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Peta V, Sandler Y, Deckmyn O, Duroselle O, Vinnitskaya E, Khomeriki S, Noskova K, Poynard T. Diagnostic performance of FibroTest-ActiTest, transient elastography, and the fibrosis-4 index in patients with autoimmune hepatitis using histological reference. World J Hepatol 2025; 17:104534. [PMID: 40177191 PMCID: PMC11959656 DOI: 10.4254/wjh.v17.i3.104534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/23/2025] [Accepted: 03/06/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Noninvasive tests are crucial for the management and follow-up of patients with autoimmune hepatitis, but their validation is limited because of insufficient data. AIM To investigate the diagnostic performance of three fibrosis noninvasive tests [FibroTest, vibration-controlled transient elastography (VCTE), and the fibrosis-4 index (FIB-4) and two activity biomarkers (alanine aminotransferase (ALT) and ActiTest]. METHODS This study enrolled 103 patients for whom liver biopsy, hepatic elastography results, and laboratory markers were available. Diagnostic performance was assessed with receiver operating characteristic (ROC) curves, the Obuchowski measure (OM), and the Bayesian latent class model. RESULTS FibroTest and VCTE outperformed FIB-4 in cases of significant fibrosis (≥ F2), with areas under the ROC curve of 0.83 [95% confidence interval (CI): 0.73-0.90], 0.86 (95%CI: 0.77-0.92), and 0.71 (95%CI: 0.60-0.80), respectively. The mean (standard error) OM values were 0.92 (0.01), 0.93 (0.01), and 0.88 (0.02) for FibroTest, VCTE, and FIB-4, respectively; FibroTest and VCTE performed comparably, and both were superior to FIB-4 (P = 0.03 and P = 0.005). The areas under the ROC curve values for activity biomarkers were 0.86 (95%CI: 0.76-0.92) for ActiTest and 0.84 (95%CI: 0.73-0.90) for ALT (P = 0.06). The OM values for ActiTest and ALT were 0.92 (0.02) and 0.90 (0.02), respectively (P = 0.005). CONCLUSION FibroTest and VCTE outperformed FIB-4 according to the OM. FibroTest-ActiTest facilitated the evaluation of both fibrosis and activity.
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Affiliation(s)
| | - Yuliya Sandler
- Department of Hepatology, Center for Diagnostics and Treatment of Liver Diseases, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | | | | | - Elena Vinnitskaya
- Department of Hepatology, Center for Diagnostics and Treatment of Liver Diseases, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | - Sergey Khomeriki
- Laboratory of Pathomorphology, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | - Karina Noskova
- Clinical Diagnostic Laboratory, Moscow Clinical Scientific and Practical Center, Moscow 111123, Russia
| | - Thierry Poynard
- BioPredictive, Paris 75007, France
- Sorbonne Université, INSERM Centre de Recherche Saint-Antoine, Paris 75012, France.
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Kuo SL, Su CH, Lai KH, Chang YC, You JS, Peng HH, Chen CH, Lin CC, Chen PJ, Hwang TL. Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice. Biomed J 2025; 48:100731. [PMID: 38677491 PMCID: PMC11745949 DOI: 10.1016/j.bj.2024.100731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 04/13/2024] [Accepted: 04/17/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is an immune-mediated hepatic disease associated with intense complications. AIH is more common in females and needs effective drugs to treat. Guizhi Fuling Wan (GZFLW) is a traditional Chinese herbal formula for treating various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH. METHODS The tandem MS-based analysis was used to identify secondary metabolites in GZFLW. Therapeutic effects of GZFLW were tested in a concanavalin A (Con A)-induced AIH model in mice. Ethnopharmacological mechanisms underlying the antiapoptotic, antioxidant, and immunomodulatory protective effects were determined. RESULTS Oral administration of GZFLW attenuates AIH in a Con A-induced hepatotoxic model in vivo. The tandem MS-based analysis identified 15 secondary metabolites in GZFLW. The Con A-induced AIH syndromes, including hepatic apoptosis, inflammation, reactive oxygen species accumulation, function failure, and mortality, were significantly alleviated by GZFLW in mice. Mechanistically, GZFLW restrained the caspase-dependent apoptosis, restored the antioxidant system, and decreased pro-inflammatory cytokine production in the livers of Con A-treated mice. Besides, GZFLW repressed the Con A-induced hepatic infiltration of inflammatory cells, splenic T cell activation, and splenomegaly in mice. CONCLUSIONS Our findings demonstrate the applicable potential of GZFLW in treating AIH. It prompts further investigation of GZFLW as a treatment option for AIH and possibly other hepatic diseases.
