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Hur YK, Lee HE, Yoo JY, Park YN, Lee IH, Bae YS. NADPH oxidase 4-SH3 domain-containing YSC84-like 1 complex participates liver inflammation and fibrosis. Free Radic Biol Med 2025; 227:246-259. [PMID: 39645205 DOI: 10.1016/j.freeradbiomed.2024.12.021] [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: 08/31/2024] [Revised: 11/19/2024] [Accepted: 12/04/2024] [Indexed: 12/09/2024]
Abstract
There is growing evidence that NADPH oxidase 4 (Nox4) in hepatocytes contributes to liver inflammation and fibrosis during the development of metabolic dysfunction-associated steatohepatitis (MASH). However, how Nox4 is regulated and leads to liver pathogenesis is unclear. Our previous studies showed that the cytosolic protein SH3 domain-containing Ysc84-like 1 (SH3YL1) regulates Nox4 activity. Here, we asked whether SH3YL1 also participates in liver inflammation and fibrosis during MASH development. We generated that whole body SH3YL1 knockout (SH3YL1-/-), Nox4 knockout (Nox4-/-) mice, and the hepatocyte-specific SH3YL1 conditional knockout (Alb-Cre/SH3YL1fl/fl) mice were fed a methionine/choline-deficient (MCD) diet to induce liver inflammation and fibrosis in pathogenesis of MASH. Palmitate-stimulated primary SH3YL1-and Nox4-deficient hepatocytes and hepatic stellate cells (HSCs) did not generate H2O2. While the liver of MCD diet-fed wild type (WT) mice demonstrated elevated 3-nitrotyrosine as a protein oxidation and 4-hydroxynonenal adducts as a lipid oxidation and increased liver inflammation, hepatocyte apoptosis, and liver fibrosis, these events were markedly reduced in SH3YL1-/-, Nox4-/-, and Alb-Cre/SH3YL1fl/fl mice. The MCD diet-fed WT mice also showed elevated hepatocyte expression of SH3YL1 protein. Similarly, liver biopsies from MASH patients demonstrated strong hepatocyte SH3YL1 protein expression, whereas hepatocytes from patients with steatosis weakly expressed SH3YL1 and histologically normal patient hepatocytes exhibited very little SH3YL1 expression. The Nox4-SH3YL1 complex in murine hepatocytes elevates their H2O2 production, which promotes the liver inflammation, hepatocyte apoptosis, and liver fibrosis that characterize MASH. This axis may also participate in MASH in humans.
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Affiliation(s)
- Yeo Kyu Hur
- Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-Gil, Seodaemoon-Gu, Seoul, 03760, South Korea
| | - Hye Eun Lee
- Celros Biotech, 52 Ewhayeodae-Gil, Seodaemoon-Gu, Seoul, 03760, South Korea
| | - Jung-Yeon Yoo
- Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-Gil, Seodaemoon-Gu, Seoul, 03760, South Korea
| | - Young Nyun Park
- Department of Pathology Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - In Hye Lee
- Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-Gil, Seodaemoon-Gu, Seoul, 03760, South Korea.
| | - Yun Soo Bae
- Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-Gil, Seodaemoon-Gu, Seoul, 03760, South Korea; Celros Biotech, 52 Ewhayeodae-Gil, Seodaemoon-Gu, Seoul, 03760, South Korea.
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Yang Y, Fan G, Lan J, Li X, Li X, Liu R. Polysaccharide-mediated modulation of gut microbiota in the treatment of liver diseases: Promising approach with significant challenges. Int J Biol Macromol 2024:135566. [PMID: 39270901 DOI: 10.1016/j.ijbiomac.2024.135566] [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: 07/09/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/15/2024]
Abstract
Liver disease represents a significant global health burden, with an increasing prevalence and a lack of efficient treatment options. The microbiota-gut-liver axis involves bidirectional communication between liver function and intestinal microorganisms. A balanced gut flora protects intestinal homeostasis, while imbalances contribute to the development of liver diseases. Distinct alterations in the structure of gut flora during illness are crucial in the management of various liver diseases. Polysaccharides derived from herbal products, fungi, and other sources have been identified to possess diverse biological activities and are well-tolerated in the treatment of liver diseases. This review provides updates on the therapeutic effects of polysaccharides on liver diseases, including fatty liver diseases, acute liver injuries and liver cancers. It also summarizes advancements in understanding the mechanisms involved, particularly from the perspective of gut microbiota and metabolites, by highlighting the changes in the composition of potentially beneficial and harmful bacteria and their correlation with the therapeutic effects of polysaccharides. Additionally, by exploring the structure-activity relationship, our review provides valuable insights for the structural modification of polysaccharides and expanding their applications. In conclusion, this review offers theoretical support and novel perspectives on developing polysaccharides-based therapeutic approaches for the treatment of liver diseases.
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Affiliation(s)
- Yang Yang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China
| | - Guifang Fan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China
| | - Jianhang Lan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China
| | - Xin Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China
| | - Xiaojiaoyang Li
- School of Life Sciences, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China
| | - Runping Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China.
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Kim W, Hwang JA, Min JH, Lee S, Lee JE, Shin J, Jeong WK. Exploring the impact of excluding intrahepatic segmental vessels on liver stiffness measurement and advanced fibrosis diagnosis using magnetic resonance elastography. Acta Radiol 2024; 65:1021-1029. [PMID: 39033394 DOI: 10.1177/02841851241263335] [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: 07/23/2024]
Abstract
BACKGROUND The impact of excluding intrahepatic segmental vessels from regions of interest (ROIs) on liver stiffness measurement (LSM) via magnetic resonance elastography (MRE) remains uncertain. PURPOSE To determine the effect of excluding intrahepatic segmental vessels from ROIs on LSM obtained from MRE. MATERIAL AND METHODS This retrospective analysis included 95 participants who underwent successful two-dimensional gradient recalled-echo MRE before hepatic tumor resection (n = 49) or living liver donation (n = 46). The conventional LSM was determined by manually drawing ROIs on the elastogram within the 95% confidence region, staying 1 cm within the liver capsule and excluding large hilar vessels, the gallbladder, hepatic lesions, and artifacts. In addition, the modified LSM was determined by excluding intrahepatic segmental vessels. LSMs obtained by the two methods were compared with paired sample signed-rank test. Diagnostic performance for advanced fibrosis was calculated and compared using McNemar's test and Delong's test. The stage of hepatic fibrosis was assessed using surgical specimens by the METAVIR system. RESULTS The modified LSM was larger than the conventional LSM (2.4 kPa vs. 2.2 kPa in reader 1; 2.7 kPa vs. 2.4 kPa in reader 2; P < 0.001). The modified LSM showed superior sensitivity (0.841 vs. 0.659 in reader 1; 0.864 vs. 0.705 in reader 2; P < 0.05) and area under the curve (0.901 vs. 0.820 in reader 1; 0.912 vs. 0.843 in reader 2; P < 0.05) for detecting advanced fibrosis (≥F3) than conventional LSM. CONCLUSION The exclusion of intrahepatic segmental vessels from ROIs in MRE affected the LSM and enhanced diagnostic performance for advanced fibrosis.
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Affiliation(s)
- Wook Kim
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeong Ah Hwang
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Hye Min
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ji Eun Lee
- Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea
| | - Jaeseung Shin
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Grossar L, Raevens S, Van Steenkiste C, Colle I, De Vloo C, Orlent H, Schouten J, Gallant M, Van Driessche A, Lefere S, Devisscher L, Geerts A, Van Vlierberghe H, Verhelst X. External validation of the IAIHG autoimmune hepatitis response criteria in a multicentric real-world cohort. JHEP Rep 2024; 6:101149. [PMID: 39247177 PMCID: PMC11379665 DOI: 10.1016/j.jhepr.2024.101149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 05/21/2024] [Accepted: 06/18/2024] [Indexed: 09/10/2024] Open
Abstract
Background & Aims The goal of treatment in autoimmune hepatitis (AIH) is induction of remission to prevent the development of liver fibrosis, cirrhosis, and its related complications. Various definitions of treatment response and remission have been used. The International Autoimmune Hepatitis Group (IAIHG) recently defined consensus criteria for treatment response. We aimed to validate the IAIHG response criteria in our cohort and establish correlations with survival endpoints. Methods We performed a retrospective, multicentric cohort study in one tertiary and seven secondary care centres in Belgium. Eligible patients were at least 18 years of age at data collection and were diagnosed with AIH by a simplified IAIHG score of ≥6. Complete biochemical response (CBR) was defined according to the IAIHG consensus criteria as normalisation of transaminases and serum IgG within the first 6 months of treatment. The primary endpoint was liver-related survival - defined as freedom from liver-related death or liver transplantation. Secondary endpoints were overall mortality and transplant-free survival. Outcomes were compared between patients attaining CBR and those with insufficient response. Results Biochemical response status could be determined in 200 patients with AIH: CBR was achieved in 128 (64.0%) individuals. Patients not achieving CBR more frequently presented with cirrhosis on initial histology (22.2% vs. 10.9%, p = 0.036). Liver-related mortality or liver transplantation as a primary outcome occurred in 26 patients (13.0%). Patients achieving CBR exhibited superior liver-related (hazard ratio 0.118; 95% CI 0.052-0.267; p <0.0001) and overall (hazard ratio 0.253; 95% CI 0.111-0.572; p = 0.0003) survival. Conclusions We externally validated the IAIHG consensus criteria for CBR and confirmed their correlation with survival endpoints in a multicentric, real-world cohort. Patients with AIH achieving CBR as an intermediate endpoint have significantly superior liver-related and overall survival. Impacts and Implications Corticosteroids remain the cornerstone of treatment to induce remission of disease activity in autoimmune hepatitis (AIH), and the majority of patients require long-term corticosteroid treatment to achieve sustained remission. Definitions of response to treatment have varied over the years, and consistently used intermediate endpoints are needed to facilitate advancements in non-corticosteroid treatment for autoimmune hepatitis. The International Autoimmune Hepatitis Group (IAIHG) defined consensus criteria on endpoints in the treatment of AIH, for which further external validation is needed. Here, we demonstrate the usefulness of the IAIHG consensus criteria and corroborate their correlation to primary endpoints, such as liver-related survival and native liver survival in a multicentric, real-world setting. The design of future studies can rely on the IAIHG consensus criteria as intermediate endpoints.
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Affiliation(s)
- Lorenz Grossar
- Department of Internal Medicine and Paediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Centre Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
| | - Sarah Raevens
- Liver Research Centre Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Christophe Van Steenkiste
- Department of Gastroenterology and Hepatology, AZ Maria Middelares, Ghent, Belgium
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - Isabelle Colle
- Department of Gastroenterology and Hepatology, ASZ Aalst, Aalst, Belgium
| | - Charlotte De Vloo
- Department of Gastroenterology and Hepatology, AZ Delta Roeselare, Roeselare, Belgium
| | - Hans Orlent
- Department of Gastroenterology and Hepatology, AZ Sint Jan Brugge, Brugge, Belgium
| | - Jeoffrey Schouten
- Department of Gastroenterology and Hepatology, VITAZ, Sint-Niklaas, Belgium
| | - Marie Gallant
- Department of Gastroenterology and Hepatology, Jan Yperman Ziekenhuis, Ieper, Belgium
| | | | - Sander Lefere
- Department of Internal Medicine and Paediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Centre Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
| | - Lindsey Devisscher
- Liver Research Centre Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
- Department of Basic & Applied Medical Sciences, Gut-Liver Immunopharmacology Unit, Ghent University, Ghent, Belgium
| | - Anja Geerts
- Liver Research Centre Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Hans Van Vlierberghe
- Liver Research Centre Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Xavier Verhelst
- Liver Research Centre Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
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Qi Y, Vianna P, Cadrin-Chênevert A, Blanchet K, Montagnon E, Belilovsky E, Wolf G, Mullie LA, Cloutier G, Chassé M, Tang A. Simulating federated learning for steatosis detection using ultrasound images. Sci Rep 2024; 14:13253. [PMID: 38858500 PMCID: PMC11164945 DOI: 10.1038/s41598-024-63969-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] [Received: 02/24/2024] [Accepted: 06/04/2024] [Indexed: 06/12/2024] Open
Abstract
We aimed to implement four data partitioning strategies evaluated with four federated learning (FL) algorithms and investigate the impact of data distribution on FL model performance in detecting steatosis using B-mode US images. A private dataset (153 patients; 1530 images) and a public dataset (55 patient; 550 images) were included in this retrospective study. The datasets contained patients with metabolic dysfunction-associated fatty liver disease (MAFLD) with biopsy-proven steatosis grades and control individuals without steatosis. We employed four data partitioning strategies to simulate FL scenarios and we assessed four FL algorithms. We investigated the impact of class imbalance and the mismatch between the global and local data distributions on the learning outcome. Classification performance was assessed with area under the receiver operating characteristic curve (AUC) on a separate test set. AUCs were 0.93 (95% CI 0.92, 0.94) for source-based partitioning scenario with FedAvg, 0.90 (95% CI 0.89, 0.91) for a centralized model, and 0.83 (95% CI 0.81, 0.85) for a model trained in a single-center scenario. When data was perfectly balanced on the global level and each site had an identical data distribution, the model yielded an AUC of 0.90 (95% CI 0.88, 0.92). When each site contained data exclusively from one single class, irrespective of the global data distribution, the AUC fell in the range of 0.34-0.70. FL applied to B-mode US images provide performance comparable to a centralized model and higher than single-center scenario. Global data imbalance and local data heterogeneity influenced the learning outcome.
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Affiliation(s)
- Yue Qi
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Pedro Vianna
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
- Institute of Biomedical Engineering, Université de Montréal, Montréal, QC, Canada
- Laboratory of Biorheology and Medical Ultrasonics - CRCHUM, Montréal, QC, Canada
| | - Alexandre Cadrin-Chênevert
- Radiology, Radiation Oncology and Nuclear Medicine Department, Université de Montréal, Montréal, QC, Canada
- CISSS de Lanaudière, Joliette, QC, Canada
| | - Katleen Blanchet
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Emmanuel Montagnon
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
- Clinical Laboratory of Image Processing - CRCHUM, Montréal, QC, Canada
| | - Eugene Belilovsky
- Mila - Quebec Artificial Intelligence Institute, Montréal, QC, Canada
- Concordia University, Montréal, QC, Canada
| | - Guy Wolf
- Mila - Quebec Artificial Intelligence Institute, Montréal, QC, Canada
- Department of Mathematics and Statistics, Université de Montréal, Montréal, QC, Canada
| | - Louis-Antoine Mullie
- Mila - Quebec Artificial Intelligence Institute, Montréal, QC, Canada
- Department of Medicine, Division of Critical Care Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada
- Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Guy Cloutier
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
- Institute of Biomedical Engineering, Université de Montréal, Montréal, QC, Canada
- Laboratory of Biorheology and Medical Ultrasonics - CRCHUM, Montréal, QC, Canada
- Radiology, Radiation Oncology and Nuclear Medicine Department, Université de Montréal, Montréal, QC, Canada
- Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Michaël Chassé
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
- Department of Medicine, Division of Critical Care Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada
- Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - An Tang
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
- Clinical Laboratory of Image Processing - CRCHUM, Montréal, QC, Canada.
- Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
- Département de Radiologie, Centre Hospitalier de l'Université de Montréal (CHUM), 1058 Rue Saint-Denis, Montréal, QC, H2X 3J4, Canada.
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Ladner DP, Gmeiner M, Hasjim BJ, Mazumder N, Kang R, Parker E, Stephen J, Polineni P, Chorniy A, Zhao L, VanWagner LB, Ackermann RT, Manski CF. Increasing prevalence of cirrhosis among insured adults in the United States, 2012-2018. PLoS One 2024; 19:e0298887. [PMID: 38408083 PMCID: PMC10896513 DOI: 10.1371/journal.pone.0298887] [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: 09/20/2023] [Accepted: 01/31/2024] [Indexed: 02/28/2024] Open
Abstract
BACKGROUND Liver cirrhosis is a chronic disease that is known as a "silent killer" and its true prevalence is difficult to describe. It is imperative to accurately characterize the prevalence of cirrhosis because of its increasing healthcare burden. METHODS In this retrospective cohort study, trends in cirrhosis prevalence were evaluated using administrative data from one of the largest national health insurance providers in the US. (2011-2018). Enrolled adult (≥18-years-old) patients with cirrhosis defined by ICD-9 and ICD-10 were included in the study. The primary outcome measured in the study was the prevalence of cirrhosis 2011-2018. RESULTS Among the 371,482 patients with cirrhosis, the mean age was 62.2 (±13.7) years; 53.3% had commercial insurance and 46.4% had Medicare Advantage. The most frequent cirrhosis etiologies were alcohol-related (26.0%), NASH (20.9%) and HCV (20.0%). Mean time of follow-up was 725 (±732.3) days. The observed cirrhosis prevalence was 0.71% in 2018, a 2-fold increase from 2012 (0.34%). The highest prevalence observed was among patients with Medicare Advantage insurance (1.67%) in 2018. Prevalence increased in each US. state, with Southern states having the most rapid rise (2.3-fold). The most significant increases were observed in patients with NASH (3.9-fold) and alcohol-related (2-fold) cirrhosis. CONCLUSION Between 2012-2018, the prevalence of liver cirrhosis doubled among insured patients. Alcohol-related and NASH cirrhosis were the most significant contributors to this increase. Patients living in the South, and those insured by Medicare Advantage also have disproportionately higher prevalence of cirrhosis. Public health interventions are important to mitigate this concerning trajectory of strain to the health system.
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Affiliation(s)
- Daniela P. Ladner
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Surgery, Division of Organ Transplantation, Northwestern University, Chicago, IL, United States of America
| | - Michael Gmeiner
- Department of Economics, London School of Economics, London, United Kingdom
| | - Bima J. Hasjim
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
| | - Nikhilesh Mazumder
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Medicine, Division of Hepatology, University of Michigan, Ann Arbor, MI, United States of America
| | - Raymond Kang
- Institute for Public Health and Medicine (IPHAM), Northwestern University, Chicago, IL, United States of America
| | | | - John Stephen
- Department of Preventive Medicine, Northwestern University, Chicago, IL, United States of America
| | - Praneet Polineni
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
| | - Anna Chorniy
- Department of Medical Social Sciences and Buehler Center for Health Policy and Economics, Northwestern University, Chicago, IL, United States of America
| | - Lihui Zhao
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Preventive Medicine, Northwestern University, Chicago, IL, United States of America
| | - Lisa B. VanWagner
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, United States of America
| | - Ronald T. Ackermann
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Institute for Public Health and Medicine (IPHAM), Northwestern University, Chicago, IL, United States of America
| | - Charles F. Manski
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Northwestern University, Chicago, IL, United States of America
- Department of Economics and Institute for Policy Research, Northwestern University, Evanston, IL, United States of America
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Castillo GM, Yao Y, Guerra RE, Jiang H, Nishimoto-Ashfield A, Lyubimov AV, Alfaro JF, Striker KA, Buynov N, Schwabl P, Bolotin EM. Subcutaneous therapy for portal hypertension: PHIN-214, a partial vasopressin receptor 1A agonist. Biomed Pharmacother 2024; 171:116068. [PMID: 38176129 PMCID: PMC10953113 DOI: 10.1016/j.biopha.2023.116068] [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: 09/27/2023] [Revised: 12/14/2023] [Accepted: 12/21/2023] [Indexed: 01/06/2024] Open
Abstract
Cirrhosis is a liver disease that leads to increased intrahepatic resistance, portal hypertension (PH), and splanchnic hyperemia resulting in ascites, variceal bleeding, and hepatorenal syndrome. Terlipressin, a prodrug that converts to a short half-life vasopressin receptor 1 A (V1a) full agonist [8-Lys]-Vasopressin (LVP), is an intravenous treatment for PH complications, but hyponatremia and ischemic side effects require close monitoring. We developed PHIN-214 which converts into PHIN-156, a more biologically stable V1a partial agonist. PHIN-214 enables once-daily subcutaneous administration without causing ischemia or tissue necrosis and has a 10-fold higher therapeutic index than terlipressin in healthy rats. As V1a partial agonists, PHIN-214 and PHIN-156 exhibited maximum activities of 28 % and 42 % of Arginine vasopressin (AVP), respectively. The potency of PHIN-156 and LVP relative to AVP is comparable for V1a (5.20 and 1.65 nM, respectively) and V1b (102 and 115 nM, respectively) receptors. However, the EC50 of PHIN-156 to the V2 receptor was 26-fold higher than that of LVP, indicating reduced potential for dilutional hyponatremia via V2 agonism compared to terlipressin/LVP. No significant off-target binding to 87 toxicologically relevant receptors were observed when evaluated in vitro at 10 µM concentration. In bile duct ligated rats with PH, subcutaneous PHIN-214 reduced portal pressure by 13.4 % ± 3.4 in 4 h. These collective findings suggest that PHIN-214 could be a novel pharmacological treatment for patients with PH, potentially administered outside of hospital settings, providing a safe and convenient alternative for managing PH and its complications.
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Affiliation(s)
| | - Yao Yao
- PharmaIN Corp., Bothell, Washington 98011, USA
| | | | - Han Jiang
- PharmaIN Corp., Bothell, Washington 98011, USA
| | | | - Alexander V Lyubimov
- University of Illinois, Toxicology Research Laboratory, Department of Pharmacology, Chicago 60612, USA
| | | | | | | | - Philipp Schwabl
- Medical University of Vienna, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Vienna, Austria
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Cabibbo G, Daniele B, Borzio M, Casadei-Gardini A, Cillo U, Colli A, Conforti M, Dadduzio V, Dionisi F, Farinati F, Gardini I, Giannini EG, Golfieri R, Guido M, Mega A, Minozzi S, Piscaglia F, Rimassa L, Romanini L, Pecorelli A, Sacco R, Scorsetti M, Viganò L, Vitale A, Trevisani F. Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments. Dig Liver Dis 2024; 56:223-234. [PMID: 38030455 DOI: 10.1016/j.dld.2023.10.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 10/07/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023]
Abstract
Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy; Gastroenterology Unit, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", Palermo, Italy.
| | - Bruno Daniele
- Oncology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Napoli, Italy
| | - Mauro Borzio
- Centro Diagnostico Italiano (CDI), Milano, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Umberto Cillo
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit, "Mons. A.R.Dimiccoli" Hospital, Barletta, ASL BT, Italy
| | - Francesco Dionisi
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute - Rome, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy
| | - Ivan Gardini
- EpaC Onlus, Italian Liver Patient Association, Turin, Italy
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Rita Golfieri
- Alma Mater Studiorum" Bologna University, Bologna, Italy; Radiology Unit Madre Fortunata Toniolo Private Hospital, coordinator of Radiology centers Medipass Bologna, Bologna, Italy
| | - Maria Guido
- Department of Medicine, University of Padova, Padova- Italy
| | - Andrea Mega
- Department of Gastronterology, Regional Hospital Bolzano, Italy
| | - Silvia Minozzi
- Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Laura Romanini
- Radiology Unit, Ospedale di Cremona, ASST Cremona, Cremona, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy; Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Viganò
- Hepatobiliary Unit, Department of Minimally Invasive General & Oncologic Surgery, Humanitas Gavazzeni University Hospital, Viale M. Gavazzeni 21, 24125 Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Viale Rita Levi Montalcini 4, 20090 Milan, Italy
| | - Alessandro Vitale
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
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Johnson E, Hyde A, Drager D, Carbonneau M, Bain V, Kowalczewski J, Tandon P. Collaborating with patients and caregivers to create web-based educational resources for people affected by cirrhosis. PEC INNOVATION 2023; 3:100201. [PMID: 37705726 PMCID: PMC10495668 DOI: 10.1016/j.pecinn.2023.100201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 08/08/2023] [Accepted: 08/20/2023] [Indexed: 09/15/2023]
Abstract
Objective To describe the development of multimodal, web-based educational resources about cirrhosis alongside patients and caregivers. Methods We used an iterative process that was guided by the Strategy for Patient Oriented Research (SPOR) patient engagement framework in describing patient engagement activities to partner with a team of 16 patients and caregivers (Patient Advisory Team (PAT)). This process included five phases: a) Prioritize and gather content, b) design and build the website and videos, c) gather and integrate feedback, d) improve user accessibility, and e) assess usability and knowledge uptake for users. Results This 2-year process resulted in a 55-page website and 78 animated and live-action videos on cirrhosis complications, procedures, nutrition, and exercise. We implemented usability testing through pre-defined tasks and a think-aloud method from individuals with no previous exposure to the website to assess navigation, appearance, and content issues. Following usability testing, we have been gathering quantitative data from each unique page about relevance and ease of use, as well as qualitative data on the value of the content itself. Conclusions Collaboration between clinicians, patients, and caregivers is key to developing high-quality digital educational resources. Lessons from our process may help other organizations looking to address disease-specific knowledge gaps. Next steps with www.cirrhosiscare.ca will be continued iterative refinement and structured impact evaluation. Innovation This project used a patient-centered approach to develop a comprehensive online educational resource for patients with cirrhosis. By having patients with cirrhosis as a key part of our team, we ensured that the site met the needs of this unique population.
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Affiliation(s)
- Emily Johnson
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Ashley Hyde
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Derek Drager
- Patient Advisory Team (PAT), Cirrhosis Care Alberta, Canada
| | - Michelle Carbonneau
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Vincent Bain
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Jan Kowalczewski
- Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
| | - Puneeta Tandon
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
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10
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Tan D, Chan KE, Wong ZY, Ng CH, Xiao J, Lim WH, Tay P, Tang A, Fu CE, Muthiah M, Nah B, Tan EX, Teng ML, Siddiqui MS, Dan YY, Lim SG, Loomba R, Huang DQ. Global Epidemiology of Cirrhosis: Changing Etiological Basis and Comparable Burden of Nonalcoholic Steatohepatitis between Males and Females. Dig Dis 2023; 41:900-912. [PMID: 37703863 PMCID: PMC10716870 DOI: 10.1159/000533946] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 08/09/2023] [Indexed: 09/15/2023]
Abstract
INTRODUCTION The etiology of liver diseases has changed significantly, but its impact on the comparative burden of cirrhosis between males and females is unclear. We estimated sex differences in the burden of cirrhosis across 204 countries and territories from 2010 to 2019. METHODS We analyzed temporal trends in the burden of cirrhosis using the methodology framework of the 2019 Global Burden of Disease study. We estimated annual frequencies and age-standardized rates (ASRs) of cirrhosis incidence, death, and disability-adjusted life-years (DALYs) by sex, region, country, and etiology. RESULTS In 2019, the frequency of incident cases, deaths, and DALYs due to cirrhosis was 1,206,125, 969,068, and 31,781,079 in males versus 845,429, 502,944, and 14,408,336 in females, respectively. From 2010 to 2019, the frequency of cirrhosis deaths increased by 9% in males and 12% in females. Incidence ASRs remained stable in males but increased in females, while death ASRs declined in both. Death ASRs for both sexes declined in all regions, except in the Americas where they remained stable. In 2019, alcohol was the leading cause of cirrhosis deaths in males, and hepatitis C in females. Death ASRs declined for all etiologies in both sexes, except in nonalcoholic steatohepatitis (NASH). The ratio of female-to-male incidence ASRs in 2019 was lowest in alcohol(0.5), and highest in NASH(1.3), while the ratio of female-to-male death ASRs was lowest in alcohol(0.3) and highest in NASH(0.8). CONCLUSION The global burden of cirrhosis is higher in males. However, incidence and death ASRs from NASH cirrhosis in females are comparable to that of males.
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Affiliation(s)
- Darren Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Zhen Yu Wong
- Nottingham Hospitals University Trust, Nottingham, UK
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Phoebe Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ansel Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Clarissa Elysia Fu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Benjamin Nah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nottingham Hospitals University Trust, Nottingham, UK
| | - Eunice X. Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Margaret L.P. Teng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Department of Internal Medicine, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Seng Gee Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Rohit Loomba
- Division of Gastroenterology, NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
- Division of Gastroenterology, NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA
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11
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Dardari L, Taha M, Dahat P, Toriola S, Satnarine T, Zohara Z, Adelekun A, Seffah KD, Salib K, Arcia Franchini AP. The Efficacy of Carvedilol in Comparison to Propranolol in Reducing the Hepatic Venous Pressure Gradient and Decreasing the Risk of Variceal Bleeding in Adult Cirrhotic Patients: A Systematic Review. Cureus 2023; 15:e43253. [PMID: 37577269 PMCID: PMC10416553 DOI: 10.7759/cureus.43253] [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: 05/14/2023] [Accepted: 08/09/2023] [Indexed: 08/15/2023] Open
Abstract
The most common cause of portal hypertension is liver cirrhosis. Portal hypertension causes many complications in cirrhotic patients; a significant complication is the formation of varices and the subsequent life-threatening variceal bleeding due to elevated portal venous pressures. Hepatic venous pressure gradient (HVPG) is the gold standard for measuring portal hypertension and guides management. Pharmacological treatments lower the HVPG, preventing the progression of varices and subsequent variceal bleeding. The pharmacological treatments frequently used in primary and secondary prophylaxis of a variceal bleed are nonselective beta (β)-adrenergic blockers. Propranolol was the first nonselective β-adrenergic blocker used for lowering HVPG and has been well studied. However, in the past decade, clinical trials have shown that carvedilol has been more effective. This study aims to establish whether carvedilol is more effective than propranolol in reducing the hepatic venous pressure gradient and decreasing the risk of variceal bleeding in adult cirrhotic patients. A systematic review has been conducted to gather relevant clinical trials comparing drugs and their effects on HVPG. Four databases: PubMed (Medical Literature Analysis and Retrieval System Online (MEDLINE)), Google Scholar, the Cochrane Library, and ScienceDirect, were analyzed, and records from January 1, 1999, to January 1, 2023, were chosen. There were a total of 1,235 potentially eligible records across the four databases. Using the eligibility criteria for this systematic review, seven studies of 533 patients were included. Across all seven clinical trials, it was found that carvedilol reduced HVPG more than propranolol and decreased the risk of variceal bleeding in adult cirrhotic patients.
