutaneous adipose tissue (SATI) ( P =0.005; OR: 1.034, 95% CI: 1.010-1.058) and myosteatosis (297 cases, 52.01%, 125 with OHE, 42.09%; P =0.003; OR: 1.973; 95% CI: 1.262-3.084) were both ascertained as independent risk factors for post-TIPS OHE. The integrated score (Score ALL =1.5760 + 0.0107 * SATI + 0.8579 * myosteatosis) was established with a cutoff value of -0.935. The akaike information criterion (AIC) of Score ALL , SATI, and myosteatosis was 655.28, 691.18, and 686.60, respectively. CONCLUSIONS SATI and myosteatosis are independent risk factors for post-TIPS OHE. However, the integrated score was more significantly associated with post-TIPS OHE than other skeletal muscle and adipose tissue factors.
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Affiliation(s)
| | - Weiguo Xu
- Zhuhai Interventional Medical Centre
| | - Ningning Fan
- Department of Ophthalmology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Yong Li
- Zhuhai Interventional Medical Centre
| | | | | | - Xiao Bai
- Zhuhai Interventional Medical Centre
| | - Yang Yang
- Zhuhai Interventional Medical Centre
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Thiele M, Johansen S, Israelsen M, Trebicka J, Abraldes JG, Gines P, Krag A. Noninvasive assessment of hepatic decompensation. Hepatology 2025; 81:1019-1037. [PMID: 37801593 PMCID: PMC11825506 DOI: 10.1097/hep.0000000000000618] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 07/19/2023] [Indexed: 10/08/2023]
Abstract
Noninvasive tests (NITs) are used in all aspects of liver disease management. Their most prominent break-through since the millennium has been in advancing early detection of liver fibrosis, but their use is not limited to this. In contrast to the symptom-driven assessment of decompensation in patients with cirrhosis, NITs provide not only opportunities for earlier diagnoses but also accurate prognostication, targeted treatment decisions, and a means of monitoring disease. NITs can inform disease management and decision-making based on validated cutoffs and standardized interpretations as a valuable supplement to clinical acumen. The Baveno VI and VII consensus meetings resulted in tangible improvements to pathways of care for patients with compensated and decompensated advanced chronic liver disease, including the combination of platelet count and transient elastography to diagnose clinically significant portal hypertension. Furthermore, circulating NITs will play increasingly important roles in assessing the response to interventions against ascites, variceal bleeding, HE, acute kidney injury, and infections. However, due to NITs' wide availability, there is a risk of inaccurate use, leading to a waste of resources and flawed decisions. In this review, we describe the uses and pitfalls of NITs for hepatic decompensation, from risk stratification in primary care to treatment decisions in outpatient clinics, as well as for the in-hospital management of patients with acute-on-chronic liver failure. We summarize which NITs to use when, for what indications, and how to maximize the potential of NITs for improved patient management.
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Affiliation(s)
- Maja Thiele
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Stine Johansen
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Mads Israelsen
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Jonel Trebicka
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
- Department of Internal Medicine B, University of Münster, Münster, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Juan G. Abraldes
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Pere Gines
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Spain
- Institute of Biomedical Investigation August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Fibrosis, Fatty Liver and Steatohepatitis Research Center Odense (FLASH), Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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Karvellas CJ, Gustot T, Fernandez J. Management of the acute on chronic liver failure in the intensive care unit. Liver Int 2025; 45:e15659. [PMID: 37365997 PMCID: PMC11815614 DOI: 10.1111/liv.15659] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/01/2023] [Accepted: 06/15/2023] [Indexed: 06/28/2023]
Abstract
Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.
