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Wen Z, Tuo S, Ran Q, Yuan J, Li Y, Zhang Y, Chang D, Li C, Dai S, Wang J, Tantai X. Effect of adipose-related parameters on mortality in patients with liver cirrhosis: a meta-analysis. Ann Med 2025; 57:2473627. [PMID: 40038873 PMCID: PMC11884100 DOI: 10.1080/07853890.2025.2473627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 02/06/2025] [Accepted: 02/13/2025] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Some adipose-related parameters exhibit distinct prognostic value in patients with cirrhosis. However, the magnitude and direction of the association between individual adipose parameter and mortality in patients with cirrhosis are unclear. AIM This study aimed to evaluate the association between individual adipose parameter and mortality in patients with cirrhosis using the meta-analysis method. METHODS The PubMed, Embase, Web of Science, China Biological Medicine, WanFang, and China National Knowledge Infrastructure databases were searched from inception through December 15, 2023, to identify eligible studies. The impact of each adipose parameter on mortality was assessed by the pooled unadjusted or adjusted hazard ratio (HR) with 95% confidence intervals (CIs) using the random effects model. RESULTS A total of 33 studies involving 9626 patients were included in our analysis, with 11 adipose parameters evaluated. The pooled prevalence of sarcopenic obesity (SO) and myosteatosis in patients with cirrhosis was 15.5% and 34.4%, respectively. In adjusted analysis, each unit increase in subcutaneous adipose tissue index (SATI) (HR: 0.99, 95% CI: 0.98-1.00) or muscle attenuation (MA) (HR: 0.94, 95% CI: 0.90-0.98) and each unit decrease in visceral-to-subcutaneous adipose tissue ratio (VSR) (HR: 1.92, 95% CI: 1.45-2.54) showed an independent association with a decreased risk of mortality. However, concurrent myosteatosis (HR: 1.88, 95% CI: 1.48-2.40) or SO (HR: 2.77, 95% CI: 1.95-3.93) significantly increased the risk of mortality in patients with cirrhosis. CONCLUSION Decreased SATI or MA, increased VSR, and concurrent myosteatosis or SO were independently associated with a higher risk of mortality in patients with cirrhosis.
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Affiliation(s)
- Zhang Wen
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Shuyue Tuo
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Qiuju Ran
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jia Yuan
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yong Li
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Ying Zhang
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Danyan Chang
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chan Li
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Shejiao Dai
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jinhai Wang
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xinxing Tantai
- Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Hu P, Miao H, Li M, Zhou R, Lou Q, Wang D, Gao J, Guo F. Identification of plasma biomarkers for non-invasive diagnosis of hepatitis B cirrhosis. J Pharm Biomed Anal 2025; 263:116909. [PMID: 40300315 DOI: 10.1016/j.jpba.2025.116909] [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: 12/10/2024] [Revised: 04/15/2025] [Accepted: 04/16/2025] [Indexed: 05/01/2025]
Abstract
Hepatitis B virus (HBV) infection represents a major public health challenge due to its potential progression to liver cirrhosis and hepatocellular carcinoma, underscoring the importance of early diagnosis for effective management. This study aimed to identify plasma biomarkers for the non-invasive diagnosis of hepatitis B cirrhosis (HBC). We employed quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry on plasma samples from 27 individuals, including 13 patients with HBC and 14 with chronic hepatitis B (CHB). Bioinformatics analysis of 963 identified proteins revealed 234 differential expressed proteins, comprising 115 upregulated and 119 downregulated proteins. Four candidate biomarkers-CHI3L1, IGFBP1, SHBG, and TIMP2-were subsequently selected and validated using ELISA in a cohort of 158 patients, all demonstrating elevated levels in HBC patients. The four-biomarker panel (4MP) demonstrated superior diagnostic performance, achieving an area under the curve (AUC) of 0.902 for distinguishing HBC from CHB. For differentiating decompensated HBC from CHB, the 4MP achieved an AUC of 0.993, with a sensitivity of 93.75 % and specificity of 98.73 %. Mostly, the 4MP also performed well in identifying severe HBC from non-severe HBC, achieving an AUC of 0.911, with a sensitivity of 81.25% and specificity of 93.65%. In conclusion, this study identifies four novel plasma biomarkers for HBC, highlighting their potential to enhance non-invasive diagnostic strategies for monitoring HBC progression.
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Affiliation(s)
- Piao Hu
- Department of Infectious Diseases, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou 311200, China
| | - Haifeng Miao
- Department of Infectious Diseases, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou 311200, China
| | - Mei Li
- Department of Infectious Diseases, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou 311200, China
| | - Ruxue Zhou
- Cosmos Wisdom Mass Spectrometry Center of Zhejiang University Medical School, Hangzhou 311200, China; Jiaxing Key Laboratory of Clinical Laboratory Diagnostics and Translational Research, Affliated Hospital of Jiaxing University, Jiaxing 314000, China
| | - Qinqin Lou
- Cosmos Wisdom Mass Spectrometry Center of Zhejiang University Medical School, Hangzhou 311200, China; Jiaxing Key Laboratory of Clinical Laboratory Diagnostics and Translational Research, Affliated Hospital of Jiaxing University, Jiaxing 314000, China
| | - Dezhen Wang
- Cosmos Wisdom Mass Spectrometry Center of Zhejiang University Medical School, Hangzhou 311200, China; Jiaxing Key Laboratory of Clinical Laboratory Diagnostics and Translational Research, Affliated Hospital of Jiaxing University, Jiaxing 314000, China
| | - Junli Gao
- Cosmos Wisdom Mass Spectrometry Center of Zhejiang University Medical School, Hangzhou 311200, China; Jiaxing Key Laboratory of Clinical Laboratory Diagnostics and Translational Research, Affliated Hospital of Jiaxing University, Jiaxing 314000, China.
| | - Feng Guo
- Department of Gastroenterology, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou 311200, China.
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Li Y, Li Z, Li J, Liu L, Liu Y, Zhu B, Shi K, Lu Y, Li Y, Zeng X, Feng Y, Wang X. The actual performance of large language models in providing liver cirrhosis-related information: A comparative study. Int J Med Inform 2025; 201:105961. [PMID: 40334344 DOI: 10.1016/j.ijmedinf.2025.105961] [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: 12/11/2024] [Revised: 04/08/2025] [Accepted: 05/03/2025] [Indexed: 05/09/2025]
Abstract
OBJECTIVE With the increasing prevalence of large language models (LLMs) in the medical field, patients are increasingly turning to advanced online resources for information related to liver cirrhosis due to its long-term management processes. Therefore, a comprehensive evaluation of real-world performance of LLMs in these specialized medical areas is necessary. METHODS This study evaluates the performance of four mainstream LLMs (ChatGPT-4o, Claude-3.5 Sonnet, Gemini-1.5 Pro, and Llama-3.1) in answering 39 questions related to liver cirrhosis. The information quality, readability and accuracy were assessed using Ensuring Quality Information for Patients tool, Flesch-Kincaid metrics and consensus scoring. The simplification and their self-correction ability of LLMs were also assessed. RESULTS Significant performance differences were observed among the models. Gemini scored highest in providing high-quality information. While the readability of all four LLMs was generally low, requiring a college-level reading comprehension ability, they exhibited strong capabilities in simplifying complex information. ChatGPT performed best in terms of accuracy, with a "Good" rating of 80%, higher than Claude (72%), Gemini (49%), and Llama (64%). All models received high scores for comprehensiveness. Each of the four LLMs demonstrated some degree of self-correction ability, improving the accuracy of initial answers with simple prompts. ChatGPT's and Llama's accuracy improved by 100%, Claude's by 50% and Gemini's by 67%. CONCLUSION LLMs demonstrate excellent performance in generating health information related to liver cirrhosis, yet they exhibit differences in answer quality, readability and accuracy. Future research should enhance their value in healthcare, ultimately achieving reliable, accessible and patient-centered medical information dissemination.
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Affiliation(s)
- Yanqiu Li
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhuojun Li
- School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing, China
| | - Jinze Li
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Long Liu
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Liu
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Bingbing Zhu
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ke Shi
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yu Lu
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yongqi Li
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xuanwei Zeng
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Feng
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Xianbo Wang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
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Abdlaty R, Abbass MA, Awadallah AM. Toward near real-time precise supervision of radiofrequency ablation for liver fibrosis using hyperspectral imaging. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 336:125994. [PMID: 40086137 DOI: 10.1016/j.saa.2025.125994] [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: 09/15/2024] [Revised: 02/17/2025] [Accepted: 03/04/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND AND AIMS Chronic liver diseases pose a significant global health concern, ranking as the 11th leading cause of death worldwide. It often progresses to organ fibrosis and severe complications such as portal hypertension and cirrhosis. Liver transplantation is the most effective treatment for such diseases, however, the persistent shortage of donors highlights the need for alternatives. Radiofrequency ablation (RFA) is a promising alternative since it is a minimally invasive procedure. RFA uses heat to destroy abnormal tissues. Its benefits include reduced recovery time compared to surgery, precise targeting of affected areas, and long-lasting symptom relief in many cases. However, RFA has challenges, such as potential risks of nerve damage, infection, or incomplete ablation, requiring repeat treatments. Although significant progress in RFA techniques, effective monitoring remains challenging due to the limited ability to accurately characterize the dynamic thermal diffusion and complex tissue responses. METHODS To address this challenge, hyperspectral imaging (HSI) shows promise in monitoring tissue necrosis post-ablation. Our study evaluated HSI's efficacy in monitoring RFA on ex vivo human fibrotic liver tissue samples. RESULTS Statistical analysis revealed correlations between spectral patterns and tissue conditions, which helped identify the optimal spectral bands of 543 nm and 579 nm for accurately distinguishing different tissue states. Analyzing the hemoglobin absorption profile indicated significant reductions in absorption of the green light band, showing approximately 40 % reduction in fibrotic tissue and around 20 % reduction in ablated tissue when compared to normal liver tissue. Additionally, a threshold was established for predicting the ablated area of liver samples, ensuring a condition of 90 % specificity. CONCLUSIONS Consequently, HSI proved to be a valuable tool for monitoring ablation and a step for improving treatment outcomes for liver fibrosis.
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Affiliation(s)
- Ramy Abdlaty
- Department of Biomedical Engineering, Military Technical College, Cairo, Egypt.
| | - Mohamed A Abbass
- Department of Biomedical Engineering, Military Technical College, Cairo, Egypt
| | - Ahmed M Awadallah
- Department of Biomedical Engineering, Military Technical College, Cairo, Egypt
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5
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Hung A, Etoori D, Modi R, Gee M, Rosenberg W. EXSPECT: ELF Cross-comparison between serum and plasma collection tubes. Clin Chim Acta 2025; 574:120332. [PMID: 40300725 DOI: 10.1016/j.cca.2025.120332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 04/23/2025] [Accepted: 04/23/2025] [Indexed: 05/01/2025]
Affiliation(s)
- Alexander Hung
- Institute for Liver and Digestive Health, UCL Division of Medicine, Royal Free Campus, Rowland Hill, London NW3 2PF, UK; Department of Hepatology, Royal Free Hospital, Royal Free London NHS Foundation Trust, London NW3 2QG, UK.
| | - David Etoori
- Institute for Liver and Digestive Health, UCL Division of Medicine, Royal Free Campus, Rowland Hill, London NW3 2PF, UK
| | - Raakesh Modi
- iQur Limited, 2 Royal College Street, London NW1 0NH, UK
| | - Matthew Gee
- Siemens Healthineers, 511 Benedict Avenue, Tarrytown, NY 10591, USA
| | - William Rosenberg
- Institute for Liver and Digestive Health, UCL Division of Medicine, Royal Free Campus, Rowland Hill, London NW3 2PF, UK; Department of Hepatology, Royal Free Hospital, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
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Zamani M, Alizadeh-Tabari S, Ajmera V, Singh S, Murad MH, Loomba R. Global Prevalence of Advanced Liver Fibrosis and Cirrhosis in the General Population: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2025; 23:1123-1134. [PMID: 39209202 DOI: 10.1016/j.cgh.2024.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 07/31/2024] [Accepted: 08/01/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND & AIMS Limited data exist regarding the estimate of the prevalence of advanced liver fibrosis and cirrhosis in the general population. Therefore, we conducted a systematic review and meta-analysis to evaluate the global prevalence and risk factors of advanced fibrosis and cirrhosis. METHODS We searched Embase, PubMed, Scopus, and Web of Science from inception to April 30 2024, with no language restriction. We included cross-sectional studies reporting the prevalence of advanced liver fibrosis and/or cirrhosis in a sample of at least 100 individuals aged ≥18 years from the general population. Subjects with cirrhosis were included in the advanced fibrosis group. The pooled prevalence proportions utilizing a random-effects model and 95% confidence intervals (CIs) were estimated using global data. RESULTS A total of 46 studies fulfilled the eligibility criteria, comprising approximately 8 million participants from 21 countries. The pooled prevalence rates of advanced liver fibrosis and cirrhosis in the general population were 3.3% (95% CI, 2.4%-4.2%) and 1.3% (95% CI, 0.9%-1.7%) worldwide, respectively. A trend was observed for an increase in the prevalence of advanced fibrosis (P = .004) and cirrhosis (P = .034) after 2016. There were significant geographic variations in the advanced fibrosis and cirrhosis prevalence at continental and national levels (P < .0001). Potential risk factors for cirrhosis were viral hepatitis, diabetes, excessive alcohol intake, obesity, and male sex. CONCLUSIONS The prevalence of advanced fibrosis and cirrhosis is considerable and increasing worldwide with significant geographic variation. Further research is needed to better understand the risk factors and how to mitigate them worldwide to address the growing global burden of cirrhosis.
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Affiliation(s)
- Mohammad Zamani
- Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Alizadeh-Tabari
- Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Veeral Ajmera
- MASLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California
| | - Siddharth Singh
- Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, University of California San Diego, La Jolla, California
| | - Mohammad Hassan Murad
- Kern Center for the Science of Healthcare Delivery Research, Mayo Clinic, Rochester, Minnesota
| | - Rohit Loomba
- MASLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California.
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Pereira Portela C, Bertaggia Calderara D, Mdawar-Bailly E, Aliotta A, Veuthey L, Gautier LA, Moradpour D, Fraga M, Zermatten MG, Alberio L. Effect of direct oral anticoagulants in cirrhosis: an in vitro study. J Thromb Haemost 2025; 23:1938-1952. [PMID: 40122463 DOI: 10.1016/j.jtha.2025.03.011] [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: 08/01/2024] [Revised: 03/06/2025] [Accepted: 03/06/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND Cirrhosis is associated with a procoagulant state that may worsen disease evolution. Anticoagulation could be of particular interest in these patients. However, evidence on the use of direct oral anticoagulants (DOAC) in patients with cirrhosis is limited. OBJECTIVES Our aim was to explore the in vitro effect of DOAC on thrombin generation (TG) in plasma from patients with cirrhosis compared to plasma from healthy controls. METHODS Platelet-poor-plasma was obtained from patients with cirrhosis (n = 87; Child-Turcotte-Pugh class: A, n = 68; B, n = 14; C, n = 5) and controls (n = 17). TG was assessed with ST-Genesia analyzer. Plasma from patients with cirrhosis and thrombomodulin-mediated inhibition of endogenous thrombin potential <20% (ThromboScreen) were defined as "highly procoagulant" (n = 36), ≥20% to 50% as "procoagulant" (n = 31), and >50% as "nonprocoagulant" (n = 20). Plasma samples were spiked with apixaban, edoxaban, rivaroxaban, or dabigatran at final concentrations of 50 and 150 ng/mL. TG was measured (DrugScreen) in plasma samples without and with DOAC. RESULTS Apixaban, edoxaban, and rivaroxaban demonstrated significantly reduced inhibition of in vitro TG parameters in highly procoagulant plasma from patients with cirrhosis compared to plasma from controls, whereas possibly artifactual results were observed with dabigatran. CONCLUSION The anticoagulant potency of DOAC differs according to the individual procoagulant potential. Highly procoagulant plasma from patients with cirrhosis is less sensitive to the anticoagulant action of apixaban, edoxaban, and rivaroxaban than control plasma. These results, if confirmed in vivo, would support the concept of personalizing anticoagulant treatment in patients with a highly procoagulant state.
