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Ojha U, Kim S, Rhee CY, You J, Choi YH, Yoon SH, Park SY, Lee YR, Kim JK, Bae SC, Lee YM. Endothelial RUNX3 controls LSEC dysfunction and angiocrine LRG1 signaling to prevent liver fibrosis. Hepatology 2025; 81:1228-1243. [PMID: 39042837 PMCID: PMC11902585 DOI: 10.1097/hep.0000000000001018] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 06/23/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND AND AIMS Liver fibrosis represents a global health burden, given the paucity of approved antifibrotic therapies. Liver sinusoidal endothelial cells (LSECs) play a major gatekeeping role in hepatic homeostasis and liver disease pathophysiology. In early tumorigenesis, runt-related transcription factor 3 (RUNX3) functions as a sentinel; however, its function in liver fibrosis in LSECs remains unclear. This study aimed to investigate the role of RUNX3 as an important regulator of the gatekeeping functions of LSECs and explore novel angiocrine regulators of liver fibrosis. APPROACH AND RESULTS Mice with endothelial Runx3 deficiency develop gradual and spontaneous liver fibrosis secondary to LSEC dysfunction, thereby more prone to liver injury. Mechanistic studies in human immortalized LSECs and mouse primary LSECs revealed that IL-6/JAK/STAT3 pathway activation was associated with LSEC dysfunction in the absence of RUNX3. Single-cell RNA sequencing and quantitative RT-PCR revealed that leucine-rich alpha-2-glycoprotein 1 ( LRG1 ) was highly expressed in RUNX3-deficient and dysfunctional LSECs. In in vitro and coculture experiments, RUNX3-depleted LSECs secreted LRG1, which activated HSCs throughTGFBR1-SMAD2/3 signaling in a paracrine manner. Furthermore, circulating LRG1 levels were elevated in mouse models of liver fibrosis and in patients with fatty liver and cirrhosis. CONCLUSIONS RUNX3 deficiency in the endothelium induces LSEC dysfunction, LRG1 secretion, and liver fibrosis progression. Therefore, endothelial RUNX3 is a crucial gatekeeping factor in LSECs, and profibrotic angiocrine LRG1 may be a novel target for combating liver fibrosis.
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Affiliation(s)
- Uttam Ojha
- Vessel-Organ Interaction Research Center, VOICE (MRC), Research Institute of Pharmaceutical Sciences, Department of Molecular Pathophysiology, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea
| | - Somi Kim
- Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea
| | - Chang Yun Rhee
- Vessel-Organ Interaction Research Center, VOICE (MRC), Research Institute of Pharmaceutical Sciences, Department of Molecular Pathophysiology, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea
| | - Jihye You
- Vessel-Organ Interaction Research Center, VOICE (MRC), Research Institute of Pharmaceutical Sciences, Department of Molecular Pathophysiology, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea
| | - Yoon Ha Choi
- Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea
| | - Soo-Hyun Yoon
- Vessel-Organ Interaction Research Center, VOICE (MRC), Research Institute of Pharmaceutical Sciences, Department of Molecular Pathophysiology, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jong Kyoung Kim
- Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea
| | - Suk-Chul Bae
- Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju, Republic of Korea
| | - You Mie Lee
- Vessel-Organ Interaction Research Center, VOICE (MRC), Research Institute of Pharmaceutical Sciences, Department of Molecular Pathophysiology, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea
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Ahmed M. Ramadan Fasting and Complications of Metabolic Dysfunction-Associated Steatotic Liver Disease: Impacts on Liver Cirrhosis and Heart Failure. J Clin Med 2025; 14:1841. [PMID: 40142648 PMCID: PMC11942711 DOI: 10.3390/jcm14061841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/03/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Metabolic-dysfunction-associated steatotic liver disease (MASLD) and heart failure are two intersecting growing pandemics. Studies have demonstrated a strong association between MASLD and heart failure. Liver cirrhosis is a well-recognized complication of MASLD. This study aimed to summarize the potential effects of Ramadan fasting on MASLD, liver cirrhosis, and heart failure. The author searched the SCOPUS and PubMed databases using specific terms. The literature review focused on research articles published in English from 2000 to 2024. Twenty-two articles were selected for this narrative review. Ramadan fasting reduced serum cholesterol serum levels, improved symptoms of heart failure and reduced anthropometric measurements. However, it increased ascitic fluid production and plasma bilirubin levels and might increase the risk of hepatic encephalopathy and upper gastrointestinal haemorrhage in liver cirrhosis. Ramadan fasting might improve symptoms of heart failure and might decrease the risk of heart failure in patients with MASLD. Further research studies are needed to confirm the efficacy and evaluate the safety of Ramadan fasting in patients with heart failure and liver cirrhosis.
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Affiliation(s)
- Musaab Ahmed
- College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates;
- Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates
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Taboada-Alquerque M, Olivero-Verbel J. Network Toxicology Analysis Reveals Molecular Mechanisms Associated with Noise Exposure to Multiple Diseases. Toxicol Mech Methods 2025:1-25. [PMID: 39898607 DOI: 10.1080/15376516.2025.2460591] [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: 05/02/2024] [Revised: 12/09/2024] [Accepted: 01/24/2025] [Indexed: 02/04/2025]
Abstract
Noise pollution is recognized as an environmental stressor that affects various biological processes beyond auditory functions, mainly through stress hormones release. This work explored the biological processes, diseases attributable to noise-regulated targets, and the main targets involved in each disease, employing a network toxicology approach. Through various databases and bioinformatics analysis, a total of 577 targets were identified as potential candidates implicated in diseases related to noise exposure, 10 from the GEO database and the rest from other databases. Noise pollution was found to regulate processes such as hormone response, cellular response to cytokines, and circulatory system functions, contributing to the development of the pathological manifestations related to the diseases like hypertension, ischemia, atherosclerosis, and cirrhosis. Hub targets for ischemia included IL-6, CASP3, AKT1, and TNF-α, while NOS3 was related to hypertension, and NOS3, TNF-α, AGT, and IL-1B to atherosclerosis. The targets were found to be linked to vascular regulation and inflammation in cardio- and cerebrovascular diseases. Molecular docking studies indicated stress hormones released by noise exposure regulates these diseases through signaling pathways, without implicating its direct binding to hub targets. The results indicate that individuals with vascular diseases are more vulnerable to the effects of prolonged noise exposure.
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Affiliation(s)
- Maria Taboada-Alquerque
- Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena 130014, Colombia
| | - Jesus Olivero-Verbel
- Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena 130014, Colombia
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Sinnanaidu RP, Poobalan K, Singh ASB, Nair K, Vijayananthan A, Mahadeva S. The Epidemiology of Ascites in a Multi-Ethnic Asian Population. JGH Open 2025; 9:e70111. [PMID: 39959453 PMCID: PMC11825974 DOI: 10.1002/jgh3.70111] [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: 10/25/2024] [Revised: 12/23/2024] [Accepted: 01/23/2025] [Indexed: 02/18/2025]
Abstract
Introduction Ascites is a common condition seen by clinicians in secondary care. Data on the epidemiology of ascites in Asians is lacking. Methodology A retrospective case record review was performed in this large, referral institution between January 2016 and December 2019. Clinical and epidemiological data of adult (age > 18 years) patients with ascites, identified from the Radiology database, were obtained from this institutions' electronic medical records. Results A total of 838 patients (median age 59.77 ± 14.46 years, 56% males, ethnicity: Chinese 41.9%, Malay 34.8%, Indian 22.7%) were included in the study. Malignancy (28.9%) and liver cirrhosis (27.9%) were the most common etiology of ascites. Most of the malignant etiology of ascites were due to female-related (breast and ovarian) and gastrointestinal (colon, liver, pancreatic, bile duct) cancer. Liver cirrhosis-related ascites was mostly due to metabolic-associated fatty liver disease (MASLD, 35.5%) and hepatitis B infection (20.5%). An increased age (> 40 years) was associated with all causes of ascites. The etiology of ascites varied with ethnicity as follows: the most common cause of ascites was malignancy (37.6%) among ethnic Chinese, heart failure (20.5%) in ethnic Malays and chronic liver disease (43.7%) in ethnic Indians. Conclusion Malignancy and liver cirrhosis are the leading cause of ascites in a multi-ethnic Asian population. Demographic factors, particularly ethnicity, have a strong influence on the etiology of ascites.
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Affiliation(s)
- Ram Prasad Sinnanaidu
- Division of Gastroenterology, Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
| | - Kumaraganapathy Poobalan
- Division of Gastroenterology, Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
| | | | - Kishvan Nair
- Division of Gastroenterology, Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
| | - Anushya Vijayananthan
- Department of Biomedical Imaging, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
| | - Sanjiv Mahadeva
- Division of Gastroenterology, Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
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Jiménez-Luévano MÁ, Jiménez-Partida AE, Sierra-Díaz E, Orozco-Alonso E, Villaseñor-García M, Bravo-Hernández A, Gutiérrez-Ortíz JA, Bravo-Cuellar A, Hernández-Flores G. Prolonged use of pentoxifylline increases the life expectancy of patients with compensated cirrhosis: A 20‑year retrospective study. Biomed Rep 2024; 21:173. [PMID: 39355527 PMCID: PMC11443491 DOI: 10.3892/br.2024.1861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 07/29/2024] [Indexed: 10/03/2024] Open
Abstract
Liver cirrhosis is a pathology of varied etiology with a high prevalence and mortality, resulting in >1 million mortalities per year. Patients with liver cirrhosis typically have a survival time of 12 years following diagnosis. The treatment for this disease is directed at the complications of cirrhosis; however, to the best of our knowledge, the long-term management of patients with cirrhosis has been scarcely studied. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with rheological activity and antioxidant, anti-inflammatory and antifibrotic properties. PTX has been used in the treatment of peripheral arterial disease, inflammatory liver diseases and hepatocellular carcinoma with encouraging results. The aim of the present study was to evaluate the effect of PTX use on the survival of patients with compensated cirrhosis. For this purpose, a cross-sectional study was performed at the Gastroenterology and Hepatitis C Department of Dr. Valentín Gómez Farias Hospital (Institute for Security and Social Services for State Workers, Zapopan, Mexico) from June, 1996 to December, 2019. The follow-up time for these patients was 22.6 years (up to the end of the study period). In the present study, 326 patient files were analyzed and 118 patients with the disease were identified, 81 of whom (68.64%) died within 12 years after diagnosis. Of the included patients, 26 received PTX combined with PEG IFN-α-2a plus ribavirin, and 11 received PTX plus propranolol, with a median treatment duration of 20.6±0.8 years. Furthermore, 16 patients (43%) did not develop co-morbidities within this time, and the transition to decompensated cirrhosis was 16.6 years, with a survival time of 20 years. Therefore, the results of the present study suggest that PTX may improve the long-term survival of patients with compensated cirrhosis, rendering PTX a candidate for repurposing in the treatment of hepatic cirrhosis.