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Affiliation(s)
- Lana Dardari
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Maher Taha
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Purva Dahat
- Medical School, St. Martinus University, Willemstad, CUW
| | - Stacy Toriola
- Pathology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Travis Satnarine
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Zareen Zohara
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ademiniyi Adelekun
- Family Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Kofi D Seffah
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Piedmont Athens Regional Medical, Athens, USA
| | - Korlos Salib
- General Practice, El Demerdash Hospital, Cairo, EGY
| | - Ana P Arcia Franchini
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Hyde AM, Johnson E, Luig T, Schroeder D, Carbonneau M, Campbell-Scherer D, Tandon P. Implementing a cirrhosis order set in a tertiary healthcare system: a theory-informed formative evaluation. BMC Health Serv Res 2023; 23:636. [PMID: 37316822 DOI: 10.1186/s12913-023-09632-z] [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: 11/04/2022] [Accepted: 06/01/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Standardized order sets are a means of increasing adherence to clinical practice guidelines and improving the quality of patient care. Implementation of novel quality improvement initiatives like order sets can be challenging. Before the COVID-19 pandemic, we conducted a formative evaluation to understand healthcare providers' perspectives on implementing clinical changes and the individual, collective and organizational contextual factors that might impact implementation at eight hospital sites in Alberta, Canada. METHODS We utilized concepts from the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT) to understand the context, past implementation experiences, and perceptions of the cirrhosis order set. Eight focus groups were held with healthcare professionals caring for patients with cirrhosis. Data were coded deductively using relevant constructs of NPT and CFIR. A total of 54 healthcare professionals, including physicians, nurses, nurse practitioners, social workers and pharmacists and a physiotherapist, participated in the focus groups. RESULTS Key findings revealed that participants recognized the value of the cirrhosis order set and its potential to improve the quality of care. Participants highlighted potential implementation challenges, including multiple competing quality improvement initiatives, feelings of burnout, lack of communication between healthcare provider groups, and a lack of dedicated resources to support implementation. CONCLUSIONS Implementing a complex improvement initiative across clinician groups and acute care sites presents challenges. This work yielded insights into the significant influence of past implementation of similar interventions and highlighted the importance of communication between clinician groups and resources to support implementation. However, by using multiple theoretical lenses to illuminate what and how contextual and social processes will influence uptake, we can better anticipate challenges during the implementation process.
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Affiliation(s)
- A M Hyde
- Division of Gastroenterology (Liver Unit), Faculty of Medicine & Dentistry, University of Alberta, 8540 112 St NW, Edmonton, AB, T6G 2P8, Canada
| | - E Johnson
- Division of Gastroenterology (Liver Unit), Faculty of Medicine & Dentistry, University of Alberta, 8540 112 St NW, Edmonton, AB, T6G 2P8, Canada
| | - T Luig
- Physician Learning Program, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada
| | - D Schroeder
- Physician Learning Program, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada
| | | | - D Campbell-Scherer
- Physician Learning Program, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada.
- Department of Family Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada.
- Office of Lifelong Learning and Physician Learning Program, Edmonton Clinic Health Academy (ECHA), 2-590, Edmonton, AB, T6G 1C9, Canada.
| | - P Tandon
- Division of Gastroenterology (Liver Unit), Faculty of Medicine & Dentistry, University of Alberta, 8540 112 St NW, Edmonton, AB, T6G 2P8, Canada.
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Razmpour F, Daryabeygi-Khotbehsara R, Soleimani D, Asgharnezhad H, Shamsi A, Bajestani GS, Nematy M, Pour MR, Maddison R, Islam SMS. Application of machine learning in predicting non-alcoholic fatty liver disease using anthropometric and body composition indices. Sci Rep 2023; 13:4942. [PMID: 36973382 PMCID: PMC10043285 DOI: 10.1038/s41598-023-32129-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, which can progress from simple steatosis to advanced cirrhosis and hepatocellular carcinoma. Clinical diagnosis of NAFLD is crucial in the early stages of the disease. The main aim of this study was to apply machine learning (ML) methods to identify significant classifiers of NAFLD using body composition and anthropometric variables. A cross-sectional study was carried out among 513 individuals aged 13 years old or above in Iran. Anthropometric and body composition measurements were performed manually using body composition analyzer InBody 270. Hepatic steatosis and fibrosis were determined using a Fibroscan. ML methods including k-Nearest Neighbor (kNN), Support Vector Machine (SVM), Radial Basis Function (RBF) SVM, Gaussian Process (GP), Random Forest (RF), Neural Network (NN), Adaboost and Naïve Bayes were examined for model performance and to identify anthropometric and body composition predictors of fatty liver disease. RF generated the most accurate model for fatty liver (presence of any stage), steatosis stages and fibrosis stages with 82%, 52% and 57% accuracy, respectively. Abdomen circumference, waist circumference, chest circumference, trunk fat and body mass index were among the most important variables contributing to fatty liver disease. ML-based prediction of NAFLD using anthropometric and body composition data can assist clinicians in decision making. ML-based systems provide opportunities for NAFLD screening and early diagnosis, especially in population-level and remote areas.
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Affiliation(s)
- Farkhondeh Razmpour
- Department of Nutrition, Faculty of Medicine, Hormozgan University of Medical Sciences, Shahid Chamran Boulevard, Bandar Abbas, Iran.
| | | | - Davood Soleimani
- Department of Nutrition, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Hamzeh Asgharnezhad
- Institute for Intelligent Systems Research and Innovation (IISRI), Geelong Waurn Ponds Victoria, Australia
| | - Afshar Shamsi
- Biomedical Machine Learning Lab, University of New South Whales, Sydney, Australia
- Concordia Institute for Information Systems Engineering, Concordia University, Montreal, Canada
| | - Ghasem Sadeghi Bajestani
- Department of Biomedical Engineering, Faculty of Engineering, Imam Reza International University, Mashhad, Iran
| | - Mohsen Nematy
- Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Ralph Maddison
- Institute for Physical Activity and Nutrition (IPAN), Deakin University, Geelong Victoria, Australia
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14
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Ringe KI, Yoon JH. Strategies and Techniques for Liver Magnetic Resonance Imaging: New and Pending Applications for Routine Clinical Practice. Korean J Radiol 2023; 24:180-189. [PMID: 36788770 PMCID: PMC9971842 DOI: 10.3348/kjr.2022.0838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/11/2022] [Accepted: 12/22/2022] [Indexed: 02/16/2023] Open
Affiliation(s)
- Kristina I. Ringe
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
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15
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Ihedioha TE, Asuzu IU, Anaga AO, Ihedioha JI, Nnadi CO. Bioassay guided fractionation, isolation and characterization of hepatotherapeutic 1, 3-di-ortho-galloyl quinic acid from the methanol extract of the leaves of Pterocarpus santalinoides. JOURNAL OF ETHNOPHARMACOLOGY 2023; 301:115864. [PMID: 36283637 DOI: 10.1016/j.jep.2022.115864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 10/18/2022] [Accepted: 10/19/2022] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Leaf extracts of Pterocarpus santalinoides DC are traditionally used to ameliorate ageing-related ailments such as heart and liver diseases, and have been reported to be protective against toxic injuries to the liver. AIM OF THE STUDY This study aimed to isolate and characterize the hepatoprotective/hepatotherapeutic principle in the methanol leaf extract of P. santalinoides. MATERIALS AND METHODS Fresh leaves of P. santalinoides were dried under shade and ground into powder. The ground leaves (2 Kg) were extracted with 80% methanol by maceration. Fractionation was carried out using column and thin layer chromatography techniques. Bioassay of fractions and sub-fractions was done using carbon tetrachloride (CCl4)-induced hepatotoxicity model in albino rats. Phytochemical analysis was carried out on the active compound. Characterization and structural elucidation of the active compound using high performance liquid chromatography and nuclear magnetic resonance spectroscopy was done. RESULTS Extraction yielded 260 g dry extract. Six fractions (F1, F2, F3, F4, F5 and F6) were obtained after column and thin layer chromatography, with F6 (Rf = 0.78; Yield = 2.13 g) being the most active hepatotherapeutic fraction that significantly (p < 0.05) lowered serum ALT activity and increased serum albumin levels in CCl4-induced hepatopathy in albino rats. Further separation of F6 yielded four sub-fractions (F61, F62, F63 and F64), of which F61 with an Rf of 0.85 and a yield of 30.0 mg was isolated as the active hepatotherapeutic compound. Stiasny and ferric chloride test of F61 showed the presence of tannins in the fraction. Characterization of F61 revealed 1, 3-di-ortho-galloyl quinic acid. CONCLUSION The hepatoprotective/hepatotherapeutic principle in the methanol extract of the leaves of P. santalinoides was identified as 1, 3-di-ortho-galloyl quinic acid.
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Affiliation(s)
- Thelma E Ihedioha
- Department of Veterinary Physiology and Pharmacology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria.
| | - Isaac U Asuzu
- Department of Veterinary Physiology and Pharmacology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria
| | - Aruh O Anaga
- Department of Veterinary Physiology and Pharmacology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria
| | - John I Ihedioha
- Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria
| | - Charles O Nnadi
- Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
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Onikanni SA, Lawal B, Bakare OS, Ajiboye BO, Ojo OA, Farasani A, Kabrah SM, Batiha GES, Conte-Junior CA. Cancer of the Liver and its Relationship with Diabetes mellitus. Technol Cancer Res Treat 2022; 21:15330338221119743. [PMID: 36533882 PMCID: PMC9772979 DOI: 10.1177/15330338221119743] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
A high increase witnessed in type II diabetes mellitus (T2DM) globally has increasingly posed a serious threat to global increases in liver cancer with the association between diabetes mellitus type II and the survival rate in liver cancer patients showing unstable findings. An increase in the development and progression of chronic liver disease from diabetes mellitus patients may be connected to cancer of the liver with several links such as Hepatitis B and C virus and heavy consumption of alcohol. The link between T2DM patients and liver cancer is centered on non-alcoholic fatty liver disease (NAFLD) which could be a serious threat globally if not clinically addressed. Several reports identified metformin treatment as linked to a lower risk of liver cancer prognosis while insulin treatment or sulphonylureas posed a serious threat. Mechanistically, the biological linkage between diabetes type II mellitus and liver cancer are still complex to understand with only the existence of a relationship between NAFLD and high level of energy intake and diabetes mellitus induces hepatic damage, increased liver weight thereby causes multiple pro-inflammatory cytokines that lead to the development of liver cancer. Therefore, this review gives an account of the pathophysiological importance of liver cancer position with T2DM, with the role of NAFLD as an important factor that bridges them.
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Affiliation(s)
- Sunday Amos Onikanni
- Department of Chemical Sciences, Biochemistry Unit, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria,College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan,Sunday Amos Onikanni, College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
| | - Bashir Lawal
- PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei,Graduate Institute for Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei
| | | | - Basiru Olaitan Ajiboye
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Ekiti State, Nigeria
| | - Oluwafemi Adeleke Ojo
- Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Laboratory (PMTCB-RL), Department of Biochemistry, Bowen University, Iwo, 232101, Nigeria
| | - Abdullah Farasani
- Biomedical Research Unit, Medical Research Center, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia,Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Saeed M Kabrah
- Department of Laboratory Medicine Faculty of Applied medical sciences, Umm Al-Qura University, Kingdom of Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira, Egypt
| | - Carlos Adam Conte-Junior
- Analytical and Molecular Laboratorial Center (CLAn), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ, 21941-909, Brazil
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Sohal A, Chaudhry H, Dhaliwal A, Singla P, Gupta G, Sharma R, Dukovic D, Prajapati D. Gender differences in esophageal variceal bleeding in the United States. Ann Med 2022; 54:2115-2122. [PMID: 35930410 PMCID: PMC9359179 DOI: 10.1080/07853890.2022.2104920] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND AND AIMS Esophageal variceal bleeding is a common reason for hospitalization in patients with cirrhosis. The main objective of this study was to analyze the effects of gender differences on outcomes in hospitalizations related to Esophageal variceal bleeding in the United States. METHODS A retrospective observational cohort study was performed using the National Inpatient Sample (NIS) database for all hospitalizations with a discharge diagnosis of esophageal varices with hemorrhage from 2016 to 2019. The primary outcome was in-hospital mortality, while secondary outcomes included rate of early endoscopy (defined as less than 1 day), AKI, blood transfusion, sepsis, ICU admission and TIPS (Transjugular Intrahepatic Portosystemic Shunt). We also compared the length of stay and total hospitalization charges. RESULTS We identified a total of 166,760 patients with variceal bleeding of which 32.7% were females. In-hospital mortality was higher in males, 9.91%, compared to females, 8.31% (adjusted odds ratio (aOR): 0.88, p-value=.008, when adjusted for confounding factors). The odds of undergoing an EGD, length of stay, or total hospitalization charges did not differ between the two groups. Compared to men, women had lower odds of receiving TIPS (aOR = 0.83, p-value=.002). CONCLUSION Women hospitalised with esophageal variceal bleeding are at a lower risk of death compared to males. Further research is needed to elucidate the factors associated with this lower risk.
