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Wehrle CJ, Maspero M, Pinna AD, Dutkowski P, Miller C, Hashimoto K, Clavien PA, Schlegel A. Age Matters: What Affects the Cumulative Lifespan of a Transplanted Liver? Ann Surg 2025; 281:485-495. [PMID: 38489660 DOI: 10.1097/sla.0000000000006259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2024]
Abstract
OBJECTIVE To assess factors affecting the cumulative lifespan of a transplanted liver. BACKGROUND Liver aging is different from other solid organs. It is unknown how old a liver can actually get after liver transplantation. METHODS Deceased donor liver transplants from 1988 to 2021 were queried from the United States UNOS registry. Cumulative liver age was calculated as donor age + recipient graft survival. RESULTS In total, 184,515 livers were included. Most were donation after brain death donors (n = 175,343). The percentage of livers achieving >70, 80, 90, and 100 years cumulative age was 7.8% (n = 14,392), 1.9% (n = 3576), 0.3% (n = 528), and 0.01% (n = 21), respectively. The youngest donor age contributing to a cumulative liver age >90 years was 59 years, with posttransplant survival of 34 years. In pediatric recipients, 736 (4.4%) and 282 livers (1.7%) survived >50 and 60 years overall, respectively. Transplanted livers achieved cumulative age >90 years in 2.86 per 1000 and >100 years in 0.1 per 1000. The U.S. population at large has a cumulative "liver age" >90 years in 5.35 per 1000 persons, and >100 years in 0.2 per 1000. Livers aged >60 years at transplant experienced both improved cumulative survival ( P < 0.0001) and interestingly improved survival after transplantation ( P < 0.0001). Recipient warm ischemia time of >30 minutes was most predictive of reduced cumulative liver survival overall (n = 184,515, hazard ratio = 1.126, P < 0.001) and excluding patients with mortality in the first 6 months (n = 151,884, hazard ratio = 0.973, P < 0.001). CONCLUSIONS In summary, transplanted livers frequently get as old as those in the average population despite ischemic-reperfusion-injury and immunosuppression. The presented results justify using older donor livers regardless of donation type, even in sicker recipients with limited options.
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Affiliation(s)
- Chase J Wehrle
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
| | - Marianna Maspero
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
- Department of Surgery, Upper GI Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Antonio D Pinna
- Department of Abdominal Transplantation, Cleveland Clinic Florida, Weston, FL
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Charles Miller
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
| | - Koji Hashimoto
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
| | - Pierre-Alain Clavien
- Department of Transplantation, Wyss Zurich, ETH Zurich, and University of Zurich, Switzerland
| | - Andrea Schlegel
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, OH
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Wang S, Xu Z, Wang Z, Yi X, Wu J. M6A methyltransferase METTL3 promotes glucose metabolism hub gene expression and induces metabolic dysfunction-associated steatotic liver disease (MASLD). BMC Genomics 2025; 26:188. [PMID: 39994526 PMCID: PMC11853331 DOI: 10.1186/s12864-025-11377-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 02/18/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND N6-methyladenosine (m6A) RNA modification plays a crucial role in various biological events and is implicated in various metabolic-related diseases. However, its role in MASLD remains unclear. This study aims to investigate the impact of METTL3 on MASLD through multi-omics analysis, with a focus on exploring its potential mechanisms of action. METHODS An MASLD mouse model was established by feeding C57BL/6J mice a high-fat diet for 12 weeks. A METTL3 stable overexpression AML12 cell model was also constructed via lentiviral transfection. Subsequent transcriptomic and proteomic analyses, as well as integrated analysis between different omics datasets, were conducted. RESULTS METTL3 expression was significantly increased in the MASLD mouse model. Through our transcriptomic and proteomic analyses, we identified 848 genes with significant inconsistencies between the transcriptomic and proteomic datasets. GO/ KEGG enrichment analyses identified terms that may be involved in post-transcriptional modifications, particularly METTL3-mediated m6A modification. Subsequently, through integrated proteomic analysis of the METTL3-overexpressed AML12 cell model and the MASLD mouse model, we selected the top 20 co-upregulated and co-downregulated GO/ KEGG terms as the main biological processes influenced by METTL3 during MASLD. By intersecting with pathways obtained from previous integrated analyses, we identified GO/ KEGG terms affected by METTL3-induced m6A modification. Protein-protein interaction analysis of proteins involved in these pathways highlighted GAPDH and TPI1 as two key hub genes. CONCLUSIONS During MASLD, METTL3 regulates the glycolytic pathway through m6A modification, influencing the occurrence and development of the disease via the key hub genes GAPDH and TPI1. These findings expand our understanding of MASLD and provide strong evidence for potential therapeutic targets and drug development.
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Affiliation(s)
- Shuowen Wang
- Gastroenterology Department, Children's Hospital Capital Institute of Pediatrics, Beijing, 100020, China
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Ziying Xu
- Bacteriology Department, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Zijun Wang
- Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Xiaoyu Yi
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Jianxin Wu
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China.
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, 100020, China.
- Beijing Tongren Hospital, Capital Medical University, Beijing, 100005, China.
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Feng G, Han Y, Yang W, Shikora S, Mahawar K, Cheung TT, Targher G, Byrne CD, Hernandez-Gea V, Tilg H, Zheng MH. Recompensation in MASLD-related cirrhosis via metabolic bariatric surgery. Trends Endocrinol Metab 2025; 36:118-132. [PMID: 38908982 DOI: 10.1016/j.tem.2024.05.009] [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: 03/10/2024] [Revised: 05/25/2024] [Accepted: 05/31/2024] [Indexed: 06/24/2024]
Abstract
The prognosis of patients with decompensated cirrhosis is poor, with significantly increased liver-related mortality rates. With the rising tide of decompensated cirrhosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD), the role of metabolic bariatric surgery (MBS) in achieving hepatic recompensation is garnering increasing attention. However, the complexity of preoperative assessment, the risk of postoperative disease recurrence, and the potential for patients to experience surgical complications of the MBS present challenges. In this opinion article we analyze the potential of MBS to induce recompensation in MASLD-related cirrhosis, discuss the mechanisms by which MBS may affect recompensation, and compare the characteristics of different MBS procedures; we highlight the therapeutic potential of MBS in MASLD-related cirrhosis recompensation and advocate for research in this complex area.
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Affiliation(s)
- Gong Feng
- Xi'an Medical University, Xi'an, China; The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yu Han
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wah Yang
- Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Avenue West, Guangzhou, China
| | - Scott Shikora
- Bariatric Surgery, Brigham and Women's Hospital, 75 Francis Street, ASBII-3rd Floor, Boston, MA 02115, USA
| | - Kamal Mahawar
- Bariatric Unit, Sunderland Royal Hospital, Sunderland, SR4 7TP, UK
| | - Tan To Cheung
- Department of Surgery, the University of Hong Kong, Hong Kong, China
| | - Giovanni Targher
- Department of Medicine, University of Verona, Verona, Italy; Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella (VR), Italy
| | - Christopher D Byrne
- Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton and University of Southampton, Southampton General Hospital, Southampton, UK
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, Zhejiang, China.
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Wong SW, Yang YY, Chen H, Xie L, Shen XZ, Zhang NP, Wu J. New advances in novel pharmacotherapeutic candidates for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) between 2022 and 2024. Acta Pharmacol Sin 2025:10.1038/s41401-024-01466-7. [PMID: 39870846 DOI: 10.1038/s41401-024-01466-7] [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: 09/14/2024] [Accepted: 12/18/2024] [Indexed: 01/29/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) covers a broad spectrum of profile from simple fatty liver, evolving to metabolic dysfunction-associated steatohepatitis (MASH), to hepatic fibrosis, further progressing to cirrhosis and hepatocellular carcinoma (HCC). MASLD has become a prevalent disease with 25% in average over the world. MASH is an active stage, and requires pharmacological intervention when there is necroptotic damage with fibrotic progression. Although there is an increased understanding of MASH pathogenesis and newly approved resmetirom, given its complexity and heterogeneous pathophysiology, there is a strong necessity to develop more drug candidates with better therapeutic efficacy and well-tolerated safety profile. With an increased list of pharmaceutical candidates in the pipeline, it is anticipated to witness successful approval of more potential candidates in this fast-evolving field, thereby offering different categories of medications for selective patient populations. In this review, we update the advances in MASH pharmacotherapeutics that have completed phase II or III clinical trials with potential application in clinical practice during the latest 2 years, focusing on effectiveness and safety issues. The overview of fast-evolving status of pharmacotherapeutic candidates for MASH treatment confers deep insights into the key issues, such as molecular targets, endpoint selection and validation, clinical trial design and execution, interaction with drug administration authority, real-world data feedback and further adjustment in clinical application.
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Affiliation(s)
- Shu Wei Wong
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Yong-Yu Yang
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Hui Chen
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Li Xie
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Xi-Zhong Shen
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China
| | - Ning-Ping Zhang
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China.
| | - Jian Wu
- Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.
- Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China.