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Affiliation(s)
- Constantine J. Karvellas
- Department of Critical Care MedicineUniversity of AlbertaEdmontonCanada
- Division of Gastroenterology (Liver Unit)University of AlbertaEdmontonCanada
| | - Thierry Gustot
- Department of Gastroenterology, Hepato‐Pancreatology and Digestive Oncology, H.U.B.CUB Hôpital ErasmeBrusselsBelgium
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital ClinicUniversity of Barcelona, IDIBAPS and CIBERehdBarcelonaSpain
- EF CLIF, EASL‐CLIF ConsortiumBarcelonaSpain
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Sakamaki A, Yokoyama K, Yamazaki H, Wakabayashi T, Kojima Y, Tominaga K, Tsuchiya A, Kamimura K, Yokoyama J, Terai S. Small Intestinal Bacterial Overgrowth Is a Predictor of Overt Hepatic Encephalopathy in Patients with Liver Cirrhosis. J Clin Med 2025; 14:1491. [PMID: 40094949 PMCID: PMC11901010 DOI: 10.3390/jcm14051491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 02/10/2025] [Accepted: 02/21/2025] [Indexed: 03/19/2025] Open
Abstract
Objective: Liver cirrhosis (LC) progression induces intestinal microbiota abnormalities, such as small intestinal bacterial overgrowth (SIBO), and these changes lead to the inflow of gut pathogens and their degradation products into the vessels, causing cirrhotic complications such as hepatic encephalopathy (HE). Methods: To clarify the relationship between the development of overt HE and SIBO, we conducted a three-year observation after assessment of SIBO in patients with LC. Results: In the analysis of 107 patients, with a mean follow-up duration of 29.4 months, 31 were diagnosed with SIBO and 30 with covert HE. In the Cox multivariate regression analysis for prognosis, the Child-Pugh score, blood urea nitrogen level, and the Union for International Cancer Control (UICC) stage of hepatocellular carcinoma were derived using the following five factors: white blood cell count, blood urea nitrogen level, Child-Pugh score, UICC stage, and serum aspartate aminotransferase and alkaline phosphatase levels (p = 0.002, hazard ratio [HR] 3.733, 95% confidence interval [CI] 1.592-8.754, p = 0.001, HR 1.076, 95% CI 1.030-1.123, and p < 0.001, HR 2.767, 95% CI 1.780-4.302, respectively). Furthermore, in the Cox multivariate regression analysis for overt HE development, covert HE and methane-producing SIBO were derived using the following four factors: methane-producing SIBO, UICC stage, covert HE, and serum ammonia levels (p = 0.038, HR 5.008, 95% CI 1.096-22.892 and p = 0.006, HR 8.597, 95% CI 1.881-39.291, respectively). Conclusions: M-SIBO positivity was a significant predictor of overt HE.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Kunihiko Yokoyama
- Division of Gastroenterology and Hepatology, Niigata Prefectural Hospital, Niigata 943-0192, Japan;
| | - Hanako Yamazaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Takuya Wakabayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Yuichi Kojima
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Kentaro Tominaga
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Kenya Kamimura
- Department of General Medicine, Niigata University School of Medicine, Niigata 951-8510, Japan;
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan;
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
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Sparacia G, Colelli G, Parla G, Mamone G, Maruzzelli L, Lo Re V, Avorio F, Miraglia R, Pichiecchio A. Brain Magnetic Resonance Imaging Radiomic Signature and Machine Learning Model Prediction of Hepatic Encephalopathy in Adult Cirrhotic Patients. Life (Basel) 2025; 15:346. [PMID: 40141691 PMCID: PMC11943475 DOI: 10.3390/life15030346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/16/2025] [Accepted: 02/20/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) may arise as a possible consequence of cirrhosis. Magnetic resonance imaging (MRI) may reveal a T1-weighted hyperintensity in the globi pallidi, indicating the deposition of paramagnetic substances. The objective of this research was to implement a machine learning-based radiomic model to predict the diagnosis and severity of chronic hepatic encephalopathy in adult patients with cirrhosis. METHODS Between October 2018 and February 2020, brain magnetic resonance imaging (MRI) was conducted on adult patients, both with and without cirrhosis. The control population consisted of individuals who did not have a previous medical record of chronic liver disease. The grade of hepatic encephalopathy (HE) was determined by considering factors such as the presence of underlying liver disease, the severity of clinical symptoms, and the frequency of encephalopathic episodes. Radiomic texture analysis based on five machine learning algorithms was applied to axial T1-weighted MR images of bilateral lentiform nuclei. Using the area under the receiver operating characteristics curve, we determined the accuracy of the five machine learning-based algorithms in predicting the presence of HE and the HE grading. RESULTS The ultimate research cohort included 124 individuals, with 70 being cirrhotic patients and 54 being non-cirrhotic controls. Of the total number of patients, 38 had a previous occurrence of HE and, among them, 22 had a grade of HE greater than 1. The multilayer perceptron algorithm classified patients versus controls with an accuracy of 100%. The k-nearest neighbor (KNN) algorithm classified patients with or without HE with an accuracy of 76.5%. The multilayer perceptron algorithm classified HE grade (HE grade 1, HE grade ≥ 2) with an accuracy of 94.1%. CONCLUSIONS The machine learning algorithms implemented provide a robust modeling technique for deriving valuable insights from brain MR images in cirrhotic patients and this can serve as an imaging tool valuable for the assessment of the burden of hepatic encephalopathy.
