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Pădureanu V, Dop D, Radu L, Rădulescu D, Pădureanu R, Pîrșcoveanu DFV, Caragea DC. Nephrological, Pulmonary, and Dermatological Complications in the Context of MAFLD/NAFLD: A Narrative Review. Metabolites 2025; 15:272. [PMID: 40278401 PMCID: PMC12029749 DOI: 10.3390/metabo15040272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/07/2025] [Accepted: 04/11/2025] [Indexed: 04/26/2025] Open
Abstract
Background: The most common cause of chronic liver disease is now known to be non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic-associated fatty liver disease (MAFLD). This review aims to synthesize current evidence on the pathophysiology and clinical implications of nephrological, pulmonary, and dermatological manifestations among NAFLD/MAFLD patients. In order to find safe and efficient treatments, NAFLD/MAFLD has emerged as a primary concern for hepatologists worldwide. Methods: We conducted a comprehensive review of the literature from major databases, focusing on studies that evaluated the extrahepatic manifestations of NAFLD/MAFLD. Emphasis was placed on identifying pathophysiological mechanisms and assessing their clinical impact on renal, pulmonary, and dermatological systems. Results: Recent developments in the management of chronic viral hepatitis have lowered the mortality rate associated with chronic liver disease. However, the prevalence of NAFLD/MAFLD continues to rise, making chronic liver disease a significant health concern for the future. An increasing percentage of patients on liver transplant waiting lists now have cirrhosis and hepatocellular carcinoma due to non-alcoholic liver disease. Furthermore, the incidence and prevalence of chronic kidney disease have surged, linking NAFLD/MAFLD to higher morbidity, mortality, and healthcare costs. Conclusions: NAFLD/MAFLD is underdiagnosed and underappreciated, yet its incidence is rapidly increasing, raising concerns about a potential global epidemic. Given its multisystemic impact-extending to renal, pulmonary, and dermatological complications-it is crucial to develop interdisciplinary strategies for early detection and effective management of the disease.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dalia Dop
- Department of Pediatrics, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Lucrețiu Radu
- Department of Hygiene, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dumitru Rădulescu
- Department of Surgery, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | | | - Daniel Cosmin Caragea
- Department of Nephrology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
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Bogdan RG, Boicean A, Anderco P, Ichim C, Iliescu-Glaja M, Todor SB, Leonte E, Bloanca VA, Crainiceanu ZP, Popa ML. From Liver to Kidney: The Overlooked Burden of Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease. J Clin Med 2025; 14:2486. [PMID: 40217935 PMCID: PMC11989420 DOI: 10.3390/jcm14072486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 03/30/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a contributor to chronic kidney disease (CKD), yet its impact remains underappreciated in clinical practice. Recent studies reveal a strong association between NAFLD and CKD progression, with evidence linking hepatic dysfunction to renal impairment through metabolic and inflammatory pathways. NAFLD not only increases the risk of CKD but also accelerates its progression, leading to worse cardiovascular outcomes and higher mortality, particularly in patients with advanced fibrosis. Despite this growing evidence, NAFLD often goes undiagnosed in CKD patients and routine hepatic evaluation is rarely integrated into nephrology care. Emerging diagnostic tools, including noninvasive biomarkers and imaging techniques, offer potential for earlier detection, yet their clinical implementation remains inconsistent. Although lifestyle modifications remain the foundation of treatment, pharmacotherapeutic strategies, including SGLT2 inhibitors and GLP-1 receptor agonists, have demonstrated potential in mitigating both hepatic and renal impairment. Recognizing the interplay between NAFLD and CKD is essential for improving patient outcomes. A multidisciplinary approach, integrating hepatology and nephrology expertise, is crucial to refining screening strategies, optimizing treatment, and reducing the long-term burden of these coexisting conditions.
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Affiliation(s)
- Razvan George Bogdan
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Adrian Boicean
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Paula Anderco
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Cristian Ichim
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Mihai Iliescu-Glaja
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Samuel Bogdan Todor
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Elisa Leonte
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Vlad Adam Bloanca
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Zorin Petrisor Crainiceanu
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Mirela Livia Popa
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
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Zhang L, Lin Y, Huang X, Zhai Z, Wei R, Mo J, Li J, Lu W. Metabolic dysfunction-associated fatty liver disease in the elderly with diabetic foot ulcers: A longitudinal cohort study. Int Wound J 2024; 21:e14586. [PMID: 38102851 PMCID: PMC10961876 DOI: 10.1111/iwj.14586] [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: 10/26/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 12/17/2023] Open
Abstract
This study aimed to explore the association between metabolic-associated fatty liver disease (MAFLD) and ulcer recurrence risk in patients with diabetic foot ulcers (DFUs) through an ambispective longitudinal cohort. From December 2013 to December 2022, a total of 482 inpatients with DFUs (PEDIS grade 3 and above with a severe infection) were eligible for inclusion in this study. This was an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 36 months. According to whether having MAFLD or not, all subjects were placed into two groups: non-MAFLD (n = 351) and MAFLD (n = 131). The association between MAFLD and ulcer recurrence in patients with DFUs was then evaluated through multivariate Cox regression analysis, stratified analyses and Kaplan-Meier survival analysis. Throughout the follow-up period, out of 482 subjects with DFUs, 68 had ulcer recurrence (14.1%). Three Cox regression models were established for data analyses. In the model I (unadjusted), MAFLD was significantly associated with the ulcer recurrence rate in patients with DFUs (HR = 1.79; 95% CI = 1.097-2.92; p = 0.02). Model II (adjusted model I with gender and age) (HR = 1.781; 95% CI = 1.09-2.912; p = 0.021) and model III (adjusted model II with CVD, duration of diabetes and Cr.) (HR = 1.743; 95% CI = 1.065-2.855; p = 0.027) also showed that MAFLD was significantly related to the ulcer recurrence risk in patients with DFUs, respectively. Stratified analysis indicated that subjects aged ≥60 had a greater risk of ulcer recurrence in MAFLD than in non-MAFLD (HR = 2.31; 95% CI = 1.268-4.206; p = 0.006). Kaplan-Meier survival curve analysis showed that ulcer recurrence rate had a significant association with MAFLD (log-rank, p = 0.018). This study indicated a close association between ulcer recurrence risk and MAFLD in patients with DFUs, especially in the elderly (aged ≥60). Therefore, special attention should be paid to the elderly with both DFUs and MAFLD because they have a higher ulcer recurrence rate than other general populations in routine clinical practice.
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Affiliation(s)
- Liya Zhang
- Department of EndocrinologyShanxi Yingkang Healthcare General HospitalYunchengPeople's Republic of China
| | - Yuanmei Lin
- Department of Endocrinology and Metabolism of Guangxi Academy of Medical SciencesPeople's Hospital of Guangxi Zhuang Autonomous RegionNanningPeople's Republic of China
| | - Xiuxian Huang
- Department of Endocrinology and Metabolism of Guangxi Academy of Medical SciencesPeople's Hospital of Guangxi Zhuang Autonomous RegionNanningPeople's Republic of China
| | - Zhenwei Zhai
- Department of Endocrinology and Metabolism of Guangxi Academy of Medical SciencesPeople's Hospital of Guangxi Zhuang Autonomous RegionNanningPeople's Republic of China
| | - Rongyan Wei
- Department of Endocrinology and Metabolism of Guangxi Academy of Medical SciencesPeople's Hospital of Guangxi Zhuang Autonomous RegionNanningPeople's Republic of China
| | - Jiacheng Mo
- Information Network Center of Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous RegionNanningPeople's Republic of China
| | - Junjun Li
- Dean's Office of Guangxi Academy of Medical SciencesPeople's Hospital of Guangxi Zhuang Autonomous RegionNanningPeople's Republic of China
| | - Wensheng Lu
- Department of Endocrinology and Metabolism of Guangxi Academy of Medical SciencesPeople's Hospital of Guangxi Zhuang Autonomous RegionNanningPeople's Republic of China
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Alem SA, Fouad Y, AbdAllah M, Attia D, Kamal I, Said E, Gomaa A, Abd-Elsalam SM, Gaber Y. Hepatologists' Awareness and Knowledge of NAFLD and the Familiarity with Renaming NAFLD to MAFLD. Endocr Metab Immune Disord Drug Targets 2024; 24:1445-1453. [PMID: 36306455 DOI: 10.2174/1871530323666221028154159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 08/08/2022] [Accepted: 10/11/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic; it is a negative diagnosis that depends mainly on the presence of hepatic steatosis with or without inflammation after the exclusion of other chronic liver diseases and excess alcohol intake. However, the new definition of MAFLD is a shift towards a diagnosis of inclusion based on the presence of metabolic dysfunction, regardless of alcohol consumption or other concomitant liver diseases. Given the growing relevance of the disease, data on hepatologists' views and understanding of NAFLD are limited, we aimed to determine hepatologists' awareness and expertise of NAFLD screening, diagnosis, and therapeutic options as well as the influence of changing the NAFLD name to MAFLD on awareness of the fatty liver disease (FLD). OBJECTIVE Most of the hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, necessitating a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD. METHODS A multicenter online questionnaire of 655 hepatologists was carried out, giving a sample of 207 respondents. A survey composed of 36 questions was used to assess the level of hepatologists' awareness and practices in the screening, diagnosis, and management of NAFLD/MAFLD, as well as their familiarity with the nomenclature change from NAFLD to MAFLD. RESULTS A total of 207 hepatologists were included, of which 107 (51.4%) were males, with a mean age was 36.4 years. 50.2% (n = 104) of the hepatologists were oriented with NAFLD. Only 41 (19.8%) realized that NAFLD may frequently result in severe hepatic disease. NAFLD is rarely screened by the majority of the participating hepatologists (118, 57%), and (135, 65.2%) of them use liver biopsy for diagnosis of NAFLD. In (104, 50.2%) hepatologists, changing the nomenclature of NAFLD was relatively familiar. Furthermore, 71.9% of hepatologists thought that the new nomenclature offers a better awareness of FLD. CONCLUSION A small percentage of hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, and around half of them realize that NAFLD necessitates a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.