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Younossi ZM, Golabi P, Price JK, Owrangi S, Gundu-Rao N, Satchi R, Paik JM. The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes. Clin Gastroenterol Hepatol 2024; 22:1999-2010.e8. [PMID: 38521116 DOI: 10.1016/j.cgh.2024.03.006] [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: 12/08/2023] [Revised: 03/01/2024] [Accepted: 03/05/2024] [Indexed: 03/25/2024]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction associated steatotic liver disease (MASLD), is closely associated with type 2 diabetes (T2D). Our aim was to estimate the most recent global prevalence of NAFLD/MASLD, nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction associated steatohepatitis (MASH), advanced fibrosis, and mortality among patients with T2D. METHODS We systematically searched PubMed and Ovid MEDLINE for terms including NAFLD, NASH, and T2D published in 1990-2023 according to PRISMA. The meta-analysis was conducted using a random-effects model. Assessment of bias risk used the Joanna Briggs Institute appraisal tool. RESULTS From 3134 studies included in the initial search, 123 studies (N = 2,224,144 patients with T2D) were eligible. Another 12 studies (N = 2733 T2D patients with liver biopsy) were eligible for histologic assessments. The global pooled prevalence of NAFLD/MASLD among patients with T2D was 65.33% (95% confidence interval, 62.35%-68.18%). This prevalence increased from 55.86% (42.38%-68.53%) in 1990-2004 to 68.81% (63.41%-73.74%) in 2016-2021 (P = .073). The highest NAFLD/MASLD prevalence among T2D patients was observed in Eastern Europe (80.62%, 75.72%-84.73%), followed by the Middle East (71.24%, 62.22%-78.84%), and was lowest in Africa (53.10%, 26.05%-78.44%). Among patients with liver biopsy data, the global pooled prevalence of NASH/MASH, significant fibrosis, and advanced fibrosis was 66.44% (56.61%-75.02%), 40.78% (24.24%-59.70%), and 15.49% (6.99%-30.99%), respectively. The pooled all-cause mortality was 16.79 per 1000 person-years (PY) (10.64-26.40), 4.19 per 1000 PY (1.34-7.05) for cardiac-specific mortality; 6.10 per 1000 PY (0.78-4.88) for extrahepatic cancer-specific mortality; and 2.15 per 1000 PY (0.00-2.21) for liver-specific mortality. CONCLUSIONS The prevalence of NAFLD/MASLD among T2D is high and growing. The majority of NAFLD/MASLD patients with T2D have NASH/MASH, and a significant proportion have advanced fibrosis.
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Affiliation(s)
- Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; The Global NASH Council, Washington, District of Columbia.
| | - Pegah Golabi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; The Global NASH Council, Washington, District of Columbia
| | - Jillian Kallman Price
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia
| | - Soroor Owrangi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia
| | | | - Romona Satchi
- The Global NASH Council, Washington, District of Columbia
| | - James M Paik
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; The Global NASH Council, Washington, District of Columbia
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Iyer JS, Juyal D, Le Q, Shanis Z, Pokkalla H, Pouryahya M, Pedawi A, Stanford-Moore SA, Biddle-Snead C, Carrasco-Zevallos O, Lin M, Egger R, Hoffman S, Elliott H, Leidal K, Myers RP, Chung C, Billin AN, Watkins TR, Patterson SD, Resnick M, Wack K, Glickman J, Burt AD, Loomba R, Sanyal AJ, Glass B, Montalto MC, Taylor-Weiner A, Wapinski I, Beck AH. AI-based automation of enrollment criteria and endpoint assessment in clinical trials in liver diseases. Nat Med 2024; 30:2914-2923. [PMID: 39112795 PMCID: PMC11485234 DOI: 10.1038/s41591-024-03172-7] [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: 05/02/2023] [Accepted: 07/03/2024] [Indexed: 09/08/2024]
Abstract
Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62-0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P < 0.0001) and stage 4 (P = 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P = 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses.
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Affiliation(s)
| | | | | | | | | | | | - Aryan Pedawi
- PathAI, Boston, MA, USA
- Atomwise, San Francisco, CA, USA
| | | | | | | | - Mary Lin
- PathAI, Boston, MA, USA
- Supernus Pharmaceuticals, Rockville, MD, USA
| | | | - Sara Hoffman
- PathAI, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Hunter Elliott
- PathAI, Boston, MA, USA
- BigHat Biosciences, San Mateo, CA, USA
| | - Kenneth Leidal
- PathAI, Boston, MA, USA
- Genesis Therapeutics, Burlingame, CA, USA
| | - Robert P Myers
- Gilead Sciences, Inc., Foster City, CA, USA
- OrsoBio, Inc., Palo Alto, CA, USA
| | - Chuhan Chung
- Gilead Sciences, Inc., Foster City, CA, USA
- Inipharm, San Diego, CA, USA
| | | | | | | | - Murray Resnick
- PathAI, Boston, MA, USA
- Rhode Island Hospital and The Miriam Hospital, Providence, RI, USA
| | | | - Jon Glickman
- PathAI, Boston, MA, USA
- Massachusetts General Hospital, Boston, MA, USA
| | - Alastair D Burt
- NIHRB Medical Research Center, Newcastle University, Newcastle, UK
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA
| | - Arun J Sanyal
- Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, VA, USA
| | | | | | | | - Ilan Wapinski
- PathAI, Boston, MA, USA
- Sanofi Pharmaceuticals, Cambridge, MA, USA
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Palma-Lara I, Ortiz-López MG, Bonilla-Delgado J, Pérez-Escobar J, Godínez-Aguilar R, Luévano-Contreras C, Espinosa-García AM, Pérez-Durán J, García Alonso-Themann P, Nolasco-Quiroga M, Flores-Estrada J, Carpinteyro-Espin P, Juárez-Ascencio D, Nieto-Velazquez NG, Palacios-Reyes C. A landscape of liver cirrhosis and transplantation in Mexico: Changing leading causes and transplant as response. Ann Hepatol 2024; 30:101562. [PMID: 39278408 DOI: 10.1016/j.aohep.2024.101562] [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: 03/14/2024] [Revised: 06/05/2024] [Accepted: 07/08/2024] [Indexed: 09/18/2024]
Abstract
Liver cirrhosis causes include alcoholism, viral infections (hepatitis B virus (HBV) and hepatitis C virus (HCV)), alcohol-associated liver disease (ALD), and metabolic dysfunction associated with steatotic liver disease (MASLD), among others. Cirrhosis frequency has increased in recent years, with a prevalence of 1395 cases per 100,000 and a mortality rate of 18 per 100,000, which corresponded to 1,472,000 deaths during 2017. In Mexico, liver disease is a public health problem since it was associated to 41,890 deaths in 2022, including liver cirrhosis (>25,000) and ALD (14,927). This represents 114 daily deaths due to these causes, and corresponds to the 4th or 5th place of all causes. The global prevalence of MASLD is estimated to affect 25% of the world's population, while in the pediatric population it could be higher. In Mexican population it is more prevalent since estimations were around 41.3% in 2023. Alcohol consumption, a global health issue due to its high prevalence and associated morbidities, is associated to ALD in 32.9%, with a mortality rate of 23.9%, primarily due to liver-related causes. In Mexico, ALD is present in 23% of all cirrhosis cases, already surpassed by hepatitis B cases in 2009. HCV and HBV frequencies changed due to programs implementing screening detection, vaccines and direct-acting antivirals during the last years. A switch of causes has occurred, increasing MASLD and diminishing viral causes. Efficient performed liver transplantation has grown as a response to increasing cirrhosis cases, including recent authorized centers. These efforts are necessary, whereas preventive strategies should be implemented according to leading causes.
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Affiliation(s)
- Icela Palma-Lara
- Laboratorio de Morfología Celular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.
| | | | - José Bonilla-Delgado
- Unidad de Investigación, Hospital Regional de Alta Especialidad de Ixtapaluca, Ixtapaluca 56530, Mexico; Departamento de Biotecnología, Escuela de Ingeniería y Ciencias, Instituto Tecnológico de Monterrey, Toluca de Lerdo 50110, Mexico.
| | - Juanita Pérez-Escobar
- Servicio de Trasplantes, División de Cirugía, Hospital Juárez de México, Mexico City 07760, Mexico.
| | | | - Claudia Luévano-Contreras
- Departamento de Ciencias Médicas, División de Ciencias de la Salud, Universidad de Guanajuato, Campus León, Guanajuato 37000, México.
| | | | - Javier Pérez-Durán
- Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, México.
| | | | - Manuel Nolasco-Quiroga
- Coordinación de Enseñanza e Investigación, Clínica Hospital Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Huauchinango 73177, Mexico.
| | | | | | | | | | - Carmen Palacios-Reyes
- Laboratorio de Morfología Celular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico; División de Investigación, Hospital Juárez de México, Mexico City 07760, Mexico; Departamento de Ciencias Médicas, División de Ciencias de la Salud, Universidad de Guanajuato, Campus León, Guanajuato 37000, México.