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Affiliation(s)
- Miguel Ángel Jiménez-Luévano
- Gastroenterology Service, Institute for Security and Social Services for State Workers, Valentín Gómez Farías General Hospital, Zapopan, Jalisco 45100, Mexico
| | - Ana Emilia Jiménez-Partida
- Gastroenterology Service, Institute for Security and Social Services for State Workers, Valentín Gómez Farías General Hospital, Zapopan, Jalisco 45100, Mexico
| | - Erick Sierra-Díaz
- Division of Immunology, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco 44340, Mexico
| | - Eduardo Orozco-Alonso
- Division of Immunology, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco 44340, Mexico
| | - Martha Villaseñor-García
- Division of Immunology, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco 44340, Mexico
- University Center of Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Jalisco 44840, Mexico
| | - Alejandro Bravo-Hernández
- Internal Medicine Service, Antonio González Guevara Civil Hospital, Tepic, Nayarit 63000, Mexico
- Program in Internal Medicine, The Autonomous University of Nayarit, Tepic, Nayarit 63000, Mexico
| | - Jesús Alejandro Gutiérrez-Ortíz
- Division of Immunology, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco 44340, Mexico
- Doctoral Program in Biomedical Science Orientation Immunology, University Center for Health Science, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico
| | - Alejandro Bravo-Cuellar
- Division of Immunology, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco 44340, Mexico
- Department of Health Sciences, Los Altos University Center, University of Guadalajara, Tepatitlán de Morelos, Jalisco 47620, Mexico
| | - Georgina Hernández-Flores
- Division of Immunology, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco 44340, Mexico
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Montoya-Buelna M, Ramirez-Lopez IG, San Juan-Garcia CA, Garcia-Regalado JJ, Millan-Sanchez MS, de la Cruz-Mosso U, Haramati J, Pereira-Suarez AL, Macias-Barragan J. Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential. World J Hepatol 2024; 16:1211-1228. [PMID: 39351515 PMCID: PMC11438597 DOI: 10.4254/wjh.v16.i9.1211] [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: 06/05/2024] [Revised: 07/31/2024] [Accepted: 08/13/2024] [Indexed: 09/23/2024] Open
Abstract
Extracellular vesicles (EVs) are small particles released by many cell types in different tissues, including the liver, and transfer specific cargo molecules from originating cells to receptor cells. This process generally culminates in activation of distant cells and inflammation and progression of certain diseases. The global chronic liver disease (CLD) epidemic is estimated at 1.5 billion patients worldwide. Cirrhosis and liver cancer are the most common risk factors for CLD. However, hepatitis C and B virus infection and obesity are also highly associated with CLD. Nonetheless, the etiology of many CLD pathophysiological, cellular, and molecular events are unclear. Changes in hepatic lipid metabolism can lead to lipotoxicity events that induce EV release. Here, we aimed to present an overview of EV features, from definition to types and biogenesis, with particular focus on the molecules related to steatosis-related liver disease, diagnosis, and therapy.
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Affiliation(s)
- Margarita Montoya-Buelna
- Laboratorio de Inmunología, Departamento de Fisiología, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Inocencia G Ramirez-Lopez
- Departamento de Ciencias de la Salud, Centro Universitario de los Valles, Universidad de Guadalajara, Ameca 46600, Jalisco, Mexico
| | - Cesar A San Juan-Garcia
- Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Jose J Garcia-Regalado
- Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Mariana S Millan-Sanchez
- Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Ulises de la Cruz-Mosso
- Red de Inmunonutrición y Genómica Nutricional en las Enfermedades Autoinmunes, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Jesse Haramati
- Laboratorio de Inmunobiología, Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan 45200, Jalisco, Mexico
| | - Ana L Pereira-Suarez
- Instituto de Investigación en Ciencias Biomédicas, Departamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Jose Macias-Barragan
- Departamento de Ciencias de la Salud, Centro Universitario de los Valles, Universidad de Guadalajara, Ameca 46600, Jalisco, Mexico.
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Sinclair S, Shearen S, Ghobrial Y, Trad G, Abdul Basit S, Shih D, Ryan JK. Review of the Effects of Antiviral Therapy on Hepatitis B/C-Related Mortality and the Regression of Fibrosis. Viruses 2024; 16:1531. [PMID: 39459866 PMCID: PMC11512229 DOI: 10.3390/v16101531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis.
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Affiliation(s)
| | | | | | | | | | | | - John K. Ryan
- Comprehensive Digestive Institute of Nevada, Las Vegas, NV 89148, USA (S.A.B.); (D.S.)
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Yutani R, Venketaraman V, Sheren N. Treatment of Acute and Long-COVID, Diabetes, Myocardial Infarction, and Alzheimer's Disease: The Potential Role of a Novel Nano-Compound-The Transdermal Glutathione-Cyclodextrin Complex. Antioxidants (Basel) 2024; 13:1106. [PMID: 39334765 PMCID: PMC11429141 DOI: 10.3390/antiox13091106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 08/21/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024] Open
Abstract
Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants-primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer's disease, that are associated with OS. These dissimilar illnesses are, in order, viral infections, metabolic disorders, ischemic events, and neurodegenerative disorders. Evidence is presented that in many illnesses, (1) OS is an early initiator and significant promotor of their progressive pathophysiologic processes, (2) early reduction of OS may prevent later serious and irreversible complications, (3) GSH deficiency is associated with OS, (4) GSH can likely reduce OS and restore adaptive physiology, (5) effective administration of GSH can be accomplished with a novel nano-product, the GSH/cyclodextrin (GC) complex. OS is an overlooked pathological process of many illnesses. Significantly, with the GSH/cyclodextrin (GC) complex, therapeutic administration of GSH is now available to reduce OS. Finally, rigorous prospective studies are needed to confirm the efficacy of this therapeutic approach.
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Affiliation(s)
- Ray Yutani
- Department of Family Medicine, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
| | - Vishwanath Venketaraman
- Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA;
| | - Nisar Sheren
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA;
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Dąbrowska A, Wilczyński B, Mastalerz J, Kucharczyk J, Kulbacka J, Szewczyk A, Rembiałkowska N. The Impact of Liver Failure on the Immune System. Int J Mol Sci 2024; 25:9522. [PMID: 39273468 PMCID: PMC11395474 DOI: 10.3390/ijms25179522] [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: 07/05/2024] [Revised: 08/26/2024] [Accepted: 08/28/2024] [Indexed: 09/15/2024] Open
Abstract
Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.
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Affiliation(s)
- Alicja Dąbrowska
- Faculty of Medicine, Wroclaw Medical University, Pasteura 1, 50-367 Wroclaw, Poland
| | - Bartosz Wilczyński
- Faculty of Medicine, Wroclaw Medical University, Pasteura 1, 50-367 Wroclaw, Poland
| | - Jakub Mastalerz
- Faculty of Medicine, Wroclaw Medical University, Pasteura 1, 50-367 Wroclaw, Poland
| | - Julia Kucharczyk
- Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
| | - Julita Kulbacka
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
| | - Anna Szewczyk
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
| | - Nina Rembiałkowska
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland
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Vijan K, Ali A, Mohamed Idrus NA, Lourdesamy P, Margammuthu S, Perumal S, Teng CL, Ahmad I. Metabolic associated fatty liver disease (MAFLD): assessing the knowledge and practice of primary care doctors in Seremban District, Negeri Sembilan. MALAYSIAN FAMILY PHYSICIAN : THE OFFICIAL JOURNAL OF THE ACADEMY OF FAMILY PHYSICIANS OF MALAYSIA 2024; 19:51. [PMID: 39220239 PMCID: PMC11366277 DOI: 10.51866/oa.629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Introduction Metabolic-associated fatty liver disease (MAFLD) is the liver manifestation of metabolic syndrome, which is commonly seen in primary care settings. This study aimed to determine the knowledge and practice of primary care physicians regarding MAFLD in Seremban District, Negeri Sembilan. Methods This cross-sectional study was conducted among medical officers in 14 health clinics in Seremban District, using a validated, self-administered online questionnaire. Results A total of 240 medical officers from 14 health clinics in Seremban District, participated in this study. Most participants (85.4%) passed the knowledge test. Their practice was acceptable, but only a minority were familiar with non-invasive testing of liver fibrosis (e.g. APRI or FIB-4), medication and specific diet for the treatment of MAFLD. Conclusion Most primary care physicians in Seremban District are knowledgeable in identifying risk factors and managing patients with MAFLD. However, there are still areas to improve in terms of management, particularly regarding the use of silymarin, vitamin E and pioglitazone.
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Affiliation(s)
- Kalaivaani Vijan
- MBBS, icFRACGP, Klinik Kesihatan Kuala Pilah Jalan Macpherson, Kampung Tebat Kening, Kuala Pilah, Negeri Sembilan, Malaysia.
| | - Athirah Ali
- MD, icFRACGP, Klinik Kesihatan Salak, Jalan Salak, Sepang, Selangor, Malaysia
| | | | - Priscilla Lourdesamy
- MBBS, Klinik Kesihatan Sikamat, Jalan Tunku Kurshiah Atas, Seremban, Negeri Sembilan, Malaysia
| | - Shamini Margammuthu
- MD, Klinik Kesihatan Jelebu, Kuala Klawang, Jelebu, Negeri Sembilan, Malaysia
| | - Suguna Perumal
- Klinik Kesihatan Port Dickson, Jalan Seremban Kampung Dhobi, Port Dickson, Negeri Sembilan, Malaysia
| | - Cheong Lieng Teng
- MBBS, M. Family Medicine, Department of Family Medicine, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit, Jalil, Kuala Lumpur, Malaysia
| | - Imran Ahmad
- MBBS, M. Family Medicine, Department of Family Medicine, Universiti Sains Malaysia, Kampus, Kesihatan, Jalan Raja Perempuan, Zainab 2, Kota Bharu, Kelantan, Malaysia
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11
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Almohaid S, Akhtar S. Diet, lifestyle factors, comorbidities, and hepatocellular carcinoma risk in a middle eastern country: a case-control study. BMC Cancer 2024; 24:694. [PMID: 38844890 PMCID: PMC11157712 DOI: 10.1186/s12885-024-12409-0] [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: 10/05/2023] [Accepted: 05/22/2024] [Indexed: 06/09/2024] Open
Abstract
BACKGROUND Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait. METHODS Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient's clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters' estimates of the final model and used for interpretation of the model. RESULTS The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9-193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2-173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2-43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04-0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05-0.71). CONCLUSIONS This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.
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Affiliation(s)
- Shaimaa Almohaid
- Department of Community Medicine and Behavioural Sciences, College of Medicine, Kuwait University, PO Box 24923, Safat, 13110, Kuwait
| | - Saeed Akhtar
- Department of Community Medicine and Behavioural Sciences, College of Medicine, Kuwait University, PO Box 24923, Safat, 13110, Kuwait.
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12
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Mubarak M. Changes in the terminology and diagnostic criteria of non-alcoholic fatty liver disease: Implications and opportunities. World J Gastrointest Pathophysiol 2024; 15:92864. [PMID: 38682023 PMCID: PMC11045356 DOI: 10.4291/wjgp.v15.i1.92864] [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: 02/08/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/19/2024] Open
Abstract
Fatty liver disease (FLD) is a highly prevalent pathological liver disorder. It has many and varied etiologies and has heterogeneous clinical course and outcome. Its proper nomenclature and classification have been problematic since its initial recognition. Traditionally, it was divided into two main categories: Alcohol-associated liver disease and nonalcoholic FLD (NAFLD). Among these, the latter condition has been plagued with nomenclature and classification issues. The two main objections to its use have been the use of negative (non-alcoholic) and stigmatizing (fatty) terms in its nomenclature. Numerous attempts were made to address these issues but none achieved universal acceptance. Just recently, NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology. FLD has been renamed steatotic liver disease (SLD), and NAFLD as metabolic dysfunction-associated SLD. Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis. This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research, diagnosis, treatment, and prognosis of the disease in the future.