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Affiliation(s)
- Aalam Sohal
- Department of Internal Medicine, University of California, Fresno, CA, USA
| | - Hunza Chaudhry
- Department of Internal Medicine, University of California, Fresno, CA, USA
| | - Armaan Dhaliwal
- Department of Internal Medicine, University of Arizona, South Campus-Tucson, AZ, USA
| | - Piyush Singla
- Dayanand Medical College and Hospital, Punjab, India
| | - Gagan Gupta
- Dayanand Medical College and Hospital, Punjab, India
| | | | - Dino Dukovic
- Ross University School of Medicine, Bridgetown, Barbados
| | - Devang Prajapati
- Department of Gastroenterology and Hepatology, University of California, Fresno, CA, USA
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18
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A Case of a Large Intraabdominal Abscess in a Patient with Cirrhosis Misdiagnosed as Spontaneous Bacterial Peritonitis. Case Reports Hepatol 2022; 2022:5951115. [PMID: 36246017 PMCID: PMC9556249 DOI: 10.1155/2022/5951115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 08/15/2022] [Indexed: 11/17/2022] Open
Abstract
Spontaneous bacterial peritonitis is a known complication of patients with decompensated cirrhosis and ascites. It is differentiated from secondary bacterial peritonitis by the absence of an intraabdominal source of infection. We present a 56-year-old man with alcoholic cirrhosis who underwent multiple paracenteses that yielded fluid with progressively increasing neutrophil counts and several different organisms, recurring despite numerous treatments for SBP. Eventually, a computed tomography (CT) of the abdomen and the pelvis revealed a large intraabdominal abscess (22 × 13 cm) treated with an ultrasound-guided drain and IV antibiotics. Recurrent episodes of SBP despite appropriate antibiotics should raise suspicion for secondary bacterial peritonitis. It is crucial to differentiate SBP from secondary bacterial peritonitis as the mortality of the latter is much higher without prompt treatment. Appropriate antibiotic regimens, prompt surgical treatment, and postoperative care are crucial to improving clinical outcomes in these patients.
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19
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Molaei S, Amiri F, Salimi R, Ferdowsi S, Bahadori M. Therapeutic effects of mesenchymal stem cells-conditioned medium derived from suspension cultivation or silymarin on liver failure mice. Mol Biol Rep 2022; 49:10315-10325. [PMID: 36097106 DOI: 10.1007/s11033-022-07785-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 07/08/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Common treatments of liver disease failed to meet all the needs in this important medical field. It results in an urgent need for proper some new adjuvant therapies. Mesenchymal stem cells (MSCs) and their derivatives are promising tools in this regard. We aimed to compare the Silymarin, as traditional treatment with mesenchymal stem cell conditioned medium (MSC-CM), as a novel strategy, both with therapeutic potentialities in term of liver failure (LF) treatment. METHODS AND RESULTS Mice models with liver failure were induced with CCl4 and were treated in the groups as follows: normal mice receiving DMEM-LG medium as control, LF-mice receiving DMEM-LG medium as sham, LF-mice receiving Silymarin as LF-SM, and LF-mice receiving MSC sphere CM as LF-MSC-CM. Biochemical, histopathological, molecular and protein level parameters were evaluated using blood and liver samples. Liver enzymes, MicroRNA-122 values as well as necrotic score were significantly lower in the LF-SM and LF-MSC-CM groups compared to sham. LF-SM showed significantly higher level of total antioxidant capacity and malondialdehyde than that of LF-MSC-CM groups. Sph-MSC-CM not only induced more down-regulated expression of fibrinogen-like protein 1 and receptor interacting protein kinases1 but also led to higher expression level of keratinocyte growth factor. LF-MSC-CM showed less mortality rate compared to other groups. CONCLUSIONS Hepato-protective potentialities of Sph-MSC-CM are comparable to those of Silymarin. More inhibition of necroptosis/ necrosis and inflammation might result in rapid liver repair in case of MSC-CM administration.
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Affiliation(s)
- Sedigheh Molaei
- Social Determinants of Health Research Center, Saveh University of Medical Sciences, Saveh, Iran
| | - Fatemeh Amiri
- Department of Medical Laboratory Sciences, School of Para Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Rasoul Salimi
- Department of Emergency Medicine, Besat Hospital, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Shirin Ferdowsi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Marzie Bahadori
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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20
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Subhani M, Sheth A, Ahmed J, Wijayasiri P, Gardezi SA, Enki D, Morling JR, Aithal GP, Ryder SD, Aravinthan AD. Incidence and prevalence of venous thromboembolism in chronic liver disease: A systematic review and meta-analysis. Thromb Res 2022; 215:19-29. [PMID: 35594737 DOI: 10.1016/j.thromres.2022.05.004] [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: 03/09/2022] [Revised: 04/22/2022] [Accepted: 05/07/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Historically, bleeding was thought to be a frequent and fatal complication of liver disease. However, thrombosis due to coagulation disorders in cirrhosis remains a real risk. We aim to systematically analyse published articles to evaluate epidemiology of venous thromboembolism (VTE) in chronic liver disease (CLD). METHOD Electronic search was conducted on Ovid Medline, EMBASE and Scopus from inception to November 2021 to identify studies presenting epidemiology VTE (deep vein thrombosis and pulmonary embolism) in CLD in inpatients and/or community settings. Random-effects meta-analysis was performed to determine pooled per-year cumulative incidence, incidence rate and prevalence. Heterogeneity was measured by I2 test, and, potential sources of heterogeneity by meta-regression and sensitivity analysis. PROSPERO registration-CRD42021239117. RESULTS Twenty-nine studies comprising 19,157,018 participants were included, of which 15,2049 (0.79%) had VTE. None of the included studies were done in the community. In hospitalised patients with CLD: pooled cumulative incidence of VTE was 1.07% (95% CI 0.80,1.38) per-year, incidence rate was 157.15 (95% CI 14.74,445.29) per 10,000 person-years, and period prevalence was 1.10% (95% CI 0.85,1.38) per year. There was significant heterogeneity and publication bias. Pooled relative risk (RR) of studies reporting incidence rate was 2.11 (95% CI 1.35,3.31). CLD patients (n = 1644), who did not receive pharmacological prophylaxis were at 2.78 times (95% CI 1.11, 6.98) increased risk of VTE compared to those receiving prophylaxis. CONCLUSION Hospitalised patients with CLD may be at an increased risk of VTE. For every 1000 hospitalised patients with CLD ten have new, and eleven have pre-existing diagnoses of VTE per-year.
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Affiliation(s)
- Mohsan Subhani
- Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK.
| | - Abhishek Sheth
- Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK.
| | - Jamal Ahmed
- Royal Gwent Unit, Royal Gwent Hospital, Newport, NP20 2UB, UK.
| | - Pramudi Wijayasiri
- Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK.
| | - Syed A Gardezi
- Royal Gwent Unit, Royal Gwent Hospital, Newport, NP20 2UB, UK.
| | - Doyo Enki
- School of Medicine, University of Nottingham, UK.
| | - Joanne R Morling
- Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK; Division of Epidemiology and Public Health, University of Nottingham, Nottingham, NG5 1PB, UK.
| | - Guruprasad P Aithal
- Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK.
| | - Stephen D Ryder
- Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK.
| | - Aloysious D Aravinthan
- Nottingham Digestive Diseases Centre (NDDC), Translational Medical Sciences, School of Medicine, University of Nottingham, NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, NG7 2UH, UK.
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21
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Abou Yassine A, Abureesh M, Hamadi R, Dahabra L, Alshami M, Liliane D. Predictors of Deep Venous Thrombosis in Hospitalized Patients With Liver Cirrhosis in the US. Cureus 2022; 14:e23450. [PMID: 35494982 PMCID: PMC9038512 DOI: 10.7759/cureus.23450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2022] [Indexed: 11/05/2022] Open
Abstract
Background Patients with liver cirrhosis were previously considered as anticoagulated; thus, their risk of developing venous thromboembolism (VTE) is lower. Recently, several studies showed contradicting results regarding deep venous thrombosis (DVT) occurrence in cirrhotic patients. The aim of this study is to evaluate the prevalence and risk associated with developing DVT in hospitalized cirrhotic patients in a large US population. Methods We queried the commercial database Explorys (IMB Inc., Armonk, New York), an aggregate of electronic health record data from 26 US healthcare systems. After excluding patients under 20 years old, a cohort of patients with a Systematized Nomenclature of Medicine - Clinical Terms of "cirrhosis of the liver" and "inpatient care" between 2015-2019 were identified, and prevalence of DVT was calculated in the exposure and the control groups. Statistical analysis for a multivariable model was performed. Factors adjusted for include gender, race, obesity, hypoalbuminemia, diabetes mellitus, viral hepatitis, and liver malignancy. Results Among 9,990,290 patients who were hospitalized between 2015 and 2019, 157,400 patients had a diagnosis of liver cirrhosis. The prevalence of DVT in hospitalized patients with liver cirrhosis was 3.29% compared to 3.18% in non-cirrhotic patients. Using the multivariate analysis model, DVT was inversely associated with cirrhosis in hospitalized patients [OR: 0.921; p<0.0001] compared to patients without liver cirrhosis. Predictors of developing DVT among patients with cirrhosis were non-Caucasian race, obesity (BMI>30), liver malignancy, hypoalbuminemia, and diabetes mellitus. Cirrhotic patients due to viral hepatitis were less likely to develop DVT [OR: 0.775; p<0.001] compared to non-cirrhotic patients. Conclusion In this database, although the prevalence of DVT in cirrhotic hospitalized patients was slightly higher than in non-cirrhotic patients (3.29% vs. 3.18%, respectively), cirrhosis as an independent factor was associated with less risk of DVT during hospitalization. This poses a question regarding DVT prophylaxis necessity in this group of patients. Further studies are needed to clarify the benefit and risks of DVT prophylaxis in cirrhotic patients.
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22
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Destrempes F, Gesnik M, Chayer B, Roy-Cardinal MH, Olivié D, Giard JM, Sebastiani G, Nguyen BN, Cloutier G, Tang A. Quantitative ultrasound, elastography, and machine learning for assessment of steatosis, inflammation, and fibrosis in chronic liver disease. PLoS One 2022; 17:e0262291. [PMID: 35085294 PMCID: PMC8794185 DOI: 10.1371/journal.pone.0262291] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
Objective To develop a quantitative ultrasound (QUS)- and elastography-based model to improve classification of steatosis grade, inflammation grade, and fibrosis stage in patients with chronic liver disease in comparison with shear wave elastography alone, using histopathology as the reference standard. Methods This ancillary study to a prospective institutional review-board approved study included 82 patients with non-alcoholic fatty liver disease, chronic hepatitis B or C virus, or autoimmune hepatitis. Elastography measurements, homodyned K-distribution parametric maps, and total attenuation coefficient slope were recorded. Random forests classification and bootstrapping were used to identify combinations of parameters that provided the highest diagnostic accuracy. Receiver operating characteristic (ROC) curves were computed. Results For classification of steatosis grade S0 vs. S1-3, S0-1 vs. S2-3, S0-2 vs. S3, area under the receiver operating characteristic curve (AUC) were respectively 0.60, 0.63, and 0.62 with elasticity alone, and 0.90, 0.81, and 0.78 with the best tested model combining QUS and elastography features. For classification of inflammation grade A0 vs. A1-3, A0-1 vs. A2-3, A0-2 vs. A3, AUCs were respectively 0.56, 0.62, and 0.64 with elasticity alone, and 0.75, 0.68, and 0.69 with the best model. For classification of liver fibrosis stage F0 vs. F1-4, F0-1 vs. F2-4, F0-2 vs. F3-4, F0-3 vs. F4, AUCs were respectively 0.66, 0.77, 0.72, and 0.74 with elasticity alone, and 0.72, 0.77, 0.77, and 0.75 with the best model. Conclusion Random forest models incorporating QUS and shear wave elastography increased the classification accuracy of liver steatosis, inflammation, and fibrosis when compared to shear wave elastography alone.
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Affiliation(s)
- François Destrempes
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Marc Gesnik
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Boris Chayer
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Marie-Hélène Roy-Cardinal
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
| | - Damien Olivié
- Department of Radiology, Radiation oncology and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada
- Department of Radiology, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
| | - Jeanne-Marie Giard
- Department of Medicine, Division of Hepatology and Liver Transplantation, Université de Montréal, Montréal, Québec, Canada
| | - Giada Sebastiani
- Department of Medicine, Division of Gastroenterology and Hepatology, McGill University Health Centre (MUHC), Montréal, Québec, Canada
| | - Bich N. Nguyen
- Department of Pathology, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
- Department of Pathology and Cellular Biology, Université de Montréal, Montréal, Québec, Canada
| | - Guy Cloutier
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montréal, Québec, Canada
- Department of Radiology, Radiation oncology and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada
- Institute of Biomedical Engineering, University of Montreal, Montréal, Québec, Canada
- * E-mail: (GC); (AT)
| | - An Tang
- Department of Radiology, Radiation oncology and Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada
- Department of Radiology, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, Québec, Canada
- Laboratory of Medical Image Analysis, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada
- * E-mail: (GC); (AT)
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23
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Matthews LA, Lucey MR. Psychosocial Evaluation in Liver Transplantation for Patients with Alcohol-Related Liver Disease. Clin Liver Dis (Hoboken) 2022; 19:17-20. [PMID: 35106144 PMCID: PMC8785917 DOI: 10.1002/cld.1160] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Interview and Audio Recording.
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Affiliation(s)
| | - Michael R. Lucey
- Division of Gastroenterology and HepatologyUniversity of WisconsinMadisonWI
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24
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Thomas KL, Root CL, Peterson JM. Transgenic overexpression of CTRP3 does not prevent alcohol induced hepatic steatosis in female mice. PLoS One 2022; 17:e0258557. [PMID: 34995284 PMCID: PMC8740976 DOI: 10.1371/journal.pone.0258557] [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: 06/03/2021] [Accepted: 09/29/2021] [Indexed: 11/19/2022] Open
Abstract
Alcoholic liver disease (ALD) is one of the leading causes of morbidity and mortality from hepatic complications. C1q/TNF-related protein 3 (CTRP3) is an adiponectin paralog and, in male mice, increased levels of circulating CTRP3 prevents ALD. Therefore, the purpose of this study was to replicate the observed hepatoprotective effect of elevated circulating CTRP3 levels in female mice. Twelve-week-old female wildtype and CTRP3 overexpressing transgenic mice were fed the Lieber-DeCarli alcohol-containing liquid diet (5% vol/vol) for 6 weeks. Unlike the previous study with male mice, CTRP3 overexpression provided no attenuation to alcohol-induced hepatic lipid accumulation, cytokine production, or overall mortality. In conclusion, there appears to be a clear sex-specific effect of CTRP3 in response to alcohol consumption that needs to be explored further.