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Affiliation(s)
- Shun-Li Kuo
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Chinese Medicine Obstetrics and Gynecology, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Han Su
- Department of Food Science, College of Human Ecology, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Kuei-Hung Lai
- Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yu-Chia Chang
- Research Center for Chinese Herbal Medicine and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Jyh-Sheng You
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Taoyuan, Taiwan
| | - Hsin-Hsin Peng
- Division of Chinese Medicine Obstetrics and Gynecology, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chun-Hong Chen
- Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan
| | - Chi-Chen Lin
- Program in Translational Medicine, National Chung-Hsing University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Po-Jen Chen
- Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, I-Shou University, Kaohsiung, Taiwan.
| | - Tsong-Long Hwang
- Research Center for Chinese Herbal Medicine and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, Taiwan; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Soufi GJ, Tooyserkani SH, Hekmatnia A, Norouzi A, Sadeghian A, Riahi F. Co-occurrence of anti-phospholipid syndrome and posterior reversible encephalopathy syndrome in a patient with Autoimmune hepatitis: A case report. Radiol Case Rep 2024; 19:4346-4353. [PMID: 39161568 PMCID: PMC11332692 DOI: 10.1016/j.radcr.2024.06.078] [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: 05/09/2024] [Revised: 06/21/2024] [Accepted: 06/30/2024] [Indexed: 08/21/2024] Open
Abstract
Posterior reversible encephalopathy syndrome (PRES) is a neurological disease characterized by a variety of neurological findings, in accordance with radiological characteristics. PRES is commonly secondary to elevated BP and/or conditions such as autoimmune patients receiving immunosuppressive drugs. Our case involves a 36-year-old female with a history of autoimmune hepatitis (AIH), who presented with sudden onset headaches from 3 weeks prior, and a single episode of seizure attack the morning before admission. In the initial examination she had highly elevated blood pressure (BP) (190/116). Her neurological examination revealed decline in force of limbs in addition to mild paresthesia. After primary stabilization, she underwent brain magnetic resonance imaging. Due to the clinical and radiological findings, the patient was diagnosed with PRES. In the following work-up of BP elevation, abdominopelvic sonography and subsequent computed tomography scan, multiple lesions were observed in spleen and both kidneys consistent with infarction. In further evaluation, Lupus-like anticoagulants were found to be elevated, which, in conjunction with the confirmed antiphospholipid syndrome (APS), suggested a possible role for APS-nephropathy as the missing link between PRES and APS. However, despite the role of an autoimmune disease in increasing the risk of developing other autoimmune conditions, APS and AIH have been rarely observed together. Our study indicates that developing APS in the context of AIH is a rare occurrence. However, APS could serve as a critical intermediary, potentially facilitating the onset of PRES despite lower BP.
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Affiliation(s)
- Ghazaleh J. Soufi
- Department of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Ali Hekmatnia
- Professor of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Norouzi
- Department of Radiology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirhossein Sadeghian
- Department of Radiology, Zabol University of Medical Sciences, Sistan and Baluchestan Province, Iran
| | - Farshad Riahi
- Department of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran
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Wenbo Z, Jianwei H, Hua L, Lei T, Guijuan C, Mengfei T. The potential of flavonoids in hepatic fibrosis: A comprehensive review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 133:155932. [PMID: 39146877 DOI: 10.1016/j.phymed.2024.155932] [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: 04/07/2024] [Revised: 07/28/2024] [Accepted: 08/01/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND Hepatic fibrosis is a pathophysiological process of extracellular matrix abnormal deposition induced by multiple pathogenic factors. Currently, there is still a lack of effective and non-toxic drugs for treating fibrosis in clinic. Flavonoids are polyphenolic compounds synthesized in plants and modern pharmacological studies confirmed flavonoids exhibit potent hepatoprotective effect. PURPOSE Summarize literature to elaborate the mechanism of HF and evaluate the potential of flavonoids in HF, aiming to provide a new perspective for future research. METHODS The literatures about hepatic fibrosis and flavonoids are collected via a series of scientific search engines including Google Scholar, Elsevier, PubMed, CNKI, WanFang, SciFinder and Web of Science database. The key words are "flavonoids", "hepatic fibrosis", "pharmacokinetic", "toxicity", "pathogenesis" "traditional Chinese medicine" and "mechanism" as well as combination application. RESULTS Phytochemical and pharmacological studies revealed that about 86 natural flavonoids extracted from Chinese herbal medicines possess significantly anti-fibrosis effect and the mechanisms maybe through anti-inflammatory, antioxidant, inhibiting hepatic stellate cells activation and clearing activated hepatic stellate cells. CONCLUSIONS This review summarizes the flavonoids which are effective in HF and the mechanisms in vivo and in vitro. However, fewer studies are focused on the pharmacokinetics of flavonoids in HF model and most studies are limited to preclinical studies, therefore there is no reliable data from clinical trials for the development of new drugs. Further in-depth research related it can be conducted to improve the bioavailability of flavonoids and serve the development of new drugs.