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Affiliation(s)
- Cindy Pereira Portela
- Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Debora Bertaggia Calderara
- Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Elise Mdawar-Bailly
- Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Alessandro Aliotta
- Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Lucas Veuthey
- Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Lucas A Gautier
- Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Montserrat Fraga
- Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Maxime G Zermatten
- Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Lorenzo Alberio
- Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
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Zhao Y, Bo Y, Zu J, Xing Z, Yang Z, Zhang Y, Deng Y, Liu Y, Zhang L, Yuan X, Wang Y, Henry L, Ji F, Nguyen MH. Global Burden of Chronic Liver Disease and Temporal Trends: A Population-Based Analysis From 1990 to 2021 With Projections to 2050. Liver Int 2025; 45:e70155. [PMID: 40421876 DOI: 10.1111/liv.70155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 04/30/2025] [Accepted: 05/19/2025] [Indexed: 05/28/2025]
Abstract
BACKGROUND AND AIMS Globally, the aetiology and epidemiology of chronic liver disease (CLD) are undergoing significant changes. We aimed to investigate the updated global burden of CLD, evaluate the cross-country inequalities, and provide 2050 predictions. METHODS Using the Global Burden of Disease Study (GBD) 2021 data resources, we analysed and forecasted CLD prevalence, incidence, and related death from 1990-2021 to 2050, respectively. We calculated average annual percent change (AAPC) by joinpoint regression model and quantified inequalities according to World Health Organisation-recommended health equity standards. RESULTS In 2021, the number of prevalent, incident CLD and related deaths globally were 1.7 billion (95% uncertainty interval (UI): 1.6-1.8), 58.4 million (95% UI: 54.2-62.8) and 1.4 million (95% UI: 1.3-1.5), respectively. During 1990-2021, the age-standardised incidence rate (ASIR) increased, especially in those aged 15-49 (AAPC: 0.49%; 95% confidence interval [CI]: 0.45%-0.53%), in Europe (AAPC: 0.41%; 95% CI: 0.41%-0.42%) and the Americas (AAPC: 0.41%; 95% CI: 0.39%-0.42%), whereas the age-standardised death rate (ASDR) decreased globally (AAPC: -1.26%; 95% CI: -1.35% [-1.17%]) and across subgroups. During 1990-2021, the ASIR of metabolic dysfunction-associated steatotic liver disease (MASLD) increased the most in those aged 15-49 (AAPC: 0.72%; 95% CI: 0.67%-0.77%) and in the Western Pacific region (AAPC: 0.73%; 95% CI: 0.59%-0.86%). Socio-demographic index (SDI)-related inequalities decreased for the age-standardised prevalence rate (ASPR) and ASIR of CLD but increased for ASDR, placing a disproportionately heavier burden on low-SDI countries. From 2022 to 2050, the ASIR of CLD is projected to increase (AAPC: 0.20%; 95% CI: 0.19%-0.20%), but the ASDR is projected to decline (AAPC: -1.91%; 95% CI: -1.96% [-1.85%]). CONCLUSIONS This study's findings highlight targeted interventions for CLD disparities, focusing on MASLD management, the younger population (15-49 years), and socio-demographic inequalities.
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Affiliation(s)
- Yunyu Zhao
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yajing Bo
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jian Zu
- School of Mathematics and Statistics, Xi'an Jiaotong University, Xi'an, China
| | - Zixuan Xing
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhanpeng Yang
- School of Mathematics and Statistics, Xi'an Jiaotong University, Xi'an, China
| | - Yue Zhang
- School of Mathematics and Statistics, Xi'an Jiaotong University, Xi'an, China
| | - Yujiao Deng
- Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yi Liu
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Lanting Zhang
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiao Yuan
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yuan Wang
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Fanpu Ji
- Department of Hepatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, Shaanxi, China
- Key Laboratory of Surgical Critical Care and Life Support (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, Shaanxi, China
- Global Health Institute, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
- Shaanxi Provincial Clinical Medical Research Center of Infectious Diseases, Xi'an, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
- Department of Epidemiology and Population Health, Stanford University, Stanford, California, USA
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Muñoz‐Espinosa LE, Torre A, Cisneros L, Montalvo I, Malé R, Mejía S, Aguilar JR, Lizardi J, Zuñiga‐Noriega J, Eugenia Icaza M, Gasca‐Díaz F, Hernández‐Hernández L, Cordero‐Pérez P, Chi L, Torres L, Rodríguez‐Alvarez F, Tapia G, Poo JL. Noninvasive Evaluation of Prolonged-Release Pirfenidone in Compensated Liver Cirrhosis. ODISEA Study, a Randomised Trial. Liver Int 2025; 45:e70131. [PMID: 40402087 PMCID: PMC12097196 DOI: 10.1111/liv.70131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 04/07/2025] [Accepted: 04/28/2025] [Indexed: 05/23/2025]
Abstract
BACKGROUND Advanced liver fibrosis (ALF) predicts an adverse prognosis in chronic liver disease. In addition to etiological treatment, a new approach to stop or reverse residual fibrosis is desirable. OBJECTIVE To assess the efficacy and safety of prolonged-release pirfenidone (PR-PFD) versus placebo in compensated cirrhosis. METHODS 180 patients with ALF (F4) were randomly assigned to: placebo, 1200 mg/d, and 1800 mg/d PR-PFD, plus standardised care, for 24mo. Frequency of lab tests: (3mo), liver stiffness measurement (LSM), FibroTest, ultrasound (US) (6mo), and endoscopy (annually). RESULTS Fibrosis evolution estimated from LSM was significantly lower only in the 1200 compared to placebo and 1800 groups (24.2 ± 2.4 vs. 15.4 ± 2.4; 27.6 ± 2.4 vs. 24.6 ± 2.4; 24.4 ± 2.3 vs. 23.3 ± 2.3 kPa, respectively, p < 0.001), in intergroup analysis, meeting the primary endpoint. Fibrotest was significantly lower only in the 1200 mg/d group, compared to baseline values (0.86 ± 0.02 vs. 0.83 ± 0.02 units, p < 0.001). Liver function test (LFT's) also improved as well as Model for End-Stage Liver Disease (MELD) score and quality of life (QoL). Decompensations occurred in 19 patients: 12 ascites (more frequent in placebo, p = 0.003), 5 variceal bleeding, 4 encephalopathies, 4 hepatocarcinomas. Adverse events were mainly mild gastrointestinal (n = 35, 48 and 46, p = 0.010) and cutaneous (n = 12, 15, and 22, p = 0.0001) in placebo, 1200 and 1800 mg/day, respectively. CONCLUSION PR-PFD at a dose of 1200 mg significantly decreased non-invasive liver fibrosis markers at 24 months and induced improvement in LFT's, MELD, and QoL in compensated cirrhosis, without safety concerns. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01046474.
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Affiliation(s)
- Linda E. Muñoz‐Espinosa
- Universidad Autónoma de Nuevo León, “Dr. José E. González” University HospitalMonterreyMexico
| | - Aldo Torre
- Instituto Nacional de Ciencias Médicas y NutriciónCiudad de MéxicoMexico
| | | | | | - René Malé
- Digestive and Hepatic Disease InstituteGuadalajaraMexico
| | | | - Juan Ramón Aguilar
- Mexican Group for the Study of Liver Diseases (PROMHEPA)Mexico CityMexico
| | - Javier Lizardi
- Mexican Group for the Study of Liver Diseases (PROMHEPA)Mexico CityMexico
| | - Jaime Zuñiga‐Noriega
- Universidad Autónoma de Nuevo León, “Dr. José E. González” University HospitalMonterreyMexico
| | | | - Frida Gasca‐Díaz
- Mexican Group for the Study of Liver Diseases (PROMHEPA)Mexico CityMexico
| | | | - Paula Cordero‐Pérez
- Universidad Autónoma de Nuevo León, “Dr. José E. González” University HospitalMonterreyMexico
| | | | - Lilian Torres
- Digestive and Hepatic Disease InstituteGuadalajaraMexico
| | | | - Graciela Tapia
- Universidad Nacional Autónoma de MéxicoMexico CityMexico
| | - Jorge Luis Poo
- Mexican Group for the Study of Liver Diseases (PROMHEPA)Mexico CityMexico
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Suárez M, Martínez R, Gómez-Molina R, Mateo J. Infection risk and management in patients with cirrhosis: A critical overview. World J Hepatol 2025; 17:104468. [DOI: 10.4254/wjh.v17.i5.104468] [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: 12/21/2024] [Revised: 02/27/2025] [Accepted: 03/13/2025] [Indexed: 05/27/2025] Open
Abstract
In this paper, we analyze the article published by El Labban et al, which explores the impact of cirrhosis on patients with necrotizing fasciitis. The authors conclude that cirrhosis is a significant risk factor for increased in-hospital morbidity and mortality in this patient population. Building upon their final observation regarding the importance of understanding this association, we will delve into the topic of infections in patients with liver cirrhosis. These patients exhibit intrinsic characteristics that make them particularly susceptible to infections, both bacterial and fungal. This heightened risk not only increases the likelihood of severe infections but also makes them a common trigger for acute decompensations, including the development of acute-on-chronic liver failure, which markedly worsens prognosis and mortality. Infections in patients with cirrhosis often require a more aggressive and rapid diagnostic and therapeutic approach due to the higher risk of nosocomial infections, multidrug-resistant organisms, and atypical clinical presentations. Delayed or inadequate management can lead to unfavorable outcomes, further complicating the course of their underlying liver disease. The aim of this article is to emphasize the importance of early and appropriate management in patients with cirrhosis with infections. Evidence supports that timely and tailored interventions not only improve clinical outcomes but also reduce mortality. By raising awareness among clinicians about the complexity of these cases, we hope to contribute to optimizing the care of this high-risk population.
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Affiliation(s)
- Miguel Suárez
- Department of Gastroenterology, Virgen de la Luz Hospital, Cuenca 16002, Castille-La Mancha, Spain
- Medical Analysis Expert Group, Institute of Technology, Universidad de Castilla-La Mancha, Cuenca 16071, Castille-La Mancha, Spain
- Medical Analysis Expert Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo 45071, Castille-La Mancha, Spain
| | - Raquel Martínez
- Department of Gastroenterology, Virgen de la Luz Hospital, Cuenca 16002, Castille-La Mancha, Spain
- Medical Analysis Expert Group, Institute of Technology, Universidad de Castilla-La Mancha, Cuenca 16071, Castille-La Mancha, Spain
- Medical Analysis Expert Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo 45071, Castille-La Mancha, Spain
| | - Raquel Gómez-Molina
- Department of Laboratory Medicine, Virgen de la Luz Hospital, Cuenca 16002, Castille-La Mancha, Spain
| | - Jorge Mateo
- Medical Analysis Expert Group, Institute of Technology, Universidad de Castilla-La Mancha, Cuenca 16071, Castille-La Mancha, Spain
- Medical Analysis Expert Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo 45071, Castille-La Mancha, Spain
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11
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Chen S, Zhu Y, Wang J, Zhao X, Zhai X, Hu L, He X, Li Z, Guo Y, Wang S, Ji D, Zou Z, Zhou G, Yang Y, Wang J, Chen Y, Lu Y. Biejia Ruangan Tablet Alleviated Liver Fibrosis in Murine Models by Hindering the Crosstalk between Hepatic Stellate Cells and M2-like Macrophages through PDGF-AA/PI3K/AKT Pathway. JOURNAL OF ETHNOPHARMACOLOGY 2025:120029. [PMID: 40414578 DOI: 10.1016/j.jep.2025.120029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 05/19/2025] [Accepted: 05/22/2025] [Indexed: 05/27/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Biejia Ruangan Tablet (BJRG) is a patented traditional Chinese medicine formula with demonstrated efficacy against liver fibrosis. However, its underlying molecular mechanisms remain unclear. AIM This study aimed to investigate the anti-fibrotic effects of BJRG and elucidate its molecular mechanisms. METHODS Liver fibrosis was induced in murine models using carbon tetrachloride (CCl4) or bile duct ligation (BDL) to evaluate the efficacy of BJRG. Network pharmacology was employed to predict the mechanisms of BJRG. The expression of PDGF-AA was assessed in both murine and human samples. The interaction between BJRG and PDGF-AA was investigated in vitro using primary mouse bone marrow-derived macrophages (BMDMs) and LX-2 cells. Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used to identify liver-entry active components of BJRG. Molecular docking was performed to predict their binding affinity with PDGF-AA. RESULTS BJRG significantly alleviated liver fibrosis in both CCl4- and BDL-induced murine models. Network pharmacology suggested that BJRG targeted the PDGF/PI3K/AKT signaling pathway. Then we revealed that BJRG specifically downregulated PDGF-AA expression and PI3K/AKT signaling in M2-like macrophages, thereby attenuating hepatic stellate cell (HSC) activation. Clinical data demonstrated that PDGF-AA was associated with liver cirrhosis, and BJRG suppressed PDGF-AA levels in patients with lower Ishak inflammation scores. Molecular docking indicated that the liver-entry components of BJRG exhibited strong binding affinity with PDGF-AA. CONCLUSION BJRG ameliorated liver fibrosis by disrupting the crosstalk between M2-like macrophages and HSCs through downregulation of the PDGF-AA/PI3K/AKT pathway.
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Affiliation(s)
- Shaoting Chen
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China; Laboratory for Research and Translation of Traditional Chinese Medicine in Managing Severe Infectious Liver Diseases, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Yanpei Zhu
- Centre for Clinical Pathology, Beijing You'an Hospital, Capital Medical University, Beijing,100069, China
| | - Jingxiao Wang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Xin Zhao
- Laboratory for Research and Translation of Traditional Chinese Medicine in Managing Severe Infectious Liver Diseases, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Xingran Zhai
- Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, China
| | - Linlan Hu
- Laboratory for Research and Translation of Traditional Chinese Medicine in Managing Severe Infectious Liver Diseases, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Xian He
- Laboratory for Research and Translation of Traditional Chinese Medicine in Managing Severe Infectious Liver Diseases, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Zhihan Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Yafei Guo
- Laboratory for Research and Translation of Traditional Chinese Medicine in Managing Severe Infectious Liver Diseases, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Sihao Wang
- Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, China
| | - Dong Ji
- Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, China
| | - Zhengsheng Zou
- Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, China
| | - Guangde Zhou
- Centre for Clinical Pathology, Beijing You'an Hospital, Capital Medical University, Beijing,100069, China
| | - Yongping Yang
- Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, China
| | - Jiabo Wang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China; Laboratory for Research and Translation of Traditional Chinese Medicine in Managing Severe Infectious Liver Diseases, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Laboratory for Clinical Medicine, Capital Medical University, Beijing 100069, China.
| | - Yan Chen
- Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, China.
| | - Yawen Lu
- Laboratory for Research and Translation of Traditional Chinese Medicine in Managing Severe Infectious Liver Diseases, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Laboratory for Clinical Medicine, Capital Medical University, Beijing 100069, China.
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12
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Zheng X, Wei W. Ascites complications risk factors of decompensated cirrhosis patients: logistic regression and prediction model. BMC Gastroenterol 2025; 25:397. [PMID: 40405077 PMCID: PMC12100819 DOI: 10.1186/s12876-025-04002-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 05/16/2025] [Indexed: 05/24/2025] Open
Abstract
OBJECTIVE The study mainly aim at exploring the ascites risk factors among decompensated cirrhosis patients via constructing the prediction model of ascites incidence. METHODS Here, we recruited 148 decompensated cirrhosis patients for analysis, their laboratory tests and complications recorded. T-test, chi-square test, single-factor logistic regression, multi-factor logistic regression, and nomogram model were used to investigate the ascites occurred factors in decompensated cirrhosis patients with ascites. To validate the data analysis results, we applied the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) to evaluate the discrimination, calibration, and clinical usefulness of the prediction model, respectively. RESULTS Serum creatinine levels were higher in the cirrhotic ascites group than in the non-ascites group. The ascites group had lower albumin and serum sodium levels, as well as a lower incidence of variceal bleeding and varicose veins compared to the non-ascites group. CONCLUSION Varicose veins, variceal bleeding, and serum sodium levels are significant factors contributing to ascites development in cirrhosis. Furthermore, decreased serum albumin and elevated creatinine levels are important indicators of poor prognosis. Nomograms can improve clinicians' informed decision-making for patients with decompensated cirrhosis, ultimately reducing ascites risk.