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Affiliation(s)
- Kristy L. Thomas
- Department of Health Sciences, East Tennessee State University, Johnson City, TN, United States of America
- Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States of America
| | - Callie L. Root
- Department of Health Sciences, East Tennessee State University, Johnson City, TN, United States of America
| | - Jonathan M. Peterson
- Department of Health Sciences, East Tennessee State University, Johnson City, TN, United States of America
- Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States of America
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25
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Aby ES, Pham NV, Yum JJ, Dong TS, Ghasham H, Bedier F, Malley C, Schaenman J, Saab S. Frailty Does Not Impact Caregiver Burden in Patients with Cirrhosis. Dig Dis Sci 2021; 66:3343-3351. [PMID: 33136228 DOI: 10.1007/s10620-020-06687-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 10/19/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Frailty is common and is associated with increased mortality, lower quality of life, and higher readmission rates in cirrhotic patients. Not only are these outcomes important, but further understanding the impact of frailty on a caregiver's life is crucial to better comprehend caregiver burden in cirrhotic patients and develop strategies to improve care for patients and their caregivers. METHODS A single-center, prospective study was conducted of cirrhotic patients and their caregivers between 4/1/2019 and 11/1/2019. Frailty testing combined aspects from the Fried Frailty Instrument, Short Physical Performance Battery, and activities of daily living. Caregivers completed questionnaires to evaluate caregiver burden using the Zarit Burden Interview (ZBI-12), and perceived social support, using the Interpersonal Support Evaluation List. RESULTS In total, 94 cirrhotic patients were included, 50% males with a median age of 63.1 years. The most common etiology of cirrhosis was nonalcoholic steatohepatitis. Frailty was prevalent (45.1%). In total, 12.8% of caregivers reported a high burden based on ZBI-12. There was no association between frailty and caregiver burden, hospitalization rates, or death. However, frailty was associated with a higher number of outpatient GI visits (p = 0.002). Lower perceived social support among caregivers was associated with a higher caregiver burden (p < 0.0001). CONCLUSION Frailty is prevalent in cirrhotic patients but is not associated with higher rates of caregiver burden. Low perceived social support among caregivers, however, was associated with higher caregiver burden. It is important to recognize the impact of caregiver burden on caregivers of cirrhotic patients and ensure caregivers have the appropriate support to mitigate burden.
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Affiliation(s)
- Elizabeth S Aby
- Departments of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Nguyen V Pham
- Departments of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Jung J Yum
- Departments of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Tien S Dong
- Departments of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Hussein Ghasham
- Departments of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Fatima Bedier
- Departments of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Claire Malley
- Departments of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Joanna Schaenman
- Departments of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- Departments of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. .,Departments of Surgery, University of California at Los Angeles, Los Angeles, CA, USA. .,Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA.
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26
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Long L, Li H, Deng G, Wang X, Lu S, Li B, Meng Z, Gao Y, Qian Z, Liu F, Lu X, Ren H, Shang J, Li H, Wang S, Zheng Y, Yan H, Yin S, Tan W, Zhang Q, Zheng X, Chen J, Luo S, Zhao J, Yuan W, Li T, Zheng R, Liu J, Liu X, Gu W, Li S, Mei X, Chen R, Huang Y. Impact of Hepatic Encephalopathy on Clinical Characteristics and Adverse Outcomes in Prospective and Multicenter Cohorts of Patients With Acute-on-Chronic Liver Diseases. Front Med (Lausanne) 2021; 8:709884. [PMID: 34409052 PMCID: PMC8365160 DOI: 10.3389/fmed.2021.709884] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/07/2021] [Indexed: 12/18/2022] Open
Abstract
Importance: Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear. Objective: We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases. Design: We conducted a cohort study of two multicenter prospective cohorts. Setting: China. Participants: Acute-on-chronic liver disease patients with various etiologies. Exposure: The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale. Main Outcome Measure: The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients. Results: A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1–4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1–2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures. Conclusions and Relevance: Hepatic encephalopathy grades 3–4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.
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Affiliation(s)
- Liyuan Long
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Hai Li
- Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.,Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China.,Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
| | - Guohong Deng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xianbo Wang
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Sihong Lu
- Department of Infectious Diseases, Institute of Infection and Immunology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Beiling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhongji Meng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yanhang Gao
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Zhiping Qian
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Feng Liu
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Hepatology, Tianjin Institute of Hepatology, Nankai University Second People's Hospital, Tianjin, China.,Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Xiaobo Lu
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Haotang Ren
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Hai Li
- Department of Infectious Diseases, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin, China
| | - Shaoyang Wang
- Department of Infectious Diseases, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China
| | - Yubao Zheng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huadong Yan
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Hepatology, Ningbo No. 2 Hospital, Ningbo, China
| | - Shan Yin
- Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.,Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Wenting Tan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xin Zheng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Department of Infectious Diseases, Institute of Infection and Immunology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Jinjun Chen
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China.,Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Sen Luo
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Jinming Zhao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Wei Yuan
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Tao Li
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Rongjiong Zheng
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Junping Liu
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Xiaoxiao Liu
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Wenyi Gu
- Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.,Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Sumeng Li
- Department of Infectious Diseases, Institute of Infection and Immunology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Xue Mei
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Ruochan Chen
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.,Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
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27
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Gajendran M, Umapathy C, Perisetti A, Loganathan P, Dwivedi A, Alvarado LA, Zuckerman MJ, Goyal H, Elhanafi S. Nationwide analysis of incidence and predictors of 30-day readmissions in patients with decompensated cirrhosis. Frontline Gastroenterol 2021; 13:295-302. [PMID: 35722599 PMCID: PMC9186038 DOI: 10.1136/flgastro-2021-101850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 06/08/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Cirrhosis is the number one cause of non-cancer deaths among gastrointestinal diseases and is responsible for significant morbidity and healthcare utilisation. The objectives were to measure the 30-day readmissions rate following index hospitalisation, to determine the predictors of readmission, and to estimate the cost of 30-day readmission in patients with decompensated cirrhosis. METHODS We performed a retrospective cohort study of patients with decompensated cirrhosis using 2014 Nationwide Readmission Database from January to November. Decompensated cirrhosis was identified based on the presence of at least one of the following: ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis and hepatorenal syndrome. We excluded patients less than 18 years of age, pregnant patients, patients with missing length of stay data, and those who died during the index admission. RESULTS Among 57 305 unique patients with decompensated cirrhosis, the 30-day readmission rate was 23.2%. The top three predictors of 30-day readmission were leaving against medical advice (AMA), ascites and acute kidney injury, which increased the risk of readmission by 47%, 22% and 20%, respectively. Index admission for variceal bleeding was associated with a lower 30-day readmission rate by 18%. The estimated total cost associated with 30-day readmission in our study population was US$234.4 million. CONCLUSION In a nationwide population study, decompensated cirrhosis is associated with a 30-day readmission rate of 23%. Leaving AMA, ascites and acute kidney injury are positively associated with readmission. Targeted interventions and quality improvement efforts should be directed toward these potential risk factors to reduce readmissions.
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Affiliation(s)
- Mahesh Gajendran
- Paul L Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA,Gastroenterology, UT Health San Antonio Long School of Medicine, San Antonio, Texas, USA
| | - Chandraprakash Umapathy
- Gastroenterology and Nutrition, UT Health San Antonio Long School of Medicine, San Antonio, Texas, USA
| | - Abhilash Perisetti
- Department of Gastroenterology and Hepatology, UAMS, Little Rock, Arkansas, USA
| | - Priyadarshini Loganathan
- Department of Medicine, Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Alok Dwivedi
- Biostatistics and Epidemiology, Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Luis A Alvarado
- Biostatistics and Epidemiology, Texas Tech University Health Sciences Center El Paso Paul L Foster School of Medicine, El Paso, Texas, USA
| | - Marc J Zuckerman
- Paul L Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA
| | - Hemant Goyal
- Gastroenterology, Wright Center for Graduate Medical Education, Scranton, Pennsylvania, USA
| | - Sherif Elhanafi
- Paul L Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA
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28
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Hyde AM, Watt M, Carbonneau M, Eboreime EA, Abraldes JG, Tandon P. Understanding Preferences Toward Virtual Care: A Pre-COVID Mixed Methods Study Exploring the Perspectives of Patients with Chronic Liver Disease. Telemed J E Health 2021; 28:407-414. [PMID: 34085869 DOI: 10.1089/tmj.2021.0099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background: Traditionally, outpatient visits for those with chronic liver disease (CLD) have been delivered in-person with the patient traveling to a centralized location to see the health care provider. The use of virtual care in health care delivery has been gaining popularity across a variety of patient populations, especially within the COVID-19 context. Performed before COVID-19, the aim of the present study was to explore the perspectives of patients with CLD toward the use of virtual care with their liver specialists. Methods: A cross-sectional, mixed methods study was used to conduct this work. Results: A total of 101 patients with CLD participated in this study. Participants had a mean age of 54.5 years (range 19-87 years). Quantitative analysis revealed that 86% were willing to attend a virtual visit with their liver specialist in the future. There was a significant relationship between both age and income level and acceptance of virtual care. The themes emerging from the qualitative analysis included: (1) past experiences attending in-person visits, (2) perspectives on the use of virtual visits, and (3) perceived challenges of virtual visits. Conclusions: Although there are many potential benefits of virtual care to both the patient and the health care system, there are instances (older age, low income level) when in-person care may be preferred by patients. A tailored approach that is mindful of the individual patient's health status, ease of access to technology, and preferences must be considered when offering virtual care. These findings are of particular relevance during COVID-19, an era that has forced us into the virtual space.
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Affiliation(s)
- Ashley M Hyde
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Makayla Watt
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Michelle Carbonneau
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.,Alberta Health Services, Edmonton, Canada
| | - Ejemai Amaize Eboreime
- Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Juan G Abraldes
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.,Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Canada
| | - Puneeta Tandon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.,Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Canada
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29
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Salman AA, Kasem MF, Kholaif KM, Ramadan M, Yousef M, Shaaban HE, Atallah M, El Sherbiny M, Ashoush O, Seif El Nasr SM. Outcomes of pregnancy in Child A liver cirrhotic patients: A retrospective multicenter study. ADVANCES IN DIGESTIVE MEDICINE 2021. [DOI: 10.1002/aid2.13205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
| | - Mohamed Fikry Kasem
- Faculty of Medicine Gynecology and Obstetrics Department, Cairo University Giza Egypt
| | - Khaled M. Kholaif
- Faculty of Medicine Gynecology and Obstetrics Department, Cairo University Giza Egypt
| | - Mohamed Ramadan
- Faculty of Medicine Gynecology and Obstetrics Department, Cairo University Giza Egypt
| | - Mohamed Yousef
- Faculty of Medicine Tropical Medicine Department, Cairo University Giza Egypt
| | - Hossam El‐Din Shaaban
- Gastroenterology Department National Hepatology and Tropical Medicine Research Institute Cairo Egypt
| | - Mohamed Atallah
- Gastroenterology Department National Hepatology and Tropical Medicine Research Institute Cairo Egypt
| | | | - Omar Ashoush
- Faculty of Medicine Internal Medicine Department, Cairo University Giza Egypt
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30
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Moghe A, Yakovchenko V, Morgan T, McCurdy H, Scott D, Rozenberg-Ben-Dror K, Rogal S. Strategies to Improve Delivery of Cirrhosis Care. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2021; 19:369-379. [PMID: 34054289 PMCID: PMC8142883 DOI: 10.1007/s11938-021-00345-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 03/16/2021] [Indexed: 11/18/2022]
Abstract
Purpose of review This review provides an overview of the current state of research around improving healthcare delivery for patients with cirrhosis in the outpatient, inpatient, and transitional care settings. Recent findings Recent studies have broadly employed changes to the model of care delivery, team composition, and technology to improve cirrhosis care. In the outpatient setting, approaches have included engaging caregivers, patient navigators, and non-physicians and using virtual care, smartphone applications, and wearables. Inpatient care approaches have focused on the role of interdisciplinary teams, education interventions, and changes to the medical record system, while post-discharge interventions have included day hospitals and care coordinator interventions. This review also describes the Veterans Health Administration's novel, population-level approach to delivery of cirrhosis care, and addressed how the pandemic has impacted the delivery of cirrhosis care. Summary Comprehensive, evidence-based approaches to delivering high-quality cirrhosis care continue to evolve to meet the needs of a growing population in an ever-changing healthcare environment.
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Affiliation(s)
- Akshata Moghe
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA USA
| | - Vera Yakovchenko
- Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Hospital, Bedford, MA USA
| | - Timothy Morgan
- Gastroenterology Section, VA Long Beach Healthcare System, Long Beach, CA USA
- Division of Gastroenterology, Department of Medicine, University of California, Irvine, CA USA
| | | | - Dawn Scott
- Central Texas Veterans Healthcare System, Temple, TX USA
| | | | - Shari Rogal
- Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Research Office Building (151R), University Drive C, Pittsburgh, PA 15240 USA
- Departments of Medicine and Surgery, University of Pittsburgh, Pittsburgh, PA USA
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31
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Zhao L, Mehmood A, Yuan D, Usman M, Murtaza MA, Yaqoob S, Wang C. Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds. Nutrients 2021; 13:nu13051612. [PMID: 34064981 PMCID: PMC8151346 DOI: 10.3390/nu13051612] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/06/2021] [Accepted: 05/08/2021] [Indexed: 12/13/2022] Open
Abstract
Alcoholic liver disease (ALD) is one type of liver disease, causing a global healthcare problem and mortality. The liver undergoes tissue damage by chronic alcohol consumption because it is the main site for metabolism of ethanol. Chronic alcohol exposure progresses from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which further lead to fibrosis, cirrhosis, and even hepatocellular cancer. Therapeutic interventions to combat ALD are very limited such as use of corticosteroids. However, these therapeutic drugs are not effective for long-term usage. Therefore, additional effective and safe therapies to cope with ALD are urgently needed. Previous studies confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. In this review article, we summarized the hepatoprotective potential of edible food plants and their bioactive compounds. The underlying mechanism for the prevention of ALD by edible food plants was as follows: anti-oxidation, anti-inflammation, lipid regulation, inhibition of apoptosis, gut microbiota composition modulation, and anti-fibrosis.