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Affiliation(s)
- Muhammed Mubarak
- Javed I. Kazi Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
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Mahmoudi A, Hajihasani MM, Majeed M, Jamialahmadi T, Sahebkar A. Effect of Calebin-A on Critical Genes Related to NAFLD: A Protein-Protein Interaction Network and Molecular Docking Study. Curr Genomics 2024; 25:120-139. [PMID: 38751599 PMCID: PMC11092913 DOI: 10.2174/0113892029280454240214072212] [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: 10/11/2023] [Revised: 01/12/2024] [Accepted: 02/01/2024] [Indexed: 05/18/2024] Open
Abstract
Background Calebin-A is a minor phytoconstituent of turmeric known for its activity against inflammation, oxidative stress, cancerous, and metabolic disorders like Non-alcoholic fatty liver disease(NAFLD). Based on bioinformatic tools. Subsequently, the details of the interaction of critical proteins with Calebin-A were investigated using the molecular docking technique. Methods We first probed the intersection of genes/ proteins between NAFLD and Calebin-A through online databases. Besides, we performed an enrichment analysis using the ClueGO plugin to investigate signaling pathways and gene ontology. Next, we evaluate the possible interaction of Calebin-A with significant hub proteins involved in NAFLD through a molecular docking study. Results We identified 87 intersection genes Calebin-A targets associated with NAFLD. PPI network analysis introduced 10 hub genes (TP53, TNF, STAT3, HSP90AA1, PTGS2, HDAC6, ABCB1, CCT2, NR1I2, and GUSB). In KEGG enrichment, most were associated with Sphingolipid, vascular endothelial growth factor A (VEGFA), C-type lectin receptor, and mitogen-activated protein kinase (MAPK) signaling pathways. The biological processes described in 87 intersection genes are mostly concerned with regulating the apoptotic process, cytokine production, and intracellular signal transduction. Molecular docking results also directed that Calebin-A had a high affinity to bind hub proteins linked to NAFLD. Conclusion Here, we showed that Calebin-A, through its effect on several critical genes/ proteins and pathways, might repress the progression of NAFLD.
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Affiliation(s)
- Ali Mahmoudi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Mahdi Hajihasani
- Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Muhammed Majeed
- Department of Chemistry, Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ, 08520, USA
| | - Tannaz Jamialahmadi
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;
| | - Amirhossein Sahebkar
- Department of Medical Biotechnology, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Wang X, Liu H, Qi J, Wang L, Yin P, Liu F, Wei L, Wang Y, Zhou M, Rao H. Trends in Mortality of Cirrhosis in China: An Analysis of the China Death Surveillance Database from 2008 to 2020. J Clin Transl Hepatol 2024; 12:236-244. [PMID: 38426195 PMCID: PMC10899872 DOI: 10.14218/jcth.2023.00454] [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: 10/10/2023] [Revised: 12/19/2023] [Accepted: 01/03/2024] [Indexed: 03/02/2024] Open
Abstract
Background and Aims China accounts for 14.9% of total cirrhosis deaths worldwide. A detailed and comprehensive understanding of the contemporary status of cirrhosis mortality in China is crucial for establishing strategies for intervention and decreasing the disease burden of cirrhosis worldwide. The study aimed to report the cirrhosis mortality rates in our whole country or province over time. Methods Mortality data from 2008 to 2020 were retrieved from the Disease Surveillance Point System (DSPs) of the Chinese Center for Disease Control and Prevention. The crude mortality rate and age-standardized mortality rate of patients with cirrhosis were stratified by sex, residential location, and region. The average annual percentage change (AAPC) in cirrhosis mortality rates from 2008 to 2020 was also calculated. Results The crude mortality rate of cirrhosis was 4.57/100,000 people in 2020. Compared with females and individuals living in urban areas, males and people living in rural areas had greater age-standardized mortality. The crude mortality rate and age-standardized mortality rate in provinces in Southwest China (Guangxi, Yunnan, Guizhou, and Qinghai) were greater than those in other provinces. Moreover, with increasing age, the age-specific mortality rate increased significantly. From 2008 to 2020, the mortality rate of cirrhosis in China decreased except for in males aged 50-59 years, females aged 45-49 years and females aged 80-84 years. Conclusions The mortality rate of patients with cirrhosis in China decreased from 2008 to 2020. In the future, interventions of cirrhosis mortality control need to pay more attention to all males, females aged 45-49 and 80-84 years, and people living in rural areas and in provinces in Southwest China.
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Affiliation(s)
- Xiaoxiao Wang
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Huixin Liu
- Department of Clinical Epidemiology and Biostatistics, Peking University People’s Hospital, Beijing, China
| | - Jinlei Qi
- National Center for Chronic Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lijun Wang
- National Center for Chronic Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Peng Yin
- National Center for Chronic Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Feng Liu
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Yu Wang
- Chinese Foundation for Hepatitis Prevention and Control, Beijing, China
| | - Maigeng Zhou
- National Center for Chronic Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Huiying Rao
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
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Choe EK, Kang HY. The association between platelet-related parameters and nonalcoholic fatty liver disease in a metabolically healthy nonobese population. Sci Rep 2024; 14:6118. [PMID: 38480828 PMCID: PMC10937929 DOI: 10.1038/s41598-024-56796-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 03/11/2024] [Indexed: 03/17/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized by subclinical inflammation and is related to obesity and metabolic syndrome (MS), but it is also frequently observed in nonobese populations. We aimed to evaluate the relationship between the white blood cell count-to-mean platelet volume ratio (WBC/MPV), platelet-to-lymphocyte count ratio (PLR) and lymphocyte-monocyte ratio (LMR) in association with NAFLD, considering the presence of obesity and MS. Additionally, we aimed to investigate whether these parameters exhibited similar correlations in metabolic dysfunction-associated steatotic liver disease (MASLD) as observed in NAFLD. This cross-sectional study included subjects who underwent a comprehensive health evaluation, including blood tests and abdominal ultrasonography. Subgroup analyses were conducted based on obesity and MS. Out of a total 5929 subjects (3271 males, mean age 49.7 ± 10.6 years), 2253 (38.0%) had NAFLD. WBC/MPV was significantly higher, and PLR was significantly lower in subjects with NAFLD. In the analysis restricted to the nonobese (BMI < 25 kg/m2) population without MS, both WBC/MPV and PLR were independently associated with NAFLD: WBC/MPV (adjusted OR 3.366; 95% CI 2.238-5.066) and PLR (adjusted OR 0.997; 95% CI 0.996-0.999). When assessing the risk of NAFLD based on the WBC/MPV and PLR quartiles, the adjusted OR and 95% CI for the lowest quartile compared to the highest were 2.055 (95% CI 1.626-2.602) for WBC/MPV and 0.660 (95% CI 0.523-0.832) for PLR in the nonobese, metabolically healthy group. The levels of WBC/MPV and PLR were independently associated with NAFLD. Furthermore, in MASLD, an association with WBC/MPV, PLR and LMR was identified, similar to the results observed in NAFLD, even after adjusting for confounding variables. In conclusion, the present study demonstrated a significant association between NAFLD and platelet-related parameters, especially in nonobese, metabolically healthy subjects.
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Affiliation(s)
- Eun Kyung Choe
- Department of Surgery, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea
| | - Hae Yeon Kang
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea.
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Chu JN, Goldman ML, Brandman D, Sohn JH, Islam K, Ross LA, Fox RK. Underrecognition and Suboptimal Quality of Care for Nonalcoholic Fatty Liver Disease Cirrhosis in Primary Care Patients with Diabetes Mellitus. Am J Med 2024; 137:172-177.e2. [PMID: 37890572 DOI: 10.1016/j.amjmed.2023.10.002] [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: 05/12/2023] [Revised: 10/10/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis but is underrecognized in primary care. Cirrhosis management requires complex monitoring, and the quality of care (QoC) for NAFLD cirrhosis patients in primary care may be inadequate. METHODS In this retrospective-prospective cohort study of primary care patients with diabetes mellitus, we identified patients with NAFLD cirrhosis by 1) evidence of cirrhosis from abdominal imaging identified by natural language processing, or 2) existence of International Classification of Diseases code for cirrhosis. A finding of either was followed by manual chart review for confirmation of both cirrhosis and NAFLD. We then determined if cirrhosis care measures were up-to-date, including hepatitis A and B vaccination, Model for End-Stage Liver Disease score components, esophagogastroduodenoscopy, and hepatocellular carcinoma screening. We created a composite score quantifying overall QoC (scale 0-8), with high QoC defined as ≥6 points. RESULTS Among 3,028 primary care patients with diabetes mellitus, we identified 51 (1.7%) with NAFLD cirrhosis. Although 78% had ≥3 average primary care visits/year, only 24% completed hepatocellular carcinoma screening at least annually in at least 75% of years since diagnosis. The average QoC composite score was 4.9 (SD 2.4), and less than one-third had high QoC. CONCLUSIONS NAFLD cirrhosis is prevalent but underdiagnosed in primary care, and receipt of comprehensive QoC was suboptimal. Given the rising incidence of NAFLD cirrhosis, primary care providers need improved awareness and mechanisms to ensure high QoC for this population.
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Affiliation(s)
- Janet N Chu
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, CA
| | - Max L Goldman
- Division of Hospital Medicine, Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA; Department of Gastroenterology, Kaiser Permanente San Francisco, CA
| | - Danielle Brandman
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, NY
| | - Jae Ho Sohn
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA
| | - Kendall Islam
- School of Medicine, University of California, San Francisco, CA
| | - Lauren A Ross
- Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH
| | - Rena K Fox
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, CA.
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Zailaie SA, Khoja BB, Siddiqui JJ, Mawardi MH, Heaphy E, Aljagthmi A, Sergi CM. Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease. Noncoding RNA 2024; 10:10. [PMID: 38392965 PMCID: PMC10891858 DOI: 10.3390/ncrna10010010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/22/2024] [Accepted: 01/27/2024] [Indexed: 02/25/2024] Open
Abstract
Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, in mRNA stabilization and translation, and in regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. In this review, we summarize NAFLD's pathogenesis and clinical features, discuss current treatment options, and review the involvement of ncRNAs as regulatory molecules in NAFLD and its progression to non-alcoholic steatohepatitis (NASH). In addition, we highlight signaling pathways dysregulated in NAFLD and review their crosstalk with ncRNAs. Having a thorough understanding of the disease process's molecular mechanisms will facilitate development of highly effective diagnostic and therapeutic treatments. Such insights can also inform preventive strategies to minimize the disease's future development.
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Affiliation(s)
- Samar A. Zailaie
- Research Center, King Faisal Specialist Hospital & Research Center-Jeddah (KFSHRC-J), Jeddah 21499, Saudi Arabia; (S.A.Z.); (B.B.K.); (E.H.); (A.A.)
| | - Basmah B. Khoja
- Research Center, King Faisal Specialist Hospital & Research Center-Jeddah (KFSHRC-J), Jeddah 21499, Saudi Arabia; (S.A.Z.); (B.B.K.); (E.H.); (A.A.)
| | - Jumana J. Siddiqui
- Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Mohammad H. Mawardi
- Medicine Department, Gastroenterology Section, King Faisal Specialist Hospital & Research Center-Jeddah (KFSHRC-J), Jeddah 21499, Saudi Arabia;
| | - Emily Heaphy
- Research Center, King Faisal Specialist Hospital & Research Center-Jeddah (KFSHRC-J), Jeddah 21499, Saudi Arabia; (S.A.Z.); (B.B.K.); (E.H.); (A.A.)
| | - Amjad Aljagthmi
- Research Center, King Faisal Specialist Hospital & Research Center-Jeddah (KFSHRC-J), Jeddah 21499, Saudi Arabia; (S.A.Z.); (B.B.K.); (E.H.); (A.A.)
| | - Consolato M. Sergi
- Children’s Hospital of Eastern Ontario (CHEO), University of Ottawa, Ottawa, ON K1H 8L1, Canada
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada
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Fowler KJ, Chernyak V. What Is in a Name: Understanding the Nomenclature Updates for Fatty Liver Disease. Radiology 2024; 310:e232771. [PMID: 38226880 DOI: 10.1148/radiol.232771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2024]
Affiliation(s)
- Kathryn J Fowler
- From the Department of Radiology, University of California San Diego, 6206 Lakewood St, San Diego, CA 92122 (K.J.F.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (V.C.)
| | - Victoria Chernyak
- From the Department of Radiology, University of California San Diego, 6206 Lakewood St, San Diego, CA 92122 (K.J.F.); and Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY (V.C.)