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Affiliation(s)
- Shereen Abdel Alem
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minia, Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Centre, Giza, Egypt
| | - Dina Attia
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Inas Kamal
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minia, Egypt
| | - Ebada Said
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Benha University, Benha, Egypt
| | - Ahmed Gomaa
- Department of Tropical Medicine, Faculty of Medicine, Fayoum University, Fayoum, Egypt
| | - Sherief M Abd-Elsalam
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Yasmine Gaber
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
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Vagurmekar PA, Ferreira AM, Vaz FS, Shah HK, Dias AS, Kulkarni MS. Prevalence of non-alcoholic fatty liver disease (NAFLD) among adults in urban Goa. THE NATIONAL MEDICAL JOURNAL OF INDIA 2023; 36:401-404. [PMID: 38909310 DOI: 10.25259/nmji_37_2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/24/2024]
Affiliation(s)
- Prajakta Ankur Vagurmekar
- Department of Community Medicine, ART Centre, Goa AIDS, Control Society, Directorate of Health Services, South Goa District Hospital, Margao, GOA, India
| | | | - Frederick Satiro Vaz
- Department of Community Medicine, Goa Medical College, Bambolim 403202, Goa, India
| | | | - Amit Savio Dias
- Department of Community Medicine, Goa Medical College, Bambolim 403202, Goa, India
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6
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Guan H, Shao G, Cheng F, Ni P, Wu M. Risk factors of nonalcoholic fatty liver disease in healthy women. Medicine (Baltimore) 2023; 102:e34437. [PMID: 37543765 PMCID: PMC10402973 DOI: 10.1097/md.0000000000034437] [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: 05/18/2023] [Revised: 06/30/2023] [Accepted: 06/30/2023] [Indexed: 08/07/2023] Open
Abstract
We investigated the risk factors of nonalcoholic fatty liver disease (NAFLD) in healthy women. This is a cross-sectional study. Healthy women who underwent physical examination were enrolled. Their basic information and medical history [including age, height, weight, body mass index (BMI)], abdominal ultrasound results, and, serological indexes [including white blood cells, platelet count, fasting blood glucose, triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDLC), uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamyl transpeptidase] were collected. Univariate and multivariate regression analysis was carried out to screen the risk factors of NAFLD. ALT/AST ratio, and BMI were significantly independent risk factors for the occurrence and severity of NAFLD. In addition, TG/HDLC ratio, and UA level also had significant independent correlation with NAFLD. ALT/AST ratio, BMI, TG/HDLC ratio, and UA are independent risk factors for the occurrence and severity of NAFLD. It is suggested that obesity, hyperlipidemia, hyperuricemia and high transaminase value are closely related to NAFLD. People with such conditions should pay more attention to early screening of NAFLD to avoid disease aggravation and the occurrence and development of other complications. In clinical practice, ALT/AST, BMI, TG/HDLC, and UA level should be closely monitored, so as to facilitate the follow-up management of the disease.
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Affiliation(s)
- Hui Guan
- Department of Ultrasound, The Second Hospital of Shandong University, Jinan, China
| | - Guangrui Shao
- Medical Image Center, The Second Hospital of Shandong University, Jinan, China
| | - Fang Cheng
- School of Public Health, Qilu Medical College of Shandong University, Jinan, China
| | - Pingjuan Ni
- Department of Ultrasound, The Second Hospital of Shandong University, Jinan, China
| | - Mei Wu
- Department of Ultrasound, The Second Hospital of Shandong University, Jinan, China
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Drapkina OM, Elkina AY, Sheptulina AF, Kiselev AR. Non-Alcoholic Fatty Liver Disease and Bone Tissue Metabolism: Current Findings and Future Perspectives. Int J Mol Sci 2023; 24:ijms24098445. [PMID: 37176153 PMCID: PMC10178980 DOI: 10.3390/ijms24098445] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 04/26/2023] [Accepted: 05/04/2023] [Indexed: 05/15/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions worldwide. Moreover, the prevalence of this liver disease is expected to increase rapidly in the near future, aligning with the rise in obesity and the aging of the population. The pathogenesis of NAFLD is considered to be complex and to include the interaction between genetic, metabolic, inflammatory, and environmental factors. It is now well documented that NAFLD is linked to the other conditions common to insulin resistance, such as abnormal lipid levels, metabolic syndrome, and type 2 diabetes mellitus. Additionally, it is considered that the insulin resistance may be one of the main mechanisms determining the disturbances in both bone tissue metabolism and skeletal muscles quality and functions in patients with NAFLD. To date, the association between NAFLD and osteoporosis has been described in several studies, though it worth noting that most of them included postmenopausal women or elderly patients and originated from Asia. However, taking into account the health and economic burdens of NAFLD, and the increasing prevalence of obesity in children and adolescents worldwide, further investigation of the relationship between osteopenia, osteoporosis and sarcopenia in NAFLD, including in young and middle-aged patients, is of great importance. In addition, this will help to justify active screening and surveillance of osteopenia and osteoporosis in patients with NAFLD. In this review, we will discuss various pathophysiological mechanisms and possible biologically active molecules that may interplay between NAFLD and bone tissue metabolism.
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Affiliation(s)
- Oxana M Drapkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
| | - Anastasia Yu Elkina
- Department of Intermediate Level Therapy, Saratov State Medical University, 410012 Saratov, Russia
| | - Anna F Sheptulina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
| | - Anton R Kiselev
- Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
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Azbazdar Y, Poyraz YK, Ozalp O, Nazli D, Ipekgil D, Cucun G, Ozhan G. High-fat diet feeding triggers a regenerative response in the adult zebrafish brain. Mol Neurobiol 2023; 60:2486-2506. [PMID: 36670270 DOI: 10.1007/s12035-023-03210-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 01/04/2023] [Indexed: 01/22/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) includes a range of liver conditions ranging from excess fat accumulation to liver failure. NAFLD is strongly associated with high-fat diet (HFD) consumption that constitutes a metabolic risk factor. While HFD has been elucidated concerning its several systemic effects, there is little information about its influence on the brain at the molecular level. Here, by using a high-fat diet (HFD)-feeding of adult zebrafish, we first reveal that excess fat uptake results in weight gain and fatty liver. Prolonged exposure to HFD induces a significant increase in the expression of pro-inflammation, apoptosis, and proliferation markers in the liver and brain tissues. Immunofluorescence analyses of the brain tissues disclose stimulation of apoptosis and widespread activation of glial cell response. Moreover, glial activation is accompanied by an initial decrease in the number of neurons and their subsequent replacement in the olfactory bulb and the telencephalon. Long-term consumption of HFD causes activation of Wnt/β-catenin signaling in the brain tissues. Finally, fish fed an HFD induces anxiety, and aggressiveness and increases locomotor activity. Thus, HFD feeding leads to a non-traumatic brain injury and stimulates a regenerative response. The activation mechanisms of a regeneration response in the brain can be exploited to fight obesity and recover from non-traumatic injuries.
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Affiliation(s)
- Yagmur Azbazdar
- Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey
- Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340, Izmir, Turkey
- Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, 90095-1662, USA
| | - Yusuf Kaan Poyraz
- Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey
- Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340, Izmir, Turkey
| | - Ozgun Ozalp
- Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey
- Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340, Izmir, Turkey
- Department of Molecular Life Sciences, University of Zurich, CH-8057, Zurich, Switzerland
| | - Dilek Nazli
- Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey
- Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340, Izmir, Turkey
| | - Dogac Ipekgil
- Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey
- Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340, Izmir, Turkey
| | - Gokhan Cucun
- Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey
- Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340, Izmir, Turkey
- Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), 3640 76021, Karlsruhe, Postfach, Germany
| | - Gunes Ozhan
- Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University Health Campus, Inciralti-Balcova, 35340, Izmir, Turkey.
- Izmir International Biomedicine and Genome Institute (IBG-Izmir), Dokuz Eylul University, Inciralti-Balcova, 35340, Izmir, Turkey.
- Department of Molecular Biology and Genetics, Izmir Institute of Technology, Urla, 35430, Izmir, Turkey.
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Zheng K, Zhou W, Ji J, Xue Y, Liu Y, Li C, Zhang Z, Lu J, Shi X, Li Y. Si-Ni-San reduces lipid droplet deposition associated with decreased YAP1 in metabolic dysfunction-associated fatty liver disease. JOURNAL OF ETHNOPHARMACOLOGY 2023; 305:116081. [PMID: 36608777 DOI: 10.1016/j.jep.2022.116081] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 12/16/2022] [Accepted: 12/20/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. However, its complex pathogenesis and lack of effective drugs for treating it present significant challenges. Si-Ni-San (SNS) is one of the representative formulas for treating patients with MAFLD in traditional Chinese medicine (TCM) clinics. According to our previous work, SNS reduces lipid droplet (LD) deposition in livers of mice with MAFLD. AIM OF THE STUDY To elucidate the mechanism of SNS in reducing LD deposition in MAFLD. MATERIALS AND METHODS First, LD areas were detected with Oil red O staining in HepG2 cells induced by oleic acid (OA). Cell Counting Kit-8 (CCK-8) assay was used to test cell viability after treatment with different concentrations of SNS serum. The expression of Yes-associated protein 1 (YAP1) was monitored by Western blot. Second, C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and gavaged with SNS decoction during the 11th and 12th weeks. Then, the weight of the body and the liver was examined. LD numbers and their locations in the liver were detected by triglyceride (TG) assay and hematoxylin and eosin staining (H&E). The expression levels of YAP1 and perilipin2 (PLIN2) were detected using Western blot and immunohistochemistry (IHC) in liver tissues. Finally, active ingredients of SNS decoction and SNS serum were identified by liquid chromatography-mass spectrometry (LC-MS). Finally, molecular docking was performed between the compounds in SNS and YAP1 to analyze their active interaction. RESULTS Cellular experiments showed that SNS serum reduced LD vacuoles and YAP1 expression in OA-induced HepG2 cells. Animal experiments confirmed that LD vacuoles, PLIN2 expression (3.16-fold), and YAP1 expression (2.50-fold) were increased in the HFD group compared with the normal diet (ND) group. SNS reduced LD vacuoles, TG content (0.84-fold), PLIN2 expression (0.33-fold), and YAP1 expression (0.27-fold) compared with the normal saline (NS) group in Yap1Flox mice with MAFLD. In SNS, baicalein-6-glucuronide, desoxylimonin, galangin-7-glucoside, glycyrrhizic-acid, licoricesaponin-K2, and nobiletin showed a high binding effect with YAP1. Knockout of hepatocyte YAP1 reduced LD vacuoles, TG content (0.40-fold), and PLIN2 expression (0.62-fold) in mice. Meanwhile, SNS reduced LD vacuoles, TG content (0.70-fold), and PLIN2 expression (0.19-fold) in Yap1LKO mice with MAFLD. The effect of SNS in reducing TG and PLIN2 was diminished in Yap1LKO mice compared with Yap1Flox mice. CONCLUSION SNS reduced LD deposition and YAP1 expression in MAFLD liver cells both in vivo and in vitro. YAP1 was highly expressed in livers with MAFLD, and knockout of hepatocellular YAP1 reduced LD deposition in mice. SNS reduced LD deposition associated with decreased YAP1 in MAFLD liver cells.