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Affiliation(s)
- Liang Zhao
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Arshad Mehmood
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Dongdong Yuan
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
- Correspondence: ; Tel.: +86-10-6898-4547
| | - Muhammad Usman
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Mian Anjum Murtaza
- Institute of Food Science and Nutrition, University of Sargodha, Sargodha 40100, Pakistan;
| | - Sanabil Yaqoob
- Department of Food Science and Technology, University of Central Punjab, Punjab 54590, Pakistan;
| | - Chengtao Wang
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
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32
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Sheu MJ, Liang FW, Lin CY, Lu TH. Changes in liver-related mortality by etiology and sequelae: underlying versus multiple causes of death. Popul Health Metr 2021; 19:22. [PMID: 33926463 PMCID: PMC8082829 DOI: 10.1186/s12963-021-00249-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/31/2021] [Indexed: 01/14/2023] Open
Abstract
Background The expanded definition of liver-related deaths includes a wide range of etiologies and sequelae. We compared the changes in liver-related mortality by etiology and sequelae for different age groups between 2008 and 2018 in the USA using both underlying and multiple cause of death (UCOD and MCOD) data. Methods We extracted mortality data from the CDC WONDER. Both the absolute (rate difference) and relative (rate ratio and 95% confidence intervals) changes were calculated to quantify the magnitude of change using the expanded definition of liver-related mortality. Result Using the expanded definition including secondary liver cancer and according to UCOD data, we identified 68,037 liver-related deaths among people aged 20 years and above in 2008 (29 per 100,000) and this increased to 90,635 in 2018 (33 per 100,000), a 13% increase from 2008 to 2018. However, according to MCOD data, the number of deaths was 113,219 (48 per 100,000) in 2008 and increased to 161,312 (58 per 100,000) in 2018, indicating a 20% increase. The increase according to MCOD was mainly due to increase in alcoholic liver disease and secondary liver cancer (liver metastasis) for each age group and hepatitis C virus (HCV) and primary liver cancer among decedents aged 65–74 years. Conclusion The direction of mortality change (increasing or decreasing) was similar in UCOD and MCOD data in most etiologies and sequelae, except secondary liver cancer. However, the extent of change differed between UCOD and MCOD data.
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Affiliation(s)
- Ming-Jen Sheu
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan.,Department of Medicinal Chemistry, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Fu-Wen Liang
- Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Yih Lin
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan
| | - Tsung-Hsueh Lu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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33
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Ahmed OM, AbouZid SF, Ahmed NA, Zaky MY, Liu H. An Up-to-Date Review on Citrus Flavonoids: Chemistry and Benefits in Health and Diseases. Curr Pharm Des 2021; 27:513-530. [PMID: 33245267 DOI: 10.2174/1381612826666201127122313] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 08/09/2020] [Indexed: 11/22/2022]
Abstract
Flavonoids, the main class of polyphenols, are characterized by the presence of 2-phenyl-benzo-pyrane nucleus. They are found in rich quantities in citrus fruits. Citrus flavonoids are classified into flavanones, flavones, flavonols, polymethoxyflavones and anthocyanins (found only in blood oranges). Flavanones are the most abundant flavonoids in citrus fruits. In many situations, there are structure-function relationships. Due to their especial structures and presence of many hydroxyls, polymethoxies and glycoside moiety, the flavonoids have an array of multiple biological and pharmacological activities. This article provides an updated overview of the differences in chemical structures of the classes and members of citrus flavonoids and their benefits in health and diseases. The review article also sheds light on the mechanisms of actions of citrus flavonoids in the treatment of different diseases, including arthritis, diabetes mellitus, cancer and neurodegenerative disorders as well as liver, kidney and heart diseases. The accumulated and updated knowledge in this review may provide useful information and ideas in the discovery of new strategies for the use of citrus flavonoids in the protection, prevention and therapy of diseases.
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Affiliation(s)
- Osama M Ahmed
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt
| | - Sameh F AbouZid
- Pharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Noha A Ahmed
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt
| | - Mohamed Y Zaky
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt
| | - Han Liu
- Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
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Zhang L, Zhou X, Dai Y, Lv C, Wu J, Wu Q, Li T, Wang Y, Xia P, Pei H, Huang B. Establishment of interleukin-18 time-resolved fluorescence immunoassay and its preliminary application in liver disease. J Clin Lab Anal 2021; 35:e23758. [PMID: 33720453 PMCID: PMC8128310 DOI: 10.1002/jcla.23758] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 02/01/2021] [Accepted: 02/27/2021] [Indexed: 12/30/2022] Open
Abstract
Background To establish a time‐resolved fluorescence immunoassay of interleukin (IL)‐18 (IL‐18‐TRFIA) and detect its concentration in different liver disease serum samples. Methods The IL‐18 coating antibody and the Eu3+‐labeled detection antibody were used for the IL‐18‐TRFIA to detect serum IL‐18 concentration in patients with liver cancer, hepatitis B, hepatitis C, autoimmune hepatitis, fatty liver disease, and healthy controls. The double‐antibody sandwich method was used and methodological evaluation was performed. Results The average intra‐ and inter‐assay coefficient of variation for IL‐18‐TRFIA was 4.80% and 5.90%, respectively. The average recovery rate was 106.19 ± 3.44%. The sensitivity (10.96 pg/mL) was higher than that obtained using the ELISA method (62.5 pg/mL). The detection range was 10.96–1000 pg/mL. IL‐6 and galectin‐3 did not cross‐react with IL‐18‐TRFIA. The serum concentration of IL‐18 was (776.99; 653.48–952.39 pg/mL) in hepatitis C, (911; 775.55–1130.03 pg/mL) in fatty liver, (1048.88; 730.04–1185.10 pg/mL) in liver cancer, and (949.12; 723.70–1160.28 pg/mL) in hepatitis B. Moreover, IL‐18 serum levels were significantly higher in patients than the healthy controls (483.09; 402.52–599.70/mL) (p < 0.0001). Autoimmune hepatitis with a serum IL‐18 concentration of 571.62; 502.47–730.31 pg/mL was not significantly different from the healthy controls (p > 0.05). Conclusion We established a highly sensitive IL‐18‐TRFIA method that successfully detected serum IL‐18 concentrations in different liver diseases. Furthermore, IL‐18 serum concentration was higher in patients with liver cancer, hepatitis C, hepatitis B, and fatty liver disease compared to healthy controls.
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Affiliation(s)
- Li Zhang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Xiumei Zhou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Yaping Dai
- Wuxi No. 5 People's Hospital, Wuxi, China
| | - Chunyan Lv
- Wuxi No. 5 People's Hospital, Wuxi, China
| | - Jian Wu
- Department of Laboratory Medicine, The First People's Hospital of Yancheng City, Yancheng, China
| | - Qingqing Wu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Ting Li
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Yigang Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Penguo Xia
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Hao Pei
- Wuxi No. 5 People's Hospital, Wuxi, China
| | - Biao Huang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
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35
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Wei X, Ma Y, Dong Z, Wang G, Lan X, Liao Z, Chen M. Dehydrodiconiferyl alcohol, a lignan from Herpetospermum pedunculosum, alleviates cholestasis by activating pathways associated with the farnesoid X receptor. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 80:153378. [PMID: 33113499 DOI: 10.1016/j.phymed.2020.153378] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 09/07/2020] [Accepted: 10/11/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND In our previous study, we demonstrated the hepatoprotective effect of Herpetospermum pedunculosum in cholestatic rats. A bioassay-guided study also led to the identification and isolation of a lignan, dihydrodiconiferyl alcohol (DA) from the seeds of H. pedunculosum. PURPOSE To investigate whether DA could alleviate cholestasis and determine the mechanisms underlying such action. METHODS Male Sprague-Dawley (SD) rats were administered with DA (10, 20 or 40 mg/kg) intragastrically once daily for 7 days prior to treatment with α-naphthylisothiocyanate (ANIT) (60 mg/kg). We then evaluated the levels of a range of serum indicators, determined bile flow, and carried out histopathological analyses. Western blotting was then used to investigate the levels of inflammatory mediators and the Farnesoid X Receptor (FXR), proteins involved in the downstream biosynthesis of bile acids, and a range of transport proteins. Molecular docking was used to simulate the interaction between DA and FXR. Cell viability of human hepatocytes (L-02) cells was determined by MTT. Then, we treated guggulsterone-inhibited L-02 cells, Si-FXR L-02 cells, and FXR-overexpression cells with the FXR agonist GW4064 (6 μM) or DA (25, 50 and 100 μM) for 24 h before detecting gene and protein expression by RT-PCR and western blotting, respectively. RESULTS DA significantly attenuated ANIT-induced cholestasis in SD rats by reducing liver function indicators in the serum, increasing bile flow, improving the recovery of histopathological injuries in the liver, and by alleviating pro-inflammatory cytokines in the liver. DA also increased the expression levels of FXR and altered the levels of downstream proteins in the liver tissues, thus indicating that DA might alleviate cholestasis by regulating the FXR. Molecular docking simulations predicted that DA was as an agonist of FXR. In vitro mechanical studies further showed that DA increased the mRNA and protein expression levels of FXR, Small Heterodimer Partner 1/2, Bile Salt Export Pump, Multidrug Resistance-associated Protein 2, and Na+/taurocholate Co-transporting Polypeptide, in both guggulsterone-inhibited and Si-FXR L-02 cells. Moreover, DA enhanced the mRNA and protein expression of FXR, and its downstream genes and proteins, in L-02 cells containing an FXR-overexpression plasmid. CONCLUSION DA may represent an effective agonist for FXR has significant therapeutic potential for the treatment of cholestatic liver injury.
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MESH Headings
- 1-Naphthylisothiocyanate/toxicity
- ATP Binding Cassette Transporter, Subfamily B, Member 11/metabolism
- Animals
- Bile/metabolism
- Bile Acids and Salts/metabolism
- Cholestasis, Intrahepatic/chemically induced
- Cholestasis, Intrahepatic/drug therapy
- Cholestasis, Intrahepatic/metabolism
- Cholestasis, Intrahepatic/pathology
- Cucurbitaceae/chemistry
- Hepatocytes/drug effects
- Humans
- Isoxazoles/pharmacology
- Liver/drug effects
- Liver/metabolism
- Liver/pathology
- Male
- Molecular Docking Simulation
- Phenols/chemistry
- Phenols/pharmacology
- Rats, Sprague-Dawley
- Receptors, Cytoplasmic and Nuclear/agonists
- Receptors, Cytoplasmic and Nuclear/chemistry
- Receptors, Cytoplasmic and Nuclear/genetics
- Receptors, Cytoplasmic and Nuclear/metabolism
- Rats
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Affiliation(s)
- Xiaodong Wei
- College of Pharmaceutical Sciences, Southwest University, No.2 Tiansheng Road, Chongqing 400715, PR China
| | - Yingxiong Ma
- College of Pharmaceutical Sciences, Southwest University, No.2 Tiansheng Road, Chongqing 400715, PR China
| | - Zhaoyue Dong
- College of Pharmaceutical Sciences, Southwest University, No.2 Tiansheng Road, Chongqing 400715, PR China
| | - Guowei Wang
- College of Pharmaceutical Sciences, Southwest University, No.2 Tiansheng Road, Chongqing 400715, PR China
| | - Xiaozhong Lan
- TAAHC-SWU Medicinal Plant R&D Center, Xizang Agriculture and Animal Husbandry College, Nyingchi, Tibet, PR China
| | - Zhihua Liao
- School of Life Sciences, Southwest University, Chongqing 400715, PR China
| | - Min Chen
- College of Pharmaceutical Sciences, Southwest University, No.2 Tiansheng Road, Chongqing 400715, PR China.
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Bloom PP, Miller SJ, Nayak RK, Hussain MS, Arvind A, Bay C, Chung RT. Cognitive Tests and Stool Frequency at Hospital Discharge Do Not Predict Outcomes in Hepatic Encephalopathy. South Med J 2020; 113:578-584. [PMID: 33140112 DOI: 10.14423/smj.0000000000001172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Hepatic encephalopathy (HE) is associated with hospital readmissions and mortality. We sought to determine whether cognitive testing and stool frequency at discharge predicted 30-day readmission or death in cirrhotic patients admitted with overt HE. METHODS We approached consecutive inpatients with cirrhosis and overt HE when they were within 48 hours of discharge. Patients underwent cognitive tests, including Psychometric Hepatic Encephalopathy Score (PHES), and stool frequency was documented. Chart review identified Model for End-Stage Liver Disease-sodium (MELD-Na) and the presence of non-HE extrahepatic organ failures. Cox proportional hazards models were used to evaluate predictors of time to the primary composite outcome of hospital readmission for HE or death within 30 days, censoring for liver transplantation. RESULTS Of 51 patients consented and enrolled, 14 patients met the primary composite outcome. In unadjusted Cox models, 4 variables predicted HE readmission or death: MELD-Na (hazard ratio [HR] 1.10 [1.01-1.20], P = 0.03), respiratory failure (HR 4.26 [1.47-12.35], P = 0.008), total number of HE extrahepatic organ failures (HR 1.79 [1.12-2.88], P = 0.02), and score on a PHES subtest, Number Connection Test A (per 30 seconds; HR 1.25 [1.06-1.47], P = 0.01). PHES and 24-hour stool frequency did not predict the primary outcome. When controlling for MELD-Na, respiratory failure predicted the primary outcome (HR 3.67 [1.24-10.86], P = 0.02). CONCLUSION Cognitive testing and stool frequency at discharge did not predict poor outcomes in patients admitted with HE, while respiratory failure appeared to be a strong predictor.
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Affiliation(s)
- Patricia P Bloom
- From the Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, and the Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts
| | - Samuel J Miller
- From the Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, and the Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts
| | - Rahul K Nayak
- From the Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, and the Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts
| | - Muhammad Sarib Hussain
- From the Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, and the Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts
| | - Ashwini Arvind
- From the Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, and the Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts
| | - Camden Bay
- From the Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, and the Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts
| | - Raymond T Chung
- From the Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, and the Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts
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Bajaj JS, Reddy KR, O'Leary JG, Vargas HE, Lai JC, Kamath PS, Tandon P, Wong F, Subramanian RM, Thuluvath P, Fagan A, White MB, Gavis EA, Sehrawat T, de la Rosa Rodriguez R, Thacker LR, Sikaroodi M, Garcia-Tsao G, Gillevet PM. Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis. Gastroenterology 2020; 159:1715-1730.e12. [PMID: 32687928 PMCID: PMC7680282 DOI: 10.1053/j.gastro.2020.07.019] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 07/02/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Inpatients with cirrhosis have high rates of acute-on-chronic failure (ACLF) development and high mortality within 30 days of admission to the hospital. Better biomarkers are needed to predict these outcomes. We performed metabolomic analyses of serum samples from patients with cirrhosis at multiple centers to determine whether metabolite profiles might identify patients at high risk for ACLF and death. METHODS We performed metabolomic analyses, using liquid chromatography, of serum samples collected at time of admission to 12 North American tertiary hepatology centers from 602 patients in the North American Consortium for the Study of End-Stage Liver Disease sites from 2015 through 2017 (mean age, 56 years; 61% men; mean model for end-stage liver disease score, 19.5). We performed analysis of covariance, adjusted for model for end-stage liver disease at time of hospital admission, serum levels of albumin and sodium, and white blood cell count, to identify metabolites that differed between patients who did vs did not develop ACLF and patients who did vs did not die during hospitalization and within 30 days. We performed random forest analysis to identify specific metabolite(s) that were associated with outcomes and area under the curve (AUC) analyses to analyze them in context of clinical parameters. We analyzed microbiomes of stool samples collected from 133 patients collected at the same time and examined associations with serum metabolites. RESULTS Of the 602 patients analyzed, 88 developed ACLF (15%), 43 died in the hospital (7%), and 72 died within 30 days (12%). Increased levels of compounds of microbial origin (aromatic compounds, secondary or sulfated bile acids, and benzoate) and estrogen metabolites, as well as decreased levels of phospholipids, were associated with development of ACLF, inpatient, and 30-day mortality and were also associated with fecal microbiomes. Random forest analysis and logistic regression showed that levels of specific microbially produced metabolites identified patients who developed ACLF with an AUC of 0.84 (95% confidence interval [CI] 0.78-0.88; P = .001), patients who died while in the hospital with an AUC of 0.81 (95% CI 0.74-0.85; P = .002), and patients who died within 30 days with an AUC of 0.77 (95% CI 0.73-0.81; P = .02). The metabolites were significantly additive to clinical parameters for predicting these outcomes. Metabolites associated with outcomes were also correlated with microbiomes of stool samples. CONCLUSIONS In an analysis of serum metabolites and fecal microbiomes of patients hospitalized with cirrhosis at multiple centers, we associated metabolites of microbial origin and lipid moieties with development of ACLF and death as an inpatient or within 30 days, after controlling for clinical features.