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Lee TB, Kueh MTW, Jain V, Razavi AC, Alebna P, Chew NWS, Mehta A. Biomarkers of Hepatic Dysfunction and Cardiovascular Risk. Curr Cardiol Rep 2023; 25:1783-1795. [PMID: 37971635 PMCID: PMC10902719 DOI: 10.1007/s11886-023-01993-5] [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] [Accepted: 10/31/2023] [Indexed: 11/19/2023]
Abstract
PURPOSE OF REVIEW The objective of this manuscript is to examine the current literature on non-alcoholic fatty liver disease (NAFLD) biomarkers and their correlation with cardiovascular disease (CVD) outcomes and cardiovascular risk scores. RECENT FINDINGS There has been a growing appreciation for an independent link between NAFLD and CVD, culminating in a scientific statement by the American Heart Association in 2022. More recently, studies have begun to identify biomarkers of the three NAFLD phases as potent predictors of cardiovascular risk. Despite the body of evidence supporting a connection between hepatic biomarkers and CVD, more research is certainly needed, as some studies find no significant relationship. If this relationship continues to be robust and readily reproducible, NAFLD and its biomarkers may have an exciting role in the future of cardiovascular risk prediction, possibly as risk-enhancing factors or as components of novel cardiovascular risk prediction models.
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Affiliation(s)
- Terence B Lee
- VCU Health, Department of Internal Medicine, Richmond, VA, USA
| | - Martin T W Kueh
- UCD School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
- Royal College of Surgeons in Ireland & University College Dublin Malaysia Campus, George Town, Malaysia
| | - Vardhmaan Jain
- Emory Clinical Cardiovascular Research Institute, Atlanta, GA, USA
| | | | | | - Nicholas W S Chew
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Anurag Mehta
- VCU Health Pauley Heart Center, Richmond, VA, USA.
- Preventive Cardiology, Internal Medicine, Virginia Commonwealth University School of Medicine, 1200 East Broad Street, PO Box 980036, Richmond, VA, 23298, USA.
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Lu W, Qu J, Yan L, Tang X, Wang X, Ye A, Zou Z, Li L, Ye J, Zhou L. Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: a systematic review and meta-analysis. Stem Cell Res Ther 2023; 14:301. [PMID: 37864199 PMCID: PMC10590028 DOI: 10.1186/s13287-023-03518-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/22/2023] [Indexed: 10/22/2023] Open
Abstract
AIM Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell therapy for patients with liver cirrhosis are limited and these studies lack the consistency of treatment effects. This article aimed to systematically investigate the efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis. METHOD The data source included PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, from inception to May 2023. Literature was screened by the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Outcome indicators of the assessment included liver functions and adverse events. Statistical analysis was performed using Review Manager 5.4. RESULTS A total of 11 clinical trials met the selection criteria. The pooled analysis' findings demonstrated that both primary and secondary indicators had improved. Compared to the control group, infusion of mesenchymal stem cells significantly increased ALB levels in 2 weeks, 1 month, 3 months, and 6 months, and significantly decreased MELD score in 1 month, 2 months, and 6 months, according to a subgroup analysis using a random-effects model. Additionally, the hepatic arterial injection favored improvements in MELD score and ALB levels. Importantly, none of the included studies indicated any severe adverse effects. CONCLUSION The results showed that mesenchymal stem cell was effective and safe in the treatment of liver cirrhosis, improving liver function (such as a decrease in MELD score and an increase in ALB levels) in patients with liver cirrhosis and exerting protective effects on complications of liver cirrhosis and the incidence of hepatocellular carcinoma. Although the results of the subgroup analysis were informative for the selection of mesenchymal stem cells for clinical treatment, a large number of high-quality randomized controlled trials validations are still needed.
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Affiliation(s)
- Wenming Lu
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- The First Clinical College of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Jiayang Qu
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- The First Clinical College of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Longxiang Yan
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- The First Clinical College of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Xingkun Tang
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Xuesong Wang
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Anqi Ye
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Zhengwei Zou
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Lincai Li
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, 341000, Jiangxi, People's Republic of China
| | - Junsong Ye
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, 341000, Jiangxi, People's Republic of China.
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.
- Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.
| | - Lin Zhou
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, 341000, Jiangxi, People's Republic of China.
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.
- Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province, Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.
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Robea MA, Balmus IM, Girleanu I, Huiban L, Muzica C, Ciobica A, Stanciu C, Cimpoesu CD, Trifan A. Coagulation Dysfunctions in Non-Alcoholic Fatty Liver Disease-Oxidative Stress and Inflammation Relevance. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1614. [PMID: 37763733 PMCID: PMC10535217 DOI: 10.3390/medicina59091614] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/29/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.
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Affiliation(s)
- Madalina Andreea Robea
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.R.); (I.-M.B.); (C.D.C.)
| | - Ioana-Miruna Balmus
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.R.); (I.-M.B.); (C.D.C.)
- Department of Exact Sciences and Natural Sciences, Institute of Interdisciplinary Research, “Alexandru Ioan Cuza” University of Iasi, Alexandru Lapusneanu Street, No. 26, 700057 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Alin Ciobica
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, No. 20A, 700505 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue, No. 8, 700506 Iasi, Romania;
- Academy of Romanian Scientists, Splaiul Independentei nr. 54, Sector 5, 050094 Bucuresti, Romania
| | - Carol Stanciu
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue, No. 8, 700506 Iasi, Romania;
| | - Carmen Diana Cimpoesu
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.R.); (I.-M.B.); (C.D.C.)
- Department of Emergency Medicine, Emergency County Hospital “Sf. Spiridon”, 700111 Iasi, Romania
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa” Iasi, Blvd. Independentei 1, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue, No. 8, 700506 Iasi, Romania;
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Kusu Y, Furuta M, Takeshita T. The Association Between Periodontal Disease and Non-Alcoholic Fatty Liver Disease is Linked to Metabolic Disorders. CURRENT ORAL HEALTH REPORTS 2023; 10:146-153. [DOI: 10.1007/s40496-023-00342-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/24/2023] [Indexed: 01/03/2025]
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Staufer K, Huber H, Zessner-Spitzenberg J, Stauber R, Finkenstedt A, Bantel H, Weiss TS, Huber M, Starlinger P, Gruenberger T, Reiberger T, Sebens S, McIntyre G, Tabibiazar R, Giaccia A, Zoller H, Trauner M, Mikulits W. Gas6 in chronic liver disease-a novel blood-based biomarker for liver fibrosis. Cell Death Discov 2023; 9:282. [PMID: 37532736 PMCID: PMC10397215 DOI: 10.1038/s41420-023-01551-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 04/18/2023] [Accepted: 07/10/2023] [Indexed: 08/04/2023] Open
Abstract
The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (CPS), model of end-stage liver disease (MELD) score, hepatic venous pressure gradient, and α-fetoprotein, respectively. A total of 1111 patients (median age 57.8 y, 67.3% male) was analyzed. Gas6/alb showed high diagnostic accuracy for the detection of significant (≥F2: AUC 0.805) to advanced fibrosis (≥F3: AUC 0.818), and was superior to Fib-4 for the detection of cirrhosis (F4: AUC 0.897 vs. 0.878). In addition, Gas6/alb was highly predictive of liver disease severity (Odds ratios for CPS B/C, MELD ≥ 15, and clinically significant portal hypertension (CSPH) were 16.534, 10.258, and 12.115), and was associated with transplant-free survival (Hazard ratio 1.031). Although Gas6 and Gas6/alb showed high diagnostic accuracy for the detection of HCC in comparison to chronic liver disease patients without cirrhosis (AUC 0.852, 0.868), they failed to discriminate between HCC in cirrhosis versus cirrhosis only. In conclusion, Gas6/alb shows a high accuracy to detect significant to advanced fibrosis and cirrhosis, and predicts severity of liver disease including CSPH.
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Affiliation(s)
- Katharina Staufer
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
- Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria
| | - Heidemarie Huber
- Center for Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
| | - Jasmin Zessner-Spitzenberg
- Center for Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
| | - Rudolf Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Armin Finkenstedt
- Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Heike Bantel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Thomas S Weiss
- Center for Liver Cell Research, Children's University Hospital (KUNO), University of Regensburg Hospital, Regensburg, Germany
| | - Markus Huber
- Department of Anesthesiology and Pain Therapy, Inselspital, University Hospital Bern, Bern, Switzerland
| | - Patrick Starlinger
- Department of Surgery, Division of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Thomas Gruenberger
- Clinicum Favoriten, HPB Center, Vienna Health Network and Sigmund Freud Private University, Vienna, Austria
| | - Thomas Reiberger
- Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria
- Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Susanne Sebens
- Institute for Experimental Cancer Research, Kiel University and University Hospital Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany
| | | | | | | | - Heinz Zoller
- Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael Trauner
- Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Mikulits
- Center for Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
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Yu Y, Paragomi P, Wang R, Liang F, Luu HN, Behari J, Yuan J. High serum magnesium is associated with lower risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease. Cancer 2023; 129:2341-2347. [PMID: 37052455 PMCID: PMC10445464 DOI: 10.1002/cncr.34799] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 03/05/2023] [Accepted: 03/14/2023] [Indexed: 04/14/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD. METHODS A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow-up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking. RESULTS Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67-1.12), 0.77 (0.57-1.04), and 0.73 (0.56-0.96), respectively, after adjustment for multiple potential confounders (P trend = .02). CONCLUSION This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD.
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Affiliation(s)
- Yi‐Chuan Yu
- Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Pedram Paragomi
- Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Renwei Wang
- Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Feiran Liang
- University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA
| | - Hung N. Luu
- Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jaideep Behari
- Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jian‐Min Yuan
- Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Shi Y, Shen W, Xu G, Wang X, Ning B. Hepatic venous pressure gradient and rebleeding risk of patients with nonalcoholic steatohepatitis cirrhosis after variceal bleeding. Front Med (Lausanne) 2023; 10:1224506. [PMID: 37564045 PMCID: PMC10411529 DOI: 10.3389/fmed.2023.1224506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 07/10/2023] [Indexed: 08/12/2023] Open
Abstract
Background and aims Hepatic venous pressure gradient (HVPG) has a strong predictive value for variceal rebleeding in cirrhotic patients, but the accuracy of HVPG may be compromised in nonalcoholic steatohepatitis (NASH) cirrhosis. This study aimed to evaluate the accuracy of HVPG and portal pressure gradient (PPG) for predicting rebleeding in NASH cirrhosis after acute variceal bleeding. Patients and methods Thirty-eight NASH cirrhosis patients and 82 hepatitis B virus (HBV) cirrhosis patients with acute variceal bleeding were included in this study. All patients recived transjugular intrahepatic portalsystemic shunt (TIPS). The prognostic value of HVPG and PPG for variceal rebleeding was evaluated. Results Compared with HBV cirrhosis, NASH cirrhosis demonstrated a lower HVPG (15.3 ± 3.8 vs. 18.0 ± 4.8; p = 0.003) and lower PPG (18.0 ± 3.7 vs. 20.0 ± 3.4; p = 0.005). HVPG (AUC = 0.82; p = 0.002) and PPG (AUC = 0.72; p = 0.027) had promising prognostic value among NASH cirrhosis patients. The optimal threshold of HVPG and PPG for predicting rebleeding in NASH cirrhosis was 17 mmHg and 20 mmHg. At multivariate analysis, HVPG ≥17 mmHg was a significant predictor of variceal rebleeding (HR 9.40; 95% CI 1.85-47.70; p = 0.007). Conclusion In the patients with cirrhosis and vairceal bleeding, the levels of HVPG and PPG were found to be low in NASH cirrhosis than HBV cirrhosis. However, the prevalence of rebleeding was similar between two groups. HVPG measurement is still an accurate way to assess the risk of variceal rebleeding in NASH cirrhosis.