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Affiliation(s)
- Xiaolong Zheng
- The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Wei Wei
- The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
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Roro GM, Annose RT, Gilja OH. Changing trends in upper gastrointestinal endoscopic findings in Ethiopia: A comparison of eighteen thousand exams across two periods. World J Gastrointest Endosc 2025; 17:106690. [DOI: 10.4253/wjge.v17.i5.106690] [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: 03/11/2025] [Revised: 04/02/2025] [Accepted: 04/24/2025] [Indexed: 05/12/2025] Open
Abstract
BACKGROUND Relative changes in the prevalence of gastrointestinal (GI) diseases have been reported worldwide over the past decades. However, data on changing trends of upper GI diseases remain scarce in sub-Saharan Africa. This study examines the shifting patterns of upper GI endoscopic findings over 35 years in Ethiopia.
AIM To analyze trends in upper GI endoscopic findings over two distinct time periods, 35 years apart, in Ethiopia.
METHODS We extracted findings from 8412 upper GI endoscopies performed between 2016 and 2024 at a tertiary referral center in Addis Ababa, Ethiopia. Patient characteristics, indications, and endoscopic findings were analyzed using descriptive statistics and presented in tables, map and graphs. These findings were compared to 10000 procedures conducted between 1979 and 1994. Key endoscopic findings were identified, and percentage changes in disease prevalence were calculated.
RESULTS Between the two study periods, the male-to-female ratio of patients undergoing upper GI endoscopy shifted from 2:1 to 1.4:1, while the median patient age increased from 36 to 40 years. The proportion of patients older than 50 years doubled (14.6% to 30.2%), and referrals from outside Addis Ababa increased from 33% to 57%. The prevalence of peptic ulcer disease and its complications decreased from 46.2% to 9.5%. Conversely, gastroesophageal varices increased from 9.5% to 21.8%, and upper GI malignancies rose from 3.6% to 18.8%.
CONCLUSION This study sheds light on critical epidemiological shifts in upper GI diseases in Ethiopia, with a decline in peptic ulcer disease and a rise in portal hypertensive lesions and malignancies which have important public health implications. These findings underscore the need for increased awareness, improved clinical practices, enhanced resource allocation, and expanded access to early diagnosis and treatment of prevailing conditions. Preventive strategies targeting immunization and treatment of viral hepatitis, schistosomiasis, and Helicobacter pylori infection are urgently needed.
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Affiliation(s)
- Guda M Roro
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Addis Ababa University, College of Health Science, Addis Ababa 9086, Ethiopia
| | - Rodas T Annose
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Addis Ababa University, College of Health Science, Addis Ababa 9086, Ethiopia
| | - Odd H Gilja
- Department of Clinical Medicine, University of Bergen 5020, Norway
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen 5020, Norway
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14
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Dhoop S, Ghazaleh S, Roberts L, Shehada M, Patel M, Smith WL, Rabeeah S, Sawaf B, Vadehra P, Hart B, Hassan M. Sodium-Glucose Cotransporter-2 Inhibitors in Liver Cirrhosis: A Systematic Review of Their Role in Ascites Management, Slowing Disease Progression, and Safety. Int J Mol Sci 2025; 26:4781. [PMID: 40429923 DOI: 10.3390/ijms26104781] [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: 03/24/2025] [Revised: 05/12/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025] Open
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are widely used for type 2 diabetes mellitus (T2DM), conferring cardiovascular and renal benefits with evidence supporting their role in metabolic-associated steatotic liver disease (MASLD), the fastest rising etiology for liver cirrhosis. Our study collects and synthesizes all available data on SGLT2I use in liver cirrhosis to summarize their potential benefits and risks. We systematically reviewed the literature on SGLT2I use in adults with cirrhosis, focusing on 6 outcome domains, including ascites reduction, disease progression, hemodynamics, acute kidney injury (AKI), electrolyte abnormalities, and infection risk. We identified 16 studies: compensated (n = 5), decompensated (n = 3), and refractory ascites (n = 8). All studies of decompensated cirrhosis (n = 11) reported ascites reduction. Most studies (7 of 9) indicated SGLT2Is slowed disease progression by reducing clinical decompensation (n = 4) or improving laboratory markers (n = 3). A minority of studies revealed safety concerns with 2 of 9 studies showing evidence of hemodynamic instability and acute kidney injury (AKI), 2 out of 13 for electrolyte abnormalities, and 2 out of 5 for infection risk. Current evidence strongly supports SGLT2Is for refractory ascites management and suggests potential benefits in slowing progression across cirrhosis severities. Longer-term prospective trials in patients with non-refractory decompensated cirrhosis and real-world safety data are essential to clarify and potentially expand the role of SGLT2Is in cirrhosis management.
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Affiliation(s)
- Sudheer Dhoop
- Department of Internal Medicine, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
| | - Sami Ghazaleh
- Division of Gastroenterology and Hepatology, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
| | - Luke Roberts
- College of Medicine and Life Sciences, The University of Toledo, 3000 Arlington Ave., Toledo, OH 43614, USA
| | - Mohammed Shehada
- Department of Internal Medicine, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
| | - Manthanbhai Patel
- Department of Internal Medicine, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
| | - Wade-Lee Smith
- University Library, The University of Toledo, 2801 W. Bancroft St., Toledo, OH 43606, USA
| | - Sana Rabeeah
- Department of Internal Medicine, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
| | - Bisher Sawaf
- Department of Internal Medicine, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
| | - Priya Vadehra
- Department of Biological Sciences, Wayne State University, 4841 Cass Ave., Detroit, MI 48201, USA
| | - Benjamin Hart
- Division of Gastroenterology and Hepatology, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
| | - Mona Hassan
- Division of Gastroenterology and Hepatology, The University of Toledo, 3333 Glendale Ave., Toledo, OH 43614, USA
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15
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Zheng K, Dai L, Zhang S, Zhao Y, Li W, Gao Y, Mang Y, Jiao L, Tang Y, Ran J. Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression. Gut Liver 2025; 19:410-426. [PMID: 38623058 PMCID: PMC12070210 DOI: 10.5009/gnl230345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 12/26/2023] [Accepted: 01/03/2024] [Indexed: 04/17/2024] Open
Abstract
Background/Aims : Liver cirrhosis involves chronic inflammation and progressive fibrosis. Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods : This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results : Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions : In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.
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Affiliation(s)
- Kepu Zheng
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
| | - Leiyang Dai
- Inspection Department of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, China
| | - Shengning Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
| | - Yingpeng Zhao
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
| | - Wang Li
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
| | - Yang Gao
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
| | - Yuanyi Mang
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
| | - Lingfeng Jiao
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
| | - Yu Tang
- Kunming Medical University, Kunming, China
| | - Jianghua Ran
- Department of Hepato-Biliary-Pancreatic Surgery, The First People's Hospital of Kunming, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
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Castaño-Jiménez PA, Baltazar-Díaz TA, González-Hernández LA, García-Salcido R, Klimov-Kravtchenko K, Andrade-Villanueva JF, Arellano-Arteaga KJ, Padilla-Sánchez MP, Del Toro-Arreola S, Bueno-Topete MR. Deciphering the Language of Intestinal Microbiota Associated with Sepsis, Organ Failure, and Mortality in Patients with Alcohol-Related Acute-on-Chronic Liver Failure (ACLF): A Pioneer Study in Latin America. Microorganisms 2025; 13:1138. [PMID: 40431310 DOI: 10.3390/microorganisms13051138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 05/05/2025] [Accepted: 05/10/2025] [Indexed: 05/29/2025] Open
Abstract
ACLF is a severe stage of liver cirrhosis, characterized by multiple organ failure, systemic inflammation, and high short-term mortality. The intestinal microbiota (IM) influences its pathophysiology; however, there are currently no studies in Latin American populations. Therefore, we analyzed IM and its relationships with sepsis, organ failure, and mortality. In parallel, we quantified serum lipopolysaccharides as a marker of bacterial translocation. Fecal samples from 33 patients and 20 healthy controls (HCs) were obtained. The IMs were characterized by 16S-rRNA amplicon sequencing, the metagenomic functional predictive profiles were analyzed by PICRUSt2, and LPS quantification was performed by ELISA. Patients with ACLF showed significant alterations in alpha and beta diversity compared to the HCs. A strong dominance index accurately predicted 28-day and 90-day mortalities. The IMs showed a polarization toward Proteobacteria associated with increased LPS. The LPS correlated with clinical severity, organ dysfunction, and higher pathogenic taxa. The Klebsiella/Faecalibacterium ratio showed good performance in identifying sepsis (AUROC = 0.83). Furthermore, Morganella, Proteus, and Klebsiella were enriched in patients with multiorgan failure. Lactobacillus, Escherichia/Shigella, Veillonella, and Ruminococcus gnavus exhibited potential in predicting 28- and 90-day mortalities. The IM alterations in ACLF may be useful as clinical biomarkers of poor prognosis, primarily for mortality and sepsis. These findings are representative of western Mexico.
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Affiliation(s)
- Paula Alejandra Castaño-Jiménez
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
| | - Tonatiuh Abimael Baltazar-Díaz
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
| | - Luz Alicia González-Hernández
- Unidad de VIH, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara 44350, Mexico
- Departamento de Clínicas Médicas, Instituto de Investigación en Inmunodeficiencias y VIH, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
| | - Roxana García-Salcido
- Unidad de Urgencias Médicas, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara 44350, Mexico
| | - Ksenia Klimov-Kravtchenko
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
| | - Jaime F Andrade-Villanueva
- Departamento de Clínicas Médicas, Instituto de Investigación en Inmunodeficiencias y VIH, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
- Unidad de Urgencias Médicas, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara 44350, Mexico
| | | | - Mayra Paola Padilla-Sánchez
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
| | - Susana Del Toro-Arreola
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
| | - Miriam Ruth Bueno-Topete
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico
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Sah AK, Afzal M, Elshaikh RH, Abbas AM, Shalabi MG, Prabhakar PK, Babker AMA, Khalimova FT, Sabrievna VA, Choudhary RK. Innovative Strategies in the Diagnosis and Treatment of Liver Cirrhosis and Associated Syndromes. Life (Basel) 2025; 15:779. [PMID: 40430206 DOI: 10.3390/life15050779] [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: 03/20/2025] [Revised: 04/27/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
Liver cirrhosis continues to be a major global health issue, contributing to high morbidity and mortality due to its progressive nature and associated complications. This review explores recent advancements in the diagnosis and treatment of liver cirrhosis and its related syndromes. Non-invasive diagnostic tools, such as elastography and serum biomarkers, have significantly improved early detection, reducing the need for liver biopsies. Advanced imaging techniques, including MRI and CT, further enhance diagnostic accuracy. In parallel, molecular and genomic research is providing new insights into the pathogenesis of the disease, paving the way for precision medicine. On the treatment front, pharmacological innovations, such as antifibrotic agents and targeted therapies, show promise in slowing disease progression. Endoscopic interventions like variceal banding are improving the management of complications, while advancements in liver transplantation and artificial liver support systems offer life-saving alternatives. Regenerative medicine, particularly stem cell therapy and tissue engineering, is emerging as a promising strategy for liver repair. Managing cirrhosis-related syndromes, including portal hypertension, ascites, hepatic encephalopathy, and hepatorenal syndrome, now involves evolving therapeutic approaches such as transjugular intrahepatic portosystemic shunt (TIPS) and novel pharmacotherapies. Prognostic scoring systems like the MELD and Child-Pugh are being refined with new biomarkers for better risk stratification. The future of cirrhosis care will likely involve the integration of artificial intelligence and machine learning for early diagnosis and personalized treatments, alongside emerging therapies currently under investigation. Despite these advancements, challenges such as costs, accessibility, and healthcare disparities remain barriers to widespread adoption. This review highlights the importance of incorporating innovative diagnostic and therapeutic strategies into clinical practice to improve the outcomes for patients with liver cirrhosis and its complications.
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Affiliation(s)
- Ashok Kumar Sah
- Department of Medical Laboratory Sciences, College of Applied and Health Sciences, A' Sharqiyah University, Ibra 400, Oman
| | - Mohd Afzal
- Department of Medical Laboratory Technology, Arogyam Institute of Paramedical & Allied Sciences (Affiliated to H.N.B. Uttarakhand Medical Education University), Roorkee 247661, India
| | - Rabab H Elshaikh
- Department of Medical Laboratory Sciences, College of Applied and Health Sciences, A' Sharqiyah University, Ibra 400, Oman
| | - Anass M Abbas
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia
| | - Manar G Shalabi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia
| | - Pranav Kumar Prabhakar
- Department of Biotechnology, School of Engineering and Technology, Nagaland University, Meriema, Kohima 797004, India
| | - Asaad M A Babker
- Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman 4184, United Arab Emirates
| | | | - Velilyaeva Aliya Sabrievna
- Department of Psychiatry, Medical Psychology, and Narcology, Samarkand State Medical University, Samarkand 140158, Uzbekistan
| | - Ranjay Kumar Choudhary
- Department of Medical Laboratory Technology, University Institute of Allied Health Sciences, Chandigarh University, Chandigarh 140413, India
- School of Paramedics and Allied Health Sciences, Centurion University of Technology and Management, Sitapur 761211, India
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18
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Yu R, Shi R, Chen J, Zheng X, Yu R. Investigating the Mechanism of the Fuzheng Huayu Formula in Treating Cirrhosis through Network Pharmacology, Molecular Docking, and Experimental Verification. ACS OMEGA 2025; 10:19019-19032. [PMID: 40385224 PMCID: PMC12079202 DOI: 10.1021/acsomega.5c01225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 04/16/2025] [Accepted: 04/17/2025] [Indexed: 05/20/2025]
Abstract
Cirrhosis, characterized by liver fibrosis and structural remodeling, is a leading cause of liver cancer. The Fuzheng Huayu formula (FZHY) has been approved for treating liver fibrosis in China since 2002, but its effects and mechanisms on cirrhosis remain largely unknown. This study employed network pharmacology, molecular docking, and in vitro experiments to elucidate the specific mechanisms of FZHY against liver cirrhosis. First, intersecting genes between FZHY and cirrhosis were obtained from the Chinese Medicine System Pharmacology Database, the Swiss Target Prediction online platform, UniProt, GeneCards, DisGeNET, and OMIM. The STRING database was used to construct a protein-protein interaction network. Subsequently, Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, followed by molecular docking analysis to verify binding affinities between active ingredients and candidate targets. These analyses provided a theoretical basis for subsequent experimental research. Finally, we identified 117 FZHY target genes associated with cirrhosis and constructed a drug-component-target-cirrhosis-pathway network. Enrichment analysis revealed the AGE-RAGE signaling pathway in diabetic complications as a key pathway. Molecular docking showed that Isotanshinone II had the highest affinity for CHUK, IKBKB, and MAPK14. In vitro experiments demonstrated that Isotanshinone II dose-dependently reduced the mRNA expression of COL1A1 and α-SMA, as well as the protein levels of MAPK p38, IKKβ, and NF-κB p65 in LX-2 cells. These results revealed the underlying mechanism by which Isotanshinone II in FZHY inhibited LX-2 cell activation and collagen production through suppression of the MAPK/NF-κB signaling pathway. These findings support Isotanshinone II as a promising compound for cirrhosis targeting the MAPK/NF-κB pathway. Further research is warranted to explore the bioavailability of Isotanshinone II and to optimize its structure for clinical applications.