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Affiliation(s)
- Kangning Zheng
- Department of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Wenhan Zhou
- Department of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Jingmin Ji
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Yu Xue
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Yiwei Liu
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Caige Li
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Zhiqin Zhang
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Junlan Lu
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Xinli Shi
- Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
| | - Yongmin Li
- Department of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
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10
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Hassan AM, Haridy MA, Shoaeir MZ, Abdel-Aziz TM, Qura MK, Kenawy EM, Mansour TMM, Salaheldin Elsayed S, Ali WE, Abdelmeguid MM, Abdel-Gawad M. Non-alcoholic fatty liver disease is associated with decreased bone mineral density in upper Egyptian patients. Sci Rep 2023; 13:4353. [PMID: 36928441 PMCID: PMC10020438 DOI: 10.1038/s41598-023-31256-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 03/08/2023] [Indexed: 03/18/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (- 2.29 ± 0.4 vs. - 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348-0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.
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Affiliation(s)
- Amro M Hassan
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt.
| | - Mustafa Ahmed Haridy
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Mohamed Z Shoaeir
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Tarek M Abdel-Aziz
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Mohamed Khairy Qura
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | - Eglal M Kenawy
- Internal Medicine Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | | | | | - Wael Esmat Ali
- Clinical Pathology Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
| | | | - Muhammad Abdel-Gawad
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
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11
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Conundrum for Psoriasis and Thyroid Involvement. Int J Mol Sci 2023; 24:ijms24054894. [PMID: 36902323 PMCID: PMC10003398 DOI: 10.3390/ijms24054894] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 02/21/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023] Open
Abstract
Strategies concerning thyroid anomalies in patients confirmed with psoriasis, either on clinical level or molecular levels, and their genetic findings remain an open issue. Identification of the exact subgroup of individuals that are candidates to endocrine assessments is also controversial. Our purpose in this work was to overview clinical and pathogenic data concerning psoriasis and thyroid comorbidities from a dual perspective (dermatologic and endocrine). This was a narrative review of English literature between January 2016 and January 2023. We included clinically relevant, original articles with different levels of statistical evidence published on PubMed. We followed four clusters of conditions: thyroid dysfunction, autoimmunity, thyroid cancer, and subacute thyroiditis. A new piece of information in this field was the fact that psoriasis and autoimmune thyroid diseases (ATD) have been shown to be related to the immune-based side effects of modern anticancer drugs-namely, immune checkpoint inhibitors (ICP). Overall, we identified 16 confirmatory studies, but with heterogeneous data. Psoriatic arthritis had a higher risk of positive antithyroperoxidase antibodies (TPOAb) (25%) compared to cutaneous psoriasis or control. There was an increased risk of thyroid dysfunction versus control, and hypothyroidism was the most frequent type of dysfunction (subclinical rather than clinical), among thyroid anomalies correlated with >2-year disease duration, peripheral > axial and polyarticular involvement. With a few exceptions, there was a female predominance. Hormonal imbalance included, most frequently, low thyroxine (T4) and/or triiodothyronine (T3) with normal thyroid stimulating hormone (TSH), followed by high TSH (only one study had higher total T3). The highest ratio of thyroid involvement concerning dermatologic subtypes was 59% for erythrodermic psoriasis. Most studies found no correlation between thyroid anomalies and psoriasis severity. Statistically significant odds ratios were as follows: hypothyroidism: 1.34-1.38; hyperthyroidism: 1.17-1.32 (fewer studies than hypo); ATD: 1.42-2.05; Hashimoto's thyroiditis (HT): 1.47-2.09; Graves' disease: 1.26-1.38 (fewer studies than HT). A total of 8 studies had inconsistent or no correlations, while the lowest rate of thyroid involvement was 8% (uncontrolled studies). Other data included 3 studies on patients with ATD looking for psoriasis, as well as 1 study on psoriasis and thyroid cancer. ICP was shown to potentially exacerbate prior ATD and psoriasis or to induce them both de novo (5 studies). At the case report level, data showed subacute thyroiditis due to biological medication (ustekinumab, adalimumab, infliximab). Thyroid involvement in patients with psoriasis thus remained puzzling. We observed significant data that confirmed a higher risk of identifying positive antibodies and/or thyroid dysfunction, especially hypothyroidism, in these subjects. Awareness will be necessary to improve overall outcomes. The exact profile of individuals diagnosed with psoriasis who should be screened by the endocrinology team is still a matter of debate, in terms of dermatological subtype, disease duration, activity, and other synchronous (especially autoimmune) conditions.
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12
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Kablawi D, Aljohani F, Palumbo CS, Restellini S, Bitton A, Wild G, Afif W, Lakatos PL, Bessissow T, Sebastiani G. Nonalcoholic Fatty Liver Disease Increases Cardiovascular Risk in Inflammatory Bowel Diseases. CROHN'S & COLITIS 360 2023; 5:otad004. [PMID: 36846097 PMCID: PMC9951742 DOI: 10.1093/crocol/otad004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. Both conditions seem more frequent in patients with inflammatory bowel disease (IBD). We aimed to assess the effect of NAFLD and liver fibrosis on intermediate-high cardiovascular risk in IBD. METHODS We prospectively included IBD patients undergoing a routine screening program for NAFLD by transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD and significant liver fibrosis were defined as CAP ≥275 dB m-1 and liver stiffness measurement by TE ≥8 kPa, respectively. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator and categorized as low if <5%, borderline if 5%-7.4%, intermediate if 7.5%-19.9%, and high if ≥20% or if previous cardiovascular event. Predictors of intermediate-high cardiovascular risk were investigated by multivariable logistic regression analysis. RESULTS Of 405 patients with IBD included, 278 (68.6%), 23 (5.7%), 47 (11.6%), and 57 (14.1%) were categorized as at low, borderline, intermediate, and high ASCVD risk, respectively. NAFLD and significant liver fibrosis were found in 129 (31.9%) and 35 (8.6%) patients, respectively. After adjusting for disease activity, significant liver fibrosis and body mass index, predictors of intermediate-high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.97, 95% CI, 1.56-5.68), IBD duration (aOR 1.55 per 10 years, 95% CI, 1.22-1.97), and ulcerative colitis (aOR 2.32, 95% CI, 1.35-3.98). CONCLUSIONS Assessment of cardiovascular risk should be targeted in IBD patients with NAFLD, particularly if they have longer IBD duration and ulcerative colitis.
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Affiliation(s)
- Dana Kablawi
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Faisal Aljohani
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | | | - Sophie Restellini
- Gastroenterology Department, University Hospital of Geneva, Geneva, Switzerland
| | - Alain Bitton
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Gary Wild
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Waqqas Afif
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Peter L Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
- 1st Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
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13
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Maestri M, Santopaolo F, Pompili M, Gasbarrini A, Ponziani FR. Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies. Front Nutr 2023; 10:1110536. [PMID: 36875849 PMCID: PMC9978194 DOI: 10.3389/fnut.2023.1110536] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/16/2023] [Indexed: 02/18/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.
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Affiliation(s)
- Marta Maestri
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
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14
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Critical Overview of Hepatic Factors That Link Non-Alcoholic Fatty Liver Disease and Acute Kidney Injury: Physiology and Therapeutic Implications. Int J Mol Sci 2022; 23:ijms232012464. [PMID: 36293317 PMCID: PMC9604121 DOI: 10.3390/ijms232012464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/13/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is defined as a combination of a group of progressive diseases, presenting different structural features of the liver at different stages of the disease. According to epidemiological surveys, as living standards improve, the global prevalence of NAFLD increases. Acute kidney injury (AKI) is a class of clinical conditions characterized by a rapid decline in kidney function. NAFLD and AKI, as major public health diseases with high prevalence and mortality, respectively, worldwide, place a heavy burden on societal healthcare systems. Clinical observations of patients with NAFLD with AKI suggest a possible association between the two diseases. However, little is known about the pathogenic mechanisms linking NAFLD and AKI, and the combination of the diseases is poorly treated. Previous studies have revealed that liver-derived factors are transported to distal organs via circulation, such as the kidney, where they elicit specific effects. Of note, while NAFLD affects the expression of many hepatic factors, studies on the mechanisms whereby NAFLD mediates the generation of hepatic factors that lead to AKI are lacking. Considering the unique positioning of hepatic factors in coordinating systemic energy metabolism and maintaining energy homeostasis, we hypothesize that the effects of NAFLD are not only limited to the structural and functional changes in the liver but may also involve the entire body via the hepatic factors, e.g., playing an important role in the development of AKI. This raises the question of whether analogs of beneficial hepatic factors or inhibitors of detrimental hepatic factors could be used as a treatment for NAFLD-mediated and hepatic factor-driven AKI or other metabolic disorders. Accordingly, in this review, we describe the systemic effects of several types of hepatic factors, with a particular focus on the possible link between hepatic factors whose expression is altered under NAFLD and AKI. We also summarize the role of some key hepatic factors in metabolic control mechanisms and discuss their possible use as a preventive treatment for the progression of metabolic diseases.
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15
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Kechagias S, Ekstedt M, Simonsson C, Nasr P. Non-invasive diagnosis and staging of non-alcoholic fatty liver disease. Hormones (Athens) 2022; 21:349-368. [PMID: 35661987 PMCID: PMC9464753 DOI: 10.1007/s42000-022-00377-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 05/19/2022] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome and is characterized by ectopic accumulation of triglycerides in the cytoplasm of hepatocytes, i.e., steatosis. NAFLD has become the most common chronic liver disease, with an estimated global prevalence of 25%. Although the majority of NAFLD patients will never experience liver-related complications, the progressive potential of NAFLD is indisputable, with 5-10% of subjects progressing to cirrhosis, end-stage liver disease, or hepatocellular carcinoma. NAFLD patients with advanced fibrosis are at the highest risk of developing cardiovascular and cirrhosis-related complications. Liver biopsy has hitherto been considered the reference method for evaluation of hepatic steatosis and fibrosis stage. Given the limitations of biopsy for widescale screening, non-invasive tests (NITs) for assessment of steatosis and fibrosis stage, including serum-based algorithms and ultrasound- and magnetic resonance-based methods, will play an increasing role in the management of NAFLD patients. This comprehensive review presents the advantages and limitations of NITs for identification of steatosis and advanced fibrosis in NAFLD. The clinical implications of using NITs to identify and manage NAFLD patients are also discussed.
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Affiliation(s)
- Stergios Kechagias
- Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden.
- Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden.
| | - Mattias Ekstedt
- Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden
- Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden
| | - Christian Simonsson
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
| | - Patrik Nasr
- Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden
- Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden
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16
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Satellite cell content and muscle regeneration in a mouse model of NAFLD. Nutrition 2022; 96:111570. [DOI: 10.1016/j.nut.2021.111570] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 11/01/2021] [Accepted: 12/05/2021] [Indexed: 12/20/2022]
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17
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Kalhori A, Rafraf M, Navekar R, Ghaffari A, Jafarabadi MA. Effect of Turmeric Supplementation on Blood Pressure and Serum Levels of Sirtuin 1 and Adiponectin in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial. Prev Nutr Food Sci 2022; 27:37-44. [PMID: 35465117 PMCID: PMC9007706 DOI: 10.3746/pnf.2022.27.1.37] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 11/14/2021] [Accepted: 12/15/2021] [Indexed: 11/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is commonly associated with obesity. This randomized, double-blind, placebo-controlled trial aimed to evaluate the effects of turmeric on serum adiponectin and sirtuin 1 (SIRT1) levels, blood pressure, and body mass index (BMI) in patients with NAFLD. A total of 46 eligible patients with NAFLD (BMI, 25.0∼39.9 kg/m2) were randomly allocated to turmeric and placebo groups using block randomization. The turmeric group (n=23) was administered 3,000 mg/d turmeric powder in six 500-mg capsules for 12 weeks, whereas the placebo group (n=23) was administered six placebo capsules/d for 12 weeks. Body weight, BMI, serum SIRT1 and adiponectin levels, and systolic and diastolic blood pressures were measured at baseline and 12 weeks after intervention. Serum SIRT1 levels increased significantly in the turmeric group compared with the placebo group. Additionally, participants in the turmeric group exhibited lower weight, BMI, and systolic blood pressure after 12 weeks of intervention compared with the baseline. Turmeric effectively improved SIRT1 levels in patients with NAFLD compared with the placebo. The efficacy of turmeric might increase with long-term use at higher doses.
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Affiliation(s)
- Ali Kalhori
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran 1477893855, Iran
| | - Maryam Rafraf
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz 51666-14711, Iran
| | - Roya Navekar
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz 51666-14711, Iran
| | - Aida Ghaffari
- Department of Nutrition Science, Islamic Azad University-Sarab Branch, Sarab, Iran
| | - Mohammad Asghari Jafarabadi
- Department of Statistics and Epidemiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan 4513956111, Iran
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18
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Xie R, Liu M. Relationship Between Non-Alcoholic Fatty Liver Disease and Degree of Hepatic Steatosis and Bone Mineral Density. Front Endocrinol (Lausanne) 2022; 13:857110. [PMID: 35360054 PMCID: PMC8964007 DOI: 10.3389/fendo.2022.857110] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 02/22/2022] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The liver and bones are both active endocrine organs that carry out several metabolic functions. However, the link between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) is still controversial. The goal of this study was to discover if there was a link between non-alcoholic fatty liver disease and bone mineral density in US persons aged 20 to 59 years of different genders and races. METHODS Using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, multivariate logistic regression models were utilized to investigate the association between NAFLD and lumbar BMD. Fitted smoothing curves and generalized additive models were also used. RESULTS The analysis included a total of 1980 adults. After controlling for various variables, we discovered that NAFLD was negatively linked with lumbar BMD. The favorable connection of NAFLD with lumbar BMD was maintained in subgroup analyses stratified by sex, race and age in men, other race and aged 20-29 years. The relationship between NAFLD and lumbar BMD in blacks and people aged 40-49 years was a U-shaped curve with the inflection point: at 236dB/m and 262dB/m. Furthermore, we discovered that liver advanced fibrosis and liver cirrhosis were independently connected with higher BMD, while no significant differences were detected in severe liver steatosis and BMD. CONCLUSIONS Our study found an independently unfavorable relationship between NAFLD and BMD in persons aged 20 to 59. We also discovered a positive link between BMD and advanced fibrosis and cirrhosis. More research is needed to back up the findings of this study and to look into the underlying issues.
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Affiliation(s)
| | - Mingjiang Liu
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
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19
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Stevanović-Silva J, Beleza J, Coxito P, Costa RC, Ascensão A, Magalhães J. Fit mothers for a healthy future: Breaking the intergenerational cycle of non-alcoholic fatty liver disease with maternal exercise. Eur J Clin Invest 2022; 52:e13596. [PMID: 34120338 DOI: 10.1111/eci.13596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/01/2021] [Accepted: 05/06/2021] [Indexed: 12/20/2022]
Abstract
UNLABELLED SPECIAL ISSUE: 'FOIEGRAS-Bioenergetic Remodelling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease'. BACKGROUND Non-alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non-pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases. METHODS Following detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed. RESULTS PE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles-metabolic, endocrine and epigenetic-could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances. CONCLUSIONS The better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.
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Affiliation(s)
- Jelena Stevanović-Silva
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - Jorge Beleza
- Department of Cell Biology, Physiology & Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain
| | - Pedro Coxito
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - Rui Carlos Costa
- Department of Communication and Art, Research Institute for Design, Media and Culture (ID+), Aveiro University, Aveiro, Portugal
| | - António Ascensão
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
| | - José Magalhães
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal
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20
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Othman N, Gheith O, Al-Otaibi T, Said T, Halim MA, Elserwy N, Nagib AM, Mahmoud F, Abduo H, Jahromi M. Effect of Structured Diabetes Education on Diabetic Angiopathies Among Kidney Transplant Recipients With Posttransplant Diabetes: Kuwait Experience. EXP CLIN TRANSPLANT 2022; 20:46-54. [PMID: 35384807 DOI: 10.6002/ect.mesot2021.o19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Diabetes knowledge among kidney transplant recipients with posttransplant diabetes has not been exhaustively assessed. Here, we evaluated the effects of structured diabetes education on development of diabetic micro- and macroangiopathies in kidney transplant patients with posttransplant diabetes. MATERIALS AND METHODS This prospective randomized controlled study categorized 210 renal transplant patients with posttransplant diabetes mellitus into 2:1 groups according to type of diabetes education. Group 1 (n = 140) received structured education, and group 2 (n = 70) received conventional education. Patient data were collected through patient identification and metabolic control parameter forms. RESULTS Most patients in groups 1 and 2, respectively, were Kuwaiti (60.7% vs 58.6%), men (57.9% vs 68.6%), and had high school-level education (43.6% vs 48.6%). Chronic glomerulonephritis was the original disease in 36.4% versus 35.4% of patients. Most patients (72.8% vs 78.6% in group 1 vs 2) received pretransplant hemodialysis. At study start, the rate of patients with diabetic neuropathy was comparable between groups (32.4% vs 27.9%). Moreover, after completion of 24 months of education, neurological evaluation by electromyograph and nerve conduction studies did not show any significant differences between the groups (P > .05). Similarly, the number of patients with fundus imaging showing retinopathy was comparable between groups at start and end of study (P > .05). Although macroangiopathic events were higher in group 1, this finding was not significant (P > .05). However, although the percentage of patients with nephropathy was comparable in both groups at start of study, the percentage decreased significantly in group 1 at 24 months after completion of education compared with group 2 and baseline value (P = .016). CONCLUSIONS Structured diabetes education was associated with reduced diabetic nephropathy but had no significant effects on other micro- or macroangiopathies. However, we recommend education for all kidney transplant recipients with diabetes.
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Affiliation(s)
- Nashwa Othman
- From the Faculty of Nursing, Mansoura University, Mansoura, Egypt
- From the Dasman Diabetes Institute, Kuwait City, Kuwait
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Abstract
PURPOSE OF REVIEW Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity and has wide ranging extrahepatic manifestations, including through cardiometabolic pathways. As such, there is growing interest in the impact of NAFLD on cerebrovascular disease and brain health more broadly. In this review, we assess recent research into understanding the association between NAFLD and brain health while highlighting potential clinical implications. RECENT FINDINGS Mechanistically, NAFLD is characterized by both a proinflammatory and proatherogenic state, which results in vascular inflammation and neurodegeneration, potentially leading to clinical and subclinical cerebrovascular disease. Mounting epidemiological evidence suggests an association between NAFLD and an increased risk and severity of stroke, independent of other vascular risk factors. Studies also implicate NAFLD in subclinical cerebrovascular disease, such as carotid atherosclerosis and microvascular disease. In contrast, there does not appear to be an independent association between NAFLD and cognitive impairment. SUMMARY The current literature supports the formulation of NAFLD as a multisystem disease that may also have implications for cerebrovascular disease and brain health. Further prospective studies are needed to better assess a temporal relationship between the two diseases, confirm these early findings, and decipher mechanistic links.
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Affiliation(s)
- Sahil Khanna
- Division of Gastroenterology & Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine
| | - Neal S. Parikh
- Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine
| | - Lisa B. VanWagner
- Division of Gastroenterology & Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
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Bellinato F, Goio I, Malara G, Rosato A, Targher G, Girolomoni G, Gisondi P. Non-Alcoholic Fatty Liver Disease Is Associated With Reduced Glomerular Filtration Rate in Patients With Chronic Plaque Psoriasis. J Cutan Med Surg 2021; 26:249-255. [PMID: 34894782 DOI: 10.1177/12034754211066906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Chronic plaque psoriasis has been associated with metabolic comorbidities, including non-alcoholic fatty liver disease (NAFLD). A causal relationship between NAFLD and chronic kidney disease (CKD) is debated. OBJECTIVES To assess whether NAFLD is associated with impaired renal function in patients with psoriasis. METHODS A multicenter, retrospective, observational study including 337 patients with moderate-to-severe chronic plaque psoriasis, who had no history of excessive alcohol consumption or other secondary causes of chronic liver and renal diseases was conducted. NAFLD was diagnosed by ultrasonography, and CKD stage ≥2 or stage ≥3 were defined by an estimated glomerular filtration rate (e-GFR) of <90 ml min-1 1.73 m-2 or <60 ml min-1 1.73 m-2, respectively. Logistic and linear regression analyses were undertaken to assess the independent association of NAFLD with CKD or eGFR levels. RESULTS Patients with NAFLD (n = 212, 62.9% of total) had significantly lower e-GFR levels (83.4 ± 18.0 vs. 93.5 ± 15.8 ml min-1 1.73 m-2, P<.001) and a remarkably higher prevalence of both CKD stage ≥2 (56.1% vs. 30.4%, P<.0001) and CKD stage ≥3 (10.4% vs. 3.2%, P<.0001) compared with their counterparts without NAFLD. Multivariable logistic regression analysis showed that NAFLD was associated with a nearly 2.5-fold increased risk of prevalent CKD stage ≥2 (adjusted-odds ratio= 2.60 95% confidence intervals 1.4-4.8, P=.02), independently of components of metabolic syndrome, psoriasis severity, and psoriatic arthritis. CONCLUSIONS Ultrasound-diagnosed NAFLD is strongly associated with a reduced eGFR in patients with moderate-to-severe psoriasis, independently of cardiometabolic risk factors and psoriasis-related variables.