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Affiliation(s)
- Gianvincenzo Sparacia
- Radiology Service, Department of Biomedicine, Neuroscience and Advanced Diagnosis (BiND), University of Palermo, 90127 Palermo, Italy
- Radiology Service, IRCCS-ISMETT, 90127 Palermo, Italy (G.M.); (L.M.); (R.M.)
- NeuroLab, Computational Neuroimaging Laboratory, IRCCS-ISMETT, 90127 Palermo, Italy
| | - Giulia Colelli
- Advanced Imaging and Radiomic Center, IRCCS Mondino Foundation, 27100 Pavia, Italy; (G.C.); (A.P.)
| | - Giuseppe Parla
- Radiology Service, IRCCS-ISMETT, 90127 Palermo, Italy (G.M.); (L.M.); (R.M.)
- NeuroLab, Computational Neuroimaging Laboratory, IRCCS-ISMETT, 90127 Palermo, Italy
| | - Giuseppe Mamone
- Radiology Service, IRCCS-ISMETT, 90127 Palermo, Italy (G.M.); (L.M.); (R.M.)
| | - Luigi Maruzzelli
- Radiology Service, IRCCS-ISMETT, 90127 Palermo, Italy (G.M.); (L.M.); (R.M.)
| | - Vincenzina Lo Re
- Neurology Service, IRCCS-ISMETT, 90127 Palermo, Italy; (V.L.R.); (F.A.)
| | - Federica Avorio
- Neurology Service, IRCCS-ISMETT, 90127 Palermo, Italy; (V.L.R.); (F.A.)
| | - Roberto Miraglia
- Radiology Service, IRCCS-ISMETT, 90127 Palermo, Italy (G.M.); (L.M.); (R.M.)
| | - Anna Pichiecchio
- Advanced Imaging and Radiomic Center, IRCCS Mondino Foundation, 27100 Pavia, Italy; (G.C.); (A.P.)
- Department of Brain and Behavioural Disorders, University of Pavia, 27100 Pavia, Italy
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Saxena R, Alexander EC, Bontemps S, Singla R, Verkade HJ, de Meijer VE, Kneyber MCJ, Deep A. Molecular adsorbent recirculating system (MARS®) and continuous renal replacement therapy for the treatment of paediatric acute liver failure - two-centre retrospective cohort study. Eur J Pediatr 2025; 184:192. [PMID: 39937316 PMCID: PMC11821745 DOI: 10.1007/s00431-025-06013-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/19/2025] [Accepted: 01/28/2025] [Indexed: 02/13/2025]
Abstract
To describe outcomes of a cohort of patients with paediatric acute liver failure (PALF) treated with either one of two extracorporeal therapies (ECT) - continuous renal replacement therapy (CRRT) and molecular adsorbent recirculatory system (MARS®). Retrospective, observational, cohort study at two European paediatric intensive care units (PICUs) - UK (2006-2017, CRRT) and the Netherlands (2003-2017, MARS® and CRRT). Patients were children (0-18 years) admitted to the PICU with PALF who required CRRT or MARS®. Between each group, we compared baseline characteristics, biochemical parameters at 0 and 24 h after commencing MARS®/CRRT, and clinical outcomes. In total, 95 patients (23 MARS®, 72 CRRT) were included. The median age at admission for the whole cohort was 4.3 years (interquartile range (IQR) 1.0-12.1), and 47/95 (49.5%) of patients had an indeterminate aetiology. A lower proportion of patients in the MARS® group were on inotropes or were ventilated at admission, and they had a lower Pediatric Index of Mortality 3 risk % than the CRRT group (14.5% (7.5-22) vs 20.4% (16.8-26.4), p = 0.002). After treatment, there were no significant differences detected between groups in survival with native liver, or overall survival (15/23 (65.2%) for MARS® and 49/72 (68.1%) for CRRT, p = 0.998). CONCLUSION We did not detect a significant difference in clinical outcomes between PALF patients treated with CRRT or MARS®, despite a relatively sicker cohort in the CRRT group. Further high-quality evidence is necessary regarding the role of extracorporeal therapies in PALF, with consideration of clinical outcomes, feasibility, and cost. WHAT IS KNOWN • Outcomes for children with paediatric acute liver failure (PALF) have improved in recent