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Affiliation(s)
- Ruixue Yu
- Medicine
College of Pingdingshan University, Pingdingshan 467000, China
| | - Run Shi
- Medicine
College of Pingdingshan University, Pingdingshan 467000, China
| | - Jinghua Chen
- Northwest
Institute of Plateau Biology, Chinese Academy
of Sciences, Xining 810008, China
| | - Xinhua Zheng
- Medicine
College of Pingdingshan University, Pingdingshan 467000, China
| | - Ruitao Yu
- Qinghai
Provincial Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy
of Sciences, Xining 810008, China
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19
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Quammie S, Crooks CJ, Aliyu A, Aithal GP, Aravinthan AD. Chronic pancreatitis and extra pancreatic cancers- A systematic review and meta analysis. Pancreatology 2025:S1424-3903(25)00088-2. [PMID: 40382256 DOI: 10.1016/j.pan.2025.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 03/11/2025] [Accepted: 05/10/2025] [Indexed: 05/20/2025]
Abstract
INTRODUCTION Chronic pancreatitis (CP) is a known risk factor for pancreatic cancer; however its association to extra pancreatic (EP) cancers remains inadequately explored. The aim of this systematic review is to investigate the evidence for CP as a risk factor for developing EP cancers. METHOD Electronic search was conducted on Ovid Medline, EMBASE and Scopus from inception to January 27, 2024 to identify patients with CP who developed EP cancers. Prevalence and incidence of each cancer were calculated where possible from the reported numbers. A random effects meta-analysis was used to pool prevalence, incidence and hazard ratios (HR) of each EP cancer. Heterogeneity was assessed using I2. PROSPERO registration: CRD42024543050. RESULTS Sixteen (16) studies consisting of 117,163 CP patients met the eligibility criteria. 4015 (3.4%) patients developed 4019 EP cancers. The overall annual prevalence and incidence of EP cancers were 7962 (95% CI 5044-10880) per 100,000 CP patients and 1039 (95% CI 649-1663) per 100,000 person years. Lung cancer had the highest annual prevalence - (1540 (95% CI 667-2413) per 100,000 CP patients) and incidence (260 (95% CI 120-390) per 100,000 person years). The pooled HR were 1.31 (95% CI 1.03-1.66) and 1.58 (95% CI 1.27-1.98) for adjusted lung cancer and crude liver cancer in patients with CP compared to patients without CP, respectively. CONCLUSION Patients with CP have an increased risk of developing EP cancers compared to patients without CP, in particular lung and liver cancer which had the highest relative risk. Shared risk factor modifications, such as smoking cessation and alcohol reduction, could lower the risk of common EP cancers. Further, implementing non-invasive screening measures may aid in early diagnosis in this high-risk group.
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Affiliation(s)
- Shauntelle Quammie
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK; Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | - Colin John Crooks
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK; Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | - Abdulsalam Aliyu
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | - Guruprasad P Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK; Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | - Aloysious D Aravinthan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK; Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
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20
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Chvatal-Medina M, Li Y, Trillos-Almanza MC, Post A, Connelly MA, Moshage H, Bakker SJL, Meijer VED, Blokzijl H, Dullaart RPF, TransplantLines Investigators. Plasma Beta-Hydroxybutyrate and All-Cause Mortality in Patients with Liver Cirrhosis. Biomedicines 2025; 13:1120. [PMID: 40426948 DOI: 10.3390/biomedicines13051120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2025] [Revised: 04/28/2025] [Accepted: 04/30/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Liver cirrhosis is often accompanied by metabolic dysfunction. Circulating β-hydroxybutyrate (BHB), the most abundant ketone body, is an emerging metabolic biomarker of mitochondrial dysfunction. Methods: In this prospective observational study, we evaluated plasma BHB concentrations in patients with cirrhosis compared to the general population and investigated their association with all-cause mortality in cirrhosis. Plasma BHB, measured by nuclear magnetic resonance spectroscopy, was compared between 125 patients with cirrhosis on the waiting list for liver transplantation (TransplantLines cohort study; NCT03272841) with 125 propensity-score-matched participants from the population-dwelling PREVEND cohort. Associations of BHB with all-cause mortality were established by tertile-based log-rank tests and Cox regression analyses. A generalized additive model was fitted to assess a potential non-linear association between BHB and mortality. Results: Patients with cirrhosis had lower plasma BHB concentrations than matched PREVEND participants (111.5 µmol/L vs. 138.4 µmol/L, p = 0.02). During 133 (interquartile range 42-375) days of follow up, 27 patients died. All-cause mortality was lowest in the middle BHB tertile and highest in the upper BHB tertile (p < 0.001 by log-rank test). A non-linear, J-shaped association between BHB levels and mortality risk was found with a higher risk of death with the highest and lowest BHB levels. In Cox regression analyses, adjusted for age, sex, MELD score, diabetes, and HDL cholesterol, mortality was highest in the highest BHB tertile (T3 vs. T2 HR: 7.6, 95% CI: 2.3-25.6, p < 0.001). Mortality also tended to be higher in the lowest vs. the middle (T1 vs. T2 HR: 3.5, 95% CI: 0.9-11.7, p = 0.06). Sensitivity analyses, excluding diabetic patients and those with metabolic dysfunction-associated steatotic liver disease, confirmed the robustness of these findings. Conclusion: BHB levels exhibit a J-shaped association with the risk of death in patients with liver cirrhosis. The highest circulating BHB levels are independently associated with increased mortality risk, potentially reflecting underlying metabolic dysregulation. Future studies are necessary to validate the utility of BHB as a prognostic target in cirrhosis.
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Affiliation(s)
- Mateo Chvatal-Medina
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | - Yakun Li
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | - María Camila Trillos-Almanza
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | - Adrian Post
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | | | - Han Moshage
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
| | - Robin P F Dullaart
- Department of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
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21
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Díaz LA, Alazawi W, Agrawal S, Arab JP, Arrese M, Idalsoaga F, Barreyro FJ, Gadano A, Marciano S, Morales JM, Villela-Nogueira C, Leite N, Couto CA, Theodoro R, Joyner de Sousa Dias Monteiro M, Oliveira CP, Pessoa MG, Alvares-da-Silva MR, Madamba E, Bettencourt R, Richards LM, Majithia AR, Khera AV, Loomba R, Ajmera V. High inherited risk predicts age-associated increases in fibrosis in patients with MASLD. J Hepatol 2025:S0168-8278(25)00294-6. [PMID: 40334848 DOI: 10.1016/j.jhep.2025.04.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 03/24/2025] [Accepted: 04/23/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND & AIMS Limited data have prevented routine genetic testing from being integrated into clinical practice in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to quantify the effect of genetic variants on changes in fibrosis severity per decade in MASLD. METHODS This cross-sectional study included prospectively recruited adults with MASLD aged 18-70 who underwent magnetic resonance elastography (MRE) and genotyping for PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13. A genetic risk score (GRS) was calculated as the sum of established risk alleles in PNPLA3 minus protective variants in HSD17B13 (0=low risk, 1=high risk). We also estimated the polygenic risk score-hepatic fat content (PRS-HFC) and the adjusted version (PRS-5). The primary endpoint was the age-related change in liver stiffness measurement (LSM) on MRE by GRS. Findings were validated using an external cohort from Latin America. RESULTS Among 570 participants, the median age was 57 [49-64] years, 56.8% were women, and 34.2% were Hispanic. Median MRE was 2.4 [2.1-3.0] kPa, and 51% had high GRS. High GRS was independently associated with increased LSM (β=0.28 kPa, 95%CI:0.12-0.44, p=0.001) per 10-year age increase, while the low GRS group showed no significant difference. Similar findings were observed using PRS-HFC and PRS-5. PNPLA3 genotype alone also predicted higher LSM (C/G: β=0.32 kPa, 95%CI:0.02-0.61, p=0.034; G/G: β=0.87 kPa, 95%CI:0.52-1.22, p<0.0001) and G/G genotype was associated with significantly higher LSM by age 44, which was consistent in the validation population. CONCLUSION GRS, PRS-HFC, PRS-5, and PNPLA3 genotypes alone are associated with greater fibrosis per decade, resulting in divergent disease trajectories starting in midlife. Assessing genetic risk in MASLD will identify high-risk patients who require more frequent monitoring. IMPACT AND IMPLICATIONS This study provides granular evidence that genetic predisposition, particularly the PNPLA3 G/G genotype, significantly influences the trajectory of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), with a more pronounced impact emerging after the fourth decade of life. These findings highlight the importance of incorporating genetic risk assessment into MASLD management, as it allows for the early identification of high-risk individuals who may benefit from more frequent monitoring and targeted interventions. Given the rising global burden of MASLD, clinicians, researchers, and policymakers should consider integrating genetic stratification into existing risk assessment frameworks to refine screening and surveillance strategies. By optimizing patient selection for non-invasive fibrosis assessment and potential therapeutic interventions, this approach could enhance precision medicine efforts and may improve long-term outcomes.
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Affiliation(s)
- Luis Antonio Díaz
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA; Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - William Alazawi
- Barts Liver Centre, Blizard Institute, Queen Mary University London, London, UK
| | - Saaket Agrawal
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
| | - Juan Pablo Arab
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Idalsoaga
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Gastroenterology and Hepatology Western University & London Health Sciences Centre, London, Canada
| | - Fernando Javier Barreyro
- Departamento de Gastroenterología, Hospital Escuela, Laboratorio de Biotecnologia Molecular, CONICET, Universidad Nacional de Misiones, Misiones, Argentina
| | - Adrian Gadano
- Unidad de Hepatología y Trasplante Hepático, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Sebastián Marciano
- Unidad de Hepatología y Trasplante Hepático, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Jorge Martínez Morales
- Unidad de Hepatología y Trasplante Hepático, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Cristiane Villela-Nogueira
- Escuela de Medicina e División de Hepatología, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Nathalie Leite
- Escuela de Medicina e División de Hepatología, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Claudia Alves Couto
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Minas Gerais, Brazil
| | - Rafael Theodoro
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Minas Gerais, Brazil
| | | | - Claudia P Oliveira
- Departamento de Gastroenterologia (LIM07), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Mario G Pessoa
- Departamento de Gastroenterologia (LIM07), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Mario Reis Alvares-da-Silva
- Serviço de Gastroenterologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Egbert Madamba
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA
| | - Ricki Bettencourt
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA
| | - Lisa M Richards
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA
| | - Amit R Majithia
- Department of Medicine, Division of Endocrinology, University of California San Diego, La Jolla, CA, USA
| | - Amit V Khera
- Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Verve Therapeutics, Boston, MA, USA
| | - Rohit Loomba
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA; Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA
| | - Veeral Ajmera
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA; Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
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22
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Brunetto B, Saraiva L, Callegari-Jacques SM, Ferri H, Lizott HB, Valões R, Fernandes SA, Hoppe L, Fornari F. Reduced Mastication Is Associated With Dynapenia Markers in Patients With Cirrhosis: A Cross-Sectional Study. Int J Hepatol 2025; 2025:5842659. [PMID: 40365525 PMCID: PMC12069846 DOI: 10.1155/ijh/5842659] [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: 12/10/2024] [Accepted: 04/09/2025] [Indexed: 05/15/2025] Open
Abstract
Background and Aim: Dental diseases are common in patients with cirrhosis. In these patients, reduced mastication might interfere with protein intake and contribute to malnutrition. We addressed the relationship between reduced mastication and dynapenia in patients with cirrhosis. Methods: This cross-sectional study involved patients with cirrhosis treated in a Brazilian center. Trained dentists performed oral examinations and tested the patients for nutritional parameters such as handgrip strength (HGS) and gait speed test (GST). Reduced mastication was presumed when a patient had molar edentulism (≥ 3 teeth), bad dental occlusion, or ill-fitting denture. Associations between mastication status and malnutrition were evaluated using multivariate linear regression analysis for continuous measures and adjusted prevalence ratio (PR (95% confidence interval)) for binary measures. Results: We included 149 patients with cirrhosis (60 ± 13 years old, 76% men, 64% Child A, 60% due to alcoholism only). Reduced mastication affected 107 patients (72%), low muscle strength (decreased HGS) occurred in 45 (30%), and decreased GST was observed in 58 (41%, among 143 patients able to walk). Thirty-one out of 143 (22%) presented decreased HGS and GST, characterizing dynapenia. Reduced mastication was associated either with decreased HGS [PR = 2.28 (1.08-4.81), p = 0.030; reduced mastication decreases the HGS mean by 12.5 kg for men (p < 0.001) and 8.1 kg for women (p = 0.065)] or with decreased GST [PR 1.97 (1.09-3.55), p = 0.024; reduced mastication increased the time of GST by 1.1 s on average (p = 0.005)], adjusting for age, alcoholic etiology, and Child-Pugh classification. Conclusions: Reduced mastication is associated with dynapenia markers in patients with cirrhosis. Further studies are needed to assess whether oral rehabilitation can change the curse of malnutrition in this population.
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Affiliation(s)
- Bruna Brunetto
- Post Graduate Program in Dentistry, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
| | - Leonardo Saraiva
- Post Graduate Program in Dentistry, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
| | | | - Hérica Ferri
- Post Graduate Program in Dentistry, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
| | | | - Ricardo Valões
- School of Medicine, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
- Hepatology Department, São Vicente de Paulo Hospital, Passo Fundo, Rio Grande do Sul, Brazil
| | - Sabrina Alves Fernandes
- Post Graduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Lisia Hoppe
- School of Medicine, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
- Hepatology Department, São Vicente de Paulo Hospital, Passo Fundo, Rio Grande do Sul, Brazil
| | - Fernando Fornari
- Post Graduate Program in Dentistry, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
- School of Medicine, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
- Hepatology Department, São Vicente de Paulo Hospital, Passo Fundo, Rio Grande do Sul, Brazil
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23
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Ma L, Jiang H, Qu N. Mendelian randomization analysis of smoking, BMI, and nonalcoholic fatty liver disease in European descent populations. Medicine (Baltimore) 2025; 104:e42308. [PMID: 40324243 PMCID: PMC12055159 DOI: 10.1097/md.0000000000042308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 12/27/2024] [Accepted: 04/14/2025] [Indexed: 05/07/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition with a steadily increasing prevalence. Evidence indicates that both smoking and obesity are significant risk factors for NAFLD, yet the extent to which smoking influences NAFLD through weight gain remains unclear. This study aimed to dissect the intricate relationship between smoking, body mass index (BMI), and NAFLD using Mendelian randomization (MR) analysis. We leveraged data from 30 genome-wide association studies involving over 1.2 million individuals, from which 123 single nucleotide polymorphisms were selected as instrumental variables for smoking. BMI data were sourced from the Genetic Investigation of Anthropometric Traits (GIANT) consortium, encompassing more than 700,000 individuals, with 521 single nucleotide polymorphisms serving as instrumental variables. NAFLD data were obtained from multiple databases, including the eMERGE Network, UK Biobank, Estonian Biobank, and FinnGen, comprising 8434 cases and 770,180 controls. All participants in this study were of European ancestry. We first applied univariate MR analysis to assess the causal relationship between smoking, NAFLD, and BMI. Subsequently, multivariate MR was used to assess the effect of smoking on NAFLD after adjusting for BMI. The coefficient product method was used to calculate the mediating effect of BMI. Results found that both smoking and high BMI were able to increase the risk of NAFLD, with odds ratios of 1.83 (95% confidence interval [CI]: 1.31-2.55) and 1.58 (95% CI: 1.42-1.77), respectively. BMI mediated 73.3% (95% CI: 62.3%-80.5%) of the effect of smoking on NAFLD. The findings support weight control and the encouragement of smoking cessation, especially in obese populations, as strategies to reduce the risk of NAFLD.
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Affiliation(s)
- Lei Ma
- The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
- The First Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China
| | - Haixing Jiang
- The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
| | - Nanfang Qu
- The First Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China
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24
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Giri S, Ingawale S, Khatana G, Gore P, Praharaj DL, Wong VWS, Huang DQ, Singhal A, Choudhury A. Metabolic Cause of Cirrhosis Is the Emerging Etiology for Primary Liver Cancer in the Asia-Oceania Region: Analysis of Global Burden of Disease (GBD) Study 2021. J Gastroenterol Hepatol 2025; 40:1188-1201. [PMID: 40016821 DOI: 10.1111/jgh.16922] [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: 12/13/2024] [Revised: 02/12/2025] [Accepted: 02/14/2025] [Indexed: 03/01/2025]
Abstract
INTRODUCTION Studies have shown a change in the etiological profile of liver cancer globally. We aimed to analyze the burden and changes in etiology of liver cancer in the Asia-Oceania region. METHODS The burden of liver cancer in Asia-Oceania was estimated using data from the 2021 Global Burden of Disease (GBD) Study. The analysis included age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALY) per 100 000 population. RESULTS The Asia-Oceania region contributed 68.6%, 68.8%, and 67.3% of the global incidence, prevalence, and mortality of liver cancer in 2021. In 2021, Mongolia, Tonga, and South Korea had the highest ASIR, ASPR, and ASMR, whereas Australia, New Zealand, and Guam had the greatest increase in incidence and mortality rates. Viral hepatitis remained the most common etiology of liver cancer, with 47.7% and 26.1% of cases being related to hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. Around 14.5% and 7.1% of cases were related to alcohol and nonalcoholic steatohepatitis (NASH), respectively; however, the annual change in the ASIR was the highest for NASH. Alcohol, drug abuse, tobacco use, and metabolic syndrome, contributed to 15.2%, 11.7%, 11.5%, and 9.0% of liver cancer mortality in 2021; however, the change in death from 1990 to 2021 was the highest for metabolic syndrome. CONCLUSION Viral hepatitis remains the most common cause of liver cancer, with NASH having the highest annual rate of change in ASIR and liver cancer deaths in Asia-Oceania.