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Affiliation(s)
- Yiqi Shi
- Digestive System Department, Yuzhong Hospital of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wenyong Shen
- Digestive System Department, Chongqing Fuling Central Hospital of Chongqing University, Chongqing, China
| | - Gang Xu
- Digestive System Department, Chongqing Fuling Central Hospital of Chongqing University, Chongqing, China
| | - Xunzheng Wang
- Digestive System Department, Jiangnan Hospital of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bo Ning
- Digestive System Department, Yuzhong Hospital of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Di Cola S, Cusi G, Lapenna L, Gazda J, Fonte S, Mattana M, Mennini G, Pasqualetti P, Merli M. Diabetes and Metabolic Disorders: Their Impact on Cardiovascular Events in Liver Transplant Patients. Can J Gastroenterol Hepatol 2023; 2023:2199193. [PMID: 37396501 PMCID: PMC10313467 DOI: 10.1155/2023/2199193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 07/04/2023] Open
Abstract
Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12-250 months). All cardiovascular events were carefully recorded and detailed in the patients' charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60-6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36-7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients.
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Affiliation(s)
- Simone Di Cola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale Dell'Università 37, Rome 00185, Italy
| | - Giulia Cusi
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale Dell'Università 37, Rome 00185, Italy
| | - Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale Dell'Università 37, Rome 00185, Italy
| | - Jakub Gazda
- 2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, Kosice 040 11, Slovakia
| | - Stefano Fonte
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale Dell'Università 37, Rome 00185, Italy
| | - Marco Mattana
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale Dell'Università 37, Rome 00185, Italy
| | - Gianluca Mennini
- Department of Hepato-Biliopancreatic and Transplant Surgery, Sapienza University of Rome, Viale Del Policlinico 155, Rome 00161, Italy
| | - Patrizio Pasqualetti
- Department of Public Health and Infectious Diseases, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome 00185, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale Dell'Università 37, Rome 00185, Italy
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Yaribeygi H, Maleki M, Jamialahmadi T, Moallem SA, Sahebkar A. Hepatic benefits of sodium-glucose cotransporter 2 inhibitors in liver disorders. EXCLI JOURNAL 2023; 22:403-414. [PMID: 37346806 PMCID: PMC10279968 DOI: 10.17179/excli2023-6022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 04/18/2023] [Indexed: 06/23/2023]
Abstract
Diabetic patients are at higher risk of liver dysfunction compared with the normal population. Thus, using hypoglycemic agents to improve liver efficiency is important in these patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are newly developed antidiabetic drugs with potent glucose-lowering effects. However, recent limited evidence suggests that they have extra-glycemic benefits and may be able to exert protective effects on the liver. Hence, these drugs could serve as promising pharmacological agents with multiple benefits against different hepatic disorders. In this review, the current knowledge about the possible effects of SGLT2 inhibitors on different forms of liver complications and possible underlying mechanisms are discussed.
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Affiliation(s)
- Habib Yaribeygi
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran
| | - Mina Maleki
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Adel Moallem
- Department of Pharmacology and Toxicology, College of Pharmacy, Al-Zahraa University for Women, Karbala, Iraq
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, Australia
- Department of Biotechnology, Mashhad University of Medical Sciences, Mashhad, Iran
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Jacoby H, Sucandy I, Ross S, Crespo K, Syblis C, App S, Rosemurgy A. Does metabolic syndrome affect perioperative outcomes in patients undergoing robotic hepatectomy? A propensity score-matched analysis. Surg Endosc 2023:10.1007/s00464-023-10047-4. [PMID: 37038021 DOI: 10.1007/s00464-023-10047-4] [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: 04/05/2022] [Accepted: 03/26/2023] [Indexed: 04/12/2023]
Abstract
BACKGROUND Metabolic syndrome is a known risk factor for postoperative complications after general surgical procedures. Literature analyzing perioperative outcomes of patients with metabolic syndrome undergoing a minimally invasive hepatectomy is limited. We sought to investigate if metabolic syndrome significantly impacts the perioperative course and outcomes of patients undergoing robotic hepatectomy. METHODS With IRB, we prospectively followed patients who underwent robotic hepatectomy from 2016 through 2020. A 1:1 propensity score-matched (PSM) analysis was applied to patients with and without metabolic syndrome. Demographic and clinical data were analyzed for those cohorts before and after PSM. Metabolic syndrome was defined as BMI ≥ 28.8 kg/m2, diabetes, and hypertension. RESULTS A total of 272 patients underwent robotic hepatectomy, 39 (14%) of whom had metabolic syndrome. After performing PSM, we ended up with 74 patients, 37 in each cohort, 28% of them had liver cirrhosis. Patients with metabolic syndrome had higher BMI (34 ± 5.6 vs. 28 ± 5.9 kg/m2, p < 0.001) and MELD scores (10 ± 4.5 vs. 8 ± 3.2, p < 0.001) compared to patients without metabolic syndrome. Additionally, patients with metabolic syndrome had an increased incidence of liver cirrhosis (33% vs. 9%, p = 0.0002). Following PSM, BMI (34 ± 5.7 vs. 26 ± 4.4 kg/m2, p < 0.001) was the only preoperative variables associated with metabolic syndrome. There were no statistical differences before and after PSM between patients with and without metabolic syndrome in terms of intraoperative metrics including operative time, blood loss, conversion to 'open,' and intraoperative complications. All postoperative outcomes metrics before and after PSM did not correlate with the presence or absence of metabolic syndrome. CONCLUSIONS Metabolic syndrome had no impact on intra- or postoperative metrics, complications, or outcomes after robotic hepatectomy. We believe that the robotic approach may mitigate the adverse effects of metabolic syndrome for patients undergoing robotic hepatectomy.
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Affiliation(s)
| | - Iswanto Sucandy
- Digestive Health Institute, Tampa, FL, USA.
- Digestive Health Institute, 3000 Medical Park Drive, Suite 500, Tampa, FL, 33613, USA.
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Alkhuder K. Raman Scattering-Based Optical Sensing Of Chronic Liver Diseases. Photodiagnosis Photodyn Ther 2023; 42:103505. [PMID: 36965755 DOI: 10.1016/j.pdpdt.2023.103505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 02/26/2023] [Accepted: 03/07/2023] [Indexed: 03/27/2023]
Abstract
Chronic liver diseases (CLDs) are a major public health problem. Despite the progress achieved in fighting against viral hepatitis, the emergence of non-alcoholic fatty liver disease might pose a serious challenge to the public's health in the coming decades. Medical management of CLDs represents a substantial burden on the public health infrastructures. The health care cost of these diseases is an additional burden that weighs heavily on the economies of developing countries. Effective management of CLDs requires the adoption of reliable and cost-effective screening and diagnosing methods to ensure early detection and accurate clinical assessment of these diseases. Vibrational spectroscopies have emerged as universal analytical methods with promising applications in various industrial and biomedical fields. These revolutionary analytical techniques rely on analyzing the interaction between a light beam and the test sample to generate a spectral fingerprint. This latter is defined by the analyte's chemical structure and the molecular vibrations of its functional groups. Raman spectroscopy and surface-enhanced Raman spectroscopy have been used in combination with various chemometric tests to diagnose a wide range of malignant, metabolic and infectious diseases. The aim of the current review is to cast light on the use of these optical sensing methods in the diagnosis of CLDs. The vast majority of research works that investigated the potential application of these spectroscopic techniques in screening and detecting CLDs were discussed here. The advantages and limitations of these modern analytical methods, as compared with the routine and gold standard diagnostic approaches, were also reviewed in details.
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Radu F, Potcovaru CG, Salmen T, Filip PV, Pop C, Fierbințeanu-Braticievici C. The Link between NAFLD and Metabolic Syndrome. Diagnostics (Basel) 2023; 13:diagnostics13040614. [PMID: 36832102 PMCID: PMC9955701 DOI: 10.3390/diagnostics13040614] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/02/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Metabolic syndrome (MetS) is characterized by an association of cardiovascular and diabetes mellitus type 2 risk factors. Although the definition of MetS slightly differs depending on the society that described it, its central diagnostic criteria include impaired fasting glucose, low HDL-cholesterol, elevated triglycerides levels and high blood pressure. Insulin resistance (IR) is believed to be the main cause of MetS and is connected to the level of visceral or intra-abdominal adipose tissue, which could be assessed either by calculating body mass index or by measuring waist circumference. Most recent studies revealed that IR may also be present in non-obese patients, and considered visceral adiposity to be the main effector of MetS' pathology. Visceral adiposity is strongly linked with hepatic fatty infiltration also known as non-alcoholic fatty liver disease (NAFLD), therefore, the level of fatty acids in the hepatic parenchyma is indirectly linked with MetS, being both a cause and a consequence of this syndrome. Taking into consideration the present pandemic of obesity and its tendency to drift towards a progressively earlier onset due to the Western lifestyle, it leads to an increased NAFLD incidence. Novel therapeutic resources are lifestyle intervention with physical activity, Mediterranean diet, or therapeutic surgical respective metabolic and bariatric surgery or drugs such as SGLT-2i, GLP-1 Ra or vitamin E. NAFLD early diagnosis is important due to its easily available diagnostic tools such as non-invasive tools: clinical and laboratory variables (serum biomarkers): AST to platelet ratio index, fibrosis-4, NAFLD Fibrosis Score, BARD Score, fibro test, enhanced liver fibrosis; imaging-based biomarkers: Controlled attenuation parameter, magnetic resonance imaging proton-density fat fraction, transient elastography (TE) or vibration controlled TE, acoustic radiation force impulse imaging, shear wave elastography, magnetic resonance elastography; and the possibility to prevent its complications, respectively, fibrosis, hepato-cellular carcinoma or liver cirrhosis which can develop into end-stage liver disease.
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Affiliation(s)
- Fabiana Radu
- Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Claudia-Gabriela Potcovaru
- Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Correspondence:
| | - Teodor Salmen
- Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Petruța Violeta Filip
- Department of Gastroenterology and Internal Medicine, Clinical Emergency University Hospital, 050098 Bucharest, Romania
| | - Corina Pop
- Department of Gastroenterology and Internal Medicine, Clinical Emergency University Hospital, 050098 Bucharest, Romania
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Prevalence of Spontaneous Bacterial Peritonitis (SBP) in Hepatitis B (HBV), and Hepatitis C (HCV) Liver Cirrhosis: A Systematic Review and Meta-Analysis. Healthcare (Basel) 2023; 11:healthcare11020275. [PMID: 36673643 PMCID: PMC9859562 DOI: 10.3390/healthcare11020275] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/23/2022] [Accepted: 01/13/2023] [Indexed: 01/18/2023] Open
Abstract
Background and Aim: Spontaneous bacterial peritonitis (SBP) is a common infection in liver cirrhosis. This systematic review and meta-analysis provide detailed information on the prevalence of SBP among hepatitis B virus (HBV) and hepatitis C virus (HCV)-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV and HCV-related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV-associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7−21.0%; I2 = 96.13%; p < 0.001)], followed by SBP in HCV-associated liver cirrhosis [4.0% (95% CI, 1.3%−11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1−66.3%), the USA (50.0%, CI: 34.6−65.4%), and Holland (31.1%, CI: 21.6−42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV + HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P < 0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed a rise in the incidence of SBP in viral hepatitis over the last decade. The latter indicates a possible future rise in the global prevalence of SBP among HBV and HCV-related liver cirrhosis.
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Yang J, Yao W, Yang H, Shen Y, Zhang Y. Design and synthesis of ERα agonists: Effectively reduce lipid accumulation. Front Chem 2022; 10:1104249. [PMID: 36569962 PMCID: PMC9772986 DOI: 10.3389/fchem.2022.1104249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022] Open
Abstract
In recent years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing worldwide. Hepatic lipid deposition is a major feature of NAFLD, and insulin resistance is one of the most important causes of lipid deposition. Insulin resistance results in the disruption of lipid metabolism homeostasis characterized by increased lipogenesis and decreased lipolysis. Estrogen receptor α (ERα) has been widely reported to be closely related to lipid metabolism. Activating ERa may be a promising strategy to improve lipid metabolism. Here, we used computer-aided drug design technology to discover a highly active compound, YRL-03, which can effectively reduce lipid accumulation. Cellular experimental results showed that YRL-03 could effectively reduce lipid accumulation by targeting ERα, thereby achieving alleviation of insulin resistance. We believe this study provides meaningful guidance for future molecular development of drugs to prevent and treat NAFLD.