years secondary to improved supportive care aimed at avoiding liver transplantation. • Extracorporeal therapies, in particular continuous renal replacement therapy (CRRT), are increasingly applied in the management of these children; however few studies have compared outcomes between different extracorporeal therapies. WHAT IS NEW • In this retrospective study across two centres, outcomes between patients with PALF treated with CRRT were compared to patients treated with MARS®. • There was no significant difference in key clinical outcomes between groups, including survival with native liver and overall survival.
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Affiliation(s)
- Romit Saxena
- Paediatric Intensive Care, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Emma C Alexander
- Paediatric Intensive Care, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
- Paediatric Intensive Care Unit, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Sander Bontemps
- Division of Paediatric Critical Care Medicine, Department of Paediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Raman Singla
- Paediatric Intensive Care, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Henkjan J Verkade
- Division of Pediatric Gastroenterology and Hepatology, Department of Paediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Vincent E de Meijer
- Division of HPB and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Martin C J Kneyber
- Division of Paediatric Critical Care Medicine, Department of Paediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- Critical Care, Anaesthesiology, Peri-Operative & Emergency Medicine (CAPE), University of Groningen, Groningen, the Netherlands
| | - Akash Deep
- Paediatric Intensive Care, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK.
- Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, SE1 7EH, UK.
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Miwa T, Hanai T, Nishimura K, Hirata S, Unome S, Nakahata Y, Imai K, Suetsugu A, Takai K, Shimizu M. Nutritional assessment using subjective global assessment identifies energy malnutrition and predicts mortality in patients with liver cirrhosis. Sci Rep 2025; 15:4831. [PMID: 39924549 PMCID: PMC11808070 DOI: 10.1038/s41598-025-89803-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 02/07/2025] [Indexed: 02/11/2025] Open
Abstract
This study aimed to evaluate whether the subjective global assessment (SGA) could effectively predict energy malnutrition, as assessed by indirect calorimetry, and mortality in hospitalized patients with cirrhosis. Energy malnutrition was defined by a nonprotein respiratory quotient (npRQ) < 0.85 using an indirect calorimetry. The usefulness of the SGA in identifying energy malnutrition and predicting mortality was assessed by the logistic regression and Cox proportional hazards models, respectively. Out of the 230 patients analyzed, 43% were found to have energy malnutrition. The distribution of SGA classifications was 54% for SGA-A, 32% for SGA-B, and 14% for SGA-C. Multivariable analysis indicated that both SGA-B (odds ratio, 3.59; 95% confidence interval [CI], 1.59-8.10) and SGA-C (odds ratio, 19.70; 95% CI, 3.46-112.00), along with free fatty acids (FFA), were independently linked to energy malnutrition. Regarding mortality, 125 patients (54%) died over a median follow-up period of 2.8 years. After adjustment, SGA-B (hazard ratio, 1.81; 95% CI, 1.08-3.03) and SGA-C (hazard ratio, 3.35; 95% CI, 1.28-8.76) were predictors of mortality in cirrhosis patients, while energy malnutrition and FFA were not. The SGA is a valuable tool for identifying energy malnutrition and predicting mortality in patients with cirrhosis.