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Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Sushrut Ingawale
- Division of Internal Medicine, Frank H. Netter MD School of Medicine, Bridgeport, Connecticut, USA
| | - Gaurav Khatana
- Department of Gastroenterology, Government Medical College, Kottayam, India
| | - Prasanna Gore
- Department of Gastroenterology, Wellness Hospital, Hyderabad, India
| | - Dibya Lochan Praharaj
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease and Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Daniel Q Huang
- Department of Medicine, 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
| | - Amit Singhal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Friesen JN, Maberry M, Olson JC, Gallo de Moraes A. Exploring Rapid Response Team Activation Impact in Patients with Cirrhosis with Acute Decompensation. J Intensive Care Med 2025; 40:528-535. [PMID: 39584698 DOI: 10.1177/08850666241302024] [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: 11/26/2024]
Abstract
Background: Cirrhosis is associated with significant healthcare utilization, yet data about in-hospital decompensations remain sparse. Additionally, the impact of liver transplant candidacy status on resuscitation and outcomes is largely unknown. Aims:We aimed to evaluate the characteristics of resuscitation events for patients with cirrhosis with acute decompensation, analyzing liver transplant candidacy and intensive care unit (ICU) transfer parameters. Methods: Retrospective single-center review of adult patients with liver cirrhosis who had a rapid response team (RRT) activation during hospitalization and no prior liver transplantation. Results: Patients with cirrhosis who were liver transplant candidates were more likely to be younger (p = .003), have a higher serum total bilirubin (p = .015), higher INR (p < .001), and higher MELD 3.0 (p = .006). There was no significant difference in ICU transfer (p = .170) after RRT activation. Liver transplant candidates had a lower 30- and 60-day mortality (p = .008, p = .014) and were less likely to have a code status discussion after decompensation (p = .001). Lower serum albumin was associated with ICU transfer (p = .001). Patients who transferred to the ICU were more likely to have a code status discussion within 24 h after RRT (p = .011) without significant difference in 30- or 60-day mortality (p = .059, p = .277). Conclusions: Liver transplant candidacy in patients with cirrhosis with acute decompensation is not clearly correlated with ICU transfer. Liver transplant candidates are more likely to be younger, have higher MELD 3.0 scores, less likely to have code status discussed after RRT, and have lower 30- and 60-day mortality rates. Patients who transfer to the ICU are more likely to have a code status discussion without any significant difference in 30- or 60-day mortality.
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Affiliation(s)
- Joelle N Friesen
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - Jody C Olson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
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Wong RJ, Gagnon-Sanschagrin P, Heimanson Z, Maitland J, Bellefleur R, Guérin A, Samson A, Olujohungbe O, Bumpass B. Real-World Trends and Future Projections of the Prevalence of Cirrhosis and Hepatic Encephalopathy Among Commercially and Medicare-Insured Adults in the United States. Clin Transl Gastroenterol 2025; 16:e00823. [PMID: 39835684 PMCID: PMC12101919 DOI: 10.14309/ctg.0000000000000823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 01/11/2025] [Indexed: 01/22/2025] Open
Abstract
INTRODUCTION Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using healthcare claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated healthcare resource utilization among commercially and Medicare-insured adults in the United States. METHODS Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020). Annual prevalence of cirrhosis, HE, overt HE (OHE) hospitalizations, and rifaximin ± lactulose use, and costs per hospitalization per year were calculated. Average year-over-year changes in prevalence of cirrhosis, and HE were estimated. Trends were extrapolated to 2030 using ordinary least-squares regression. RESULTS From 2007 to 2020, the prevalence of cirrhosis increased by an average of 4.6% year-over-year in the Commercial population and 8.1% in the Medicare population; the prevalence of HE increased by 4.3% and 2.5%, respectively. Rates of OHE hospitalizations decreased from 27.5% to 5.5% (Commercial) and from 26.2% to 9.5% (Medicare), and rates of liver transplantation increased. Average payer costs (Commercial) and provider charges (Medicare) per OHE hospitalization increased (from $40,881 to $77,699 and from $45,913 to $74,894, respectively). Use of rifaximin ± lactulose showed an increasing trend during the observation period, whereas lactulose use declined steadily. DISCUSSION The healthcare burden of cirrhosis and HE in the United States is increasing. Trends are projected to continue unless action is taken, such as improving medication access and developing policies addressing the contributing factors.
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Affiliation(s)
- Robert J. Wong
- Gastroenterology and Hepatology Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
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Ichikawa T, Yamashima M, Yamamichi S, Koike M, Nakano Y, Yajima H, Miyazaki O, Ikeda T, Okamura T, Komatsu N, Sugio S, Yoshino M, Miyaaki H. Pemafibrate Reduced Liver Stiffness in Patients with Metabolic Dysfunction-associated Steatotic Liver Disease Complicated with Hyperlipidemia and Liver Fibrosis with a Fibrosis-4 Index Above 1.3. Intern Med 2025; 64:1296-1302. [PMID: 39293976 DOI: 10.2169/internalmedicine.4337-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/20/2024] Open
Abstract
Objective To evaluate the effect of pemafibrate (PEM) on metabolic dysfunction-associated steatotic liver disease (MASLD). Methods We retrospectively evaluated 43 patients with hyperlipidemia and MASLD to determine changes in clinical factors between the start of PEM treatment and 0.5 years later. Using FibroScan, 39 of 43 patients were evaluated for liver stiffness (LS; kPa) and controlled attenuation parameter (CAP; dB/m). None of the patients had decompensated cirrhosis. Results Thirty patients were women, the median age was 66 years old, the median fibrosis-4 (FIB-4) score was 2.52, the median LS was 8.05 kPa, and the median CAP was 280.5 dB/m at the start of PEM treatment. AST, ALT, ALP, γGTP, and triglyceride levels decreased 0.5 years after starting PEM treatment, but FIB-4, LS, and CAP values did not decrease. However, LS decreased in patients with a FIB-4 index ≥1.3 at the start of PEM treatment, whereas it did not change in patients with a FIB-4 index <1.3. Similarly, LS decreased in patients with a value ≥8 kPa at the start of treatment and did not change in those with <8 kPa. The decreased LS group had higher baseline ALT and LS levels and lower ALT levels during 0.5 years of follow-up than the increased LS group. Conclusion At the initiation of PEM treatment, the LS decreased in patients with MASLD complicated by hyperlipidemia and moderate LS (FIB-4>1.3 or LS >8 kPa). Although there is currently no approved treatment for MASLD, PEM may be a viable treatment option for MASLD with mild LS.
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Affiliation(s)
- Tatsuki Ichikawa
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
- Department of Comprehensive Community Care Systems, Graduate School of Biomedical Sciences, Nagasaki University, Japan
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
| | - Mio Yamashima
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Shinobu Yamamichi
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Makiko Koike
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
| | - Yusuke Nakano
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
| | - Hiroyuki Yajima
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Osamu Miyazaki
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Tomonari Ikeda
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Takuma Okamura
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
- Department of Comprehensive Community Care Systems, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Naohiro Komatsu
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Sayuri Sugio
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Miruki Yoshino
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
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Behroozi Z, Hassani D, Mobini M, Bahadori T, Peyghami K, Judaki MA, Khoshnoodi J, Amiri MM, Golsaz-Shirazi F, Shokri F. Production and characterization of monoclonal antibodies against hepatitis B e-antigen and their potential application for development of HBeAg detection ELISA. Biologicals 2025; 90:101819. [PMID: 39892062 DOI: 10.1016/j.biologicals.2025.101819] [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: 11/06/2024] [Revised: 01/08/2025] [Accepted: 01/24/2025] [Indexed: 02/03/2025] Open
Abstract
Despite global vaccination efforts, hepatitis B virus (HBV) infection remains a major health threat, causing over a million deaths annually. Hepatitis B e-antigen (HBeAg) is an indicator of HBV replication and high infectivity. HBeAg is an essential serological marker for monitoring response to treatment and/or determining the stage of chronic HBV infection. Here, we produced a panel of mouse hybridomas secreting monoclonal antibodies (MAbs) to HBeAg by fusing a mouse myeloma cell line with splenocytes from mice immunized with recombinant HBeAg. Anti-HBe MAbs were then characterized by competition ELISA and Western blotting. We designed and optimized an in-house sandwich ELISA using HBeAg-specific rabbit polyclonal and mouse monoclonal antibodies. The diagnostic performance of the assay was then compared to a commercial HBeAg detection ELISA kit using 176 HBeAg[-] and 44 HBeAg[+] serum samples, showing a significant positive correlation (r = 0.8250; P < 0.0001). The in-house ELISA showed reasonable sensitivity (97.56 %) and specificity (99.40 %), with a cut-off value and area under the curve of 0.193 and 0.9884, respectively. Additionally, the assay showed high repeatability, with intra- and inter-assay coefficients of variation of 2.46 % and 11.38 %, respectively. Our designed HBeAg-detecting sandwich ELISA has the potential for use in clinical diagnosis.
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Affiliation(s)
- Zeinab Behroozi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Danesh Hassani
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Mobini
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Tannaz Bahadori
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Kiana Peyghami
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Judaki
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Jalal Khoshnoodi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Mehdi Amiri
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Forough Golsaz-Shirazi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
| | - Fazel Shokri
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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Abad-Jordà L, Martínez-Alcocer A, Guixé-Muntet S, Hunt NJ, Westwood LJ, Lozano JJ, Gallego-Durán R, Cogger VC, Fernández-Iglesias A, Gracia-Sancho J. miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease. Hepatol Commun 2025; 9:e0700. [PMID: 40304581 PMCID: PMC12045533 DOI: 10.1097/hc9.0000000000000700] [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: 10/24/2024] [Accepted: 02/19/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND During chronic liver diseases, LSECs undergo a dedifferentiation process contributing to the development of hepatic microvascular dysfunction. Although microRNAs (miRNAs) have been associated with chronic liver disease, their role as modulators of liver endothelial phenotype is mostly unknown. Therefore, the aim of this study was to analyze miRNAs as regulators of hepatic sinusoidal endothelial dysfunction in chronic liver disease to suggest novel and translatable therapeutic options for cirrhosis. METHODS Global expression of miRNAs was determined in primary LSECs from healthy and cirrhotic patients (alcohol abuse) and rats (CCl4 inhalation). LSECs were transfected with the mimetic or inhibitor of dysregulated miRNAs or with quantum dot nano-complexes containing miR-27b-3p or negative control, and endothelial phenotype was analyzed by RNA sequencing, quantitative PCR, and western blot. Endothelial or mesenchymal phenotypes were analyzed in LSEC by RNA sequencing, followed by pathway analyses and gene deconvolution. RESULTS In all, 30 and 69 dysregulated miRNAs were identified in human and rat cirrhosis, respectively, of which 6 miRNAs were commonly dysregulated. Specific exogenous downregulation of miR-27b-3p was associated with the upregulation of target genes, suggesting a correlation between loss of miR-27b-3p and LSEC dedifferentiation. Finally, the expression of miR-27b-3p was efficiently and physiologically re-established in cirrhotic LSECs using nano-miR-27b-3p, leading to modulation of 1055 genes compared with the negative control, ultimately leading to inhibition of the endothelial-to-mesenchymal transition process observed in cirrhosis. CONCLUSIONS Loss of miR-27b-3p expression contributes to LSECs dedifferentiation in cirrhosis. The use of nano-miR-27b-3p represents a new therapeutic option for hepatic diseases coursing with endothelial dysfunction.
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Affiliation(s)
- Laia Abad-Jordà
- Liver Vascular Biology Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain
| | - Ana Martínez-Alcocer
- Liver Vascular Biology Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain
| | - Sergi Guixé-Muntet
- Liver Vascular Biology Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Nicholas J. Hunt
- ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, New South Wales, Australia
- Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Camperdown, New South Wales, Australia
| | - Lara J. Westwood
- ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, New South Wales, Australia
- Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Camperdown, New South Wales, Australia
| | - Juan José Lozano
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Rocío Gallego-Durán
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- SeLiver Group, Instituto de Biomedicina de Sevilla/CSIC/Hospital Virgen del Rocío, Sevilla, Spain
| | - Victoria C. Cogger
- ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, New South Wales, Australia
- Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Camperdown, New South Wales, Australia
| | - Anabel Fernández-Iglesias
- Liver Vascular Biology Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Jordi Gracia-Sancho
- Liver Vascular Biology Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Gu Y, Guo C, Liu Z, Zhang Y, Han X, Zhang X, Zhao S, Wang H, Zhang T. The trend in incidence of non-alcoholic fatty liver disease and its impact on cirrhosis and liver cancer: An analysis from Global Burden of Disease 2021. Public Health 2025; 242:79-86. [PMID: 40037155 DOI: 10.1016/j.puhe.2025.02.028] [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: 08/21/2024] [Revised: 02/04/2025] [Accepted: 02/20/2025] [Indexed: 03/06/2025]
Abstract
OBJECTIVES We aimed to recognize the burden of NAFLD and support public health policy development for its prevention and management. STUDY DESIGN A cross-sectional analysis of GBD 2021 results was conducted. METHODS We collected incidence data on NAFLD from 1990 to 2021 using Global Burden of Disease Study in 2021. Estimated annual percentage changes (EAPCs) in NAFLD age standardized incidence rate (ASR) were calculated to quantify the temporal trends in NAFLD ASR. Bayesian age-period-cohort models were constructed to project NAFLD incidence rates and cases up to 2050. Additionally, we assessed the percentage of cirrhosis and liver cancer attributable to NAFLD. RESULTS Globally, the newly-occurred cases of NAFLD increased by 94.49 % from 24, 856, 159 in 1990 to 48, 353, 272 in 2021. The case number will further increase to 78,602,984 in 2050, and ASR will increase from 5.93 per 1000 in 2021 to 7.26 per 1000 in 2050. The most pronounced increases were observed in young people and men. In 2021, NAFLD accounted for 82.7 % of cirrhosis and other chronic liver diseases and 8.0 % of liver cancer cases. CONCLUSIONS From 1990 to 2021, the incidence of NAFLD has been continuously increasing and is expected to continue rising until 2050. The increases in young people and men highlight their priority in future schedules. The rising proportions of cirrhosis and liver cancer caused by NAFLD further underscore the serious health risks.
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Affiliation(s)
- Yu Gu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Chengnan Guo
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Zhenqiu Liu
- Fudan University Taizhou Institute of Health Sciences, Taizhou, 225300, China; State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, 200032, China
| | - Yujiao Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Xinyu Han
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Xin Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Shuzhen Zhao
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Haili Wang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Tiejun Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, 200032, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, 225300, China; Yiwu Research Institute, Fudan University, Yiwu, 200032, China.
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Lim J, Lee HY, Sang H, Jeong SJ, Kim HI. Association of nucleos(t)ide analogue therapy with Parkinson disease in chronic hepatitis B patients. Sci Rep 2025; 15:15192. [PMID: 40307244 PMCID: PMC12044151 DOI: 10.1038/s41598-025-00110-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 04/24/2025] [Indexed: 05/02/2025] Open
Abstract
Prolonged therapy using nucleos(t)ide analogs (NUC) is inevitable in patients with chronic hepatitis B (CHB) infection, but its long-term impact on Parkinson's disease (PD) risk remains unclear. This study evaluated the association between NUC therapy and PD incidence in a nationwide CHB cohort. The study population comprised the National Health Insurance Service claims database from January 1, 2013, to December 31, 2013, only included treatment naïve CHB patients and those without previously diagnosed with PD. Participants were followed until PD diagnosis or study completion. The primary outcome was PD incidence, comparing patients who initiated NUC therapy at cohort entry with those who did not. Over the 7.9-year study period, the incidence rate of PD in NUC-treated patients was 1.48 per 1000 persons, compared to 1.95 per 1000 persons in the untreated group. In an adjusted competing risk model, the 3-year follow-up showed a statistically significant reduction in risk (hazard ratio [HR]: 0.61; 95% confidence interval [CI] 0.39-0.97). In the propensity score-matched cohort of 18,365 pairs, the cumulative incidence during 2-4 years of follow-up was significantly lower in the NUC-treated group compared to the untreated group. However, no statistically significant difference in cumulative PD incidence was observed between the groups at the early or late stages of the follow-up period. NUC therapy initially reduced PD incidence, but this protective effect diminished over time, indicating a time-varying effect. Regular PD screening may be needed for long-term NUC users.