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Affiliation(s)
- Francesco Bellinato
- 19051 Section of Dermatology and Venereology, Department of Medicine, University of Verona, Italy
| | - Isotta Goio
- 19051 Section of Dermatology and Venereology, Department of Medicine, University of Verona, Italy
| | - Giovanna Malara
- 18647 Department of Dermatology, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Alessio Rosato
- Internal Medicine Department, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Italy
| | - Giampiero Girolomoni
- 19051 Section of Dermatology and Venereology, Department of Medicine, University of Verona, Italy
| | - Paolo Gisondi
- 19051 Section of Dermatology and Venereology, Department of Medicine, University of Verona, Italy
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Dhaliwal HS, Singh R, Abraham AM, Sharma R, Goyal NK, Soloman R, Bansal P, Goyal A. Perception of Illness and Its Association with Treatment Willingness in Patients with Newly Diagnosed Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2021; 66:4197-4207. [PMID: 33409801 DOI: 10.1007/s10620-020-06794-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 12/14/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease of immense public health relevance. Understanding illness perceptions in the NAFLD population will provide sound scientific evidence for planning high-quality patient-centered care and implementing effective interventions. The Brief Illness Perception Questionnaire (BIPQ) is a robust psychometric tool to systematically assess the dimensions of illness perceptions in various chronic ailments. METHODS In a cross-sectional study enrolling patients with newly diagnosed NAFLD, the sociodemographic, anthropometric, biochemical, and radiological determinants of enhanced illness perceptions (measured by the BIPQ score) were investigated using univariate and multivariable binary logistic regression analyses. Finally, the association between individual domains of the BIPQ and willingness to participate in comprehensive medical management was explored. RESULTS In total, 264 patients (mean age 53 ± 11.9 years, 59.8% males) were enrolled in the final analysis. The mean and median BIPQ scores in the study population were 30.3 ± 12.8 and 31.0 (IQR, 22.0-40.0), respectively. The variables having a significant independent association with heightened perceptions (BIPQ > 31) were family history of liver disease (aOR, 5.93; 95% CI, 1.42-24.74), obesity (aOR, 3.33; 95% CI, 1.57-7.05), diabetes mellitus (aOR, 2.35; 95% CI, 1.01-5.49), and transaminitis (aOR, 2.85; 95% CI, 1.42-5.69). Patients with a higher level of illness perceptions (31.6 ± 12.9 vs 27.8 ± 12.3, p = 0.022) were more likely to express a willingness to participate in the comprehensive management plan, with 3 of the 8 domains (consequence, identity, and treatment control) mainly affecting willingness. CONCLUSION A family history of liver disease, obesity, diabetes, and transaminitis were independently associated with increased illness perceptions. A belief in serious consequences, a strong illness identity, and higher perceived treatment control were significantly associated with the willingness to undergo comprehensive care for NAFLD.
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Affiliation(s)
- Harpal S Dhaliwal
- Department of Gastroenterology, GTBS (C) Hospital, Ludhiana, Punjab, 141002, India.
| | - Ripudaman Singh
- Department of Gastroenterology, GTBS (C) Hospital, Ludhiana, Punjab, 141002, India
| | - Abin M Abraham
- Department of Internal Medicine, Christian Medical College and Hospital, Ludhiana, Punjab, India
| | - Rajan Sharma
- Department of Internal Medicine, GTBS (C) Hospital, Ludhiana, Punjab, India
| | - N K Goyal
- Department of Psychiatry, GTBS (C) Hospital, Ludhiana, Punjab, India
| | - Rajat Soloman
- Department of Psychiatry, Government Medical College, Rajnandgaon, Chhattisgarh, India
| | - Pankaj Bansal
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic School of Medicine and Science, Eau Claire, WI, 54702, USA
| | - Amandeep Goyal
- Department of Internal Medicine, Marietta Memorial Hospital, Marietta, OH, 45750, USA
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Pădureanu V, Dop D, Drăgoescu AN, Pădureanu R, Mușetescu AE, Nedelcu L. Non-alcoholic fatty liver disease and hematologic manifestations (Review). Exp Ther Med 2021; 22:1355. [PMID: 34659501 PMCID: PMC8515549 DOI: 10.3892/etm.2021.10790] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/16/2021] [Indexed: 11/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, and it is associated with numerous extra-hepatic manifestations or additional co-occurring diseases. The aim of the present review was the identification and management of the hematologic manifestations of NAFLD. One of the triggers is considered to be iron abnormalities. Increased ferritin levels, hepatic iron deposits and iron overload are associated with NAFLD. The iron overload degree and severity are associated with the level of liver fibrosis and with the risk for hepatocellular carcinoma. Excess iron deposits refers to the dysmetabolic iron overload syndrome (DIOS) and it is characterized by steatosis associated with moderate tissue iron deposition and increased levels of serum ferritin, while the serum transferrin saturation was normal. Further prospective studies are necessary to determine whether NAFLD has an independent risk for hematologic symptoms, besides the known risk factors. Future studies are also needed in order to assess the increasing impact of NAFLD on the micro- and macro-vascular complications of this systemic disease.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dalia Dop
- Department of Pediatrics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Alice Nicoleta Drăgoescu
- Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, Emergency Clinical County Hospital of Craiova, 200642 Craiova, Romania
| | - Anca Emanuela Mușetescu
- Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Laurențiu Nedelcu
- Department of Internal Medicine, Faculty of Medicine, Transylvania University Brasov, 500019 Brașov, Romania
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Pan B, Yan J, Zhao P, Liu J, Fu S. Relationship between nonalcoholic fatty liver disease and bone mineral density in type 2 diabetic patients. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-01022-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Gaber Y, AbdAllah M, Salama A, Sayed M, Abdel Alem S, Nafady S. Metabolic-associated fatty liver disease and autoimmune hepatitis: an overlooked interaction. Expert Rev Gastroenterol Hepatol 2021; 15:1181-1189. [PMID: 34263707 DOI: 10.1080/17474124.2021.1952867] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Metabolic-associated fatty liver disease (MAFLD) is the most common liver disease globally, and affects about a quarter of the general population. Autoimmune hepatitis (AIH) is a severe (sometimes fatal) liver disease that affects children and adults, with a rising prevalence. Thus, not surprisingly, both conditions can frequently coexist, with potential synergistic impact on the course of the disease and response to therapy of both entities. AREAS COVERED In this work, the authors aimed to provide a narrative updated review on this interaction, diagnosis, and management of MAFLD/AIH and the current challenges. EXPERT OPINION Clarifying the nature of the complex interaction between the two diseases was hampered by a myriad of factors, particularly the previous diagnosis of exclusion for fatty liver disease associated with metabolic dysfunction. The recent redefinition of fatty liver disease that led to the development of positive diagnostic criteria for MAFLD has the premise to help in circumventing some of these challenges.
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Affiliation(s)
- Yasmine Gaber
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Center, Giza, Egypt
| | - Asmaa Salama
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-suef, Egypt
| | - Manar Sayed
- Tropical Medicine Department, Faculty of Medicine, Fayoum University, Al Fayoum, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Shaymaa Nafady
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-suef, Egypt
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Hsu CS, Kao JH. Management of non-alcoholic fatty liver disease in patients with sarcopenia. Expert Opin Pharmacother 2021; 23:221-233. [PMID: 34541964 DOI: 10.1080/14656566.2021.1978978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Sarcopenia usually occurs with aging, sedentary lifestyle, unhealthy dietary habits, and chronic disorders pathophysiologically and bi-directionally linked to obesity and nonalcoholic fatty liver disease (NAFLD). Because of the global increase in aging and obesity populations, patients with concomitant sarcopenia and NAFLD are common, accompanied by various disorders relevant to obesity and sarcopenia, with across-the-board impact on socio-economic and public health life worldwide. Therefore, developing effective and practical management of these patients has become a pressing clinical issue. AREAS COVERED The authors searched literature from PubMed and Ovid MEDLINE up until Feb 2020. Emerging data on the management of sarcopenia and nonalcoholic fatty liver disease were examined and discussed. EXPERT OPINION Although NAFLD in patients with sarcopenia has become a critical problem worldwide, we still don't know much about the management of such patients. Based on theoretical speculations, we can recommend lifestyle intervention, including diet control with adequate protein intake, exercise intervention, and weight reduction as the mainstay of management at the first stage. More studies are needed in the future to identify the most suitable treatment and solve this important problem.
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Affiliation(s)
- Ching-Sheng Hsu
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.,School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Taiwan, Hualien, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
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28
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Zhang S, Gan S, Zhang Q, Liu L, Meng G, Yao Z, Wu H, Gu Y, Wang Y, Zhang T, Wang X, Sun S, Wang X, Zhou M, Jia Q, Song K, Qi L, Niu K. Ultra-processed food consumption and the risk of non-alcoholic fatty liver disease in the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. Int J Epidemiol 2021; 51:237-249. [PMID: 34528679 DOI: 10.1093/ije/dyab174] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 08/01/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Growing evidence supports a link between ultra-processed food consumption and human health outcomes. However, the association between ultra-processed food consumption and non-alcoholic fatty liver disease (NAFLD) is not known. We aimed to explore the association between ultra-processed food consumption and risk of NAFLD. METHODS The prospective study included 16 168 participants aged 18-90 years from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study. Information on ultra-processed food consumption was collected at baseline using a validated food frequency questionnaire. NAFLD was defined as the presence of sonographic fatty liver in the absence of significant alcohol intake (≥210 g/week for men and ≥140 g/week for women, respectively) and other liver diseases. Multivariable Cox proportional hazards models were used to examine the association between ultra-processed food consumption and risk of NAFLD. RESULTS During 56 935 person-years of follow-up, we documented 3752 incident NAFLD cases. After adjusting for age, sex, body mass index, smoking, alcohol drinking, education, occupation, income, physical activity, total energy intake, personal and family history of disease and overall diet quality, the multivariable hazard ratios (95% confidence interval) of NAFLD across increasing quartiles of ultra-processed food consumption were 1.00 (reference), 0.99 (0.90, 1.08), 1.13 (1.03, 1.25) and 1.18 (1.07, 1.30), respectively (P for trend <0.0001). The hazard ratio (95% confidence interval) per one standard deviation increase in ultra-processed food consumption, equivalent to a 62.7 g/1000 kcal per day, was 1.06 (1.03, 1.09), P = 0.0001. CONCLUSIONS Our study indicates that higher ultra-processed food consumption is associated with a higher risk of NAFLD. This finding suggests that ultra-processed food, which is widely consumed worldwide, might be a modifiable dietary target to reduce the risk of NAFLD.