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Wu Z, Xia F, Wang W, Zhang K, Fan M, Lin R. Worldwide burden of liver cancer across childhood and adolescence, 2000-2021: a systematic analysis of the Global Burden of Disease Study 2021. EClinicalMedicine 2024; 75:102765. [PMID: 39170941 PMCID: PMC11338123 DOI: 10.1016/j.eclinm.2024.102765] [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: 05/17/2024] [Revised: 07/13/2024] [Accepted: 07/15/2024] [Indexed: 08/23/2024] Open
Abstract
Background Liver cancer is a significant contributor to the global disease burden, of which hepatoblastomas are the most common liver tumors in children, with 90% of cases occurring within the first 5 years of life. It is important for pediatricians and subspecialists in pediatric gastroenterology and hepatology to have knowledge of the epidemiology and incidence trends of pediatric hepatic cancer, despite its rarity. In the present study, we first provide estimates of the incidence and mortality burden of hepatoblastoma and liver cancer from 2000 to 2021 in the childhood and adolescence. Methods Liver cancer burden and its attributable risk factors were estimated using data from the Global Burden of Disease Study (GBD) 2021. Percentage change was estimated to show the trend of liver cancer estimates from 2000 to 2021. The age-standardized rate (ASR) and estimated annual percentage change (EAPC) were utilized for measuring hepatoblastomas incidence and deaths rate trends. In accordance with the GBD framework, 95% uncertainty intervals (UIs) for all estimates by averaging the data from 1000 draws, with the lower and upper bounds of the 95% UIs. Findings Globally, from 2000 to 2021 in the age 5-19 years group, the incidence cases and deaths cases due to liver cancer decreased from 2449.2 (95% UI: 2235.9-2689.8) to 1692.9 (95% UI: 1482.0-1992.5) and 2248.5 (95% UI: 2053.7-2474.9) to 1516.6 (95% UI: 1322.1-1797.9), respectively. Meanwhile, from 2000 to 2021 in the age 20-24 years group, the incidence cases and deaths cases due to liver cancer decreased from 1453.5 (95% UI: 1327.8-1609.4) to 1285.1 (95% UI: 1159.2-1447.2) and 1432.3 (95% UI: 1307.6-1585.7) to 1195.5 (95% UI: 1066.1-1355.2), respectively. In addition, the prevalence of liver cancer decreased from 41.9% (95% UI: 18.7%-64.7%) to 26.4% (95% UI: 14.2%-39.1%) in the age 5-19 years group, and 46.6% (95% UI: 42.8%-51.5%) to 36.5% (95% UI: 33.1%-40.9%) in the age 20-24 years. From 2000 to 2021, in the age group of 5-19 years, the proportion of liver cancer incidence due to hepatitis B has decreased from 42.2% to 37.9%, while the proportion due to hepatitis C has increased from 1.1% to 1.6%. Additionally, there has been an increase in the proportion of NASH-induced liver cancer incidence from 5.2% to 9.4%, and alcohol use induced liver cancer incidence has also increased from 0.5% to 0.7% over the same period. Globally, from 2000 to 2021, the incidence cases and deaths cases due to hepatoblastoma decreased from 6131.8 (95% UI: 5234.8-6961.9) to 4045.6 (95% UI: 3250-4995.8) and 4059.2 (95% UI: 3494.5-4621.2) to 2416 (95% UI: 1940.2-3022.5), respectively. There was some variation in age-related sex-specific patterns, the highest number of hepatoblastoma incidence cases occurred in children between 2 and 4 years old and females in the age range of 12 months to 9 years had a higher number of new cases. Importantly, the incidence of hepatoblastoma was started to increase sharply after the age of 1 month. Interpretation The results of the present study are significant for liver health policy and practice in childhood and adolescence. Differentiated intervention and outreach strategies based on age and gender would be necessary to reduce the impact of liver cancer. Early screening and interventions for hepatoblastoma is important especially in the population of under 9 years old. Funding This study was supported by the National Key R&D Program of China (grant numbers 2023YFC2307000), National Natural Science Foundation of China [grant numbers 82170571 and 81974068], China Postdoctoral Science Foundation (grant numbers 2023M741283).
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Affiliation(s)
- Zenghong Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fangnan Xia
- Biomedical Materials Engineering Research Center, Hubei Key Laboratory of Polymer Materials, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, School of Materials Science & Engineering, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, China
| | - Weijun Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kun Zhang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mengke Fan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rong Lin
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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9
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Favre-Bulle T, Moradpour D, Marques-Vidal P, Vaucher J. Trends in the burden of hospitalised patients with cirrhosis in Switzerland: a cross-sectional study of cirrhosis-related hospitalisations between 1998 and 2020. BMJ Open 2024; 14:e081822. [PMID: 39181561 PMCID: PMC11344505 DOI: 10.1136/bmjopen-2023-081822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 08/05/2024] [Indexed: 08/27/2024] Open
Abstract
OBJECTIVE Liver cirrhosis is an increasing cause of morbidity and mortality worldwide with a heavy load on healthcare systems. We analysed the trends in hospitalisations for cirrhosis in Switzerland. DESIGN Cross-sectional study. SETTING Large nationwide inpatient database, years between 1998 and 2020. PARTICIPANTS Hospitalisations for cirrhosis of adult patients were selected. MAIN OUTCOMES AND MEASURES Hospitalisations with either a primary diagnosis of cirrhosis or a cirrhosis-related primary diagnosis with a mandatory presence of cirrhosis as a secondary diagnosis were considered following the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. Trends in demographic and clinical characteristics, in-hospital mortality and length of stay were analysed. Causes and costs of cirrhosis-related hospitalisations were available from 2012 onwards. RESULTS Cirrhosis-related hospitalisations increased from 1631 in 1998 to 4052 in 2020. Of the patients, 68.7% were men. Alcohol-related liver disease was the leading cause, increasing from 44.1% (95% CI, 42.4% to 45.9%) in 2012 to 47.9% (95% CI, 46.4% to 49.5%) in 2020. Assessed by exclusion of other coded causes, non-alcoholic fatty liver disease was the second cause at 42.7% (95% CI, 41.2% to 44.3%) in 2020. Hepatitis C virus-related cirrhosis decreased from 12.3% (95% CI, 11.2% to 13.5%) in 2012 to 3.2% (95% CI, 2.7% to 3.8%) in 2020. Median length of stay decreased from 11 to 8 days. Hospitalisations with an intensive care unit stay increased from 9.8% (95% CI, 8.4% to 11.4%) to 15.6% (95% CI, 14.5% to 16.8%). In-hospital mortality decreased from 12.1% (95% CI, 10.5% to 13.8%) to 9.7% (95% CI, 8.8% to 10.7%). Total costs increased from 54.4 million US$ (51.4 million €) in 2012 to 92.6 million US$ (87.5 million €) in 2020. CONCLUSIONS Cirrhosis-related hospitalisations and related costs increased in Switzerland from 1998 to 2020 but in-hospital mortality decreased. Alcohol-related liver disease and non-alcoholic fatty liver disease were the most prevalent and preventable aetiologies of cirrhosis-related hospitalisations.
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Affiliation(s)
- Timothee Favre-Bulle
- Service of Internal Medicine, Etablissements Hospitaliers du Nord Vaudois, Yverdon-les-Bains, Switzerland
- Department of Medicine, University of Lausanne Faculty of Biology and Medicine, Lausanne, Switzerland
| | - Darius Moradpour
- Department of Medicine, Service of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland
| | | | - Julien Vaucher
- Department of Medicine, University of Lausanne, Lausanne, Switzerland
- Department of Medicine and Specialties, University of Fribourg, Fribourg, Switzerland
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10
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Harrison SA. Use of Resmetirom in Patients With Metabolic Dysfunction-Associated Steatohepatitis. Gastroenterol Hepatol (N Y) 2024; 20:355-359. [PMID: 39193263 PMCID: PMC11346006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Affiliation(s)
- Stephen A Harrison
- Visiting Professor of Hepatology Radcliffe Department of Medicine, University of Oxford Chairman and Founder, Pinnacle Clinical Research Chairman and Co-Founder, Summit Clinical Research Founder and CEO, Apex Mobile Clinical Research
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11
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Peng J, Huang S, Wang P, Luo R, Zhang W, Shi X, Shi L, Zhong X, Lü M, Peng Y, Tang X. Burden of non-alcoholic fatty liver disease-related cirrhosis and other chronic liver diseases from 1990 to 2019 in China and disease burden trend prediction to 2030. Chin Med J (Engl) 2024:00029330-990000000-01151. [PMID: 39030075 PMCID: PMC11407810 DOI: 10.1097/cm9.0000000000003211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Indexed: 07/21/2024] Open
Affiliation(s)
- Jieyu Peng
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Shu Huang
- Department of Gastroenterology, Lianshui County People' Hospital, Huaian, Jiangsu 223400, China
- Department of Gastroenterology, Lianshui People' Hospital of Kangda College Affiliated to Nanjing Medical University, Huaian, Jiangsu 223400, China
| | - Ping Wang
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Rui Luo
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Wei Zhang
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Xiaomin Shi
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Lei Shi
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Xiaolin Zhong
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Muhan Lü
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Yan Peng
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
| | - Xiaowei Tang
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China
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12
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Martin SP, Mehta N, Emamaullee J. Immune checkpoint inhibitors in liver transplantation: Current practice, challenges, and opportunities. Liver Transpl 2024; 30:742-752. [PMID: 38345379 DOI: 10.1097/lvt.0000000000000350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 02/08/2024] [Indexed: 06/15/2024]
Abstract
Immune checkpoint inhibitors are becoming a mainstay of cancer treatment. While first studied and approved for patients with unresectable disease, due to their efficacy, they are becoming increasingly used in the perioperative period across many cancer types. In patients with HCC, immune checkpoint inhibitors have now become the standard of care in the advanced setting and have shown promising results in the adjuvant setting after liver resection. While these drugs continue to show promise, their role in the peritransplant setting still remains a question. In this review, we explore the current use of this class of medications in patients with HCC, as well as the immunologic role of the pathways that they inhibit. We also identify potential for future research opportunities to better understand the role of these medications.