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Affiliation(s)
- Jinfei Yang
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China,*Correspondence: Jinfei Yang, ; Yuanyuan Zhang,
| | - Weiwei Yao
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China
| | - Huihui Yang
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China
| | - Yajing Shen
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China
| | - Yuanyuan Zhang
- West China School of Pharmacy, Sichuan University, Chengdu, China,*Correspondence: Jinfei Yang, ; Yuanyuan Zhang,
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Arowolo O, Salemme V, Suvorov A. Towards Whole Health Toxicology: In-Silico Prediction of Diseases Sensitive to Multi-Chemical Exposures. TOXICS 2022; 10:764. [PMID: 36548597 PMCID: PMC9784704 DOI: 10.3390/toxics10120764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/15/2022] [Accepted: 12/07/2022] [Indexed: 06/17/2023]
Abstract
Chemical exposures from diverse sources merge on a limited number of molecular pathways described as toxicity pathways. Changes in the same set of molecular pathways in different cell and tissue types may generate seemingly unrelated health conditions. Today, no approaches are available to predict in an unbiased way sensitivities of different disease states and their combinations to multi-chemical exposures across the exposome. We propose an inductive in-silico workflow where sensitivities of genes to chemical exposures are identified based on the overlap of existing genomic datasets, and data on sensitivities of individual genes is further used to sequentially derive predictions on sensitivities of molecular pathways, disease states, and groups of disease states (syndromes). Our analysis predicts that conditions representing the most significant public health problems are among the most sensitive to cumulative chemical exposures. These conditions include six leading types of cancer in the world (prostatic, breast, stomach, lung, colorectal neoplasms, and hepatocellular carcinoma), obesity, type 2 diabetes, non-alcoholic fatty liver disease, autistic disorder, Alzheimer's disease, hypertension, heart failure, brain and myocardial ischemia, and myocardial infarction. Overall, our predictions suggest that environmental risk factors may be underestimated for the most significant public health problems.
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Affiliation(s)
- Olatunbosun Arowolo
- Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, USA
| | - Victoria Salemme
- Department of Pharmacology, University of California, 1275 Med Science, Davis, CA 95616, USA
| | - Alexander Suvorov
- Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, USA
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Khan A, Ross HM, Parra NS, Chen SL, Chauhan K, Wang M, Yan B, Magagna J, Beiriger J, Shah Y, Shahzad T, Halegoua-DeMarzio D. Risk Prevention and Health Promotion for Non-Alcoholic Fatty Liver Diseases (NAFLD). LIVERS 2022; 2:264-282. [DOI: 10.3390/livers2040022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a serious clinicopathological condition that is recognized as the most frequent chronic liver disease, affecting 14–30% of the world’s population. The prevalence of NAFLD has rapidly grown and is correlated with the growth in obesity and type 2 diabetes, among other factors. NAFLD often results in long-term complications including cardiovascular disease, liver cirrhosis, and liver fibrosis. This paper provides an updated overview of NAFLD with a focus on epidemiology, etiology, pathophysiology, screening, complications, and pharmacological therapies to identify effective risk prevention and health promotion.
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Affiliation(s)
- Adnan Khan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Heather M. Ross
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Natalia Salinas Parra
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Sarah L. Chen
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Kashyap Chauhan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Makala Wang
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Brian Yan
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - John Magagna
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Jake Beiriger
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Yash Shah
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Taha Shahzad
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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35
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Nong YB, Huang HN, Huang JJ, Du YQ, Song WX, Mao DW, Zhong YX, Zhu RH, Xiao XY, Zhong RX. Rare leptin in non-alcoholic fatty liver cirrhosis: A case report. World J Clin Cases 2022; 10:10293-10300. [PMID: 36246792 PMCID: PMC9561580 DOI: 10.12998/wjcc.v10.i28.10293] [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: 05/19/2022] [Revised: 07/27/2022] [Accepted: 08/25/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD)-related cirrhosis is mainly caused by NAFLD by causing inflammation which leads to fibrosis. The role of leptin in NAFLD-related cirrhosis has been rarely reported.
CASE SUMMARY This study presents the case of a 65-year-old male patient who was referred to The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China, for diagnosis and treatment for liver cirrhosis. Initially, the cause of liver cirrhosis was unknown. After radiology, laboratory examination, pathological results and analysis of the patient’s signs and symptoms, the case was finally diagnosed with final NAFLD-related cirrhosis. Although this study reports a single case, the findings might expand the understanding of leptin’s role in NAFLD-related cirrhosis and might provide a basis for the clinical diagnostic criteria, pathological features and treatment of NAFLD-related cirrhosis.
CONCLUSION Although the occurrence of marasmus NAFLD-related cirrhosis is rare, it needs to be distinguished from other liver diseases, including viral hepatitis, drug-induced liver disease, Wilson's disease and autoimmune liver disease. Aggressive treatment is needed to prevent the progression of NAFLD-related cirrhosis.
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Affiliation(s)
- Yao-Bin Nong
- The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Hong-Na Huang
- Department of Internal Medicine of Traditional Chinese Medicine,The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Jing-Jing Huang
- Department of Spleen and Stomach Liver Diseases, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Yuan-Qin Du
- The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Wen-Xuan Song
- The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - De-Wen Mao
- Department of Hepatology, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yue-Xue Zhong
- The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Rong-Huo Zhu
- The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Xi-Yu Xiao
- The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Rui-Xi Zhong
- The First Clinical Medical College, Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
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36
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Scheinberg AR, John BV. MAFLD Versus NAFLD: Which Better Predicts the Risk of Atherosclerotic Cardiovascular Disease? Dig Dis Sci 2022; 67:4606-4608. [PMID: 35579800 DOI: 10.1007/s10620-022-07512-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/29/2022] [Indexed: 12/14/2022]
Affiliation(s)
- Andrew R Scheinberg
- Division of Digestive Health and Liver Diseases, Miami VA Medical Center, University of Miami Miller School of Medicine, University of Miami, 1201 NW 16th Street, Miami, FL, 33125, USA.,Department of Gastroenterology and Hepatology, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL, USA.,Division of Gastroenterology and Hepatology, Miami VA Medical Center, Miami, FL, USA
| | - Binu V John
- Division of Digestive Health and Liver Diseases, Miami VA Medical Center, University of Miami Miller School of Medicine, University of Miami, 1201 NW 16th Street, Miami, FL, 33125, USA. .,Division of Gastroenterology and Hepatology, Miami VA Medical Center, Miami, FL, USA.
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Bellini MI, Urciuoli I, Del Gaudio G, Polti G, Iannetti G, Gangitano E, Lori E, Lubrano C, Cantisani V, Sorrenti S, D’Andrea V. Nonalcoholic fatty liver disease and diabetes. World J Diabetes 2022; 13:668-682. [PMID: 36188142 PMCID: PMC9521438 DOI: 10.4239/wjd.v13.i9.668] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 05/03/2022] [Accepted: 08/06/2022] [Indexed: 02/05/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.
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Affiliation(s)
- Maria Irene Bellini
- Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
| | - Irene Urciuoli
- Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
| | - Giovanni Del Gaudio
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome 00161, Italy
| | - Giorgia Polti
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome 00161, Italy
| | - Giovanni Iannetti
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome 00161, Italy
| | - Elena Gangitano
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, Sapienza University of Rome, Rome 00161, Italy
| | - Eleonora Lori
- Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
| | - Carla Lubrano
- Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, Sapienza University of Rome, Rome 00161, Italy
| | - Vito Cantisani
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome 00161, Italy
| | - Salvatore Sorrenti
- Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
| | - Vito D’Andrea
- Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
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Costante F, Airola C, Santopaolo F, Gasbarrini A, Pompili M, Ponziani FR. Immunotherapy for nonalcoholic fatty liver disease-related hepatocellular carcinoma: Lights and shadows. World J Gastrointest Oncol 2022; 14:1622-1636. [PMID: 36187401 PMCID: PMC9516656 DOI: 10.4251/wjgo.v14.i9.1622] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/05/2022] [Accepted: 07/05/2022] [Indexed: 02/05/2023] Open
Abstract
About one-fourth of adults globally suffer from nonalcoholic fatty liver disease (NAFLD), which is becoming a leading cause of chronic liver disease worldwide. Its prevalence has rapidly increased in recent years, and is projected to increase even more. NAFLD is a leading cause of hepatocellular carcinoma (HCC), the sixth-most prevalent cancer worldwide and the fourth most common cause of cancer-related death. Although the molecular basis of HCC onset in NAFLD is not completely known, inflammation is a key player. The tumor microenvironment (TME) is heterogeneous in patients with HCC, and is characterized by complex interactions between immune system cells, tumor cells and other stromal and resident liver cells. The etiology of liver disease plays a role in controlling the TME and modulating the immune response. Markers of immune suppression in the TME are associated with a poor prognosis in several solid tumors. Immunotherapy with immune checkpoint inhibitors (ICIs) has become the main option for treating cancers, including HCC. However, meta-analyses have shown that patients with NAFLD-related HCC are less likely to benefit from therapy based on ICIs alone. Conversely, the addition of an angiogenesis inhibitor showed better results regarding the objective response rate and progression-free survival. Adjunctive diagnostic and therapeutic strategies, such as the application of novel biomarkers and the modulation of gut microbiota, should be considered in the future to guide personalized medicine and improve the response to ICIs in patients with NAFLD-related HCC.
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Affiliation(s)
- Federico Costante
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma 00168, Italy
| | - Carlo Airola
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma 00168, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma 00168, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma 00168, Italy
- Catholic University, Largo Francesco Vito 1, 00168 Roma, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma 00168, Italy
- Catholic University, Largo Francesco Vito 1, 00168 Roma, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma 00168, Italy
- Catholic University, Largo Francesco Vito 1, 00168 Roma, Italy
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Piras IS, Raju A, Don J, Schork NJ, Gerhard GS, DiStefano JK. Hepatic PEMT Expression Decreases with Increasing NAFLD Severity. Int J Mol Sci 2022; 23:ijms23169296. [PMID: 36012560 PMCID: PMC9409182 DOI: 10.3390/ijms23169296] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/12/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Choline deficiency causes hepatic fat accumulation, and is associated with a higher risk of nonalcoholic fatty liver disease (NAFLD) and more advanced NAFLD-related hepatic fibrosis. Reduced expression of hepatic phosphatidylethanolamine N-methyltransferase (PEMT), which catalyzes the production of phosphatidylcholine, causes steatosis, inflammation, and fibrosis in mice. In humans, common PEMT variants impair phosphatidylcholine synthesis, and are associated with NAFLD risk. We investigated hepatic PEMT expression in a large cohort of patients representing the spectrum of NAFLD, and examined the relationship between PEMT genetic variants and gene expression. Hepatic PEMT expression was reduced in NAFLD patients with inflammation and fibrosis (i.e., nonalcoholic steatohepatitis or NASH) compared to participants with normal liver histology (β = −1.497; p = 0.005). PEMT levels also declined with increasing severity of fibrosis with cirrhosis < incomplete cirrhosis < bridging fibrosis (β = −1.185; p = 0.011). Hepatic PEMT expression was reduced in postmenopausal women with NASH compared to those with normal liver histology (β = −3.698; p = 0.030). We detected a suggestive association between rs7946 and hepatic fibrosis (p = 0.083). Although none of the tested variants were associated with hepatic PEMT expression, computational fine mapping analysis indicated that rs4646385 may impact PEMT levels in the liver. Hepatic PEMT expression decreases with increasing severity of NAFLD in obese individuals and postmenopausal women, and may contribute to disease pathogenesis in a subset of NASH patients.