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Affiliation(s)
- Shunming Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shinan Gan
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qing Zhang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Zhanxin Yao
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Institute of Environmental & Operational Medicine, Tianjin, China
| | - Hongmei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yeqing Gu
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Yawen Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Tingjing Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xuena Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shaomei Sun
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Xing Wang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiyu Jia
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Kun Song
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kaijun Niu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China.,Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China.,Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China
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29
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Zhang S, Meng G, Zhang Q, Liu L, Yao Z, Wu H, Gu Y, Wang Y, Zhang T, Wang X, Zhang J, Sun S, Wang X, Zhou M, Jia Q, Song K, Wang Y, Qi L, Niu K. Consumption of Preserved Egg Is Associated with Modestly Increased Risk of Nonalcoholic Fatty Liver Disease in Chinese Adults. J Nutr 2021; 151:2741-2748. [PMID: 34049388 DOI: 10.1093/jn/nxab163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/12/2021] [Accepted: 04/29/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Although preserved egg is a traditional Chinese delicacy widely consumed in China and Southeast Asian countries, whether habitual preserved egg consumption is associated with nonalcoholic fatty liver disease (NAFLD) remains unknown. OBJECTIVES This study aimed to examine the association between preserved egg consumption and risk of NAFLD in a cohort of Chinese adults. METHODS This prospective cohort study included 15,883 participants aged 19-88 y (58% women) from the TCLSIH (Tianjin Chronic Low-grade Systemic Inflammation and Health) cohort study who were free of liver diseases, cancer, and cardiovascular disease at baseline. Preserved egg consumption was assessed using an FFQ at baseline. NAFLD was diagnosed by transabdominal sonography during an annual health examination. Multivariable Cox proportional hazards regression models were used to calculate HRs and 95% CIs across categories of preserved egg consumption. RESULTS During 56,002 person-years of follow-up, 3683 first incident cases of NAFLD were recorded. After adjustment for sociodemographic characteristics, lifestyle risk factors, total energy intake, egg intake, and eating patterns, the multivariable HRs (95% CIs) of incident NAFLD according to categories of preserved egg consumption were 1.00 (reference) for never, 1.05 (0.98, 1.14) for <1 time/wk, 1.09 (0.96, 1.24) for 1 time/wk, and 1.26 (1.09, 1.46) for ≥2 times/wk (P-trend < 0.01). The results were robust to a series of sensitivity analyses. CONCLUSIONS Habitual preserved egg consumption is associated with a modestly higher risk of NAFLD among the Chinese adult population. The mechanism underlying this association warrants further research.This trial was registered at www.umin.ac.jp/ctr/ as UMIN000027174.
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Affiliation(s)
- Shunming Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qing Zhang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhanxin Yao
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Institute of Environmental & Operational Medicine, Tianjin, China
| | - Hongmei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yeqing Gu
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Yawen Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Tingjing Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xuena Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Juanjuan Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shaomei Sun
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Xing Wang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiyu Jia
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Kun Song
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Yaogang Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kaijun Niu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China.,Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China
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The most appropriate region-of-interest position for attenuation coefficient measurement in the evaluation of liver steatosis. J Med Ultrason (2001) 2021; 48:615-621. [PMID: 34453648 DOI: 10.1007/s10396-021-01124-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 07/15/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE Attenuation imaging (ATI) is a new noninvasive ultrasound technique for assessing steatosis grade (S). However, validated region-of-interest (ROI) sampling strategies are not currently available. We investigated the diagnostic performance of various ATI-ROI positions for determining histopathologic S in patients with nonalcoholic fatty liver disease (NAFLD). METHODS This retrospective study included 105 patients with biopsy-proven NAFLD. All attenuation coefficient (AC, dB/cm/MHz) measurements were obtained by the same hepatologist using a commercially available ultrasound system on the same day as liver biopsy. Mean (± standard deviation) age and body mass index of the patients were 53 (± 18) years and 27.1 (± 4.1) kg/m2, respectively. The numbers of patients with steatosis affecting < 5%, 5-33%, 33-66%, and > 66% of hepatocytes were 8, 50, 29, and 18, respectively. The ATI-ROI was placed at three different positions for AC measurement using a dedicated workstation: the upper edge of the area ROI, twice the depth of the liver capsule, and the lower edge of the area ROI. Diagnostic performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS The AUCs of AC at the three ATI-ROI positions were 0.734 (95% confidence interval [CI]: 0.470-0.998), 0.750 (0.639-0.861), and 0.878 (0.788-0.968) for S ≥ 1; 0.503 (0.392-0.615), 0.824 (0.741-0.907), and 0.809 (0.724-0.895) for S ≥ 2; and 0.606 (0.486-0.726), 0.849 (0.767-0.932), and 0.737 (0.626-0.848) for S = 3, respectively. CONCLUSION For accurate steatosis grade assessment, the ATI-ROI should not be placed at the upper edge of the area ROI.
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Bariatric Surgery and Liver Disease: General Considerations and Role of the Gut-Liver Axis. Nutrients 2021; 13:nu13082649. [PMID: 34444807 PMCID: PMC8399840 DOI: 10.3390/nu13082649] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 07/23/2021] [Accepted: 07/27/2021] [Indexed: 02/07/2023] Open
Abstract
Weight loss is a therapeutic solution for many metabolic disorders, such as obesity and its complications. Bariatric surgery aims to achieve lasting weight loss in all patients who have failed after multiple dietary attempts. Among its many benefits, it has been associated with the regression of non-alcoholic fatty liver disease (NAFLD), which is often associated with obesity, with evidence of substantial improvement in tissue inflammation and fibrosis. These benefits are mediated not only by weight loss, but also by favorable changes in systemic inflammation and in the composition of the gut microbiota. Changes in microbial metabolites such as short-chain fatty acids (SCFAs), capable of acting as endocrine mediators, and bile acids (BAs) as well as modifications of the gut-brain axis, are among the involved mechanisms. However, not all bariatric surgeries show beneficial effects on the liver; those leading to malabsorption can cause liver failure or a marked worsening of fibrosis and the development of cirrhosis. Nevertheless, there are still many unclear aspects, including the extent of the benefits and the magnitude of the risks of bariatric surgery in cirrhotic patients. In addition, the usefulness and the safety of these procedures in patients who are candidates to or who have undergone liver transplant need solid supporting evidence. This paper aims to review literature data on the use of bariatric surgery in the setting of chronic liver disease.
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Reja M, Patel R, Pioppo L, Tawadros A, Bhurwal A, Marino D, Rustgi V. Renal Failure is Associated With Increased Mortality and Hospital Utilization in Patients Admitted With Nonalcoholic Steatohepatitis. J Clin Gastroenterol 2021; 55:433-438. [PMID: 32740097 DOI: 10.1097/mcg.0000000000001389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 06/04/2020] [Indexed: 12/13/2022]
Abstract
GOALS We aimed to investigate the mortality and hospital utilization outcomes of hospitalized nonalcoholic steatohepatitis (NASH) patients with and without kidney failure in a nationwide cohort. BACKGROUND NASH is a common medical condition associated with significant morbidity and mortality. A paucity of data exists regarding the impact of kidney failure (defined as acute and chronic kidney failure) on outcomes of NASH hospitalizations. MATERIALS AND METHODS We conducted a retrospective cohort study using the 2016 Nationwide Inpatient Sample dataset of adult patients hospitalized for NASH, stratified for the presence of renal failure. The primary outcome was inpatient mortality, predictors were analyzed using multivariate logistic regression. Secondary outcomes were the length of stay and mean total hospitalization charges. RESULTS The overall sample included 7,135,090 patients. Among 6855 patients admitted for NASH, 598 or 8.7% had comorbid kidney failure. After multivariate regression analysis, NASH patients with renal failure had increased in-hospital mortality [odds ratio=28.72, 95% confidence interval (CI): 8.99-91.73], length of stay (β=3.02, 95% CI: 2.54-3.5), total hospital charges (β=$37,045, 95% CI: $31,756.18-$42,335.62). Positive predictors of mortality in the renal failure group were Charlson Comorbidity Index ≥3 [adjusted odds ratio (aOR)=3.46, 95% CI: 1.04-11.51], variceal bleeding (aOR=3.02, 95% CI: 1.06-8.61), and hepatic encephalopathy (aOR=26.38, 95% CI: 1.29-540.56). Predictors of decreased mortality were Medicaid (aOR=0.047, 95% CI: 0.28-0.79) and private insurance (aOR=0.56, 95% CI: 0.38-0.83). CONCLUSIONS The prevalence of renal failure in NASH hospitalizations is associated with markedly increased mortality, hospital costs, and length of stay. As a result, clinicians should be vigilant in treating kidney failure in this population.
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Affiliation(s)
| | | | | | | | | | - Daniel Marino
- Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Vinod Rustgi
- Center for Liver Diseases and Masses, Rutgers Robert Wood Johnson Medical School
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Gil-Gómez A, Brescia P, Rescigno M, Romero-Gómez M. Gut-Liver Axis in Nonalcoholic Fatty Liver Disease: the Impact of the Metagenome, End Products, and the Epithelial and Vascular Barriers. Semin Liver Dis 2021; 41:191-205. [PMID: 34107545 DOI: 10.1055/s-0041-1723752] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a systemic, dynamic, heterogeneous, and multiaxis entity, the pathogenesis of which is still uncertain. The gut-liver axis is regulated and stabilized by a complex network encompassing a metabolic, immune, and neuroendocrine cross-talk between the gut, the microbiota, and the liver. Changes in the gut-liver axis affect the metabolism of lipids and carbohydrates in the hepatocytes, and they impact the balance of inflammatory mediators and cause metabolic deregulation, promoting NAFLD and its progression to nonalcoholic steatohepatitis. Moreover, the microbiota and its metabolites can play direct and indirect roles in gut barrier function and fibrosis development. In this review, we will highlight findings from the recent literature focusing on the gut-liver axis and its relation to NAFLD. Finally, we will discuss the impact of technical issues, design bias, and other limitations on current knowledge of the gut microbiota in the context of NAFLD.