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Affiliation(s)
- Zhu Wenbo
- Faculty of Chinese Medicine, Jiangsu College of Nursing, Huaian 223001, China.
| | - Han Jianwei
- Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin 150000, China
| | - Liu Hua
- NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha, Hunan 410008, China
| | - Tang Lei
- Faculty of Chinese Medicine, Jiangsu College of Nursing, Huaian 223001, China
| | - Chen Guijuan
- Faculty of Chinese Medicine, Jiangsu College of Nursing, Huaian 223001, China
| | - Tian Mengfei
- Faculty of Chinese Medicine, Jiangsu College of Nursing, Huaian 223001, China
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Xu Y, Wang XS, Zhou XL, Lu WM, Tang XK, Jin Y, Ye JS. Mesenchymal stem cell therapy for liver fibrosis need "partner": Results based on a meta-analysis of preclinical studies. World J Gastroenterol 2024; 30:3766-3782. [PMID: 39221071 PMCID: PMC11362880 DOI: 10.3748/wjg.v30.i32.3766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/22/2024] [Accepted: 08/06/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.
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Affiliation(s)
- Yan Xu
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Xue-Song Wang
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Xiao-Lei Zhou
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Wen-Ming Lu
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Xing-Kun Tang
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Department of Medical Genetics, School of Medicine, Tongji University, Shanghai 200092, China
| | - Yu Jin
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Jun-Song Ye
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cere-brovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Jiangxi Provincal Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
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Daza J, Bezerra LS, Santamaría L, Rueda-Esteban R, Bantel H, Girala M, Ebert M, Van Bömmel F, Geier A, Aldana AG, Yau K, Alvares-da-Silva M, Peck-Radosavljevic M, Ridruejo E, Weinmann A, Teufel A. Evaluation of four chatbots in autoimmune liver disease: A comparative analysis. Ann Hepatol 2024; 30:101537. [PMID: 39147133 DOI: 10.1016/j.aohep.2024.101537] [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: 03/26/2024] [Revised: 05/24/2024] [Accepted: 06/13/2024] [Indexed: 08/17/2024]
Abstract
INTRODUCTION AND OBJECTIVES Autoimmune liver diseases (AILDs) are rare and require precise evaluation, which is often challenging for medical providers. Chatbots are innovative solutions to assist healthcare professionals in clinical management. In our study, ten liver specialists systematically evaluated four chatbots to determine their utility as clinical decision support tools in the field of AILDs. MATERIALS AND METHODS We constructed a 56-question questionnaire focusing on AILD evaluation, diagnosis, and management of Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Primary Sclerosing Cholangitis (PSC). Four chatbots -ChatGPT 3.5, Claude, Microsoft Copilot, and Google Bard- were presented with the questions in their free tiers in December 2023. Responses underwent critical evaluation by ten liver specialists using a standardized 1 to 10 Likert scale. The analysis included mean scores, the number of highest-rated replies, and the identification of common shortcomings in chatbots performance. RESULTS Among the assessed chatbots, specialists rated Claude highest with a mean score of 7.37 (SD = 1.91), followed by ChatGPT (7.17, SD = 1.89), Microsoft Copilot (6.63, SD = 2.10), and Google Bard (6.52, SD = 2.27). Claude also excelled with 27 best-rated replies, outperforming ChatGPT (20), while Microsoft Copilot and Google Bard lagged with only 6 and 9, respectively. Common deficiencies included listing details over specific advice, limited dosing options, inaccuracies for pregnant patients, insufficient recent data, over-reliance on CT and MRI imaging, and inadequate discussion regarding off-label use and fibrates in PBC treatment. Notably, internet access for Microsoft Copilot and Google Bard did not enhance precision compared to pre-trained models. CONCLUSIONS Chatbots hold promise in AILD support, but our study underscores key areas for improvement. Refinement is needed in providing specific advice, accuracy, and focused up-to-date information. Addressing these shortcomings is essential for enhancing the utility of chatbots in AILD management, guiding future development, and ensuring their effectiveness as clinical decision-support tools.