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Affiliation(s)
- Sean P Martin
- Department of Surgery, Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Surgery, Division of Transplantation, Penn State Health Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Neil Mehta
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, UCSF, San Francisco, California, USA
| | - Juliet Emamaullee
- Department of Surgery, Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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13
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Wang XM, Zhang XJ. Role of radiomics in staging liver fibrosis: a meta-analysis. BMC Med Imaging 2024; 24:87. [PMID: 38609843 PMCID: PMC11010385 DOI: 10.1186/s12880-024-01272-x] [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: 06/13/2023] [Accepted: 04/10/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND Fibrosis has important pathoetiological and prognostic roles in chronic liver disease. This study evaluates the role of radiomics in staging liver fibrosis. METHOD After literature search in electronic databases (Embase, Ovid, Science Direct, Springer, and Web of Science), studies were selected by following precise eligibility criteria. The quality of included studies was assessed, and meta-analyses were performed to achieve pooled estimates of area under receiver-operator curve (AUROC), accuracy, sensitivity, and specificity of radiomics in staging liver fibrosis compared to histopathology. RESULTS Fifteen studies (3718 patients; age 47 years [95% confidence interval (CI): 42, 53]; 69% [95% CI: 65, 73] males) were included. AUROC values of radiomics for detecting significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4) were 0.91 [95%CI: 0.89, 0.94], 0.92 [95%CI: 0.90, 0.95], and 0.94 [95%CI: 0.93, 0.96] in training cohorts and 0.89 [95%CI: 0.83, 0.91], 0.89 [95%CI: 0.83, 0.94], and 0.93 [95%CI: 0.91, 0.95] in validation cohorts, respectively. For diagnosing significant fibrosis, advanced fibrosis, and cirrhosis the sensitivity of radiomics was 84.0% [95%CI: 76.1, 91.9], 86.9% [95%CI: 76.8, 97.0], and 92.7% [95%CI: 89.7, 95.7] in training cohorts, and 75.6% [95%CI: 67.7, 83.5], 80.0% [95%CI: 70.7, 89.3], and 92.0% [95%CI: 87.8, 96.1] in validation cohorts, respectively. Respective specificity was 88.6% [95% CI: 83.0, 94.2], 88.4% [95% CI: 81.9, 94.8], and 91.1% [95% CI: 86.8, 95.5] in training cohorts, and 86.8% [95% CI: 83.3, 90.3], 94.0% [95% CI: 89.5, 98.4], and 88.3% [95% CI: 84.4, 92.2] in validation cohorts. Limitations included use of several methods for feature selection and classification, less availability of studies evaluating a particular radiological modality, lack of a direct comparison between radiology and radiomics, and lack of external validation. CONCLUSION Although radiomics offers good diagnostic accuracy in detecting liver fibrosis, its role in clinical practice is not as clear at present due to comparability and validation constraints.
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Affiliation(s)
- Xiao-Min Wang
- School of Medical Imaging, Tianjin Medical University, No.1, Guangdong Road, Hexi District, Tianjin, 300203, China.
| | - Xiao-Jing Zhang
- Department of Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
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14
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Maldonado SS, Cedars MI, Yates KP, Wilson LA, Gill R, Terrault NA, Suzuki A, Sarkar MA. Antimullerian Hormone, a Marker of Ovarian Reserve, Is Protective Against Presence and Severity of NASH in Premenopausal Women. Clin Gastroenterol Hepatol 2024; 22:339-346.e5. [PMID: 37678489 PMCID: PMC10840970 DOI: 10.1016/j.cgh.2023.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/26/2023] [Accepted: 08/11/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND & AIMS Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH levels influence nonalcoholic fatty liver disease (NAFLD) is unknown. METHODS Leveraging the NASH Clinical Research Network we determined the association of AMH levels within 6 months of liver biopsy with presence and severity of histologic measures of NAFLD in premenopausal women. Outcomes included presence of nonalcoholic steatohepatitis (NASH), presence and severity of fibrosis, and NAFLD Activity Score and its components. Logistic and ordinal logistic regression models were adjusted for age, race/ethnicity, homeostatic model assessment for insulin resistance, body mass index, dyslipidemia, polycystic ovary syndrome, estrogen-progestin use, and menstrual cyclicity. RESULTS Median cohort age was 35 years; 73% were white and 24% Hispanic. Thirty-three percent had diabetes, 81% had obesity, and 95% had dyslipidemia. On biopsy 71% had NASH, 68% had any fibrosis, and 15% had advanced fibrosis. On adjusted analysis (n = 205), higher AMH quartiles were inversely associated with NAFLD histology including prevalent NASH (adjusted odds ratio [AOR], 0.64; 95% confidence interval [CI], 0.41-1.00), NAFLD Activity Score ≥5 (AOR, 0.52; 95% CI, 0.35-0.77), Mallory hyaline (AOR, 0.54; 95% CI, 0.35-0.82), and higher fibrosis stage (AOR, 0.70; 95% CI, 0.51-0.98). The protective effects of AMH were more pronounced among women without polycystic ovary syndrome (n = 164), including lower odds of NASH (AOR, 0.53; 95% CI, 0.32-0.90) and any NASH fibrosis (AOR, 0.54; 95% CI, 0.32-0.93). CONCLUSIONS AMH may reflect a unique biomarker of NASH in premenopausal women and findings suggest a novel link between reproductive aging and histologic severity of NAFLD in women.
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Affiliation(s)
- Stephanie S Maldonado
- Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California
| | - Marcelle I Cedars
- Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of California, San Francisco, San Francisco, California
| | - Katherine P Yates
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland
| | - Laura A Wilson
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland
| | - Ryan Gill
- Department of Pathology, University of California, San Francisco, San Francisco, California
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Ayako Suzuki
- Division of Gastroenterology, Duke University, Durham, North Carolina
| | - Monika A Sarkar
- Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California.
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15
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Liu ZP, Ouyang GQ, Huang GZ, Wei J, Dai L, He SQ, Yuan GD. Global burden of cirrhosis and other chronic liver diseases due to nonalcoholic fatty liver disease, 1990-2019. World J Hepatol 2023; 15:1210-1225. [DOI: 10.4254/wjh.v15.i11.1210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/29/2023] [Accepted: 10/30/2023] [Indexed: 11/24/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of cirrhosis and other chronic liver diseases (COCLDs).
AIM To conduct a comprehensive and comparable updated analysis of the global, regional, and national burden of COCLDs due to NAFLD in 204 countries and territories from 1990 and 2019 by age, sex, and sociodemographic index.
METHODS Data on COCLDs due to NAFLD were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Numbers and age-standardized prevalence, death, and disability-adjusted life years (DALYs) were estimated through a systematic analysis of modelled data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. The estimated annual percentage change was used to determine the burden trend.
RESULTS In 2019, the global age-standardized prevalence rate of COCLDs due to NAFLD was 15022.90 per 100000 population [95% uncertainty interval (UI): 13493.19-16764.24], which increased by 24.51% (22.63% to 26.08%) from 1990, with an estimated annual percentage change of 0.78 (95% confidence interval: 0.74-0.82). In the same year, however, the age-standardized death rate and age-standardized DALYs per 100000 population were 1.66 (95%UI: 1.20-2.17) and 43.69 (95%UI: 31.28-58.38), respectively. North Africa and the Middle East had the highest prevalence rates of COCLDs due to NAFLD. The death rate increased with age up to the 95+ age group for both sexes. Males had higher numbers of prevalence, death rate, and DALYs than females across all age groups before the 65-69 age group. The sociodemographic index was negatively correlated with the age-standardized DALYs.
CONCLUSION Globally, the age-standardized prevalence rate has increased during the past three decades. However, the age-standardized death rate and age-standardized DALYs decreased. There is geographical variation in the burden of COCLDs due to NAFLD. It is strongly recommended to improve the data quality of COCLDs due to NAFLD across all countries and regions to facilitate better monitoring of the burden of COCLDs due to NAFLD.