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Affiliation(s)
- Antonio Gil-Gómez
- SeLiver Group at Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, Seville, Spain.,Hepatic and Digestive Diseases Networking Biomedical Research Centre (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Paola Brescia
- Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy
| | - Maria Rescigno
- Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy
| | - Manuel Romero-Gómez
- SeLiver Group at Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, Seville, Spain.,Hepatic and Digestive Diseases Networking Biomedical Research Centre (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.,UCM Digestive Diseases, Virgen del Rocío University Hospital, Seville, Spain
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Kontrick AV, VanWagner LB, Yeh C, Courtney DM. Hepatic Steatosis: An Incidental Finding That Deserves Attention. Acad Emerg Med 2021; 28:578-581. [PMID: 33210438 DOI: 10.1111/acem.14174] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 11/05/2020] [Accepted: 11/13/2020] [Indexed: 12/24/2022]
Affiliation(s)
- Amy V. Kontrick
- From the Department of Emergency Medicine and Medical Education Northwestern University Feinberg School of Medicine Chicago ILUSA
| | - Lisa B. VanWagner
- the Department of Medicine‐Gastroenterology & Hepatology and Preventive Medicine‐Epidemiology Northwestern University Feinberg School of Medicine Chicago ILUSA
| | - Chen Yeh
- and the Division of Biostatistics Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago ILUSA
| | - D. Mark Courtney
- and the Department of Emergency Medicine UT Southwestern Medical Center Dallas TXUSA
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Sbeit W, Greener T, Kadah A, Mari A, Goldin E, Khoury T, Mahamid M. Pancreatobiliary manifestations of nonalcoholic fatty liver disease: a retrospective case-control multicenter study. Eur J Gastroenterol Hepatol 2021; 33:722-726. [PMID: 32483086 DOI: 10.1097/meg.0000000000001780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease. Several extrahepatic manifestations have been reported in relation to NAFLD. However, data regarding pancreatobiliary manifestation are scarce. AIM We aimed to explore the association of pancreatobiliary manifestation with NAFLD. METHODS A retrospective multicenter study that included all patients who underwent an endoscopic ultrasound performed for hepatobiliary indications and for whom the endosonographer reported on the presence or absence of fatty liver. The endoscopic ultrasound reports were reviewed and all pathological findings were reported. RESULTS Overall, 545 patients were included in the study, among them, 278 patients had fatty liver (group A) as compared to 267 who did not have (group B). The average age in group A was 64.5 ± 13.5 years vs. 61.2 ± 14.7 years in group B. Male sex constituted 49.6 and 58% in groups A and B, respectively. On multivariate analysis, fatty pancreas [odds ratio (OR) 4.02; P = 0.001], serous cystadenoma (SCA) (OR 5.1; P = 0.0009), mucinous cystadenoma (MCA) (OR 9.7; P = 0.005), side-branch intraductal papillary mucinous neoplasm (IPMN) (OR 2.76; P < 0.0001), mixed-type IPMN (OR 16.4; P = 0.0004), pancreatic neuroendocrine tumor (NET) (OR 8.76; P < 0.0001), gallbladder stones (OR 1.9; P = 0.02) and hilar lymphadenopathy (OR 6.8; P < 0.0001) were significantly higher among patients with NAFLD. After adjustment for fatty pancreas, the association remained significant for SCA (OR 3; P = 0.01), MCA (OR 4.6; P = 0.03), side-branch IPMN (OR 1.7; P = 0.02), mixed-type IPMN (OR 5.5; P = 0.01) and pancreatic NET (OR 4.5; P = 0.001). CONCLUSION Pancreatobiliary manifestations are common among patients with NAFLD. Assessment of these coexistent manifestations should be considered in the setting of patients with NAFLD.
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Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed
| | - Tomer Greener
- Gastroenterology Department, Shaare Zedek Medical Center, Jerusalem
| | - Anas Kadah
- Department of Gastroenterology, Galilee Medical Center, Nahariya
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed
| | - Amir Mari
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed
- Gastroenterology and Endoscopy Units, The Nazareth Hospital, EMMS, Nazareth, Israel
| | - Eran Goldin
- Gastroenterology Department, Shaare Zedek Medical Center, Jerusalem
| | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed
| | - Mahmud Mahamid
- Gastroenterology Department, Shaare Zedek Medical Center, Jerusalem
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Wijarnpreecha K, Aby ES, Ahmed A, Kim D. Evaluation and management of extrahepatic manifestations of nonalcoholic fatty liver disease. Clin Mol Hepatol 2021; 27:221-235. [PMID: 33317243 PMCID: PMC8046623 DOI: 10.3350/cmh.2020.0239] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/23/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease and a rapidly growing cause of chronic liver disease in children and adults worldwide. Diagnosis and management of extrahepatic manifestations of NAFLD, including cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, obstructive sleep apnea, polycystic ovarian syndrome, hypothyroidism, psoriasis, and extrahepatic malignancy are crucial for the treatment of patients with NAFLD. The leading cause of death in NAFLD is primarily from CVD, followed by liver-related mortality, extrahepatic cancer, liver cancer, and diabetes-related mortality. Therefore, clinicians need to identify high-risk patients earlier in the disease course and be aware of the extrahepatic manifestations of NAFLD to improve liver disease outcomes. In this review, we focus on the monitoring and management of the extrahepatic manifestations of NAFLD.
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Affiliation(s)
- Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Jacksonville, FL, USA
| | - Elizabeth S. Aby
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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Lactobacillus acidophilus LA5 improves saturated fat-induced obesity mouse model through the enhanced intestinal Akkermansia muciniphila. Sci Rep 2021; 11:6367. [PMID: 33737543 PMCID: PMC7973717 DOI: 10.1038/s41598-021-85449-2] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 02/23/2021] [Indexed: 12/18/2022] Open
Abstract
Obesity, a major healthcare problem worldwide, induces metabolic endotoxemia through the gut translocation of lipopolysaccharides (LPS), a major cell wall component of Gram-negative bacteria, causing a chronic inflammatory state. A combination of several probiotics including Lactobacillus acidophilus 5 (LA5), a potent lactic acid-producing bacterium, has previously been shown to attenuate obesity. However, data on the correlation between a single administration of LA5 versus microbiota alteration might be helpful for the probiotic adjustment. LA5 was administered daily together with a high-fat diet (HFD) for 8 weeks in mice. Furthermore, the condition media of LA5 was also tested in a hepatocyte cell-line (HepG2 cells). Accordingly, LA5 attenuated obesity in mice as demonstrated by weight reduction, regional fat accumulation, lipidemia, liver injury (liver weight, lipid compositions, and liver enzyme), gut permeability defect, endotoxemia, and serum cytokines. Unsurprisingly, LA5 improved these parameters and acidified fecal pH leads to the attenuation of fecal dysbiosis. The fecal microbiome analysis in obese mice with or without LA5 indicated; (i) decreased Bacteroidetes (Gram-negative anaerobes that predominate in non-healthy conditions), (ii) reduced total fecal Gram-negative bacterial burdens (the sources of gut LPS), (iii) enhanced Firmicutes (Gram-positive bacteria with potential benefits) and (iv) increased Verrucomycobia, especially Akkermansia muciniphila, a bacterium with the anti-obesity property. With LA5 administration, A. muciniphila in the colon were more than 2,000 folds higher than the regular diet mice as determined by 16S rRNA. Besides, LA5 produced anti-inflammatory molecules with a similar molecular weight to LPS that reduced cytokine production in LPS-activated HepG2 cells. In conclusion, LA5 attenuated obesity through (i) gut dysbiosis attenuation, partly through the promotion of A. muciniphila (probiotics with the difficulty in preparation processes), (ii) reduced endotoxemia, and (iii) possibly decreased liver injury by producing the anti-inflammatory molecules.
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Shengir M, Chen T, Guadagno E, Ramanakumar AV, Ghali P, Deschenes M, Wong P, Krishnamurthy S, Sebastiani G. Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis. JGH OPEN 2021; 5:434-445. [PMID: 33860093 PMCID: PMC8035436 DOI: 10.1002/jgh3.12512] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 01/30/2021] [Accepted: 02/08/2021] [Indexed: 12/13/2022]
Abstract
Background and Aim Non‐alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta‐analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. Methods Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random‐effect model, and heterogeneity was addressed through I2. Subgroup analyses and meta‐regression for various covariates were performed. Results Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5‐fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20–2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27–5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85–2.67) and Asia (OR 2.63, 95% CI 2.20–3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44–2.71 and OR 3.39, 95% CI 2.42–4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta‐regression, with a regression coefficient of −2.219 (95% CI −3.927 to −0.511) and −1.929 (95% CI −3.776 to −0.0826), respectively. Conclusions This meta‐analysis indicates that premenopausal PCOS patients are associated with 2.5‐fold increase in the risk of NAFLD, and BMI seems to be the main cofactor.
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Affiliation(s)
- Mohamed Shengir
- Division of Experimental Medicine McGill University Montreal Quebec Canada
| | - Tianyan Chen
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | - Elena Guadagno
- Harvey E. Beardmore Division of Pediatric Surgery The Montreal Children's Hospital, McGill University Health Centre Montreal Quebec Canada
| | | | - Peter Ghali
- Department of Medicine University of Florida Jacksonville Florida USA
| | - Marc Deschenes
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | - Philip Wong
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | | | - Giada Sebastiani
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
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Singeap AM, Stanciu C, Huiban L, Muzica CM, Cuciureanu T, Girleanu I, Chiriac S, Zenovia S, Nastasa R, Sfarti C, Cojocariu C, Trifan A. Association between Nonalcoholic Fatty Liver Disease and Endocrinopathies: Clinical Implications. Can J Gastroenterol Hepatol 2021; 2021:6678142. [PMID: 33505943 PMCID: PMC7814954 DOI: 10.1155/2021/6678142] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/31/2020] [Indexed: 02/08/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has a rising prevalence worldwide. Its potential for evolution towards liver cirrhosis and hepatocellular carcinoma, as well as associations with extrahepatic manifestations, represents a double burden for patients and physicians alike. Recently, there has been increasing evidence of the association between NAFLD and a number of endocrinopathies, such as hypothyroidism, polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism, and hypercortisolism. Definite correlations are supported by clear evidence so far, but further studies are needed in order to completely clarify the pathogenic mechanisms and, especially, to identify therapeutic implications. In this review, we present the main relationships between NAFLD and endocrinopathies, emphasizing the reciprocal causality, evolutive interconnections, and current clinical scenarios of presentations of which the clinicians should be aware.