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Affiliation(s)
- Jimmy Daza
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lucas Soares Bezerra
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | | | | | - Heike Bantel
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marcos Girala
- Department of Gastroenterology, Hospital de Clínicas, Universidad Nacional de Asunción, Asunción, Paraguay
| | - Matthias Ebert
- Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Clinical Cooperation Unit Healthy Metabolism, Center for Digital Medicine and Prevention, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Florian Van Bömmel
- Department of Medicine II, Clinic of Gastroenterology, Hepatology, Infectious Diseases and Pneumology, Leipzig University Medical Center, Leipzig, Germany
| | - Andreas Geier
- Department of Internal Medicine II, Division of Hepatology, University Hospital Würzburg, Würzburg, Germany
| | - Andres Gomez Aldana
- Texas Liver Institute, University of Texas Health Science Center, San Antonio, United States
| | - Kevin Yau
- Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Mario Alvares-da-Silva
- Department of Gastroenterology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Markus Peck-Radosavljevic
- Internal Medicine and Gastroenterology (IMuG), Clinic Klagenfurt am Woerthersee, Klagenfurt, Austria
| | - Ezequiel Ridruejo
- Department of Medicine, Section of Hepatology, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Buenos Aires, Argentina
| | - Arndt Weinmann
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Andreas Teufel
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Clinical Cooperation Unit Healthy Metabolism, Center for Digital Medicine and Prevention, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Xiang X, Li Q, Wan J, Chen C, Guo M, He Z, Wang D, Zhao X, Xu L. The role of amino acid metabolism in autoimmune hepatitis. Biomed Pharmacother 2024; 173:116452. [PMID: 38503235 DOI: 10.1016/j.biopha.2024.116452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 03/04/2024] [Accepted: 03/15/2024] [Indexed: 03/21/2024] Open
Abstract
Autoimmune hepatitis (AIH) is an inflammatory chronic liver disease with persistent and recurrent immune-mediated liver injury. The exact cause of AIH is still not fully understood, but it is believed to be primarily due to an abnormal activation of the immune system, leading to autoimmune injury caused by the breakdown of autoimmune tolerance. Although the pathogenesis of AIH remains unclear, recent studies have shown that abnormalities in amino acid metabolism play significant roles in its development. These abnormalities in amino acid metabolism can lead to remodeling of metabolic processes, activation of signaling pathways, and immune responses, which may present new opportunities for clinical intervention in AIH. In this paper, we first briefly outline the recent progress of clinically relevant research on AIH, focusing on the role of specific amino acid metabolism (including glutamine, cysteine, tryptophan, branched-chain amino acids, etc.) and their associated metabolites, as well as related pathways, in the development of AIH. Furthermore, we discuss the scientific issues that remain to be resolved regarding amino acid metabolism, AIH development and related clinical interventions, with the aim of contributing to the future development of amino acid metabolism-based as a new target for the clinical diagnosis and treatment of AIH.
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Affiliation(s)
- Xiaorong Xiang
- Nanshan Class, Zunyi Medical University, Zunyi 563000, China; Guizhou Key Laboratory of Gene Detection and Therapy, Zunyi 563000, China
| | - Qihong Li
- Guizhou Key Laboratory of Gene Detection and Therapy, Zunyi 563000, China
| | - Jiajia Wan
- Guizhou Key Laboratory of Gene Detection and Therapy, Zunyi 563000, China
| | - Chao Chen
- Guizhou Key Laboratory of Gene Detection and Therapy, Zunyi 563000, China
| | - Mengmeng Guo
- Guizhou Key Laboratory of Gene Detection and Therapy, Zunyi 563000, China
| | - Zhixu He
- Innovation Center for Tissue Damage Repair, Ministry of Education, Zunyi, Guizhou 563000, China
| | - Donghong Wang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China.
| | - Xu Zhao
- Medical College of Guizhou University, Guiyang 550025, China.
| | - Lin Xu
- Guizhou Key Laboratory of Gene Detection and Therapy, Zunyi 563000, China; Innovation Center for Tissue Damage Repair, Ministry of Education, Zunyi, Guizhou 563000, China.