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Affiliation(s)
- Ignazio S. Piras
- Translational Genomics Research Institute, Phoenix, AZ 85004, USA
| | - Anish Raju
- Translational Genomics Research Institute, Phoenix, AZ 85004, USA
| | - Janith Don
- Translational Genomics Research Institute, Phoenix, AZ 85004, USA
| | | | - Glenn S. Gerhard
- Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19122, USA
| | - Johanna K. DiStefano
- Translational Genomics Research Institute, Phoenix, AZ 85004, USA
- Correspondence:
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Association between Coronary Artery Plaque Progression and Liver Fibrosis Biomarkers in Population with Low Calcium Scores. Nutrients 2022; 14:nu14153163. [PMID: 35956339 PMCID: PMC9370134 DOI: 10.3390/nu14153163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 11/17/2022] Open
Abstract
Background: The severity of nonalcoholic fatty liver disease (NAFLD) has been found to be associated with atherosclerosis burden. However, whether liver fibrosis scores can be used to predict atherosclerosis progression, especially for patients with low calcium scores, remains undetermined. Methods: A total of 165 subjects who underwent repeated coronary computed tomography angiography (CCTA) and had low calcium scores (<100) were enrolled. The segment stenosis score (SSS) from the CCTA was measured, and the association between SSS progression and biochemical parameters was analyzed in addition to liver fibrosis scores, including nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), and Forns score. Results: When compared with those without plaque at baseline (SSS = 0), subjects with plaque had higher blood pressure, higher coronary artery calcium (CAC) scores, and higher liver fibrosis scores, including Forns score, Fib-4, and NFS. During the medium follow-up interval of 24.7 months, 60 (39.4%) patients displayed SSS progression, while the remaining 105 (63.6%) patients showed no CAD progression. In a multivariate analysis, being male having a high diastolic blood pressure (DBP), and having a high NFS liver fibrosis score were independently associated with the odds ratio for SSS progression. Conclusions: Higher baseline blood pressure and liver fibrosis markers are associated with the presence of coronary artery disease (CAD) plaques in subjects in early CAD stages. For disease progression, the male gender, DBP, and NFS appear to be independently associated with coronary atherosclerosis plaque progression in subjects with low calcium scores.
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41
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Xiong J, Chen X, Zhao Z, Liao Y, Zhou T, Xiang Q. A potential link between plasma short‑chain fatty acids, TNF‑α level and disease progression in non‑alcoholic fatty liver disease: A retrospective study. Exp Ther Med 2022; 24:598. [PMID: 35949337 PMCID: PMC9353543 DOI: 10.3892/etm.2022.11536] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 06/30/2022] [Indexed: 12/03/2022] Open
Abstract
The onset and progression of non-alcoholic fatty liver disease (NAFLD) remains unclear, but short-chain fatty acids (SCFAs) in circulation may participate in its pathogenesis by acting as inflammation inhibitors. The aim of this retrospective study was to investigate plasma concentrations of general SCFAs in healthy individuals and in patients with distinct stages of NAFLD. Three main SCFAs (including acetate, propionate and butyrate) were analyzed by gas chromatography. The plasma TNF-α concentration was measured by ELISA. One-way ANOVA, Spearman's correlation and Pearson's correlation analysis were performed to estimate the associations between SCFAs, TNF-α and disease progression. Multiple linear stepwise regression was computed to explore the predictor variables of TNF-α in circulation. A total of 71 patients with NAFLD [including 27 patients with NAFL, 20 patients with non-alcoholic steatohepatitis (NASH) and 24 patients with NAFLD-related cirrhosis (NAFLD-cirrhosis)] and 9 healthy control (HC) subjects were enrolled for analysis. Although not statistically significant, plasma SCFAs were elevated in patients with NAFL compared with HC subjects, whereas the vast majority of SCFAs were statistically reduced in patients with NASH or NAFLD-cirrhosis compared with patients with NAFL. Plasma SCFAs had no significant differences in NASH or NAFLD-cirrhosis patients compared with HC subjects. In addition, significant negative correlations were observed between TNF-α and SCFAs. The progression of NAFLD (β=0.849; P<0.001) and the decline of the total three SCFA concentrations (β=-0.189; P<0.001) were recognized as independent risk variables related to the elevated peripheral TNF-α in the multiple linear stepwise regression model. Plasma SCFA concentrations may alter with the development of NAFLD and may have a potential link to TNF-α and the progression of NAFLD, which may serve a protective role toward disease advancement. Further mechanistic studies, such as analysis of gastrointestinal microecology, signaling pathways and functions involved in TNF-α, need to be performed. Also, therapeutic supplementation of SCFAs for NASH and NAFLD-cirrhosis needs further research and verification.
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Affiliation(s)
- Jing Xiong
- Department of Gastroenterology, The Sixth People's Hospital of Chengdu, Chengdu, Sichuan 610051, P.R. China
| | - Xia Chen
- Department of Gastroenterology, The Sixth People's Hospital of Chengdu, Chengdu, Sichuan 610051, P.R. China
| | - Zhijing Zhao
- Department of Gastroenterology, The Sixth People's Hospital of Chengdu, Chengdu, Sichuan 610051, P.R. China
| | - Ying Liao
- Department of Gastroenterology, The Sixth People's Hospital of Chengdu, Chengdu, Sichuan 610051, P.R. China
| | - Ting Zhou
- Department of Gastroenterology, The Sixth People's Hospital of Chengdu, Chengdu, Sichuan 610051, P.R. China
| | - Qian Xiang
- Department of Gastroenterology, The Sixth People's Hospital of Chengdu, Chengdu, Sichuan 610051, P.R. China
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Tang ASP, Chan KE, Quek J, Xiao J, Tay P, Teng M, Lee KS, Lin SY, Myint MZ, Tan B, Sharma VK, Tan DJH, Lim WH, Kaewdech A, Huang D, Chew NWS, Siddiqui MS, Sanyal AJ, Muthiah M, Ng CH. Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals. Clin Mol Hepatol 2022; 28:483-496. [PMID: 35232007 PMCID: PMC9293613 DOI: 10.3350/cmh.2021.0406] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/27/2022] [Accepted: 03/02/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. METHODS Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. RESULTS From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36-43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37-4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74-9.09%) with an odds ratio of 1.88 (95% CI, 1.23-2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. CONCLUSION This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.
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Affiliation(s)
- Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Phoebe Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Margaret Teng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Keng Siang Lee
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - May Zin Myint
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Benjamin Tan
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Vijay K Sharma
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Nicholas WS Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome in Women: Effects of Lifestyle Modifications. J Clin Med 2022; 11:jcm11102759. [PMID: 35628889 PMCID: PMC9146022 DOI: 10.3390/jcm11102759] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/11/2022] [Accepted: 05/11/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most widespread liver disease, characterized by fatty acids liver accumulation and subsequent fibrosis. NAFLD prevalence ranges from 80% to 90% in obese subjects and is estimated to be around 50% in patients with metabolic syndrome. In this clinical scenario, diet and lifestyle modifications can play an important role. There are several imaging techniques that can accurately diagnose fatty liver. Recently, ultrasound has acquired a leading role in the diagnosis and follow-up of fatty liver disease. Furthermore, elastosonography represents a valid alternative to liver biopsy. Shear wave elastosonography evaluates the elastic and mechanical properties of liver tissue. The aim is to evaluate the effects of lifestyle and nutritional interventions and a loss of body weight during hepatic steatosis through ultrasonographic and elastosonographic techniques. Thirty-two female subjects with metabolic syndrome were subjected to clinical, anthropometric, and laboratory assessments, as well as abdominal ultrasonographic/elastosonographic measurements taken from enrollment time (T0) and after 3 months (T1) of lifestyle modifications. After 3 months of lifestyle changes, significant weight loss was observed, with a marked improvement in all adiposity indices. The laboratory parameters at T1 showed significant decreases in total and LDL cholesterol, triglycerides, basal blood glucose, 120 min glycaemia, basal insulin and HOMA Index (p < 0.001). A similar improvement was observed at T1 for steatosis degree (p < 0.01) and elastosonographic measurements (Kpa p < 0.001). The linear regression analysis of the baseline conditions documented that the size of the liver positively correlated with body weight, BMI, neck and waist circumferences, waist to height ratio (WhtR), insulin and HOMA Index, fat mass and visceral fat, and steatosis grade. After 3 months, the liver size showed improvement with positive correlations to all previous variables. Hepatic stiffness (Kpa) positively correlated with neck circumference, visceral fat, and ALT, with basal insulin, gamma-GT, and AST, and with waist circumference, WhtR, and fat mass. The degree of steatosis was positively correlated with more variables and with greater statistical significance at T1 with respect to T0. Particularly, the positive correlations between the degree of steatosis and neck circumference (p < 0.001), HOMA Index, and triglycerides (p < 0.001) appeared to be very significant. NAFLD management in women with metabolic syndrome should be focused on lifestyle modifications. Moreover, liver involvement and improvement at follow-up could be evaluated in a non-invasive manner through ultrasonographic and elastosonographic techniques.
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Dangl M, Eisenberg T, Grant JK, Vincent L, Colombo R, Sancassani R, Braghiroli J, Martin P, Vianna R, Nicolau-Raducu R, Mendoza C. A comprehensive review of coronary artery disease in patients with end-stage liver disease. Transplant Rev (Orlando) 2022; 36:100709. [DOI: 10.1016/j.trre.2022.100709] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 05/02/2022] [Accepted: 05/17/2022] [Indexed: 11/16/2022]
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Ahmed NR, Kulkarni VV, Pokhrel S, Akram H, Abdelgadir A, Chatterjee A, Khan S. Comparing the Efficacy and Safety of Obeticholic Acid and Semaglutide in Patients With Non-Alcoholic Fatty Liver Disease: A Systematic Review. Cureus 2022; 14:e24829. [PMID: 35693370 PMCID: PMC9173657 DOI: 10.7759/cureus.24829] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 05/08/2022] [Indexed: 11/05/2022] Open
Abstract
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of developing progressive fibrosis, cirrhosis, and hepatocellular carcinoma. As of now, there are no FDA-approved treatments for NAFLD/non-alcoholic steatohepatitis (NASH) or its associated fibrosis. Although many drugs are under clinical trial, both obeticholic acid (OCA) and semaglutide are among the few that have reached phase III clinical trials, but they were never compared. We decided to conduct a systematic review of randomized controlled trials and meta-analyses. A total of 6,589 articles were found after searching PubMed, OVID Embase, OVID Medline, PubMed Central, and clinicaltrials.gov. Only full-text peer-reviewed articles published in the past six years were put through the Cochrane bias assessment tool or the Assessment of Multiple Systematic Reviews (AMSTAR) tool to screen for bias. After strict quality assessment, data from five randomized controlled trials (n=2,694) and three systematic reviews/meta-analysis (n=8,898) was extracted and included. The data extraction from these studies showed that semaglutide and OCA cause histological improvement, but NASH resolution is exclusive to semaglutide. Although high doses of OCA can cause dyslipidemia and severe pruritus, it is the only therapeutic that causes improvement in NASH-associated hepatic fibrosis. Semaglutide is the safest option among the two and leads to significant weight loss compared to OCA; thus, a better outcome on hepatic steatosis follows. The indications of each of these drugs should be based on the NAFLD activity score and NASH fibrosis stage. OCA should be used with caution among patients with hyperlipidemia and ischemic heart disease as it may make these conditions worst.