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Affiliation(s)
- Zhi-Peng Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guo-Qing Ouyang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guo-Zhen Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Luo Dai
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Song-Qing He
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guan-Dou Yuan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Sakuma I, Vatner DF. Fatty Acid Esterification as a NASH Therapeutic Target. Cell Mol Gastroenterol Hepatol 2023; 17:311-312. [PMID: 37984466 PMCID: PMC10829519 DOI: 10.1016/j.jcmgh.2023.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 10/20/2023] [Accepted: 10/24/2023] [Indexed: 11/22/2023]
Affiliation(s)
- Ikki Sakuma
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Daniel F Vatner
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut; Program in Translational Biomedicine, Yale School of Medicine, New Haven, Connecticut; Department of Medicine, Veterans Affairs Medical Center, West Haven, Connecticut.
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17
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Sawada K, Chung H, Softic S, Moreno-Fernandez ME, Divanovic S. The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease. Cell Metab 2023; 35:1852-1871. [PMID: 37939656 PMCID: PMC10680147 DOI: 10.1016/j.cmet.2023.10.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 10/13/2023] [Accepted: 10/13/2023] [Indexed: 11/10/2023]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an unabated risk factor for end-stage liver diseases with no available therapies. Dysregulated immune responses are critical culprits of MASLD pathogenesis. Independent contributions from either the innate or adaptive arms of the immune system or their unidirectional interplay are commonly studied in MASLD. However, the bidirectional communication between innate and adaptive immune systems and its impact on MASLD remain insufficiently understood. Given that both innate and adaptive immune cells are indispensable for the development and progression of inflammation in MASLD, elucidating pathogenic contributions stemming from the bidirectional interplay between these two arms holds potential for development of novel therapeutics for MASLD. Here, we review the immune cell types and bidirectional pathways that influence the pathogenesis of MASLD and highlight potential pharmacologic approaches to combat MASLD based on current knowledge of this bidirectional crosstalk.
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Affiliation(s)
- Keisuke Sawada
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA
| | - Hak Chung
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Samir Softic
- Department of Pediatrics and Gastroenterology, University of Kentucky, Lexington, KY 40536, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA
| | - Maria E Moreno-Fernandez
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
| | - Senad Divanovic
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA; Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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18
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Lim WH, Lin SY, Ng CH, Tan DJH, Xiao J, Yong JN, Tay PWL, Syn N, Chin YH, Chan KE, Khoo CM, Chew N, Foo RSY, Shabbir A, Tan EX, Huang DQ, Noureddin M, Sanyal AJ, Siddiqui MS, Muthiah MD. Foregut bypass vs. restrictive bariatric procedures for nonalcoholic fatty liver disease: a meta-analysis of 3,355 individuals. Hepatobiliary Surg Nutr 2023; 12:658-670. [PMID: 37886204 PMCID: PMC10598314 DOI: 10.21037/hbsn-21-520] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/12/2022] [Indexed: 10/28/2023]
Abstract
Background Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease (NAFLD). However, there remains inadequate data regarding the effects of different bariatric procedures on various NAFLD parameters, especially for histological outcomes. Thus, this meta-analysis aimed to compare the effects of restrictive bariatric procedures and foregut bypass on the metabolic, biochemical, and histological parameters for patients with NAFLD. Methods Medline and Embase were searched for articles relating to bariatric procedures and NAFLD. Pairwise meta-analysis was conducted to compare efficacy of bariatric procedures pre- vs. post-procedure with subgroup analysis to further compare restrictive against foregut bypass procedures. Results Thirty-one articles involving 3,355 patients who underwent restrictive bariatric procedures (n=1,460) and foregut bypass (n=1,895) were included. Both foregut bypass (P<0.01) and restrictive procedures (P=0.03) significantly increased odds of fibrosis resolution. Compared to restrictive procedures, foregut bypass resulted in a borderline non-significant decrease in fibrosis score (P=0.06) and significantly lower steatosis score (P<0.001). For metabolic parameters, foregut bypass significantly lowered body mass index (P=0.003) and low-density lipoprotein (P=0.008) compared to restrictive procedures. No significant differences were observed between both procedures for aspartate aminotransferase (P=0.17) and alkaline phosphatase (P=0.61). However, foregut bypass resulted in significantly lower gamma-glutamyl transferase than restrictive procedures (P=0.01) while restrictive procedures resulted in significantly lower alanine transaminase than foregut bypass (P=0.02). Conclusions The significant histological and metabolic advantages and comparable improvements in biochemical outcomes support the choice of foregut bypass over restrictive bariatric procedures in NAFLD management.
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Affiliation(s)
- Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Phoebe Wen Lin Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yip Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chin Meng Khoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Nicholas Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
| | - Roger S. Y. Foo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
| | - Asim Shabbir
- Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, Singapore, Singapore
| | - Eunice X. Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Centre, Los Angeles, CA, USA
| | - Arun J. Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark D. Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
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Cipriani AL, Petz CA, Nielsen EM, Marsden J, Schreiner AD. Statin prescribing patterns in patient-centered medical home patients with NAFLD. THE AMERICAN JOURNAL OF MANAGED CARE 2023; 29:408-413. [PMID: 37616147 PMCID: PMC10507683 DOI: 10.37765/ajmc.2023.89406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/25/2023]
Abstract
OBJECTIVES Cardiovascular disease is the leading cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD), and statins play a pivotal role in the primary prevention of cardiovascular events. This study investigates statin prescribing in primary care patients with NAFLD to identify opportunities to address cardiovascular disease risk in this cohort. STUDY DESIGN Retrospective cohort study of primary care electronic health record data from 2012-2018. METHODS This cohort included 652 patients with radiographic evidence of hepatic steatosis and no evidence of competing chronic liver disease. A statin prescription identified at any time during the study period was the primary outcome. Univariate and multivariable analyses were performed to evaluate the association of clinical signals and comorbidities with statin prescribing. RESULTS Of the 652 patients in the NAFLD cohort, 56% received a statin prescription during the study period. Elevations in aminotransferases were not associated with statin prescribing (adjusted odds ratio [AOR], 1.17; 95% CI, 0.78-1.76), whereas older patients (AOR, 1.06; 95% CI, 1.05-1.08) and those with diabetes (AOR, 2.61; 95% CI, 1.73-3.92), hypertension (AOR, 2.76; 95% CI, 1.70-4.48), and a BMI greater than or equal to 30 kg/m2 (AOR, 1.49; 95% CI, 1.01-2.22) had higher odds of having a statin prescribed. Of the 288 patients without a statin prescription, 49% had an indication for statin therapy by atherosclerotic cardiovascular disease risk. In total, 16% of included patients did not have lipid panel results during the study period. CONCLUSIONS This study showed no association between NAFLD and statin prescribing, and the findings highlight opportunities to improve primary prevention of cardiovascular disease in these at-risk patients.
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Affiliation(s)
- Allison L Cipriani
- Medical University of South Carolina, 171 Ashley Ave,Charleston, SC 29425.
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20
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Castellanos-Fernandez MI, Pal SC, Arrese M, Arab JP, George J, Méndez-Sánchez N. Nonalcoholic Fatty Liver Disease in Latin America and Australia. Clin Liver Dis 2023; 27:301-315. [PMID: 37024209 DOI: 10.1016/j.cld.2023.01.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
The epidemiologic and demographical features of nonalcoholic fatty liver disease (NAFLD) vary significantly across countries and continents. In this review, we analyze current data regarding prevalence of NAFLD in Latin America and Caribbean and Australia and review some peculiarities found in these regions. We stress the need of greater awareness of NAFLD and the development of cost-effective risk stratification strategies and clinical care pathways of the disease. Finally, we highlight the need of effective public health policies to control the main risk factors for NAFLD.
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Affiliation(s)
| | - Shreya C Pal
- Faculty of Medicine, National Autonomous University of Mexico, Av. Universidad 3000, Coyoacán, Mexico City, Mexico; Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
| | - Marco Arrese
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile; Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Alimentiv, London, Ontario, Canada
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, New South Wales, Australia
| | - Nahum Méndez-Sánchez
- Faculty of Medicine, National Autonomous University of Mexico, Av. Universidad 3000, Coyoacán, Mexico City, Mexico; Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
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21
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Iyer JS, Pokkalla H, Biddle-Snead C, Carrasco-Zevallos O, Lin M, Shanis Z, Le Q, Juyal D, Pouryahya M, Pedawi A, Hoffman S, Elliott H, Leidal K, Myers RP, Chung C, Billin AN, Watkins TR, Resnick M, Wack K, Glickman J, Burt AD, Loomba R, Sanyal AJ, Montalto MC, Beck AH, Taylor-Weiner A, Wapinski I. AI-based histologic scoring enables automated and reproducible assessment of enrollment criteria and endpoints in NASH clinical trials. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.04.20.23288534. [PMID: 37162870 PMCID: PMC10168404 DOI: 10.1101/2023.04.20.23288534] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Clinical trials in nonalcoholic steatohepatitis (NASH) require histologic scoring for assessment of inclusion criteria and endpoints. However, guidelines for scoring key features have led to variability in interpretation, impacting clinical trial outcomes. We developed an artificial intelligence (AI)-based measurement (AIM) tool for scoring NASH histology (AIM-NASH). AIM-NASH predictions for NASH Clinical Research Network (CRN) grades of necroinflammation and stages of fibrosis aligned with expert consensus scores and were reproducible. Continuous scores produced by AIM-NASH for key histological features of NASH correlated with mean pathologist scores and with noninvasive biomarkers and strongly predicted patient outcomes. In a retrospective analysis of the ATLAS trial, previously unmet pathological endpoints were met when scored by the AIM-NASH algorithm alone. Overall, these results suggest that AIM-NASH may assist pathologists in histologic review of NASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient therapeutic response.