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Ferro A, Saccu G, Mattivi S, Gaido A, Herrera Sanchez MB, Haque S, Silengo L, Altruda F, Durazzo M, Fagoonee S. Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases. Biomolecules 2024; 14:277. [PMID: 38540698 PMCID: PMC10967855 DOI: 10.3390/biom14030277] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/15/2024] [Accepted: 02/21/2024] [Indexed: 01/03/2025] Open
Abstract
In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies.
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Affiliation(s)
- Arianna Ferro
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Gabriele Saccu
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Simone Mattivi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Andrea Gaido
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Maria Beatriz Herrera Sanchez
- 2i3T, Società per la Gestione Dell’incubatore di Imprese e per il Trasferimento Tecnologico, University of Torino, 10126 Turin, Italy;
- Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy; (L.S.); (F.A.)
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia;
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 13306, United Arab Emirates
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut 1102 2801, Lebanon
| | - Lorenzo Silengo
- Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy; (L.S.); (F.A.)
| | - Fiorella Altruda
- Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy; (L.S.); (F.A.)
| | - Marilena Durazzo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.F.); (G.S.); (S.M.); (A.G.); (M.D.)
| | - Sharmila Fagoonee
- Institute for Biostructure and Bioimaging, National Research Council (CNR), Molecular Biotechnology Centre “Guido Tarone”, 10126 Turin, Italy
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9
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Zhao Y, Dai E, Dong L, Yuan J, Zhao Y, Wu T, Kong R, Li M, Wang S, Zhou L, Yang Y, Kong H, Zhao Y, Qu H. Available and novel plant-based carbon dots derived from Vaccaria Semen carbonisata alleviates liver fibrosis. Front Mol Biosci 2023; 10:1282929. [PMID: 38116381 PMCID: PMC10729316 DOI: 10.3389/fmolb.2023.1282929] [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: 08/25/2023] [Accepted: 10/27/2023] [Indexed: 12/21/2023] Open
Abstract
Background: Liver fibrosis represents an intermediate stage in the progression of liver disease, and as of now, there exists no established clinical therapy for effective antifibrotic treatment. Purpose: Our aim is to explore the impact of Carbon dots derived from Vaccaria Semen Carbonisata (VSC-CDs) on carbon tetrachloride-induced liver fibrosis in mice. Methods: VSC-CDs were synthesized employing a modified pyrolysis process. Comprehensive characterization was performed utilizing various techniques, including transmission electron microscopy (TEM), multiple spectroscopies, X-ray photoelectron spectroscopy (XPS), and high-performance liquid chromatography (HPLC). A hepatic fibrosis model induced by carbon tetrachloride was utilized to evaluate the anti-hepatic fibrosis effects of VSC-CDs. Results: VSC-CDs, exhibiting a quantum yield (QY) of approximately 2.08%, were nearly spherical with diameters ranging from 1.0 to 5.5 nm. The VSC-CDs prepared in this study featured a negative charge and abundant chemical functional groups. Furthermore, these particles demonstrated outstanding dispersibility in the aqueous phase and high biocompatibility. Moreover, VSC-CDs not only enhanced liver function and alleviated liver damage in pathomorphology but also mitigated the extent of liver fibrosis. Additionally, this study marks the inaugural demonstration of the pronounced activity of VSC-CDs in inhibiting inflammatory reactions, reducing oxidative damage, and modulating the TGF-β/Smad signaling pathway. Conclusion: VSC-CDs exerted significant potential for application in nanodrugs aimed at treating liver fibrosis.
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Affiliation(s)
- Yafang Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Ertong Dai
- Qingdao Eighth People’s Hospital, Qingdao, Shandong, China
| | - Liyang Dong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jinye Yuan
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yusheng Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Tong Wu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Ruolan Kong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Menghan Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Shuxian Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Long Zhou
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yingxin Yang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Kong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yan Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Huihua Qu
- Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing, China
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10
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Wang ZY, Gao PP, Li L, Chen TT, Li N, Qi M, Zhang SN, Xu YP, Wang YH, Zhang SH, Zhang LL, Wei W, Du M, Sun WY. Dextran sulfate sodium-induced gut microbiota dysbiosis aggravates liver injury in mice with S100-induced autoimmune hepatitis. Immunol Lett 2023; 263:70-77. [PMID: 37797724 DOI: 10.1016/j.imlet.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 08/20/2023] [Accepted: 10/02/2023] [Indexed: 10/07/2023]
Abstract
Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.