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Affiliation(s)
- Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Kayoko Nishimura
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Sachiyo Hirata
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu, Japan
| | - Shinji Unome
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Yuki Nakahata
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
- Department of Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Kenji Imai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Atsushi Suetsugu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Koji Takai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
- Division for Regional Cancer Control, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
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48
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Bao J, Zhang X, Ye M, Yang Y, Xu L, He L, Guo J, Yao D, Wang S, Zhang J, Tian X. Exploration of Novel Metabolic Mechanisms Underlying Primary Biliary Cholangitis Using Hepatic Metabolomics, Lipidomics, and Proteomics Analysis. J Proteome Res 2025; 24:562-578. [PMID: 39792460 DOI: 10.1021/acs.jproteome.4c00708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
Metabolic reprogramming is important in primary biliary cholangitis (PBC) development. However, studies investigating the metabolic signature within the liver of PBC patients are limited. In this study, liver biopsies from 31 PBC patients and 15 healthy controls were collected, and comprehensive metabolomics, lipidomics, and proteomics analysis were conducted to characterize the metabolic landscape in PBC. We observed distinct lipidome remodeling in PBC with increased polyunsaturated fatty acid levels and augmented fatty acid β-oxidation (FAO), evidenced by the increased acylcarnitine levels and upregulated expression of proteins involved in FAO. Notably, PBC patients exhibited an increase in glucose-6-phosphate (G6P) and purines, alongside a reduction in pyruvate, suggesting impaired glycolysis and increased purines biosynthesis in PBC. Additionally, the accumulation of bile acids as well as a decrease in branched chain amino acids and aromatic amino acids were observed in PBC liver. We also observed an aberrant upregulation of proteins associated with ductular reaction, apoptosis, and autophagy. In conclusion, our study highlighted substantial metabolic reprogramming in glycolysis, fatty acid metabolism, and purine biosynthesis, coupled with aberrant upregulation of proteins associated with apoptosis and autophagy in PBC patients. Targeting the specific metabolic reprogramming may offer potential targets for the therapeutic intervention of PBC.
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Affiliation(s)
- Jie Bao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Xuan Zhang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China
| | - Mao Ye
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China
| | - Yiqin Yang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China
| | - Leiming Xu
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China
| | - Lulu He
- Department of Biobank, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Jixin Guo
- School of Stomatology, Wuhan University, Wuhan 430072, China
| | - Daoke Yao
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Suhua Wang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China
| | - Ji Zhang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China
| | - Xin Tian
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China
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49
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Chen DF, Farrque M, Karakis I, Gupta N, Rodriguez Ruiz A, Kandiah P. Continuous Electroencephalography in Acute Liver Failure: Findings and Prognostic Value. Neurocrit Care 2025:10.1007/s12028-025-02216-1. [PMID: 39920548 DOI: 10.1007/s12028-025-02216-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 01/13/2025] [Indexed: 02/09/2025]
Abstract
BACKGROUND Neurologic complications contribute significantly to morbidity and mortality in acute liver failure (ALF). However, clinical assessment of neurologic function in this population is often challenging. Continuous electroencephalography (cEEG) is a low-risk, noninvasive diagnostic tool that can monitor real-time cerebral function. We aimed to investigate cEEG findings and prognostic significance of specific EEG features in a cohort of strictly defined patients with ALF. METHODS This was a retrospective, single-center study of adult patients with ALF who underwent cEEG monitoring for at least 6 h between 2013 and 2022. Clinical, laboratory, imaging, and treatment characteristics were evaluated. cEEG variables included background continuity, background frequency, the presence of sporadic epileptiform discharges, rhythmic or periodic patterns, and electrographic or electroclinical seizures. The primary outcome was mortality or transition to end-of-life care during the index admission. RESULTS A total of 32 patients with ALF were included. 56.3% of patients had rhythmic or periodic patterns, of which the majority were generalized periodic discharges (37.5%). 12.5% of patients had sporadic epileptiform discharges, and 6.3% of patients demonstrated electrographic or clinical seizures. Eighteen (56.3%) patients died or were transitioned to end-of-life care during the index admission. Worsening background continuity or frequency over the course of the cEEG recording was significantly associated with poor outcome (p = 0.001, p = 0.007, respectively), with a 100% mortality rate in patients demonstrating these EEG trends. A worst recorded continuity of suppression, attenuation, and burst-suppression was also associated with poor outcome (p = 0.012). The presence of rhythmic or periodic patterns, sporadic epileptiform discharges, or seizures was not predictive of outcome. CONCLUSIONS Worsening cEEG background continuity or frequency is associated with poor outcome in adults with ALF. cEEG may contribute useful prognostic information in these patients, in conjunction with other laboratory and clinical markers of disease severity.