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Affiliation(s)
| | | | | | - Oscar Carrasco-Zevallos
- PathAI, Boston, MA, USA
- Affiliation shown is that during the time of study; current affiliation is Johnson & Johnson, New Brunswick, NJ, USA
| | | | | | | | | | - Maryam Pouryahya
- PathAI, Boston, MA, USA
- Affiliation shown is that during the time of study; current affiliation is AstraZeneca, Gaithersburg, MD, USA
| | - Aryan Pedawi
- PathAI, Boston, MA, USA
- Affiliation shown is that during the time of study; current affiliation is Atomwise, San Francisco, CA, USA
| | | | - Hunter Elliott
- PathAI, Boston, MA, USA
- Affiliation shown is that during the time of study; current affiliation is BigHat Biosciences, San Mateo, CA, USA
| | - Kenneth Leidal
- PathAI, Boston, MA, USA
- Affiliation shown is that during the time of study; current affiliation is Genesis Therapeutics, Burlingame, CA, USA
| | - Robert P. Myers
- Gilead Sciences, Inc., Foster City, CA, USA
- Affiliation shown is that during the time of study; current affiliation is OrsoBio, Inc., Palo Alto, CA, USA
| | - Chuhan Chung
- Gilead Sciences, Inc., Foster City, CA, USA
- Affiliation shown is that during the time of study; current affiliation is Inipharm, San Diego, CA, USA
| | | | | | - Murray Resnick
- PathAI, Boston, MA, USA
- Affiliation shown is that during the time of study; current affiliation is Rhode Island Hospital and The Miriam Hospital, Providence, RI, USA
| | | | | | | | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA
| | - Arun J. Sanyal
- Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, VA, USA
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Yip TCF, Vilar-Gomez E, Petta S, Yilmaz Y, Wong GLH, Adams LA, de Lédinghen V, Sookoian S, Wong VWS. Geographical similarity and differences in the burden and genetic predisposition of NAFLD. Hepatology 2023; 77:1404-1427. [PMID: 36062393 DOI: 10.1002/hep.32774] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/28/2022] [Accepted: 09/01/2022] [Indexed: 12/13/2022]
Abstract
NAFLD has become a major public health problem for more than 2 decades with a growing prevalence in parallel with the epidemic of obesity and type 2 diabetes (T2D). The disease burden of NAFLD differs across geographical regions and ethnicities. Variations in prevalence of metabolic diseases, extent of urban-rural divide, dietary habits, lifestyles, and the prevalence of NAFLD risk and protective alleles can contribute to such differences. The rise in NAFLD has led to a remarkable increase in the number of cases of cirrhosis, hepatocellular carcinoma, hepatic decompensation, and liver-related mortality related to NAFLD. Moreover, NAFLD is associated with multiple extrahepatic manifestations. Most of them are risk factors for the progression of liver fibrosis and thus worsen the prognosis of NAFLD. All these comorbidities and complications affect the quality of life in subjects with NAFLD. Given the huge and growing size of the population with NAFLD, it is expected that patients, healthcare systems, and the economy will suffer from the ongoing burden related to NAFLD. In this review, we examine the disease burden of NAFLD across geographical areas and ethnicities, together with the distribution of some well-known genetic variants for NAFLD. We also describe some special populations including patients with T2D, lean patients, the pediatric population, and patients with concomitant liver diseases. We discuss extrahepatic outcomes, patient-reported outcomes, and economic burden related to NAFLD.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Medical Data Analytics Center, Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong
- State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Department of Medicine , Indiana University School of Medicine , Indianapolis , Indiana , USA
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE) , University of Palermo , Palermo , Italy
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine , Recep Tayyip Erdogan University , Rize , Turkey
- Liver Research Unit , Institute of Gastroenterology , Marmara University , Istanbul , Turkey
| | - Grace Lai-Hung Wong
- Medical Data Analytics Center, Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong
- State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong
| | - Leon A Adams
- Department of Hepatology , Sir Charles Gairdner Hospital , Perth , Australia
- Medical School , University of Western Australia , Perth , Australia
| | - Victor de Lédinghen
- Hepatology Unit , Hôpital Haut Lévêque, Bordeaux University Hospital , Bordeaux , France
- INSERM U1312 , Bordeaux University , Bordeaux , France
| | - Silvia Sookoian
- School of Medicine, Institute of Medical Research A Lanari , University of Buenos Aires , Ciudad Autónoma de Buenos Aires , Argentina
- Department of Clinical and Molecular Hepatology, Institute of Medical Research (IDIM) , National Scientific and Technical Research Council (CONICET), University of Buenos Aires , Ciudad Autónoma de Buenos Aires , Argentina
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Center, Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong
- State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong
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23
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Sex differences in the relationship between hepatic steatosis, mood and anxiety disorders. J Psychosom Res 2023; 168:111216. [PMID: 36913766 DOI: 10.1016/j.jpsychores.2023.111216] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 02/22/2023] [Accepted: 03/03/2023] [Indexed: 03/15/2023]
Abstract
OBJECTIVE To investigate the association between non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), mental symptoms (mood, anxiety disorders and distress) by sex. METHODS This a cross-sectional study performed in working-age adults from a Health Promotion Center (primary care) in São Paulo, Brazil. Self-reported mental symptoms from rating scales (21-item Beck Anxiety Inventory, Patient Health Questionnaire-9, and K6 distress scale) were evaluated by hepatic steatosis (NAFLD and ALD). Logistic regression models estimated the association between hepatic steatosis subtypes and mental symptoms by Odds ratios (OR) adjusted by confounders in the total sample and sex stratified. RESULTS Among 7241 participants (70.5% men, median age: 45 years), the frequency of steatosis was of 30.7% (25.1% NAFLD), being higher in men than women (70.5% vs. 29.5%, p < 0.0001), regardless of the steatosis subtype. Metabolic risk factors were similar in both subtypes of steatosis, but not mental symptoms. Overall, NAFLD was inversely associated with anxiety (OR = 0.75, 95%CI 0.63-0.90) and positively associated with depression (OR = 1.17, 95%CI 1.00-1.38). On the other hand, ALD was positively associated with anxiety (OR = 1.51; 95%CI 1.15-2.00). In sex-stratified analyses, only men presented an association of anxiety symptoms with NAFLD (OR = 0.73; 95%CI 0.60-0.89) and ALD (OR = 1.60; 95%CI 1.18-2.16). CONCLUSIONS The complex association between different types of steatosis (NAFLD and ALD), mood and anxiety disorders indicates the need for a deeper understanding of their common causal pathways.
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Martinez-Castillo M, Altamirano-Mendoza I, Zielinski R, Priebe W, Piña-Barba C, Gutierrez-Reyes G. Collagen matrix scaffolds: Future perspectives for the management of chronic liver diseases. World J Clin Cases 2023; 11:1224-1235. [PMID: 36926129 PMCID: PMC10013111 DOI: 10.12998/wjcc.v11.i6.1224] [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: 10/10/2022] [Revised: 11/21/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023] Open
Abstract
Approximately 1.5 billion chronic liver disease (CLD) cases have been estimated worldwide, encompassing a wide range of liver damage severities. Moreover, liver disease causes approximately 1.75 million deaths per year. CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process, cell death, over deposition of extracellular matrix proteins, and dysregulated regeneration. Overall, these processes impair the correct function of this vital organ. Cirrhosis and liver cancer are the main complications of CLD, which accounts for 3.5% of all deaths worldwide. Liver transplantation is the optimal therapeutic option for advanced liver damage. The liver is one of the most common organs transplanted; however, only 10% of liver transplants are successful. In this context, regenerative medicine has made significant progress in the design of biomaterials, such as collagen matrix scaffolds, to address the limitations of organ transplantation (e.g., low donation rates and biocompatibility). Thus, it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.