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Affiliation(s)
- Zi-Ying Wang
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Ping-Ping Gao
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Ling Li
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Ting-Ting Chen
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Nan Li
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Meng Qi
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Sheng-Nan Zhang
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Ya-Ping Xu
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Yu-Han Wang
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Shi-Hao Zhang
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Ling-Ling Zhang
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Wei Wei
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China
| | - Min Du
- Department of Gastrointestinal Surgery, the Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230032, China.
| | - Wu-Yi Sun
- Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, China.
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11
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Cheng L, Shi J, Peng H, Tong R, Hu Y, Yu D. Probiotics and liver fibrosis: An evidence-based review of the latest research. J Funct Foods 2023; 109:105773. [DOI: 10.1016/j.jff.2023.105773] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
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12
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Natarajan A, Daniel AR, Mangal RK, Stead TS, Ganti L. Geographic Liver. Cureus 2023; 15:e45563. [PMID: 37868471 PMCID: PMC10585187 DOI: 10.7759/cureus.45563] [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] [Accepted: 09/19/2023] [Indexed: 10/24/2023] Open
Abstract
The authors present the case of a man with a relatively benign clinical presentation who had a computed tomography scan that revealed a "geographic liver" pattern. The radiologic appearance of hepatic steatosis, its significance, and its association with metabolic syndrome highlight the importance of this radiologic finding.
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Affiliation(s)
- Ariya Natarajan
- Biomedical Sciences, University of Central Florida, Orlando, USA
| | | | - Rohan K Mangal
- Medicine, University of Miami Miller School of Medicine, Miami, USA
| | - Thor S Stead
- Medicine, The Warren Alpert Medical School of Brown University, Providence, USA
| | - Latha Ganti
- Medical Sciences, The Warren Alpert Medical School of Brown University, Providence, USA
- Emergency Medicine & Neurology, University of Central Florida College of Medicine, Orlando, USA
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13
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Yadav V, Irfan R, Safdar S, Sunkara V, Ekhator C, Pendyala PR, Devi M, Shahzed SMI, Das A, Affaf M, Bellegarde SB, Shrestha R, Naseem MA, Al Khalifa A. Advances in Understanding and Managing Autoimmune Hepatitis: A Narrative Review. Cureus 2023; 15:e43973. [PMID: 37622052 PMCID: PMC10446851 DOI: 10.7759/cureus.43973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2023] [Indexed: 08/26/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated destruction of hepatocytes, leading to inflammation and fibrosis. In recent years, significant advances have been made in understanding the pathogenesis, epidemiology, diagnosis, and treatment of AIH. This comprehensive narrative review aims to provide an up-to-date overview of these advances. The review begins by outlining the historical background of AIH, dating back to its initial recognition in the 1940s, and highlights the evolution of diagnostic criteria and classification based on autoantibody profiles. The epidemiology of AIH is explored, discussing its varying prevalence across different regions and the role of genetic predisposition, viral infections, and drug exposure as risk factors. Furthermore, the review delves into the pathogenesis of AIH, focusing on the dysregulated immune response, involvement of T cells, and potential contribution of the gut microbiome. Clinical presentation, diagnostic criteria, and liver biopsy as crucial tools for diagnosis are also discussed. Regarding management, the review provides an in-depth analysis of the standard first-line treatments involving glucocorticoids and azathioprine, as well as alternative therapies for non-responsive cases. Additionally, emerging second and third-line treatment options are examined. In conclusion, this narrative review highlights the complexity of AIH and underscores the importance of early diagnosis and individualized treatment approaches to improve patient outcomes. Further research and clinical trials are needed to optimize AIH management and ensure a better long-term prognosis for affected individuals.
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Affiliation(s)
- Vikas Yadav
- Internal Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, IND
| | | | | | | | - Chukwuyem Ekhator
- Neuro-Oncology, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, USA
| | - Praful R Pendyala
- Neurology, Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar, IND
| | | | | | - Archana Das
- Internal Medicine, North East Medical College and Hospital, Sylhet, BGD
| | - Maryam Affaf
- Medicine, Khyber Medical University, Peshawar, PAK
| | - Sophia B Bellegarde
- Pathology and Laboratory Medicine, American University of Antigua, St. John's, ATG
| | - Riya Shrestha
- Medicine, Nepal Medical College and Teaching Hospital, Kathmandu, NPL
| | | | - Ahmed Al Khalifa
- Medical School, College of Medicine, Sulaiman Alrajhi University, Al Bukayriyah, SAU
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