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Affiliation(s)
- Jasmohan S Bajaj
- Department of Medicine, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia.
| | - K Rajender Reddy
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Hugo E Vargas
- Department of Medicine, Mayo Clinic, Phoenix, Arizona
| | - Jennifer C Lai
- Department of Medicine, University of California, San Francisco, California
| | | | - Puneeta Tandon
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Florence Wong
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | | | - Paul Thuluvath
- Department of Medicine, Mercy Medical Center, Baltimore, Maryland
| | - Andrew Fagan
- Department of Medicine, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Melanie B White
- Department of Medicine, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | - Edith A Gavis
- Department of Medicine, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia
| | | | | | - Leroy R Thacker
- Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia
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cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease. Biomolecules 2020; 10:biom10101433. [PMID: 33050657 PMCID: PMC7600246 DOI: 10.3390/biom10101433] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/07/2020] [Accepted: 10/08/2020] [Indexed: 02/07/2023] Open
Abstract
The importance of cyclic adenosine monophosphate (cAMP) in cellular responses to extracellular signals is well established. Many years after discovery, our understanding of the intricacy of cAMP signaling has improved dramatically. Multiple layers of regulation exist to ensure the specificity of cellular cAMP signaling. Hence, disturbances in cAMP homeostasis could arise at multiple levels, from changes in G protein coupled receptors and production of cAMP to the rate of degradation by phosphodiesterases. cAMP signaling plays critical roles in metabolism, inflammation and development of fibrosis in several tissues. Alcohol-associated liver disease (ALD) is a multifactorial condition ranging from a simple steatosis to steatohepatitis and fibrosis and ultimately cirrhosis, which might lead to hepatocellular cancer. To date, there is no FDA-approved therapy for ALD. Hence, identifying the targets for the treatment of ALD is an important undertaking. Several human studies have reported the changes in cAMP homeostasis in relation to alcohol use disorders. cAMP signaling has also been extensively studied in in vitro and in vivo models of ALD. This review focuses on the role of cAMP in the pathobiology of ALD with emphasis on the therapeutic potential of targeting cAMP signaling for the treatment of various stages of ALD.
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Spiewak T, Taefi A, Patel S, Li CS, Chak E. Racial disparities of Black Americans hospitalized for decompensated liver cirrhosis. BMC Gastroenterol 2020; 20:245. [PMID: 32727386 PMCID: PMC7391571 DOI: 10.1186/s12876-020-01392-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Accepted: 07/21/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Racial disparities have been reported in liver transplantation and chronic hepatitis C treatment outcomes. Determining causes of these disparities is important given the racially diverse American population and the economic burden associated with chronic liver disease. METHODS A retrospective study was performed among 463 patients diagnosed with cirrhosis admitted from (January 1, 2013 to January 1, 2018) to a tertiary care academic medical center. Patients were identified based on the International Classification of Diseases (ICD-10) for cirrhosis or its complications. Demographic information, laboratory data, medical comorbidities, insurance and adherence to cirrhosis quality care indicators were recorded to determine their relationship to readmission rates and other healthcare outcomes. RESULTS A total of 463 individual patients with cirrhosis were identified including Whites (n = 241), Hispanics (n = 106), Blacks (n = 50), Asian and Pacific Islander Americans (API, n = 27) and Other (n = 39). A significantly higher proportion of Blacks had Medicaid insurance compared to Whites (40% versus 20%, p = 0.0002) and Blacks had lower median income than Whites ($45,710 versus $54,844, p = 0.01). All groups received high quality cirrhosis care. Regarding healthcare outcomes, Black patients had the highest mean total hospital admissions (6.1 ± 6.3, p = 0.01) and the highest mean number of 30-day re-admissions (2.1 ± 3.7, p = 0.05) compared to all other racial groups. Multivariable proportional odds regression analysis showed that race was a statistically significant predictor of 90-day readmission (p = 0.03). CONCLUSIONS Black Americans hospitalized for complications of cirrhosis may experience significant disparities in healthcare outcomes compared to Whites despite high quality cirrhosis care. Socioeconomic factors may contribute to these disparities.
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Affiliation(s)
- Ted Spiewak
- Department of Internal Medicine, UC Davis Medical Center, Sacramento, California, USA
| | - Amir Taefi
- Department of Gastroenterology and Hepatology, UC Davis Medical Center, 4150 V Street, PSSB 3500, Sacramento, CA, 95817, USA
| | - Shruti Patel
- Department of Internal Medicine, UC Davis Medical Center, Sacramento, California, USA
| | - Chin-Shang Li
- School of Nursing, The State University of New York at Buffalo, Buffalo, New York, USA
| | - Eric Chak
- Department of Gastroenterology and Hepatology, UC Davis Medical Center, 4150 V Street, PSSB 3500, Sacramento, CA, 95817, USA.
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Biological Effects of Korean Red Ginseng Polysaccharides in Aged Rat Using Global Proteomic Approach. Molecules 2020; 25:molecules25133019. [PMID: 32630349 PMCID: PMC7412055 DOI: 10.3390/molecules25133019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/20/2020] [Accepted: 06/29/2020] [Indexed: 01/07/2023] Open
Abstract
Much has been written on the physiological benefits of Korean Red Ginseng (KRG). Among its various components, ginsenosides have been widely investigated for their various pharmacological effects. However, polysaccharides are a major KRG component that has not received scrutiny similar to that of ginsenosides. The present study aims to fill that gap in the existing literature and to investigate the possible functions of polysaccharide in KRG. The researchers evaluated proteomic changes in non-saponin fractions with rich polysaccharides (NFP) in KRG. Based on the serum analysis, proteomics analysis of the liver and the spleen was additionally conducted to identify related functions. We validated the suggested functions of NFP with the galactosamine-induced liver injury model and the cyclophosphamide-induced immunosuppression model. Then, we evaluated the antimetastatic potential of NFP in the lungs. Further proteomics analysis of the spleen and liver after ingestion confirmed functions related to immunity, cancer, hepatoprotection, and others. Then, we validated the suggested corresponding functions of the NFP in vivo model. NFP showed immune-enhancing effects, inhibited melanoma cell metastasis in the lung, and decreased liver damage. The results show that using the proteomic approach uncovers the potential effects of polysaccharides in KRG, which include enhancing the immune system and protecting the liver.
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Carbonneau M, Eboreime EA, Hyde A, Campbell-Scherer D, Faris P, Gramlich L, Tsuyuki RT, Congly SE, Shaheen AA, Sadler M, Zeman M, Spiers J, Abraldes JG, Sugars B, Sia W, Green L, Abdellatif D, Schaefer JP, Selvarajah V, Marr K, Ryan D, Westra Y, Bakshi N, Varghese JC, Tandon P. The cirrhosis care Alberta (CCAB) protocol: implementing an evidence-based best practice order set for the management of liver cirrhosis - a hybrid type I effectiveness-implementation trial. BMC Health Serv Res 2020; 20:558. [PMID: 32552833 PMCID: PMC7301349 DOI: 10.1186/s12913-020-05427-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Liver cirrhosis is a leading cause of morbidity, premature mortality and acute care utilization in patients with digestive disease. In the province of Alberta, hospital readmission rates for patients with cirrhosis are estimated at 44% at 90 days. For hospitalized patients, multiple care gaps exist, the most notable stemming from i) the lack of a structured approach to best practice care for cirrhosis complications, ii) the lack of a structured approach to broader health needs and iii) suboptimal preparation for transition of care into the community. Cirrhosis Care Alberta (CCAB) is a 4-year multi-component pragmatic trial which aims to address these gaps. The proposed intervention is initiated at the time of hospitalization through implementation of a clinical information system embedded electronic order set for delivering evidence-based best practices under real-world conditions. The overarching objective of the CCAB trial is to demonstrate effectiveness and implementation feasibility for use of the order set in routine patient care within eight hospital sites in Alberta. METHODS A mixed methods hybrid type I effectiveness-implementation design will be used to evaluate the effectiveness of the order set intervention. The primary outcome is a reduction in 90-day cumulative length of stay. Implementation outcomes such as reach, adoption, fidelity and maintenance will also be evaluated alongside other patient and service outcomes such as readmission rates, quality of care and cost-effectiveness. This theory-based trial will be guided by Normalization Process Theory, Consolidated Framework on Implementation Research (CFIR) and the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) Framework. DISCUSSION The CCAB project is unique in its breadth, both in the comprehensiveness of the multi-component order set and also for the breadth of its roll-out. Lessons learned will ultimately inform the feasibility and effectiveness of this approach in "real-world" conditions as well as adoption and adaptation of these best practices within the rest of Alberta, other provinces in Canada, and beyond. TRIAL REGISTRATION ClinicalTrials.gov: NCT04149223, November 4, 2019.
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Affiliation(s)
- Michelle Carbonneau
- Alberta Health Services, Edmonton & Calgary, AB, Canada
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada
| | - Ejemai Amaize Eboreime
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada
| | - Ashley Hyde
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada
| | - Denise Campbell-Scherer
- Department of Family Medicine, University of Alberta, Edmonton, AB, Canada
- Office of Lifelong Learning and the Physician Learning Program, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Peter Faris
- Alberta Health Services, Edmonton & Calgary, AB, Canada
| | - Leah Gramlich
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada
| | - Ross T Tsuyuki
- Department of Medicine, Division of Cardiology, University of Alberta, Edmonton, AB, Canada
- Department of Pharmacology, University of Alberta, Edmonton, AB, Canada
| | - Stephen E Congly
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
- O'Brien Institute of Public Health, University of Calgary, Calgary, AB, Canada
| | - Abdel Aziz Shaheen
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
- O'Brien Institute of Public Health, University of Calgary, Calgary, AB, Canada
| | - Matthew Sadler
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
| | - Marilyn Zeman
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada
| | - Jude Spiers
- Faculty of Nursing, University of Alberta, Edmonton, AB, Canada
| | - Juan G Abraldes
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, AB, T6G2X8, Canada
| | - Benjamin Sugars
- Department of Medicine, Division of General Internal Medicine, University of Alberta, Edmonton, AB, Canada
| | - Winnie Sia
- Department of Medicine, Division of General Internal Medicine, University of Alberta, Edmonton, AB, Canada
| | - Lee Green
- Department of Family Medicine, University of Alberta, Edmonton, AB, Canada
| | - Dalia Abdellatif
- Department of Family Medicine, University of Alberta, Edmonton, AB, Canada
| | - Jeffrey P Schaefer
- Department of Medicine, Division of General Internal Medicine, University of Calgary, Calgary, AB, Canada
| | - Vijeyakumar Selvarajah
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada
| | - Kaleb Marr
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
| | - David Ryan
- Central Alberta Digestive Disease Specialists, Red Deer, AB, Canada
| | - Yolande Westra
- Department of Medicine, Division of General Internal Medicine, University of Alberta, Edmonton, AB, Canada
| | - Neeja Bakshi
- Department of Medicine, Division of General Internal Medicine, University of Alberta, Edmonton, AB, Canada
| | - Jayant C Varghese
- Department of Medicine, Division of General Internal Medicine, University of Alberta, Edmonton, AB, Canada
| | - Puneeta Tandon
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, AB, T6G2X8, Canada.
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, AB, T6G2X8, Canada.
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Yang Y, Ji J, Di L, Li J, Hu L, Qiao H, Wang L, Feng Y. Resource, chemical structure and activity of natural polysaccharides against alcoholic liver damages. Carbohydr Polym 2020; 241:116355. [PMID: 32507196 DOI: 10.1016/j.carbpol.2020.116355] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/11/2020] [Accepted: 04/19/2020] [Indexed: 12/19/2022]
Abstract
Many natural polysaccharides from bio-resources hold advantages of multi-functions, high efficiency, non-toxicity or low side effect, and have strong potentials in protection against alcoholic liver damages. This review summarized the bio-resources, chemical and structural characteristics of natural polysaccharides with potentials in inhibition against alcoholic liver damages, and also emphasized knowledge on correlations between their chemical structure and function. Approximately 95 species were confirmed in generation of hepatoprotective polysaccharides. Products as crude polysaccharides originated from 17 species were sum up despite the indetermination of their accurate structure. Additional four polysaccharides were described for their known chemical structures. Possible roles of hepatoprotective polysaccharides were provided with evidence on antioxidant promotion, lipids regulation, apoptosis inhibition and anti-inflammation, as well as confirmations in immune enhancement, iron removal and anti-fibrosis when currently treated against the alcoholic liver damages. To sum up, this overview could serve to guide development and utilization of natural hepatoprotective polysaccharides.