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Affiliation(s)
- Moises Martinez-Castillo
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Itzel Altamirano-Mendoza
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
| | - Rafal Zielinski
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Waldemar Priebe
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Cristina Piña-Barba
- Materials Research Institute, Universidad Nacional Autónoma de México, Mexico City 06726, Mexico City, Mexico
| | - Gabriela Gutierrez-Reyes
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
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Han SK, Baik SK, Kim MY. Non-alcoholic fatty liver disease: Definition and subtypes. Clin Mol Hepatol 2023; 29:S5-S16. [PMID: 36577427 PMCID: PMC10029964 DOI: 10.3350/cmh.2022.0424] [Citation(s) in RCA: 73] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/21/2022] [Accepted: 12/24/2022] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
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26
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Li J, Wang Q, Ni W, Liu C, Li Z, Qi X. Global health burden of cirrhosis and other chronic liver diseases (CLDs) due to non-alcoholic fatty liver disease (NAFLD): A systematic analysis for the global burden of disease study 2019. GLOBAL TRANSITIONS 2023; 5:160-169. [DOI: 10.1016/j.glt.2023.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Zhai M, Jiang Q, Liu S, Long J, Zhang D, Ren C, Gong Y, Li Y. DALY trend and predictive analysis of COPD in China and its provinces: Findings from the global burden of disease study. Front Public Health 2022; 10:1046773. [PMID: 36620296 PMCID: PMC9816410 DOI: 10.3389/fpubh.2022.1046773] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
Abstract
Background Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease in the world, especially in China. Few studies have explored the trend of COPD in China and its provinces. This study aimed to demonstrate and predict the trend of COPD DALY in China and its provinces based on the global burden of disease (GBD) data. Methods The data on COPD disability-adjusted life year (DALY) were collected from GBD 2017, GBD 2019, and the National Bureau of Statistics of China. The age-standardized rate (ASR) was used to evaluate the trend of COPD DALY by gender, age, and risk factors in China and its provinces. In addition, the trend of COPD considering the aging population in the next 10 years was also predicted. Results In China, the COPD DALY was 20.4 million in 2017, which decreased to 24.16% from 1990 to 2017. Most provinces showed a downward trend, with the exception of Taiwan which increased by 127.78%. The ASR of DALY was 1445.53 per 100,000 people in 2017 and demonstrated a significant decrease. Among all provinces, only Taiwan (97.78%) and Hubei (2.21%) demonstrated an increased trend of ASR. In addition, Tibet ranked third with a decline of 56.95%, although its ASR was the highest in 1990. Smoking and air pollution were the main risk factors for COPD and varied with regions, gender, and age. The proportion of COPD DALY attributable to smoking was higher in the middle-aged and elderly male population and did not decrease in China. Moreover, the ASR attributable to air pollution of the elderly decreased significantly in China. Socio-demographic index (SDI) and educational level were also found to be related to ASR. By predicting the ASR trend in the next 10 years, we found that the ASR attributable to smoking might increase significantly among men. The ASR attributable to air pollution showed a significant decrease in women. Unfortunately, ASR attributable to second-hand smoke was found to increase in women. Conclusion Chronic obstructive pulmonary disease is the leading contributor to the burden of global diseases. Although China and its provinces demonstrated a downward trend of COPD DALY, some provinces still faced challenges. Moreover, ASR attributable to risk factors was different in regions, gender, age, and years. The predicted trend of COPD was also different. Therefore, more targeted strategies should be formulated to reduce the burden of COPD in China and its provinces.
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Affiliation(s)
- Mimi Zhai
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China,Xiangya Nursing School, Central South University, Changsha, Hunan, China
| | - Qin Jiang
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Sushun Liu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jianhai Long
- Department of Respiratory, Beijing Tiantan Hospital, Capital Medicine University, Beijing, China
| | - Dan Zhang
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chutong Ren
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yi Gong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China,*Correspondence: Yi Gong ✉ ; ✉
| | - Yamin Li
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China,Xiangya Nursing School, Central South University, Changsha, Hunan, China,Yamin Li ✉
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Liu YB, Chen MK. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol 2022; 28:5910-5930. [PMID: 36405106 PMCID: PMC9669831 DOI: 10.3748/wjg.v28.i41.5910] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/30/2022] [Accepted: 10/20/2022] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis causes a heavy global burden. In this review, we summarized up-to-date epidemiological features of cirrhosis and its complications. Recent epidemiological studies reported an increase in the prevalence of cirrhosis in 2017 compared to in 1990 in both men and women, with 5.2 million cases of cirrhosis and chronic liver disease occurring in 2017. Cirrhosis caused 1.48 million deaths in 2019, an increase of 8.1% compared to 2017. Disability-adjusted life-years due to cirrhosis ranked 16th among all diseases and 7th in people aged 50-74 years in 2019. The global burden of hepatitis B virus and hepatitis C virus-associated cirrhosis is decreasing, while the burden of cirrhosis due to alcohol and nonalcoholic fatty liver disease (NAFLD) is increasing rapidly. We described the current epidemiology of the major complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, renal disorders, and infections. We also summarized the epidemiology of hepatocellular carcinoma in patients with cirrhosis. In the future, NAFLD-related cirrhosis will likely become more common due to the prevalence of metabolic diseases such as obesity and diabetes, and the prevalence of alcohol-induced cirrhosis is increasing. This altered epidemiology should be clinically noted, and relevant interventions should be undertaken.
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Affiliation(s)
- Yuan-Bin Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei Province, China
| | - Ming-Kai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430000, Hubei Province, China
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Bhujade H, Mishra S, Butt AS, Kamani L, Premkumar M. Work-up for Incidentally Detected NAFLD: How Far is It Worth? Euroasian J Hepatogastroenterol 2022; 12:S26-S36. [DOI: 10.5005/jp-journals-10018-1364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Liangpunsakul S. A Path Toward Improving Nonalcoholic Fatty Liver Disease Care Among Non-hepatologists. Endocr Pract 2022; 28:456-457. [PMID: 35569885 DOI: 10.1016/j.eprac.2022.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Suthat Liangpunsakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202; Roudebush Veterans Administration Medical Center, Indianapolis, Indiana; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
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Amini M, Looha MA, Zarean E, Pourhoseingholi MA. Global pattern of trends in incidence, mortality, and mortality-to-incidence ratio rates related to liver cancer, 1990-2019: a longitudinal analysis based on the global burden of disease study. BMC Public Health 2022; 22:604. [PMID: 35351047 PMCID: PMC8961994 DOI: 10.1186/s12889-022-12867-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 02/25/2022] [Indexed: 12/30/2022] Open
Abstract
Background Liver cancer (LC) is considered as one of the most dominant malignant tumors which ranked 4th and 6th in terms of global mortality and incidence, respectively. This work aimed to investigate the global temporal trends in LC mortality-to-incidence ratio (MIR) and its components, with a particular focus on examining long-term effect of human development index (HDI) on these metrics in a 30-year follow-up. Methods The age-standardized LC incidence and mortality data were derived from the global burden of disease (GBD) study 2019. We first leveraged joinpoint piecewise linear regression analysis to ascertain time trends in LC incidence, mortality, and MIR complement [1-MIR] and the average annual percentage change (AAPC) of the rates over the period 1990–2019. Then, the association between the metrics and HDI was explored through longitudinal multilevel models (LMMs). Results The incidence rates paralleled the mortality rates worldwide and they had similar significant monotonic decrementing trends with AAPC values of − 1.10% (95% confidence interval (CI): − 1.40, − 0.90%) and − 1.40% (− 1.50, − 1.30%), respectively from 1990 to 2019. The [1-MIR] rates were around 0 and showed an increasing pattern from 1.70 to 8.10 per 100,000 people (AAPC, 4.90%) at the same period of time. Results from the LMMs displayed that the majority of the variation lies at the country level accounted for about 88% of the total variance. Moreover, our analysis supported that the HDI was negatively associated with either incidence or mortality over time (p < 0.05). Conclusions Our findings highlighted that the global long-term temporal trends of LC incidence and mortality decreased slightly during 1990–2019 which may reflect improved therapeutic strategies and public health interventions. Besides, the low rates of [1-MIR] revealed the five-year relative survival rate was poor implying LC is diagnosed late in its development. Thereby, the policymakers’ focus must be on early screening and detection of liver cancer.
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Affiliation(s)
- Maedeh Amini
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mehdi Azizmohammad Looha
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elaheh Zarean
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
| | - Mohamad Amin Pourhoseingholi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Akhtar S. Preoperative evaluation of geriatric patients undergoing liver transplantation. Curr Opin Anaesthesiol 2022; 35:96-104. [PMID: 34878418 DOI: 10.1097/aco.0000000000001084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW As the population of the world is aging the number of geriatric patients undergoing liver transplantation (LT) is also increasing. They pose a unique challenge for the caregivers, as they have age-related physiological changes, multiple comorbidities and cirrhosis-related pathologies. RECENT FINDINGS Twenty-two percent of patients who undergo LT are older than 65 years. Many patients suffer from nonalcoholic steatohepatitis (NASH), hepatocellular carcinoma and hepatitis-C virus. Incidence of NASH tends to increase with age, obesity, diabetes and metabolic syndrome. Elderly patients require comprehensive cognitive, cardiac and pulmonary evaluation prior to LT. Cirrhotic cardiomyopathy, hepatopulmonary syndrome, portopulmonary hypertension and frailty are of specific concern. SUMMARY Proportion of elderly patients who are undergoing LT continues to increase. These patients require comprehensive cardiopulmonary and frailty evaluation. Consensus-based practice advisories need to be developed to standardize preoperative evaluation of geriatric patients awaiting LT.