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Affiliation(s)
- Jihye Lim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyo Young Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Hyunji Sang
- Department of Endocrinology and Metabolism, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Su Jin Jeong
- Clinical Research Institute, Kyung Hee University Medical Center, 24, Kyunghee dae-ro, Dongdaemun-gu, Seoul, 02453, Republic of Korea.
| | - Ha Il Kim
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, 153, Gyeongchun-ro, Guri, 11923, Republic of Korea.
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Ahmed KAA, Al-Qaisi TS, A J Jabbar A, Ismail PAS, Hussein M Raouf MM, Althagbi HI, Wahab BAA, Hassan RR, Abdulla MA, Al-Dabhawi AH, Saleh MI. A flavonoid Ombuin ameliorates thioacetamide-mediated liver cirrhosis in vivo: biochemical, immunohistochemical, inflammatory approaches. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04147-2. [PMID: 40304746 DOI: 10.1007/s00210-025-04147-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Accepted: 04/04/2025] [Indexed: 05/02/2025]
Abstract
Liver cirrhosis is posing a global public health concern despite improvements in early diagnosis and therapeutic innovations. The present work evaluates the acute toxicity and prophylactic effects of an O-methylated flavonoid (Ombuin) in thioacetamide (TAA)-induced liver injury in rats and its underlying mechanisms. Thirty Sprague-Dawley rats were aligned into five cages and treated for two months as follows: group A ingested orally 1% CMC + distilled water (i.p.); group B had 1% CMC + 200 mg/kg TAA i.p. (three times weekly); group C had 50 mg/kg silymarin + 200 mg/kg TAA; group D had 30 mg/kg Ombuin + TAA; group E had 60 mg/kg Ombuin + mg/kg TAA. The non-toxic effects of Ombuin were evidenced by the lack of any toxicity incidence in rats ingested with up to 500 mg/kg. The TAA inoculation provoked significant hepatic intoxication confirmed by histopathological indications, alteration of tissue architecture, cellular proliferation, endothelial injury, enlarged hepatic nucleus, cytoplasmic vacuolation, collagen deposition, and elevated necrotizing tissues. The oxidative stress and inflammation process was noticeably initiated following TAA delivery to rats evidenced by down-regulation of SOD, CAT, GPx, and IL- 10, while, up-regulating the MDA and TNF-α and IL- 6 cytokines. TAA injection stimulated cellular proliferation and apoptotic actions in injured liver tissues, indicated by increased proliferating cell nuclear antigen (PCNA) and elevated expression of Bcl- 2-associated X (Bax) proteins. Ombuin supplementation showed significant resistance against TAA-mediated hepatotoxicity, reversed those cellular alterations, and restored liver functions. These results demonstrate significant ameliorative effects of Ombuin in TAA hepatotoxic rats, which could be attributed to its anti-apoptotic, antioxidant, and anti-inflammatory potentials, making it a possible viable hepatoprotective agent for inflammatory-related hepatitis.
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Affiliation(s)
- Khaled Abdul-Aziz Ahmed
- Department of Basic Dental Sciences, Faculty of Dentistry, Al-Ahliyya Amman University, Amman, 19328, Jordan
| | - Talal Salem Al-Qaisi
- Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, P.O. Box 59911, Abu Dhabi, United Arab Emirates
| | - Ahmed A J Jabbar
- Department of Medical Laboratory Technology, Erbil Technical Health and Medical College, Erbil Polytechnic University, Erbil, 44001, Iraq.
| | | | - Mohammed M Hussein M Raouf
- Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Kurdistan Region, Erbil, 44001, Iraq
| | | | - Bassam Ali Abed Wahab
- Department of Physiology, Biochemistry and Pharmacology, Faculty of Vet Medicine, University of Kufa, Kufa, Iraq
| | - Rawaz Rizgar Hassan
- Department of Medical Laboratory Science, College of Science, Knowledge University, Kirkuk Road, Erbil, 44001, Iraq
| | - Mahmood Ameen Abdulla
- Department of Medical Analysis, Faculty of Applied Science, Tishk International University, Erbil, Iraq
| | | | - Musher Ismael Saleh
- Department of Chemistry, Faculty of Science and Health, Koya University, Koya KOY45, Kurdistan Region, Erbil, 44001, Iraq
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Chiu SH, Kesselman A, Yoon L, Kamaya A, Tse JR. LI-RADS CT/MRI Radiation Treatment Response Algorithm Version 2024: Category Redistribution and Short-Term Outcomes in Patients Undergoing Y-90 Radioembolization for HCC. AJR Am J Roentgenol 2025. [PMID: 40304670 DOI: 10.2214/ajr.25.32745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2025]
Abstract
Background: LI-RADS CT/MRI Radiation Treatment Response Algorithm (TRA) version 2024 (v2024) addresses a pitfall of the earlier algorithm relating to expected persistent enhancement of hepatocellular carcinoma (HCC) responding to radiation. v2024 removes LR-TR Equivocal, introduces LR-TR Nonprogressing (stable or decreasing masslike enhancement), and more narrowly defines LR-TR Viable (new or increasing masslike enhancement). Objective: To evaluate in patients with HCC treated by Y-90 radioembolization the redistribution of categories in LI-RADS CT/MRI Radiation TRA v2024 versus LI-RADS CT/MRI TRA version 2018 (v2018) and to assess short-term outcomes of v2024 categories. Methods: This retrospective study included 242 patients (57 women, 185 men; median age, 65 years) with 319 HCCs treated by Y-90 radioembolization from February 2011 to March 2022 and evaluated by initial 3-month posttreatment CT or MRI. Two radiologists assigned v2018 and v2024 categories; a third radiologist resolved discrepancies. The radiologists also assessed available second posttreatment CT or MRI examinations using v2024. Overall survival (OS) was determined. Results: On initial follow-up, by v2018, 18 (5.6%) lesions were LR-TR Nonviable, 21 (6.6%) LR-TR Equivocal, and 280 (87.8%) LR-TR Viable; by v2024, 18 (5.6%) were LR-TR Nonviable, 182 (57.1%) LR-TR Nonprogressing, and 119 (37.3%) LR-TR Viable. All LR-TR Equivocal and 161 (57.5%) LR-TR Viable lesions by v2018 were recategorized as LRTR Nonprogressing by v2024. Of 96 LR-TR Nonprogressing lesions with second follow-up, 63 (65.6%) remained LRTR Nonprogressing, 19 (19.8%) transitioned to LR-TR Nonviable, and 14 (14.6%) transitioned to LR-TR Viable. Of 29 LR-TR Viable lesions by v2024 with second follow-up, 23 (79.3%) remained LR-TR Viable, and 6 (20.7%) transitioned to LR-TR Nonprogressing. By Kaplan-Meier analysis using initial categories, OS showed no significant difference between LR-TR Equivocal and LR-TR Viable for v2018 (p=.05) but was significantly worse for LR-TR Viable than LRTR Nonprogressing for v2024 (p<.001). Conclusion: For v2024, LR-TR Viable was substantially less frequent versus v2018, and the majority of lesions were assigned LR-TR Nonprogressing. Using v2024, most LR-TR Viable lesions and the majority of LR-TR Nonprogressing lesion on initial follow-up remained as such on later imaging. Initial v2024 categories were associated with OS. Clinical Impact: The findings support the revisions in v2024.
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Affiliation(s)
- Sung-Hua Chiu
- Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Room H-1307, Stanford, CA 94305
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu District, Taipei City, Taiwan
| | - Andrew Kesselman
- Department of Radiology, Stanford University School of Medicine, 453 Quarry Road, MC 5659, Stanford, CA 94305
| | - Luke Yoon
- Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Room H-1307, Stanford, CA 94305
| | - Aya Kamaya
- Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Room H-1307, Stanford, CA 94305
| | - Justin R Tse
- Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Room H-1307, Stanford, CA 94305
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Elias TP, Shewaye AB, Fisseha H, Nur AM, Berhane KA, Minyilshewa AT, Kumsa KB, Seid BM. Predictors of in-hospital mortality among cirrhotic patients in Ethiopia: A multicenter retrospective study. PLoS One 2025; 20:e0322532. [PMID: 40299844 PMCID: PMC12040200 DOI: 10.1371/journal.pone.0322532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 03/24/2025] [Indexed: 05/01/2025] Open
Abstract
BACKGROUND In Ethiopia, cirrhosis is the 6th leading cause of death and is responsible for high hospitalization and mortality rates. However, until now, factors affecting in-hospital mortality of patients with liver cirrhosis are poorly understood. This study assessed the predictors of in-hospital mortality among cirrhotic patients in Ethiopia. METHODS A retrospective cross-sectional study using data collected from the electronic medical records of patients who were admitted for complications of liver cirrhosis between January 1, 2023, and March 31, 2024, in the medical wards of Adera Medical Center, St. Paul's Hospital Millennium Medical College, and Tikur Anbessa Specialized Hospital. Frequency and cross-tabulation were used for descriptive statistics. Predictor variables with a p-value <0.25 in bivariate analyses were included in the logistic regression. RESULTS Of the 299 patients included in the final analysis, the majority (79.6%) were males, and the median age of the study participants was 45 (IQR, 36-56) years. Hepatitis B virus (32.1%) was the most common etiology, followed by alcohol (30.1%) and hepatitis C virus (13.4%). Ascites (69.2%), upper gastrointestinal bleeding (50.5%), and hepatic encephalopathy (44.8%) were the most common forms of presentation. The in-hospital mortality rate was 25.4%. West Haven grade III or IV hepatic encephalopathy (AOR: 12.0; 95% CI 2.33-61.63; P < 0.01), hepatocellular carcinoma (AOR: 9.05; 95% CI 2.18-37.14; P: 0.01), history of previous admission within one year period (AOR: 6.80; 95% CI 2.18-21.18; P < 0.01), acute kidney injury (AOR: 6.47; 95% CI 1.77-23.64; P < 0.01), and model for end-stage liver disease - sodium score (AOR: 1.17; 95% CI 1.05-1.30; P: 0.02), were found to be predictors of in-hospital mortality. CONCLUSION In-hospital mortality of cirrhotic patients is high in Ethiopia. West Haven grade III or IV hepatic encephalopathy is the leading cause of mortality. Hence, prompt identification and management of hepatic encephalopathy and its precipitant at an earlier stage is crucial for better treatment outcomes and survival.
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Affiliation(s)
- Tamrat Petros Elias
- Department of Internal Medicine, Adera Medical and Surgical Center, Addis Ababa, Ethiopia
- Department of Internal Medicine, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Abate Bane Shewaye
- Department of Internal Medicine, Adera Medical and Surgical Center, Addis Ababa, Ethiopia
- Department of Internal Medicine, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Henok Fisseha
- Department of Internal Medicine, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Abdulsemed Mohammed Nur
- Department of Internal Medicine, Adera Medical and Surgical Center, Addis Ababa, Ethiopia
- Department of Internal Medicine, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
| | - Kaleb Assefa Berhane
- Department of Internal Medicine, Adera Medical and Surgical Center, Addis Ababa, Ethiopia
| | | | - Kibrab Bulto Kumsa
- Department of Internal Medicine, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Biruck Mohammed Seid
- Department of Internal Medicine, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
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Tu S, Jing X, Bu X, Zhang Q, Liao S, Zhu X, Guo Y, Sha W. Identification of pyroptosis-associated gene to predict fibrosis and reveal immune characterization in non-alcoholic fatty liver disease. Sci Rep 2025; 15:14944. [PMID: 40301412 PMCID: PMC12041580 DOI: 10.1038/s41598-025-96158-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 03/26/2025] [Indexed: 05/01/2025] Open
Abstract
Despite advances in research, studies on predictive models for Non-Alcoholic Fatty Liver Disease (NAFLD)-related fibrosis remain limited. Identifying new biomarkers to distinguish Non-Alcoholic Steatohepatitis (NASH) from NAFLD would aid in the treatment of NASH. Gene expression and clinical profiles of NAFL and NASH patients were collected from databases. Differentially expressed genes with prognostic value were used to construct predictive model. Validation of fibrosis stage-related pyroptosis-related genes (PRGs) was performed using Sprague-Dawley rats liver fibrosis models induced by CCl4 or PS. Immune cell infiltration assessment demonstrated that stromal score, immune score, and ESTIMATE score were higher in patients with NASH compared to those with NAFL. BAX, BAK1, PYCARD, and NLRP3 were identified as hub genes that exhibit a strong correlation with fibrosis stage. Additionally, the expression of these genes was increased in fibrotic liver tissues induced by CCl4 and PS. The pyroptosis-associated gene signature effectively predicts the degree of liver fibrosis in NASH patients. Our study indicates that BAX, BAK1, PYCARD, and NLRP3 might serve as biomarkers for NASH-associated fibrosis.
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Affiliation(s)
- Sha Tu
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Xi Jing
- School of Nursing, Jinan University, Guangzhou, 510632, China
| | - Xiaoling Bu
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Qingfang Zhang
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Shanying Liao
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Xiaobo Zhu
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Ying Guo
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Weihong Sha
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China.
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Valenti M, Ceolin C, Rossato M, Curreri C, Devita M, Tonon M, Campodall’Orto C, Vanin J, Gambato M, Cillo U, Burra P, Angeli P, Sergi G, De Rui M. The impact of age and frailty on hospitalization and survival in older liver transplant recipients: a longitudinal cohort study. FRONTIERS IN AGING 2025; 6:1539688. [PMID: 40357266 PMCID: PMC12066423 DOI: 10.3389/fragi.2025.1539688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 03/28/2025] [Indexed: 05/15/2025]
Abstract
Purpose Frailty is a well-established risk factor for adverse outcomes, particularly in liver transplant candidates. This study investigates the impact of age and frailty on key clinical outcomes-hospitalizations, waitlist survival, and post-transplant mortality-in cirrhotic patients evaluated for liver transplantation. Methods This study included older adults with chronic liver disease under consideration for transplantation. Data collected encompassed medical history, Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores, Mini-Mental State Examination (MMSE), Mini Nutritional Assessment (MNA), and frailty status, assessed using both the Liver Frailty Index (LFI) and the Survey of Health, Ageing, and Retirement in Europe Frailty Index (SHARE-FI). Clinical outcomes, including mortality and hospitalizations, were tracked over a 24-month period. Results Among 100 patients (67% male), those under 70 exhibited higher MNA, MMSE, and SHARE-FI scores. Based on frailty classification, 25 patients were frail, 28 pre-frail, and 47 robust. Younger patients experienced more hospitalizations during follow-up (p = 0.03) and had a higher probability of hospitalization within 24 months (p = 0.002). Although transplant-free survival did not differ significantly across groups, frail patients had a significantly higher mortality rate (p = 0.04). Overall, 24 patients underwent transplantation, while 26 died, including six post-transplant deaths. MELD and CTP scores were strong predictors of mortality, while among frailty measures, only SHARE-FI demonstrated significant predictive value. In multivariate Cox models, MELD [HR = 1.17, p = 0.001; HR = 1.11, p = 0.002], CTP [HR = 1.43, p = 0.003; HR = 1.41, p = 0.006], and LFI (HR = 1.69, p = 0.04) were significantly associated with mortality. Conclusion Frailty, rather than age, emerges as a key predictor of mortality in liver transplant candidates. Further research is needed to validate these findings and enhance frailty assessment, ultimately improving candidate selection for transplantation.