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Affiliation(s)
- Nabeel R Ahmed
- Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Medicine, Dow International Medical College, Karachi, PAK
| | | | - Sushil Pokhrel
- Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Hamna Akram
- Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Arowa Abdelgadir
- Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Abanti Chatterjee
- Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Clinical Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Costello E, Rock S, Stratakis N, Eckel SP, Walker DI, Valvi D, Cserbik D, Jenkins T, Xanthakos SA, Kohli R, Sisley S, Vasiliou V, La Merrill MA, Rosen H, Conti DV, McConnell R, Chatzi L. Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis. ENVIRONMENTAL HEALTH PERSPECTIVES 2022; 130:46001. [PMID: 35475652 PMCID: PMC9044977 DOI: 10.1289/ehp10092] [Citation(s) in RCA: 209] [Impact Index Per Article: 69.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
BACKGROUND Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver. OBJECTIVE The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies. METHODS PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human studies, at least three observational studies per PFAS were used to conduct a weighted z-score meta-analysis to determine the direction and significance of associations. For rodent studies, data were synthesized to qualitatively summarize the direction and significance of effect. RESULTS Our search yielded 85 rodent studies and 24 epidemiological studies, primarily of people from the United States. Studies focused primarily on legacy PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid. Meta-analyses of human studies revealed that higher ALT levels were associated with exposure to PFOA (z-score= 6.20, p<0.001), PFOS (z-score= 3.55, p<0.001), and PFNA (z-score= 2.27, p=0.023). PFOA exposure was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in humans. In rodents, PFAS exposures consistently resulted in higher ALT levels and steatosis. CONCLUSION There is consistent evidence for PFAS hepatotoxicity from rodent studies, supported by associations of PFAS and markers of liver function in observational human studies. This review identifies a need for additional research evaluating next-generation PFAS, mixtures, and early life exposures. https://doi.org/10.1289/EHP10092.
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Affiliation(s)
- Elizabeth Costello
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Sarah Rock
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Nikos Stratakis
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Sandrah P. Eckel
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Douglas I. Walker
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Damaskini Valvi
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Dora Cserbik
- Barcelona Institute for Global Health, Barcelona, Spain
| | - Todd Jenkins
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Stavra A. Xanthakos
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Rohit Kohli
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital Los Angeles, Los Angeles, California, USA
| | - Stephanie Sisley
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Vasilis Vasiliou
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
| | - Michele A. La Merrill
- Department of Environmental Toxicology, University of California, Davis, Davis, California, USA
| | - Hugo Rosen
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - David V. Conti
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Rob McConnell
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Leda Chatzi
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Toda-Oti KS, Stefano JT, Cavaleiro AM, Carrilho FJ, Correa-Gianella ML, Oliveira CPMDSD. Association of UCP3 Polymorphisms with Nonalcoholic Steatohepatitis and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease Brazilian Patients. Metab Syndr Relat Disord 2022; 20:114-123. [PMID: 35020496 DOI: 10.1089/met.2020.0104] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background: We investigated the possible association of uncoupling protein 3 gene (UCP3) single nucleotide polymorphisms (SNPs) with nonalcoholic steatohepatitis (NASH) and metabolic syndrome (MetS) in nonalcoholic fatty liver disease (NAFLD) Brazilian patients. Methods:UCP3 SNPs rs1726745, rs3781907, and rs11235972 were genotyped in 158 biopsy-proven NAFLD Brazilian patients. Statistics was performed with JMP, R, and SHEsis softwares. Results: The TT genotype of rs1726745 was associated with less occurrence of MetS (P = 0.006) and with lower body mass index (BMI) in the entire NAFLD sample (P = 0.01) and in the NASH group (P = 0.02). The rs1726745-T was associated with lower values of AST (P = 0.001), ALT (P = 0.0002), triglycerides (P = 0.01), and total cholesterol (P = 0.02) in the entire NAFLD sample. Between groups, there were lower values of aminotransferases strictly in individuals with NASH (AST, P = 0.002; ALT, P = 0.0007) and with MetS (AST, P = 0.002; ALT, P = 0.001). The rs3781907-G was associated with lower GGT elevation values in the entire NAFLD sample (P = 0.002), in the NASH group (P = 0.004), and with MetS group (P = 0.003) and with protection for advanced fibrosis (P = 0.01). The rs11235972-A was associated with lower GGT values in the entire NAFLD sample (P = 0.006) and in the NASH group (P = 0.01) and with MetS group (P = 0.005), with fibrosis absence (P = 0.01) and protection for advanced fibrosis (P = 0.01). The TAA haplotype was protective for NASH (P = 0.002), and TGG haplotype was protective for MetS (P = 0.01). Conclusion:UCP3 gene variants were associated with protection against NASH and MetS, in addition to lower values of liver enzymes, lipid profile, BMI and, lesser fibrosis severity in the studied population.
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Affiliation(s)
- Karla Sawada Toda-Oti
- Departamento de Gastroenterologia, Faculdade de Medicina da, Universidade de São Paulo, São Paulo, Brazil
| | - José Tadeu Stefano
- Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Departamento de Gastroenterologia e Hepatologia, Faculdade de Medicina, Hospital das Clínicas HC-FMUSP, Universidade de São Paulo, São Paulo, Brazil
| | - Ana Mercedes Cavaleiro
- Laboratório de Carboidratos e Radioimunensaio (LIM-18), Hospital das Clínicas HC-FMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Flair José Carrilho
- Departamento de Gastroenterologia, Faculdade de Medicina da, Universidade de São Paulo, São Paulo, Brazil
- Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Departamento de Gastroenterologia e Hepatologia, Faculdade de Medicina, Hospital das Clínicas HC-FMUSP, Universidade de São Paulo, São Paulo, Brazil
| | - Maria Lúcia Correa-Gianella
- Laboratório de Carboidratos e Radioimunensaio (LIM-18), Hospital das Clínicas HC-FMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
- Programa de Pós-graduação em Medicina, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil
| | - Cláudia Pinto Marques de Souza de Oliveira
- Departamento de Gastroenterologia, Faculdade de Medicina da, Universidade de São Paulo, São Paulo, Brazil
- Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Departamento de Gastroenterologia e Hepatologia, Faculdade de Medicina, Hospital das Clínicas HC-FMUSP, Universidade de São Paulo, São Paulo, Brazil
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Fridén M, Rosqvist F, Ahlström H, Niessen HG, Schultheis C, Hockings P, Hulthe J, Gummesson A, Wanders A, Rorsman F, Risérus U, Vessby J. Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease. Front Med (Lausanne) 2022; 8:814951. [PMID: 35083257 PMCID: PMC8784562 DOI: 10.3389/fmed.2021.814951] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 12/17/2021] [Indexed: 12/12/2022] Open
Abstract
Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited. Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0–1) or significant fibrosis (F2–4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions. Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis. Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.
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Affiliation(s)
- Michael Fridén
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - Fredrik Rosqvist
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - Håkan Ahlström
- Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.,Antaros Medical AB, BioVenture Hub, Mölndal, Sweden
| | - Heiko G Niessen
- Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
| | - Christian Schultheis
- Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
| | - Paul Hockings
- Antaros Medical AB, BioVenture Hub, Mölndal, Sweden.,MedTech West, Chalmers University of Technology, Gothenburg, Sweden
| | | | - Anders Gummesson
- Department of Clinical Genetics and Genomics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Alkwin Wanders
- Department of Pathology, Aalborg University Hospital, Aalborg, Denmark
| | - Fredrik Rorsman
- Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden
| | - Ulf Risérus
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - Johan Vessby
- Department of Medical Sciences, Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden
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Xie C, Zhang Z, Yang M, Cao C, Zhou Y, Zhu Z, Gong W, Xu C, Yan L, Hu Z, Ai L, Peng Y. Lactiplantibacillus plantarum AR113 Exhibit Accelerated Liver Regeneration by Regulating Gut Microbiota and Plasma Glycerophospholipid. Front Microbiol 2022; 12:800470. [PMID: 35154031 PMCID: PMC8834300 DOI: 10.3389/fmicb.2021.800470] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 11/29/2021] [Indexed: 12/11/2022] Open
Abstract
Emerging evidence indicates that probiotics have been proved to influence liver injury and regeneration. In the present study, the effects of Lactiplantibacillus plantarum AR113 on the liver regeneration were investigated in 70% partial hepatectomy (PHx) rats. Sprague-Dawley (SD) rats were gavaged with L. plantarum AR113 suspensions (1 × 1010 CFU/mL) both before and after partial hepatectomy. The results showed that L. plantarum AR113 administration 2 weeks before partial hepatectomy can accelerate liver regeneration by increased hepatocyte proliferation and tumor necrosis factor-α (TNF-α), hepatocyte growth factor (HGF), and transforming growth factor-β (TGF-β) expression. Probiotic administration enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome. Meanwhile, L. plantarum AR113 showed decline of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidyl serine (PS), and lysophosphatidyl choline (LysoPC) levels in the serum of the rats after the L. plantarum AR113 administration. Moreover, L. plantarum AR113 treated rats exhibited higher concentrations of L-leucine, L-isoleucine, mevalonic acid, and lower 7-oxo-8-amino-nonanoic acid in plasma than that in PHx. Spearman correlation analysis revealed a significant correlation between changes in gut microbiota composition and glycerophospholipid. These results indicate that L. plantarum AR113 is promising for accelerating liver regeneration and provide new insights regarding the correlations among the microbiome, the metabolome, and liver regeneration.
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Affiliation(s)
- Chunliang Xie
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Zhoumei Zhang
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Manyi Yang
- Department of Hepatobiliary and Pancreatic Surgery, NHC Key Laboratory of Nanobiological Technology, Xiangya Hospital, Central South University, Changsha, China
| | - Cha Cao
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Yingjun Zhou
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Zuohua Zhu
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Wenbing Gong
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Chao Xu
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Li Yan
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Zhenxiu Hu
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Lianzhong Ai
- Shanghai Engineering Research Center of Food Microbiology, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China
- *Correspondence: Lianzhong Ai,
| | - Yuande Peng
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
- Yuande Peng,
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50
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Yu YC, Luu HN, Wang R, Thomas CE, Glynn NW, Youk AO, Behari J, Yuan JM. Serum Biomarkers of Iron Status and Risk of Hepatocellular Carcinoma Development in Patients with Nonalcoholic Fatty Liver Disease. Cancer Epidemiol Biomarkers Prev 2022; 31:230-235. [PMID: 34649958 PMCID: PMC9204666 DOI: 10.1158/1055-9965.epi-21-0754] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/27/2021] [Accepted: 10/04/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has become a major contributor to the rising incidence of hepatocellular carcinoma (HCC) in the United States and other developed countries. Iron, an essential metal primarily stored in hepatocytes, may play a role in the development of NAFLD-related HCC. Epidemiologic data on iron overload without hemochromatosis in relation to HCC are sparse. This study aimed to examine the associations between serum biomarkers of iron and the risk of HCC in patients with NAFLD. METHODS We identified 18,569 patients with NAFLD using the University of Pittsburgh Medical Center electronic health records from 2004 through 2018. After an average 4.34 years of follow-up, 244 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of HCC incidence associated with elevated levels of iron biomarkers with adjustment for age, sex, race, body mass index, history of diabetes, and tobacco smoking. RESULTS The HRs (95% CIs) of HCC for clinically defined elevation of serum iron and transferrin saturation were 2.91 (1.34-6.30) and 2.02 (1.22-3.32), respectively, compared with their respective normal range. No statistically significant association was observed for total iron-binding capacity or serum ferritin with HCC risk. CONCLUSIONS Elevated levels of serum iron and transferrin saturation were significantly associated with increased risk of HCC among patients with NAFLD without hemochromatosis or other major underlying causes of chronic liver diseases. IMPACT Clinical surveillance of serum iron level may be a potential strategy to identify patients with NAFLD who are at high risk for HCC.
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Affiliation(s)
- Yi-Chuan Yu
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Hung N Luu
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Renwei Wang
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Claire E Thomas
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Nancy W Glynn
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Ada O Youk
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Jaideep Behari
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Jian-Min Yuan
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
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