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Affiliation(s)
- Shamsuddin Akhtar
- Department of Anesthesiology and Pharmacology, Yale School of Medicine, New Haven, Connecticut, USA
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Shalimar, Elhence A, Bansal B, Gupta H, Anand A, Singh TP, Goel A. Prevalence of Non-alcoholic Fatty Liver Disease in India: A Systematic Review and Meta-analysis. J Clin Exp Hepatol 2022; 12:818-829. [PMID: 35677499 PMCID: PMC9168741 DOI: 10.1016/j.jceh.2021.11.010] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 11/18/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) contributes to a large proportion of liver disease burden in the world. Several groups have studied the prevalence of NAFLD in the Indian population. AIM A systematic review of the published literature and meta-analysis was carried out to estimate the prevalence of NAFLD in the Indian population. METHODS English language literature published until April 2021 was searched from electronic databases. Original data published in any form which had reported NAFLD prevalence in the Indian population were included. The subgroup analysis of prevalence was done based on the age (adults or children) and risk category, i.e., average-risk group (community population, participants of control arm, unselected participants, hypothyroidic individuals, athletes, aviation crew, and army personnel) and high-risk group (obesity or overweight, diabetes mellitus, coronary artery disease, etc.). The prevalence estimates were pooled using the random-effects model. Heterogeneity was assessed with I2. RESULTS Sixty-two datasets (children 8 and adults 54) from 50 studies were included. The pooled prevalence of NAFLD was estimated from 2903 children and 23,581 adult participants. Among adults, the estimated pooled prevalence was 38.6% (95% CI 32-45.5). The NAFLD prevalence in average-risk and high-risk subgroups was estimated to be 28.1% (95% CI 20.8-36) and 52.8% (95% CI 46.5-59.1), respectively. The estimated NAFLD prevalence was higher in hospital-based data (40.8% [95% CI 32.6-49.3%]) than community-based data (28.2% [95% CI 16.9-41%]). Among children, the estimated pooled prevalence was 35.4% (95% CI 18.2-54.7). The prevalence among non-obese and obese children was 12.4 (95% CI 4.4-23.5) and 63.4 (95% CI 59.4-67.3), respectively. CONCLUSION Available data suggest that approximately one in three adults or children have NAFLD in India.
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Key Words
- ALT, Alanine aminotransferase
- AST, Aspartate aminotransferase
- BMI, Body mass index
- CAD, Coronary artery disease
- CI, Confidence interval
- DM, Diabetes mellitus
- GBD, Global burden of disease
- GDM, Gestational diabetes mellitus
- GDP, Gross domestic product
- HC, Healthy control
- IGT, Impaired glucose tolerance
- NAFLD, Non-alcoholic fatty liver disease
- NASH, Non-alcoholic steatohepatitis
- NPCDCS, National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke
- OSA, Obstructive sleep apnea
- PCOS, Polycystic ovarian syndrome
- UT, Union Territories
- diabetes mellitus
- fatty liver
- metabolic syndrome
- obesity
- steatohepatitis
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Affiliation(s)
- Shalimar
- All India Institute of Medical Sciences, New Delhi, India
| | - Anshuman Elhence
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Bhavik Bansal
- All India Institute of Medical Sciences, New Delhi, India
| | - Hardik Gupta
- All India Institute of Medical Sciences, New Delhi, India
| | - Abhinav Anand
- All India Institute of Medical Sciences, New Delhi, India
| | - Thakur P. Singh
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Amit Goel
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India,Address for correspondence: Amit Goel, Additional Professor, Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
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Dahiya DS, Kichloo A, Shaka H, Singh J, Singh G, Wani F, Masudi S, Koul H, Pisipati S. Hepatopulmonary Syndrome: A Nationwide Analysis of Epidemiological Trends and Outcomes From 2012 to 2018. Gastroenterology Res 2021; 14:252-258. [PMID: 34527095 PMCID: PMC8425794 DOI: 10.14740/gr1448] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 08/13/2021] [Indexed: 11/11/2022] Open
Abstract
Background This study was designed to determine the epidemiological trends and adverse outcomes of hepatopulmonary syndrome (HPS). Methods This retrospective interrupted trend study analyzed data from the Nationwide Inpatient Sample (NIS) for the years 2012, 2014, 2016 and 2018 to identify adult (≥ 18 years) hospitalizations with a diagnosis of HPS. We highlighted epidemiological trends for HPS. Inpatient mortality, mean length of stay (LOS) and mean total hospital charge (THC) were estimated using multivariate regression trend analysis. Results We observed an increase in the total number of HPS hospitalizations from 1,565 in 2012 to 2,495 in 2018, with mean age ranging from 55.8 to 58.1 years. There was a trend towards increasing hospitalizations (P-trend < 0.001) with increasing mean age (P-trend = 0.003) for HPS. Whites made up most of the study population. The inpatient mortality for HPS ranged from 12.4% to 12.6%, but there was no statistically significant trend for mortality (P-trend = 0.534) between 2012 and 2018. Additionally, there was no change in both mean LOS (P-trend = 0.545) and mean THC (P-trend = 0.534) for HPS for these years. Conclusions Hospitalizations and mean age for HPS were on the rise. Inpatient mortality ranged from 12.4% to 12.6%; however, a statistically significant trend for mortality was absent.
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Affiliation(s)
- Dushyant Singh Dahiya
- Department of Internal Medicine, Central Michigan University College of Medicine, 1000 Houghton Ave, Saginaw, MI 48602, USA
| | - Asim Kichloo
- Department of Internal Medicine, Central Michigan University College of Medicine, 1000 Houghton Ave, Saginaw, MI 48602, USA.,Department of Internal Medicine, Samaritan Medical Center, Watertown, NY, USA
| | - Hafeez Shaka
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, 1969 Ogden Ave, Chicago, IL 60612, USA
| | - Jagmeet Singh
- Department of Internal Medicine, Guthrie Robert Packer Hospital, 1 Guthrie Square, Sayre, PA 18840, USA
| | - Gurdeep Singh
- Department of Internal Medicine and Endocrinology, Lady of Lourdes Memorial Hospital, 169 Riverside Dr, Binghamton, NY 13905, USA
| | - Farah Wani
- Department of Family Medicine, Samaritan Medical Center, 830 Washington St, Watertown, NY 13601, USA
| | - Sundas Masudi
- Department of Internal Medicine, University of Liverpool School of Medicine, Cedar House, Ashton St, Liverpool, L693GE, UK
| | - Hazique Koul
- Department of Internal Medicine, Jaharul Islam Medical College, Bajitpur, BD 2336, Bangladesh
| | - Sailaja Pisipati
- Department of Gastroenterology and Hepatology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
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Abstract
Antifibrotic therapies for the treatment of liver fibrosis represent an unconquered area of drug development. The significant involvement of the gut microbiota as a driving force in a multitude of liver disease, be it pathogenesis or fibrotic progression, suggest that targeting the gut–liver axis, relevant signaling pathways, and/or manipulation of the gut’s commensal microbial composition and its metabolites may offer opportunities for biomarker discovery, novel therapies and personalized medicine development. Here, we review potential links between bacterial translocation and deficits of host-microbiome compartmentalization and liver fibrosis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies, translated from our current knowledge of the gut–liver axis, targeted at restoring intestinal eubiosis, ameliorating hepatic fibrosis and rising portal hypertension that characterize and define the course of decompensated cirrhosis.
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Muscate F, Woestemeier A, Gagliani N. Functional heterogeneity of CD4 + T cells in liver inflammation. Semin Immunopathol 2021; 43:549-561. [PMID: 34463867 PMCID: PMC8443520 DOI: 10.1007/s00281-021-00881-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/14/2021] [Indexed: 12/24/2022]
Abstract
CD4+ T cells play an essential role in orchestrating adequate immunity, but their overactivity has been associated with the development of immune-mediated inflammatory diseases, including liver inflammatory diseases. These cells can be subclassified according to their maturation stage, cytokine profile, and pro or anti-inflammatory functions, i.e., functional heterogeneity. In this review, we summarize what has been discovered so far regarding the role of the different CD4+ T cell polarization states in the progression of two prominent and still different liver inflammatory diseases: non-alcoholic steatohepatitis (NASH) and autoimmune hepatitis (AIH). Finally, the potential of CD4+ T cells as a therapeutic target in both NASH and AIH is discussed.
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Affiliation(s)
- Franziska Muscate
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anna Woestemeier
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nicola Gagliani
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Venniyoor A, Al Farsi AA, Al Bahrani B. The Troubling Link Between Non-alcoholic Fatty Liver Disease (NAFLD) and Extrahepatic Cancers (EHC). Cureus 2021; 13:e17320. [PMID: 34557366 PMCID: PMC8449927 DOI: 10.7759/cureus.17320] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a fast-spreading epidemic across the globe and has serious implications far beyond that of a "benign" liver condition. It is usually an outcome of ectopic fat storage due to chronic positive energy balance leading to obesity and is associated with multiple health problems. While association with cardiovascular disease and hepatocellular cancer is well recognized, it is becoming clear the NAFLD carries with it an increased risk of cancers of extrahepatic tissues. Studies have reported a higher risk for cancers of the colon, breast, prostate, lung, and pancreas. Fatty liver is associated with increased mortality; there is an urgent need to understand that fatty liver is not always benign, and not always associated with obesity. It is, however, a reversible condition and early recognition and intervention can alter its natural history and associated complications.
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Affiliation(s)
- Ajit Venniyoor
- Medical Oncology, National Oncology Center, The Royal Hospital, Muscat, OMN
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