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Affiliation(s)
- Denise F Chen
- Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
| | - Mirza Farrque
- Department of Neurocritical Care, Emory University School of Medicine, Atlanta, GA, USA
| | - Ioannis Karakis
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
- Department of Neurology, University of Crete School of Medicine, Heraklion, Greece
| | - Navnika Gupta
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
| | | | - Prem Kandiah
- Department of Neurocritical Care, Emory University School of Medicine, Atlanta, GA, USA
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50
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Bozon-Rivière P, Rudler M, Weiss N, Thabut D. TIPS and hepatic encephalopathy in patients with cirrhosis. Metab Brain Dis 2025; 40:117. [PMID: 39903376 DOI: 10.1007/s11011-025-01541-w] [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: 07/06/2024] [Accepted: 01/17/2025] [Indexed: 02/06/2025]
Abstract
Despite a better understanding in its prognosis and pathogenesis, hepatic encephalopathy (HE) remains one of the major complications of Transjugular Intrahepatic Portosystemic Shunt (TIPS) with a prevalence ranging from 35 to 50%. Its epidemiology differs according to the indication for TIPS (salvage/rescue TIPS, preemptive (pTIPS) or elective TIPS). In salvage/rescue TIPS, the prognosis is linked to that of bleeding, and HE should not be a contraindication to TIPS, especially as bleeding is a common precipitating factor of HE. In pTIPS, i.e. TIPS performed within the 72 h after stabilization of acute variceal bleeding in high-risk patients, the risk rebleeding and HE is reduced, when compared to endoscopic and drugs treatment. As a consequence, the Baveno VII recommendations state that HE at admission should not be considered as a contraindication to pTIPS placement. In elective situations, such as refractory (intractable ascites (intolerance to diuretics) or resistant ascites (i.e. despite optimal diuretic treatment (spironolactone 400 mg/d and Furosemide 160 mg/d combined with low-salt treatment (< 5.2 g/day) or recurrent ascites (the need for at least 3 paracenteses per year) and secondary prophylaxis of variceal bleeding, it is recommended to systematically look for risk factors for HE, and chronic or refractory HE remain not recommended to TIPS in most centers. Chronic HE involves persistent neurological symptoms with fluctuating acute episodes. Recurrent HE refers to repeated episodes occurring within 6 months, while refractory HE is resistant to standard treatments, often requiring more aggressive management (Vilstrup et al. 2014). A careful selection of patients is mandatory before elective TIPS decision. Risk factors must be identified and corrected if possible before any TIPS decision is made. Management of HE after TIPS is based on identification of precipitating factors, curative treatment with lactulose as first-line therapy and rifaximin as second-line therapy, and nutritional management. In elective TIPS, prophylactic administration of rifaximin is recommended in order to decrease the risk of further HE development in selected patients (not in everyone, at least according to Baveno VII). Liver transplantation (LT) should be discussed with a multidisciplinary team as an alternative option to TIPS in case of high-risk of post-TIPS HE, and in case of refractory HE after TIPS.
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Affiliation(s)
- Pauline Bozon-Rivière
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France
| | - Marika Rudler
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
| | - Nicolas Weiss
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Neurology Intensive Care Unit, Neurology Department, AP-HP, Sorbonne Université, La Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
| | - Dominique Thabut
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
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