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Affiliation(s)
- Matteo Valenti
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
| | - Chiara Ceolin
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Aging Research Center, Stockholm, Sweden
| | - Marco Rossato
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
| | - Chiara Curreri
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
| | - Maria Devita
- Department of Medicine - DIMED, University of Padua, Italy
- Department of General Psychology - DPG, University of Padua, Italy
| | - Marta Tonon
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Hepatobiliary Surgery and Liver Transplantation, DIDAS Surgery Department, University - Hospital of Padua, Padua, Italy
| | - Carlotta Campodall’Orto
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
| | - Jessica Vanin
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy, University of Padova, Padua, Italy
| | - Umberto Cillo
- Division of Hepatobiliary Surgery and Liver Transplantation, DIDAS Surgery Department, University - Hospital of Padua, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology - DISCOG, University of Padua, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology - DISCOG, University of Padua, Italy
- Gastroenterological Endoscopy Unit, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
| | - Paolo Angeli
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Hepatobiliary Surgery and Liver Transplantation, DIDAS Surgery Department, University - Hospital of Padua, Padua, Italy
| | - Giuseppe Sergi
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
| | - Marina De Rui
- Department of Medicine - DIMED, University of Padua, Italy
- Division of Geriatrics, DIDAS Medicine Department, University - Hospital of Padua, Padua, Italy
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Garbuzenko DV. Role of etiological therapy in achieving recompensation of decompensated liver cirrhosis. World J Hepatol 2025; 17:105127. [PMID: 40308818 PMCID: PMC12038422 DOI: 10.4254/wjh.v17.i4.105127] [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: 01/13/2025] [Revised: 03/22/2025] [Accepted: 04/09/2025] [Indexed: 04/25/2025] Open
Abstract
The traditional view of the decompensated stage as a point of no return in the natural history of liver cirrhosis (LC) is currently being questioned. This is due to the appearance of data indicating the possibility of restoring the structure and function of the liver, reducing the portal pressure with a positive effect on complications associated with portal hypertension and decreasing the risk of developing hepatocellular carcinoma after elimination of the etiological factor. To create a unified understanding the recompensation of decompensated LC, at the Baveno VII consensus workshop were developed criteria confirming it. At the moment, the efficacy of etiological therapy in achieving established criteria for recompensation has been evaluated only in patients with alcohol-related, as well as hepatitis B virus-related and hepatitis C virus-related decompensated LC. The purpose of the review is to provide up-to-date information on the role of etiological therapy in achieving recompensation of decompensated LC according to Baveno VII criteria. So far, only the first steps have been taken in studying this problem. To further understand it, research is needed to identify pathophysiological mechanisms, modifying factors, predictors, and potential noninvasive biomarkers of recompensation of decompensated LC.
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Affiliation(s)
- Dmitry V Garbuzenko
- Department of Faculty Surgery, South Ural State Medical University, Chelyabinsk 454092, Russia.
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Su WX, Li YF, Zhu YJ, Li DW. Nursing care for patients with liver cirrhosis undergoing surgery for esophageal variceal bleeding in an integrated healthcare system. World J Gastrointest Surg 2025; 17:100400. [PMID: 40291891 PMCID: PMC12019073 DOI: 10.4240/wjgs.v17.i4.100400] [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: 11/28/2024] [Revised: 12/23/2024] [Accepted: 02/11/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Globally, Liver cirrhosis is the 14th leading cause of death and poses a significant threat to human health. AIM To investigate the effects of a multidisciplinary collaboration model on postoperative recovery and psychological stress in patients with liver cirrhosis undergoing esophageal variceal bleeding (EVB) surgery within an integrated healthcare system. METHODS Between January 2022 and March 2024, a total of 180 patients with cirrhosis and EVB were admitted and randomly assigned to either a control group (standard care) or an observation group (standard care plus the multidisciplinary collaboration model), with 90 patients in each group. Postoperative recovery indicators (time to symptom improvement, time to start eating, time to bowel sound recovery, time to first flatus, and hospital stay), psychological stress responses [self-rating anxiety scale (SAS); self-rating depression scale (SDS)], subjective well-being, and incidence of complications were compared between the two groups. RESULTS Compared to the control group, the observation group showed earlier symptom improvement, earlier return to eating, bowel sound recovery, first flatus, and a shorter hospital stay. Pre-intervention SAS and SDS scores were not significantly different between the groups, but post-intervention scores were significantly lower in the observation group. Similarly, there was no significant difference in the subjective well-being scores before the intervention between the two groups. After the intervention, both groups showed improved scores, with the observation group scoring significantly higher than the control group. CONCLUSION The observation group also had a lower incidence of complications. Therefore, for patients with liver cirrhosis undergoing EVB surgery, a multidisciplinary collaboration model within an integrated healthcare system can promote early postoperative recovery, reduces psychological stress, improves subjective well-being, and reduces complications and rebleeding.
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Affiliation(s)
- Wen-Xiu Su
- Department of Critical Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Yun-Fei Li
- Department of Critical Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Yi-Jun Zhu
- Department of Critical Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Di-Wen Li
- Department of Critical Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
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Wang W, Gao X, Niu W, Yin J, He K. Targeting Metabolism: Innovative Therapies for MASLD Unveiled. Int J Mol Sci 2025; 26:4077. [PMID: 40362316 PMCID: PMC12071536 DOI: 10.3390/ijms26094077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 04/01/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted the critical role of metabolism in the disease's pathophysiology. This innovative nomenclature signifies a shift from the previous designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the condition's progressive nature. Simultaneously, MASLD has become one of the most prevalent liver diseases worldwide, highlighting the urgent need for research to elucidate its etiology and develop effective treatment strategies. This review examines and delineates the revised definition of MASLD, exploring its epidemiology and the pathological changes occurring at various stages of the disease. Additionally, it identifies metabolically relevant targets within MASLD and provides a summary of the latest metabolically targeted drugs under development, including those in clinical and some preclinical stages. The review finishes with a look ahead to the future of targeted therapy for MASLD, with the goal of summarizing and providing fresh ideas and insights.
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Affiliation(s)
- Weixin Wang
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; (W.W.); (W.N.)
| | - Xin Gao
- School of Public Health, Jilin University, Changchun 130021, China;
| | - Wentong Niu
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; (W.W.); (W.N.)
| | - Jinping Yin
- NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130041, China;
| | - Kan He
- Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; (W.W.); (W.N.)
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Magyar CTJ, Jones O, Rajendran L, Carrique L, Lynch MJ, Li Z, Claasen MPAW, Ivanics T, Choi WJ, Gaviria F, Ghanekar A, Winter E, Bucur R, Shwaartz C, Reichman T, Sayed BA, Selzner M, Bhat M, Tsien C, Jaeckel E, Lilly LB, McGilvray ID, Cattral MS, Sapisochin G, Selzner N. Living Donor Liver Transplantation for Alcohol-related Liver Disease: An Intention-to-treat Analysis. Transplantation 2025:00007890-990000000-01070. [PMID: 40269339 DOI: 10.1097/tp.0000000000005410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2025]
Abstract
BACKGROUND Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation (LT) in the Western world. Although 6 mo of abstinence is no longer a criterion for patients with ALD, the outcomes of living donor LT (LDLT) versus deceased donor LT (DDLT) are not well established. METHODSS We performed an intention-to-treat analysis to evaluate the impact of listing and pursuing primary LDLT (pLDLT) compared with primary DDLT (pDDLT). The primary endpoint was overall survival from date of listing, evaluated using Cox regression (hazard ratios). RESULTS Two hundred thirty-three patients with ALD were listed for LT, of which 27 (12%) were pLDLT. The overall median model for end-stage liver disease (MELD) score at listing was 20 and Na-MELD 24, a median abstinence of 4.5 mo, and 128 (55%) underwent transplantation. There was no statistically significant adjusted difference at 3-y overall survival between pLDLT versus pDDLT (adjusted hazard ratio [HR] 0.72; P = 0.550) and in the as-treated analysis (HR 1.22; P = 0.741). No patients were delisted in the pLDLT group, whereas 86 (42%) patients were delisted in the pDDLT group; primarily because of death (46 [50%]) and medical improvement (24 [28%]). Alcohol use since the time of listing was documented in 29 (13%) patients; immortal time bias adjusted analysis found no significant difference between pLDLT and pDDLT (adjusted HR 1.07; P = 0.900) and the as-treated analysis (HR 2.95; P = 0.130). CONCLUSIONS Patients with ALD benefit from intention pLDLT with lower rates of waitlist dropout and delisting, attributable to mortality or medical deterioration, and should be encouraged to pursue this option.
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Affiliation(s)
- Christian T J Magyar
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Owen Jones
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Luckshi Rajendran
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Lauren Carrique
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Marie-Josée Lynch
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Centre for Mental Health, University Health Network, Toronto, ON, Canada
| | - Zhihao Li
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Marco P A W Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, Henry Ford Hospital, Detroit, MI
- Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Woo Jin Choi
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Felipe Gaviria
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Anand Ghanekar
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Erin Winter
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Roxana Bucur
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Chaya Shwaartz
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Trevor Reichman
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Blayne A Sayed
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Markus Selzner
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Cynthia Tsien
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Elmar Jaeckel
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Leslie B Lilly
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Ian D McGilvray
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Mark S Cattral
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Surgery, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
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Dorff EM, Crooker K, Teng T, Hickey T, HoddWells M, Sarathy A, Muniz S, Lor J, Chang A, Singh D, Dejace J, Riser E, Tompkins BJ, Hale AJ. Clinical Characteristics and Outcomes of Patients with Cirrhosis Who Develop Infective Endocarditis. Infect Dis Rep 2025; 17:37. [PMID: 40277964 PMCID: PMC12027125 DOI: 10.3390/idr17020037] [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: 03/10/2025] [Revised: 04/01/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
Background: Infective endocarditis (IE) is an increasingly common infection that results in significant morbidity and mortality. An important but under-analyzed subpopulation of patients with IE are those with concomitant cirrhosis. This study compared the characteristics and outcomes of patients with and without cirrhosis who were hospitalized with IE. Methods: The authors conducted a retrospective cohort study in adult patients with IE admitted at a single center from 2010 to 2020, comparing outcomes between those with and without cirrhosis at the time of admission. Results: A total of 22 patients with a history of cirrhosis and 356 patients without a history of cirrhosis were included. Over a quarter (27.3%) of those with cirrhosis experienced a decompensation event within two years of their admission for IE. Clinical features, microbiology, and direct complications from IE were largely similar between groups. There was no significant difference in IE-related mortality rates between groups, although, in an overall survival analysis, the group with cirrhosis did have a higher risk of all-cause mortality at 2 years (HR = 2.85; p = 0.012). Conclusions: This study highlights that IE in patients with cirrhosis may contribute to or trigger decompensation events. Further research is warranted to better understand morbidity outcomes in patients with cirrhosis who develop IE.
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Affiliation(s)
- Erika M. Dorff
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
| | - Kyle Crooker
- Department of Medicine, Henry Ford Hospital, Detroit, MI 48202, USA
| | - Torrance Teng
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Tess Hickey
- Department of Medicine, University of Utah Hospital, Salt Lake City, UT 84132, USA
| | - Max HoddWells
- Department of Medicine, Maine Medical Center, Portland, ME 04102, USA
| | - Ashwini Sarathy
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Sean Muniz
- Department of Emergency Medicine, University of Utah Hospital, Salt Lake City, UT 84132, USA
| | - Jennifer Lor
- Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA
| | - Amy Chang
- Department of Medicine, Highland Hospital, Oakland, CA 94602, USA
| | - Devika Singh
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Jean Dejace
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Elly Riser
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Bradley J. Tompkins
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
| | - Andrew J. Hale
- Department of Medicine, University of Vermont Medical Center, Burlington, VT 05401, USA; (E.M.D.)
- Larner College of Medicine at the University of Vermont, Burlington, VT 05401, USA
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Iakovleva V, de Jong YP. Gene-based therapies for steatotic liver disease. Mol Ther 2025:S1525-0016(25)00298-9. [PMID: 40254880 DOI: 10.1016/j.ymthe.2025.04.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 03/26/2025] [Accepted: 04/16/2025] [Indexed: 04/22/2025] Open
Abstract
Advances in nucleic acid delivery have positioned the liver as a key target for gene therapy, with adeno-associated virus vectors showing long-term effectiveness in treating hemophilia. Steatotic liver disease (SLD), the most common liver condition globally, primarily results from metabolic dysfunction-associated and alcohol-associated liver diseases. In some individuals, SLD progresses from simple steatosis to steatohepatitis, cirrhosis, and eventually hepatocellular carcinoma, driven by a complex interplay of genetic, metabolic, and environmental factors. Genetic variations in various lipid metabolism-related genes, such as patatin-like phospholipase domain-containing protein 3 (PNPLA3), 17β-hydroxysteroid dehydrogenase type 13 (HSD17B13), and mitochondrial amidoxime-reducing component 1 (MTARC1), impact the progression of SLD and offer promising therapeutic targets. This review largely focuses on genes identified through clinical association studies, as they are more likely to be effective and safe for therapeutic intervention. While preclinical research continues to deepen our understanding of genetic factors, early-stage clinical trials involving gene-based SLD therapies, including transient antisense and small-molecule approaches, are helping prioritize therapeutic targets. Meanwhile, hepatocyte gene editing technologies are advancing rapidly, offering alternatives to transient methods. As such, gene-based therapies show significant potential for preventing the progression of SLD and enhancing long-term liver health.
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Affiliation(s)
- Viktoriia Iakovleva
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, USA
| | - Ype P de Jong
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, USA.
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Lim J, Gu H, Sang H, Jeong SJ, Kim HI. Impact of nucleos(t)ide analogue therapy on the incidence of Alzheimer's disease in patients with chronic hepatitis B virus infection. Alzheimers Res Ther 2025; 17:84. [PMID: 40241196 PMCID: PMC12004639 DOI: 10.1186/s13195-025-01729-3] [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: 12/28/2024] [Accepted: 03/31/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Long-term therapy with nucleos(t)ide analogs (NUCs) is inevitable for chronic hepatitis B (CHB) patients. However, how NUC therapy on the developing Alzheimer's disease (AD) in these patients remains controversial. METHODS This retrospective cohort study used the Korean National Health Insurance Service claims database from January 1, 2013, to December 31, 2013, treatment naïve CHB patients and those without previously diagnosed with AD. Participants were followed from the index date until either the diagnosis of AD or the study's conclusion on December 31, 2021. The primary outcome was the incidence of AD, compared between the group with initiated NUC therapy (n = 18,365) at cohort entry and the group without NUC therapy (n = 212,820). RESULTS During the study, 416 patients were diagnosed with AD. After propensity-score matching (18,365 pairs), the 5- to 7-year follow-up showed a significantly lower hazard ratio (HR) in the NUC-treated group compared to the untreated group (HR 0.31-0.40), with HRs remaining constant over time. Subgroup analysis showed more pronounced benefits of NUC therapy in patients under 65 years (HRs: 0.22 vs. 1.23; P < 0.05) and those without dyslipidemia (HRs: 0.14 vs. 1.09; P < 0.05). Protective effects were also observed across subgroups with hypertension, chronic kidney disease, heart disease, and a history of brain trauma, consistent with AD risk factor trends. CONCLUSIONS Our study analyses suggest that NUC therapy appears to have a protective effect against the development of AD in patients with CHB.
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Affiliation(s)
- Jihye Lim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Hyundam Gu
- Epidemiologic & Biostatistical Methods for Public Health & Clinical Research, Bloomberg School of Public Health, Johns Hopkins, Baltimore, Maryland, USA
| | - Hyunji Sang
- Department of Endocrinology and Metabolism, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Su Jin Jeong
- Clinical Research Institute, Kyung Hee University Medical Center, 24 Kyunghee dae-ro, Seoul, , Dongdaemun-gu 02453, South Korea.
| | - Ha Il Kim
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Guri, , 153 Gyeongchun-ro 11923, South Korea.
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Jiao H, Wang H, Li J, Yang Z, Sun C. The Molecular Pathogenesis of Sarcopenia/Frailty in Cirrhosis. Semin Liver Dis 2025. [PMID: 40239708 DOI: 10.1055/a-2564-7551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
Cirrhosis is an important cause of morbidity and death in patients with chronic liver disease. It can be divided into compensatory and decompensated stages. During the decompensation period, complications such as esophageal and gastric varices hemorrhage, hepatic encephalopathy, infection, and hepatorenal syndrome are often incurred, which has a high mortality rate and leverages huge economic burden on society, healthcare resources, and individuals. Sarcopenia and frailty are common in patients with cirrhosis. The pathogenesis of sarcopenia and frailty in the context of cirrhosis is complicated and multifactorial, including overwhelming systemic inflammation, imbalance of muscle protein metabolism, malnutrition, endocrine and metabolic dysfunctions, intestinal microecological disorders, lack of physical exercise, and other aspects. Notably, accumulating evidence implicates that many patients experience sarcopenia/frailty even before the onset of liver cirrhosis. In this regard, the magnitude of liver fibrosis is closely linked to the progression of sarcopenia with reciprocal impact. In conclusion, this review article will shed light on the pathogenesis of cirrhosis complicated with sarcopenia/frailty, aimed at facilitating early diagnosis and effective management.