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Affiliation(s)
- Ying Yang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, 210023, PR China
| | - Jing Ji
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, 210023, PR China
| | - Liuqing Di
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, 210023, PR China
| | - Junsong Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, 210023, PR China
| | - Lihong Hu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, 210023, PR China
| | - Hongzhi Qiao
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, 210023, PR China
| | - Lingchong Wang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, 210023, PR China; School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
| | - Yibin Feng
- School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
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Hamaguchi M, Obora A, Okamura T, Hashimoto Y, Kojima T, Fukui M. Changes in metabolic complications in patients with alcoholic fatty liver disease monitored over two decades: NAGALA study. BMJ Open Gastroenterol 2020; 7:e000359. [PMID: 32337056 PMCID: PMC7170409 DOI: 10.1136/bmjgast-2019-000359] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 03/05/2020] [Accepted: 03/12/2020] [Indexed: 12/17/2022] Open
Abstract
Objective The social conditions are changing in the world, which may contribute to the change in lifestyle, including alcohol consumption and dietary intake; however, changes in metabolic complications in patients with alcoholic fatty liver disease (AFLD) have never been reported. Therefore, here we compare the metabolic complications in current AFLD with those of two decades ago. Methods We performed this cross-sectional study in a Japanese health check-up centre. Consecutive participants who visited the facilities between June 1994 and December 1997 or between January 2014 and December 2017 were enrolled. A total of 7499 participants (4804 men, 2695 women) in the past cohort and 20 029 participants (11 676 men, 8353 women) in the current cohort were entered to this study. Results The prevalence of drinkers in the current cohort was significantly lower (4.7%) than that in the past cohort in men (5.9%, p<0.001) but significantly higher in women (1.9% in the current vs 1.1% in the past, p<0.001). The prevalence of fatty liver in drinkers has increased in men (22.3% in the past cohort, 36.6% in the current cohort; p<0.001) but not in women (13.3% in the past cohort, 14.7% in the current cohort; p=1.0), while the prevalence of all fatty liver has increased in men and women (men: 24.0% in the past cohort, 36.2% in the current cohort, p<0.001; women: 9.3% in the past cohort, 12.8% in the current cohort, p<0.001). Regarding metabolic abnormalities, the prevalence of hyperglycaemia increased from 25.4% to 43.0% in men with AFLD (p<0.001) and from 25.1% to 39.1% in women with AFLD (p=1.0). Conclusions AFLD currently tends to be accompanied by hyperglycaemia. The prevalence of fatty liver in drinkers increased in men, although alcoholic consumptions did not increase. We should pay attention to fatty liver combined with hyperglycaemia for individuals who consume alcohol today.
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Affiliation(s)
- Masahide Hamaguchi
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akihiro Obora
- Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Takuro Okamura
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshitaka Hashimoto
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takao Kojima
- Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Michiaki Fukui
- Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Koola JD, Ho SB, Cao A, Chen G, Perkins AM, Davis SE, Matheny ME. Predicting 30-Day Hospital Readmission Risk in a National Cohort of Patients with Cirrhosis. Dig Dis Sci 2020; 65:1003-1031. [PMID: 31531817 PMCID: PMC7073276 DOI: 10.1007/s10620-019-05826-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 09/04/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Early hospital readmission for patients with cirrhosis continues to challenge the healthcare system. Risk stratification may help tailor resources, but existing models were designed using small, single-institution cohorts or had modest performance. AIMS We leveraged a large clinical database from the Department of Veterans Affairs (VA) to design a readmission risk model for patients hospitalized with cirrhosis. Additionally, we analyzed potentially modifiable or unexplored readmission risk factors. METHODS A national VA retrospective cohort of patients with a history of cirrhosis hospitalized for any reason from January 1, 2006, to November 30, 2013, was developed from 123 centers. Using 174 candidate variables within demographics, laboratory results, vital signs, medications, diagnoses and procedures, and healthcare utilization, we built a 47-variable penalized logistic regression model with the outcome of all-cause 30-day readmission. We excluded patients who left against medical advice, transferred to a non-VA facility, or if the hospital length of stay was greater than 30 days. We evaluated calibration and discrimination across variable volume and compared the performance to recalibrated preexisting risk models for readmission. RESULTS We analyzed 67,749 patients and 179,298 index hospitalizations. The 30-day readmission rate was 23%. Ascites was the most common cirrhosis-related cause of index hospitalization and readmission. The AUC of the model was 0.670 compared to existing models (0.649, 0.566, 0.577). The Brier score of 0.165 showed good calibration. CONCLUSION Our model achieved better discrimination and calibration compared to existing models, even after local recalibration. Assessment of calibration by variable parsimony revealed performance improvements for increasing variable inclusion well beyond those detectable for discrimination.
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Affiliation(s)
- Jejo D Koola
- Tennessee Valley Healthcare System (TVHS) VA Medical Center, Veterans Health Administration, Nashville, TN, USA.
- Division of Hospital Medicine, Department of Medicine, University of California, San Diego, CA, USA.
- Health System Department of Biomedical Informatics, University of California, San Diego, CA, USA.
| | - Sam B Ho
- VA San Diego Healthcare System, San Diego, CA, USA
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, CA, USA
- Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai, UAE
| | - Aize Cao
- Tennessee Valley Healthcare System (TVHS) VA Medical Center, Veterans Health Administration, Nashville, TN, USA
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Guanhua Chen
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA
| | - Amy M Perkins
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sharon E Davis
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael E Matheny
- Tennessee Valley Healthcare System (TVHS) VA Medical Center, Veterans Health Administration, Nashville, TN, USA
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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Telemedicine Based Remote Home Monitoring After Liver Transplantation: Results of a Randomized Prospective Trial. Ann Surg 2020; 270:564-572. [PMID: 31356267 DOI: 10.1097/sla.0000000000003425] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study assesses the impact of a telemedicine-based home management program (THMP) on patient adherence, hospital readmissions, and quality of life (QOL) after liver transplantation (LT). SUMMARY OF BACKGROUND DATA Telemedicine interventions represent an opportunity to personalize care and can lead to improved adherence and patient satisfaction. However, there is limited data on impact of these interventions on outcomes after LT. Therefore, we conducted the first randomized controlled trial (RCT) of a THMP compared to standard of care (SOC) after LT. METHODS One hundred six consecutive LT recipients were randomized (1:1) to 1 of 2 posttransplant care strategies: SOC or THMP. The THMP included an electronic tablet and bluetooth devices to support daily text messages, education videos, and video FaceTime capability; data was cyber-delivered into our electronic medical record daily. Endpoints were THMP participation, 90-day hospital readmission rate, and QOL. RESULTS One hundred patients completed the study with 50 enrolled in each arm. Participation and adherence with telemedicine was 86% for basic health sessions (vital sign recording), but only 45% for using messaging or FaceTime. The THMP group had a lower 90-day readmission rate compared to SOC (28% vs 58%; P = 0.004). The THMP cohort also showed improved QOL in regards to physical function (P = 0.02) and general health (P = 0.05) at 90 days. CONCLUSIONS To our knowledge, this is the first RCT demonstrating the impact of THMP after LT. The magnitude of effect on LT outcomes, hospital readmissions, and QOL suggests that the adoption of telemedicine has great potential for other major operations.
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Patel H, Balar B, Irigela M, Vootla V, Chandrala C, Hashmi H, Abdulsamad M, Makker J. Risk Factors for Liver Cirrhosis-Related Readmissions in the Largest Ethnic Minority in United States. Gastroenterology Res 2020; 13:11-18. [PMID: 32095168 PMCID: PMC7011917 DOI: 10.14740/gr1227] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 01/10/2020] [Indexed: 11/30/2022] Open
Abstract
Background There are very limited data available on 30-day readmissions for ethnic minority patients with cirrhosis. The aim of the study was to identify the risk factors for 30-day readmission in ethnic minority patients admitted for cirrhosis. Methods We did a retrospective review of 1,373 electronic medical records of patients with cirrhosis admitted from 2009 to 2011. Several parameters including alcohol use history, discharge location and cirrhosis severity scores - model for end-stage liver disease (MELD) score and Child-Pugh-Turcotte (CPT) at first admission were assessed. Statistical analysis was done using Chi-square test and t-test for categorical and continuous variables, respectively. Results There were 79 patients in the readmission group (63% male, 54% Hispanics and 22% African Americans) and 104 in the no readmission group (62% male, 58% Hispanics and 24% African Americans). History of alcohol use within a month prior to admission (55% vs. 33%, P = 0.002), platelet count at discharge (89,000 vs. 124,000, P = 0.003), and discharge with more than seven medications per day (7.3 vs. 5.2, P = 0.005) were identified as risk factors for readmissions by multivariate analysis. Conclusion Platelet count, active alcohol use and more than seven medications at discharge are predictors of readmission. These parameters can guide future interventions to reduce readmission rate and health care costs related to cirrhosis readmissions.
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Affiliation(s)
- Harish Patel
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
| | - Bhavna Balar
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
| | - Maheswara Irigela
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
| | - Vamshidhar Vootla
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
| | - Chaitanya Chandrala
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
| | - Hafiz Hashmi
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
| | - Molham Abdulsamad
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
| | - Jasbir Makker
- Department of Medicine, BronxCare Health System, 1650 Selwyn Ave., Bronx, NY 10457, USA
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Maassel NL, Fleming MM, Luo J, Zhang Y, Pei KY. Model for End-Stage Liver Disease Sodium as a Predictor of Surgical Risk in Cirrhotic Patients With Ascites. J Surg Res 2020; 250:45-52. [PMID: 32018142 DOI: 10.1016/j.jss.2019.12.037] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 12/11/2019] [Accepted: 12/30/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The Model for End-Stage Liver Disease Sodium (MELD-Na) incorporates hyponatremia into the MELD score and has been shown to correlate with surgical outcomes. The pathophysiology of hyponatremia parallels that of ascites, which purports greater surgical risk. This study investigates whether MELD-Na accurately predicts morbidity and mortality in patients with ascites undergoing general surgery procedures. MATERIALS AND METHODS We used the National Surgical Quality Improvement Program database (2005-2014) to examine the adjusted risk of morbidity and mortality of cirrhotic patients with and without ascites undergoing inguinal or ventral hernia repair, cholecystectomy, and lysis of adhesions for bowel obstruction. Patients were stratified by the MELD-Na score and ascites. Outcomes were compared between patients with and without ascites for each stratum using low MELD-Na and no ascites group as a reference. RESULTS A total of 30,391 patients were analyzed. Within each MELD-Na stratum, patients with ascites had an increased risk of complications compared with the reference group (low MELD-Na and no ascites): low MELD-Na with ascites odds ratio (OR) 4.33 (95% confidence interval [CI] 1.96-9.59), moderate MELD-Na no ascites OR 1.70 (95% CI 1.52-1.9), moderate MELD-Na with ascites OR 3.69 (95% CI 2.49-5.46), high MELD-Na no ascites OR 3.51 (95% CI 3.07-4.01), and high MELD-Na ascites OR 7.18 (95% CI 5.33-9.67). Similarly, mortality risk was increased in patients with ascites compared with the reference: moderate MELD-Na no ascites OR 3.55 (95% CI 2.22-5.67), moderate MELD-Na ascites OR 13.80 (95% CI 5.65-33.71), high MELD-Na no ascites OR 8.34 (95% CI 5.15-13.51), and high MELD-Na ascites OR 43.97 (95% CI 23.76-81.39). CONCLUSIONS MELD-Na underestimates morbidity and mortality risk for general surgery patients with ascites.
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Affiliation(s)
- Nathan L Maassel
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
| | - Matthew M Fleming
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut
| | - Jiajun Luo
- Section of Surgical Outcomes and Epidemiology, Department of Surgery, Yale School of Medicine, New Haven, Connecticut
| | - Yawei Zhang
- Section of Surgical Outcomes and Epidemiology, Department of Surgery, Yale School of Medicine, New Haven, Connecticut; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut
| | - Kevin Y Pei
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut; Department of Surgery, Weill Cornell Medical College, Houston Methodist Hospital, Houston, Texas
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Abstract
BACKGROUND AND AIMS Gender disparities exist in outcomes among patients with cirrhosis. We sought to evaluate the role of gender on hospital course and in-hospital outcomes in patients with cirrhosis to help better understand these disparities. STUDY We analyzed data from the National Inpatient Sample (NIS), years 2009 to 2013, to identify patients with any diagnosis of cirrhosis. We calculated demographic and clinical characteristics by gender, as well as cirrhosis complications. Our primary outcome was inpatient mortality. We used logistic regression to associate baseline characteristics and cirrhosis complications with inpatient mortality. RESULTS Our cohort included 553,017 patients with cirrhosis admitted from 2009 to 2013. Women made up 39% of the cohort; median age was 57 with 66% non-Hispanic white. Women were more likely than men to have noncirrhosis comorbidities, including diabetes and hypertension but were less likely to have most cirrhosis complications, including ascites and variceal bleeding. Women were more likely than men to have acute bacterial infections (34.9% vs. 28.2%; P<0.001), and were less likely than men to die in the hospital on univariable (odds ratio, 0.88; 95% confidence interval, 0.86-0.90; P<0.001) and multivariable (odds ratio, 0.86; 95% confidence interval, 0.83-0.88; P<0.001) analysis. CONCLUSIONS In patients hospitalized with cirrhosis, women have lower rates of hepatic decompensating events and higher rates of nonhepatic comorbidities and infections, resulting in lower in-hospital mortality. Understanding differences in indications for and disposition following hospitalization may help with the development of gender-specific cirrhosis management programs to improve long-term outcomes in women and men living with cirrhosis.
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Ginsenosides: potential therapeutic source for fibrosis-associated human diseases. J Ginseng Res 2019; 44:386-398. [PMID: 32372860 PMCID: PMC7195584 DOI: 10.1016/j.jgr.2019.12.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 10/25/2019] [Accepted: 12/10/2019] [Indexed: 12/11/2022] Open
Abstract
Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epithelial-mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.
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Umbelliferone Ameliorates CCl 4-Induced Liver Fibrosis in Rats by Upregulating PPARγ and Attenuating Oxidative Stress, Inflammation, and TGF-β1/Smad3 Signaling. Inflammation 2019; 42:1103-1116. [PMID: 30741365 DOI: 10.1007/s10753-019-00973-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Umbelliferone (UMB) is a natural coumarin that has diverse biological activities. However, its potential to protect against liver fibrosis has not been reported yet. This study aimed to investigate the protective effect of UMB against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats received CCl4 and UMB for 8 weeks and samples were collected for analyses. CCl4 induced a significant increase in serum levels of liver function markers and pro-inflammatory cytokines. Treatment with UMB significantly ameliorated liver function markers and pro-inflammatory cytokines and prevented CCl4-induced histological alterations. CCl4 promoted significant upregulation of α-smooth muscle actin (SMA), collagen I, collagen III, NF-κB p65, TGF-β1, and p-Smad3. Masson's trichrome staining revealed a significant fibrogenesis in CCl4-induced rats. Treatment with UMB suppressed TGF-β1/Smad3 signaling and downregulated α-SMA, collagen I, collagen III, and NF-κB p65. In addition, UMB diminished malondialdehyde and nitric oxide levels, boosted reduced glutathione and antioxidant enzymes, and upregulated the expression of PPARγ. In conclusion, our results demonstrated that UMB prevented CCl4-induced liver fibrosis by attenuating oxidative stress, inflammation, and TGF-β1/Smad3 signaling, and upregulating PPARγ. Therefore, UMB may be a promising candidate for preventing hepatic fibrogenesis, given that further research is needed to delineate the exact molecular mechanisms underlying its antifibrotic efficacy.
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