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Affiliation(s)
- Huanli Jiao
- Department of Health Management, Tianjin Hospital, Hexi District, Tianjin, People's Republic of China
| | - Han Wang
- Department of Health Management, Tianjin Hospital, Hexi District, Tianjin, People's Republic of China
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
| | - Ziyi Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, People's Republic of China
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Büyük M, Berker N, Bağbudar S, Çavuş B, Güllüoğlu M. Hepatic progenitor cell activation and ductular reaction in metabolic dysfunction-associated steatotic liver disease (MASLD): Indicators for disease activity and the degree of fibrosis: The pilot study. Medicine (Baltimore) 2025; 104:e42108. [PMID: 40228280 PMCID: PMC11999437 DOI: 10.1097/md.0000000000042108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Accepted: 03/27/2025] [Indexed: 04/16/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) spectrum encompasses steatosis, metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis and metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma. We evaluated the histomorphologic findings, portal-periportal biliary epithelial cell changes, and factors that may be associated with the degree of fibrosis in liver biopsies of MASLD patients. Hematoxylin-eosin, masson-trichrome, keratin7, keratin19, CD34, and glutamine synthetase-stained biopsies of 34 patients and 10 healthy liver donors (as controls) were retrospectively analyzed. Lobular inflammation was significantly correlated to the ballooning degeneration (P = .023), portal inflammation (P = .003), ductular reaction (DR) grade (P = .027), and the degree of fibrosis (P = .003). Ballooning degeneration (P = .004), and NAS (P = .008) were significantly related to the degree of fibrosis. Portal inflammation had a significant relationship with both DR grade (P < .001) and the degree of fibrosis (P = .002). The presence of hepatic progenitor cells (HPCs) was related to NAS (P = .005) and correlated with the DR grade (P = .002) and the degree of fibrosis (P = .038). Both DR (P < .001) and biliary metaplasia (P = .024) were significantly correlated with the degree of fibrosis. In multivariate analysis, biliary metaplasia (P = .015) and DR (P = .02) were found to be independent factors related to degree of fibrosis. Our results showed that HPC and DR were closely associated with disease activity and degree of fibrosis and might be good indicators of disease progression in MASLD. As pathologists, we might integrate the degree of HPCs and the grade of DR in our pathology reports as these findings might contribute to the disease progression risk categorization of the patients.
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Affiliation(s)
- Melek Büyük
- Department of Pathology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Neslihan Berker
- Department of Pathology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Sidar Bağbudar
- Department of Pathology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Bilger Çavuş
- Department of Gastroenterology and Hepatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
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Ding Z, Wang L, Sun J, Zheng L, Tang Y, Tang H. Hepatocellular carcinoma: pathogenesis, molecular mechanisms, and treatment advances. Front Oncol 2025; 15:1526206. [PMID: 40265012 PMCID: PMC12011620 DOI: 10.3389/fonc.2025.1526206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 03/21/2025] [Indexed: 04/24/2025] Open
Abstract
Hepatocellular Carcinoma (HCC), a highly prevalent malignancy, poses a significant global health challenge. Its pathogenesis is intricate and multifactorial, involving a complex interplay of environmental and genetic factors. Viral hepatitis, excessive alcohol consumption, and cirrhosis are known to significantly elevate the risk of developing HCC. The underlying biological processes driving HCC are equally complex, encompassing aberrant activation of molecular signaling pathways, dysregulation of hepatocellular differentiation and angiogenesis, and immune dysfunction. This review delves into the multifaceted nature of HCC, exploring its etiology and the intricate molecular signaling pathways involved in its development. We examine the role of immune dysregulation in HCC progression and discuss the potential of emerging therapeutic strategies, including immune-targeted therapy and tumor-associated macrophage interventions. Additionally, we explore the potential of traditional Chinese medicine (TCM) monomers in inhibiting tumor growth. By elucidating the complex interplay of factors contributing to HCC, this review aims to provide a comprehensive understanding of the disease and highlight promising avenues for future research and therapeutic development.
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Affiliation(s)
- Zhixian Ding
- General Clinical Research Center, Wanbei Coal-Electricity Group General Hospital, Suzhou, China
- Laboratory of Inflammation and Repair of Liver Injury and Tumor Immunity, Wanbei Coal-Electricity Group General Hospital, Hefei, China
| | - Lusheng Wang
- General Clinical Research Center, Wanbei Coal-Electricity Group General Hospital, Suzhou, China
- Laboratory of Inflammation and Repair of Liver Injury and Tumor Immunity, Wanbei Coal-Electricity Group General Hospital, Hefei, China
| | - Jiting Sun
- General Clinical Research Center, Wanbei Coal-Electricity Group General Hospital, Suzhou, China
- Laboratory of Inflammation and Repair of Liver Injury and Tumor Immunity, Wanbei Coal-Electricity Group General Hospital, Hefei, China
| | - Lijie Zheng
- General Clinical Research Center, Wanbei Coal-Electricity Group General Hospital, Suzhou, China
- Laboratory of Inflammation and Repair of Liver Injury and Tumor Immunity, Wanbei Coal-Electricity Group General Hospital, Hefei, China
| | - Yu Tang
- General Clinical Research Center, Wanbei Coal-Electricity Group General Hospital, Suzhou, China
- Laboratory of Inflammation and Repair of Liver Injury and Tumor Immunity, Wanbei Coal-Electricity Group General Hospital, Hefei, China
| | - Heng Tang
- General Clinical Research Center, Wanbei Coal-Electricity Group General Hospital, Suzhou, China
- Laboratory of Inflammation and Repair of Liver Injury and Tumor Immunity, Wanbei Coal-Electricity Group General Hospital, Hefei, China
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Hou M, Gu Q, Cui J, Dou Y, Huang X, Li J, Qiao L, Nan Y. Proportion and clinical characteristics of metabolic-associated fatty liver disease and associated liver fibrosis in an urban Chinese population. Chin Med J (Engl) 2025; 138:829-837. [PMID: 39183555 PMCID: PMC11970824 DOI: 10.1097/cm9.0000000000003141] [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: 12/21/2023] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) is the predominant form of chronic liver disease worldwide. This study was designed to investigate the proportion and characteristics of MAFLD within the general Chinese population and to identify the contributory risk factors for liver fibrosis among MAFLD individuals. METHODS The participants were recruited from a cohort undergoing routine health evaluations at the Third Hospital of Hebei Medical University between May 2019 and March 2023. The diagnosis of MAFLD was based on the established clinical practice guidelines. The fibrosis-4 index score (FIB-4) was employed to evaluate hepatic fibrosis, with a FIB-4 score of ≥1.3 indicating significant fibrosis. Binary logistic regression analyses were used to determine risk factors associated with significant hepatic fibrosis in MAFLD. RESULTS A total of 22,970 participants who underwent comprehensive medical examinations were included in the analysis. The overall proportion of MAFLD was 28.77% (6608/22,970), with 16.87% (1115/6608) of these patients showing significant fibrosis as assessed using FIB-4. Independent risk factors for significant liver fibrosis in MAFLD patients were male (odds ratio [OR] = 0.676, 95% confidence interval [CI]: 0.558-0.821), hepatitis B surface antigen (HBsAg) positivity (OR = 2.611, 95% CI: 1.557-4.379), body mass index ≥23.00 kg/m 2 (OR = 0.632, 95% CI: 0.470-0.851), blood pressure ≥130/85 mmHg (OR = 1.885, 95% CI: 1.564-2.272), and plasma glucose ≥5.6 mmol/L (OR = 1.815, 95% CI: 1.507-2.186) (all P <0.001). CONCLUSIONS The proportion of MAFLD in an urban Chinese population is 28.77%. About 16.87% of MAFLD patients presented with significant liver fibrosis. Independent risk factors for significant liver fibrosis in MAFLD patients should be noticed.
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Affiliation(s)
- Mengmeng Hou
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China
| | - Qi Gu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China
| | - Jiawei Cui
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China
| | - Yao Dou
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China
| | - Xiuhong Huang
- Healthy Physical Examination Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China
| | - Liang Qiao
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China
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Zezulinski D, Hoteit MA, Kaplan DE, Simeone A, Zhan T, Doria C, Ahmed FY, Roberts LR, Block TM, Sayeed A. Detection of Circulating mRNA Variants in Hepatocellular Carcinoma Patients Using Targeted RNAseq. Liver Cancer 2025:1-32. [PMID: 40331063 PMCID: PMC12052365 DOI: 10.1159/000545366] [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: 09/06/2024] [Accepted: 03/02/2025] [Indexed: 05/08/2025] Open
Abstract
Introduction Mutations in circulating nucleic acids can be used as biomarkers for the early detection and management of hepatocellular carcinoma (HCC). However, while circulating tumor DNA and microRNA have been extensively explored, circulating tumor mRNA and circulating mRNA mutants (ctmutRNA), which may provide advantages over other analytes, remain less well described. We previously reported the identification of 288 HCC selective ctmutRNA variants, called "candidates," from a small cohort of HCC patients using total RNAseq. The objective of the current study was to use targeted RNAseq to validate the specificity and sensitivity of these HCC selective variants in an independent cohort of patients with liver cirrhosis (LC). Methods Several methods to isolate small extracellular vesicles and amplify mRNA from the circulation were compared. RNA was isolated, and the primers and probes selective for the 288 regions of interest were used with RNA from HCC (N = 50) and LC and no HCC (N = 35) patients. HCC tumor tissues (N = 11), a normal liver tissue and 3 cell lines were also studied. cDNA synthesis was followed by library construction using QIAseq RNA Fusion XP panel. QC analysis was carried out with an Agilent Bioanalyzer before sequencing on a NextSeq 550 instrument. A GATK HaplotypeCaller was used for variant calling and annotation carried out using snpEff. Results Among the test panel of 288 ctmutRNA candidates in the original cohort, 75 were detected in the new cohort of plasma samples. Moreover, 388 other variants in proximity to the original lesions were also found in multiple HCC but not LC plasma samples. A subset of 36 HCC selective variants was able to identify all HCC patients. The most common tumor specific variants were Indels and SNPs. Novel mRNA fusion variants, corresponding to SENP7, HYI, SAR1A, RASA2, TUBA transcripts, etc., were identified in HCC and LC patients. Conclusion Circulating RNA could be a robust analyte for noninvasive early detection of HCC and circulating RNA panels could be powerful tools in the entire spectrum of clinical management.
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Affiliation(s)
| | - Maarouf A. Hoteit
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
- The Corporal Michael J. Crescenz Veterans Administration Hospital, Philadelphia, PA, USA
| | | | - Tingting Zhan
- Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA
| | | | - Fowsiyo Y. Ahmed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Aejaz Sayeed
- Baruch S. Blumberg Institute, Doylestown, PA, USA
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Ng WH, Yeo YH, Kim H, Seki E, Rees J, Ma KSK, Moylan CA, Rodriquez LM, Abdelmalek M, Villanueva A, Noureddin M, Yang JD. Renin-angiotensin-aldosterone system inhibitor use improves clinical outcomes in patients with metabolic dysfunction-associated steatotic liver diseases: Target trial emulation using real-world data. Hepatology 2025:01515467-990000000-01228. [PMID: 40178454 DOI: 10.1097/hep.0000000000001333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/19/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND AND AIMS Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) prevent fibrosis progression in a preclinical model of steatotic liver disease. Our objective was to assess the impact of ACEi/ARB use on clinical outcomes in patients with metabolic dysfunction-associated steatotic liver diseases. APPROACH AND RESULTS Using TriNetX, a nationwide database, we identified all patients with metabolic dysfunction-associated steatotic liver diseases from January 1, 2011, to December 31, 2019. Using a target trial emulation framework, ACEi/ARB users were matched with calcium channel blocker (CCB) users using propensity score matching (PSM). Patients were followed up to 10 years after the index date. Cox proportional hazards regression was used to determine the risk of mortality, major adverse liver outcomes, major adverse cardiac events, and incident cancers. Of the 35,988 eligible patients, 28,423 were ACEi/ARB users, and 7565 were CCB users. After PSM, 7238 pairs were well-balanced. ACEi/ARB use was associated with a significantly decreased mortality risk (HR: 0.59, 95% CI: 0.51-0.68). ACEi/ARB was associated with a significantly reduced risk of developing major adverse liver outcomes (HR: 0.70, 95% CI: 0.61-0.80), including ascites (HR: 0.78, 95% CI: 0.63-0.98) and HE (HR: 0.67, 95% CI: 0.57-0.78). ACEi/ARB use was also associated with a lower risk of major adverse cardiac events (HR: 0.82, 95% CI: 0.76-0.90) but not incident cancer (HR: 0.97, 95% CI: 0.86-1.10) compared with CCB. CONCLUSIONS ACEi/ARB use in patients with metabolic dysfunction-associated steatotic liver diseases was associated with a reduced risk of mortality, major adverse liver outcomes, and major adverse cardiac events compared with CCB use. A large prospective study is needed for external validation.
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Affiliation(s)
- Wee Han Ng
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Yee Hui Yeo
- Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Hyunseok Kim
- Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Ekihiro Seki
- Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Jonathan Rees
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Kevin Sheng-Kai Ma
- Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Cynthia A Moylan
- Department of Medicine, Division of Gastroenterology, Duke University Health System, Durham, North Carolina, USA
| | - Luz María Rodriquez
- Gastrointestinal & Other Cancers Research Group, NCI, Rockville, Maryland, USA
- Department of Surgery, Walter Reed National Medical Center, Bethesda, Maryland, USA
| | - Manal Abdelmalek
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Augusto Villanueva
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Mazen Noureddin
- Houston Research Institute, Houston Methodist Hospital, Houston, Texas, USA
| | - Ju Dong Yang
- Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Shao C, Lan W, Ding Y, Ye L, Huang J, Liang X, He Y, Zhang J. JTCD attenuates HF by inhibiting activation of HSCs through PPARα-TFEB axis-mediated lipophagy. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 139:156501. [PMID: 39978277 DOI: 10.1016/j.phymed.2025.156501] [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: 10/10/2024] [Revised: 12/28/2024] [Accepted: 02/11/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND Hepatic fibrosis (HF) is an intermediate stage in the progression of chronic liver disease to cirrhosis and has been shown to be a reversible pathological process. Known evidence suggests that activation of hepatic stellate cells (HSCs) and degradation of their lipid droplets (LDs) play an indispensable role in the process of HF. Jiawei Taohe Chengqi Decoction (JTCD) can inhibit the activation of HSCs in the process of HF, but the exact mechanism remains to be elucidated. PURPOSE The aim of this study is to determine whether JTCD inhibits lipophagy and to explore the possible mechanisms of its HF effect in HSCs by regulating the PPARα/TFEB axis. METHODS Network pharmacology and molecular docking were firstly applied to predict the potential mechanism of JTCD for the treatment of HF. In vivo, a mouse model of HF was constructed using carbon tetrachloride (CCl4) solution, and the efficacy of JTCD was assessed by staining of pathological sections, oil red O staining, immunofluorescence (IF), immunohistochemistry (IHC) staining, Western blotting and qRT-PCR. The intervention of JTCD was verified in vitro by induction of activated LX-2 cells with TGF-β solution and intervention using agonists and antagonists of PPARα. Finally, transient transfection of cells using TFEB siRNA was performed for validation studies. RESULTS JTCD effectively alleviated CCl4-induced HF in mice and reduced the levels of HF markers α-smooth muscle actin (α-SMA) and collagen I (COL1A1), and inhibited PPARα expression and lipophagy process. In vitro, JTCD delayed the degradation of LDs and reduced lipophagy in LX-2 cells, suggesting a mechanism involving PPARα/TFEB axis signaling regulation.
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Affiliation(s)
- Chang Shao
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Wenfang Lan
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Ying Ding
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Linmao Ye
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Jiaxin Huang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Xiaofan Liang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Yi He
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Junjie Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
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