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Affiliation(s)
- Ana-Maria Singeap
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Carol Stanciu
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Laura Huiban
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Cristina Maria Muzica
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Irina Girleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Robert Nastasa
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
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Liu J, Guan L, Zhao M, Li Q, Song A, Gao L, Lin H, Zhao J. Association Between the Triglyceride-Glucose Index and Outcomes of Nonalcoholic Fatty Liver Disease: A Large-Scale Health Management Cohort Study. Diabetes Metab Syndr Obes 2021; 14:2829-2839. [PMID: 34188506 PMCID: PMC8232855 DOI: 10.2147/dmso.s316864] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 05/28/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is increasingly becoming a major health burden. Due to the difficulty of liver biopsy, there is no reliable indicator to evaluate the outcomes of NAFLD. The triglyceride-glucose (TyG) index is a simple and convenient marker of insulin resistance for use in medical practice. Whether the TyG index is predictive of later risk of NAFLD remains unknown. OBJECTIVE To evaluate the relationship between TyG index with NAFLD progression and improvement during a median follow-up period of 21 months. MATERIAL AND METHODS A total of 11,424 subjects (9327 men) diagnosed with NAFLD were included. The TyG index was calculated as follows: ln [fasting triglycerides (mg/dL) * fasting glucose (mg/dL)/2]. Multivariable Cox regression analysis was applied to analyze the data. RESULTS In this study, the severity of NAFLD remained the same in 38.8% of subjects, worsened in 17.4% of subjects, and improved in 43.8% of subjects. Compared with the lowest quartile of the TyG index, the adjusted HR of NAFLD progression in the highest quartile (TyG≥9.34) was 1.448 (1.229 to 1.706), and the adjusted HR of NAFLD improvement was 0.817 (0.723 to 0.923). Subgroup analysis found that smoking increased the correlation between the TyG index and the risk of NAFLD progression, while female, vegan diet, and weight control enhanced the correlation between the TyG index and the risk of NAFLD improvement. CONCLUSION The TyG index may be a simple and helpful indicator for further risk appraisal of NAFLD in daily clinical practice.
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Affiliation(s)
- Jing Liu
- Department of Endocrinology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Shandong Institute of Endocrine and Metabolic Disease, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
| | - Liying Guan
- Health Management Center, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
| | - Meng Zhao
- Department of Endocrinology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Qihang Li
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Shandong Institute of Endocrine and Metabolic Disease, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - An Song
- Peking Union Medical College Hospital, Affiliated to Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China
| | - Ling Gao
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Department of Scientific Center, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Haiyan Lin
- Health Management Center, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
- Correspondence: Haiyan Lin Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jing 5 Road, Jinan, Shandong, 250021, People’s Republic of ChinaTel +86-531-68776123 (Clin.)Fax +86-531-87068707 Email
| | - Jiajun Zhao
- Department of Endocrinology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
- Shandong Clinical Medical Center of Endocrinology and Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China
- Jiajun Zhao Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jing 5 Road, Jinan, Shandong, 250021, People’s Republic of ChinaTel +86-531-68776375 (Clin.); +86-531-68776094 (Lab.)Fax +86-531-87068707 Email
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Cojocariu C, Singeap AM, Girleanu I, Chiriac S, Muzica CM, Sfarti CV, Cuciureanu T, Huiban L, Stanciu C, Trifan A. Nonalcoholic Fatty Liver Disease-Related Chronic Kidney Disease. Can J Gastroenterol Hepatol 2020; 2020:6630296. [PMID: 33457399 PMCID: PMC7785379 DOI: 10.1155/2020/6630296] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/16/2020] [Indexed: 02/08/2023] Open
Abstract
Nonalcoholic fatty liver disease has become the main concern of hepatologists around the world and the main research topic for identifying effective and safe therapy. Advances in the treatment of chronic viral hepatitis in recent years have opened the way towards reducing mortality in patients with chronic liver disease. This goal has not yet been reached, as the burden of chronic liver disease remains a future major health problem as the incidence of the nonalcoholic fatty liver disease continues to rise. The proportion of patients with liver cirrhosis and those with hepatocellular carcinoma due to nonalcoholic liver disease on the liver transplant waiting list has increased in the last years. The upward trend in the incidence and prevalence of the disease in recent decades raises concern over a possible global epidemic, especially as the disease is still underestimated and underdiagnosed. Chronic kidney disease presented an increase in incidence and prevalence during the last years, and it has been associated not only with increased morbidity and mortality but also with high costs for the health system. During the last decade, several studies have shown the association between nonalcoholic fatty disease and chronic kidney disease, two major worldwide health problems.
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Affiliation(s)
- Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Cristina M. Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Catalin Victor Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Carol Stanciu
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, Iasi 700115, Romania
- St. Spiridon Emergency Hospital, Iasi 700115, Romania
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Gill MG, Majumdar A. Metabolic associated fatty liver disease: Addressing a new era in liver transplantation. World J Hepatol 2020; 12:1168-1181. [PMID: 33442446 PMCID: PMC7772736 DOI: 10.4254/wjh.v12.i12.1168] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/08/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD), previously termed non-alcoholic fatty liver disease, is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation. The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management, including in the setting of liver transplantation. Patients with MAFLD present significant challenges in the pre-, peri- and post-transplant settings, largely due to the presence of medical comorbidities that include obesity, metabolic syndrome and cardiovascular risk factors. As the community prevalence of MAFLD increases concurrently with the obesity epidemic, donor liver steatosis is also a current and future concern. This review outlines current epidemiology, nomenclature, management issues and outcomes of liver transplantation in patients with MAFLD.
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Affiliation(s)
- Madeleine G Gill
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia
| | - Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, New South Wales, Australia
- Central Clinical School, The University of Sydney, Sydney 2050, New South Wales, Australia
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43
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Zhang S, Kumari S, Gu Y, Wu X, Li X, Meng G, Zhang Q, Liu L, Wu H, Wang Y, Zhang T, Wang X, Cao X, Li H, Liu Y, Wang X, Sun S, Wang X, Zhou M, Jia Q, Song K, Sun Z, Niu K. Soy Food Intake Is Inversely Associated with Newly Diagnosed Nonalcoholic Fatty Liver Disease in the TCLSIH Cohort Study. J Nutr 2020; 150:3280-3287. [PMID: 33097932 DOI: 10.1093/jn/nxaa297] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/15/2020] [Accepted: 09/08/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Animal studies have shown that soy protein and isoflavones can increase antioxidant capacity and improve insulin resistance, and thus ameliorate nonalcoholic fatty liver disease (NAFLD). However, only limited epidemiological studies have examined the association of soy food intake with NAFLD. OBJECTIVES We investigated the association between soy food intake and NAFLD in a Chinese cohort. METHODS A total of 24,622 participants aged 20-90 y were included in the study. Diet information was collected using a validated 100-item FFQ. NAFLD was defined as having fatty liver diagnosed by ultrasonography and excluding men and women who consumed >210 g alcohol/wk and >140 g/wk, respectively. Logistic regression analysis was used to assess the association of soy food intake with NAFLD. RESULTS After adjustment for potential confounders, and taking those with <1 time/wk soy food intake as the reference group, the ORs for NAFLD across soy food intake frequency were 0.94 (95% CI: 0.83, 1.07) for 1 time/wk, 0.88 (95% CI: 0.78, 0.99) for 2-3 times/wk, and 0.75 (95% CI: 0.65, 0.87) for ≥4 times/wk (P-trend <0.0001). The results were similar when participants were categorized by the energy-adjusted soy food intake (grams per 1000 kilocalories) quartiles (OR = 0.80; 95% CI: 0.71, 0.91; comparing extreme quartiles). CONCLUSIONS Higher soy food intake was associated with a lower prevalence of NAFLD in Chinese adults. Further prospective studies and randomized clinical trials are necessary to confirm if soy food intake is inversely related to the risk of NAFLD.
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Affiliation(s)
- Shunming Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shubham Kumari
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yeqing Gu
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Xiaohui Wu
- College of Pharmacy, Tianjin Medical University, Tianjin, China
| | - Xiaoyue Li
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qing Zhang
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Hongmei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yawen Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Tingjing Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xuena Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xingqi Cao
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Huiping Li
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yunyun Liu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xiaohe Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shaomei Sun
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Xing Wang
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiyu Jia
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Kun Song
- Health Management Center, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhong Sun
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Kaijun Niu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Health Management Center, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition, and Public Health, Tianjin, China.,Center for International Collaborative Research on Environment, Nutrition, and Public Health, Tianjin, China
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44
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Shengir M, Krishnamurthy S, Ghali P, Deschenes M, Wong P, Chen T, Sebastiani G. Prevalence and predictors of nonalcoholic fatty liver disease in South Asian women with polycystic ovary syndrome. World J Gastroenterol 2020; 26:7046-7060. [PMID: 33311949 PMCID: PMC7701948 DOI: 10.3748/wjg.v26.i44.7046] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/30/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Polycystic ovary disease (PCOS) may be a risk factor for nonalcoholic fatty liver disease (NAFLD) due to common pathogenetic pathways, including insulin resistance and obesity. Both PCOS and NAFLD are more severe in South Asian women. Data on NAFLD in South Asian women with PCOS are lacking.
AIM To investigate prevalence and predictors of NAFLD and liver fibrosis in PCOS patients from South Asia.
METHODS We conducted an observational routine screening program by means of transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD was defined as CAP ≥ 288 decibels per meter. Significant liver fibrosis (stage 2 and higher out of 4) was defined as TE measurement ≥ 8.0 kilopascals. Elevated alanine aminotransferase (ALT) was defined as ALT > 24 IU/L, as per upper limit of normal reported in South Asian women. Biochemical hyperandrogenism was defined as free androgen index > 5. Predictors of NAFLD were determined by logistic regression analysis.
RESULTS 101 PCOS patients (mean age 36.3 years) with no significant alcohol intake or viral hepatitis were included. Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%, respectively. Elevated ALT was observed in 40% and 11.5% of patients with and without NAFLD, respectively. After adjusting for duration of PCOS and insulin resistance measured by homeostasis model for assessment of insulin resistance, independent predictors of NAFLD were higher body mass index [adjusted odds ratio (aOR) 1.30, 95% confidence interval (CI): 1.13-1.52], hyperandrogenism (aOR: 5.32, 95%CI: 1.56-18.17) and elevated ALT (aOR: 3.54, 95%CI: 1.10-11.47). Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD (0.31 ± 0.11 vs 0.26 ± 0.13).
CONCLUSION Despite their young age, NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher body mass index and hyperandrogenism. Non-invasive screening strategies could help early diagnosis and initiation of interventions, including counselling on weight loss, cardiovascular risk stratification and linkage to hepatology care where appropriate.
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Affiliation(s)
- Mohamed Shengir
- Department of Experimental Medicine, McGill University, Montreal H4A3J1, Canada
| | - Srinivasan Krishnamurthy
- Department of Obstetrics and Gynecology, McGill University Health Centre, Montreal H4A3J1, Canada
| | - Peter Ghali
- Department of Medicine, McGill University Health Centre, Montreal H4A3J1, Canada
| | - Marc Deschenes
- Department of Medicine, McGill University Health Centre, Montreal H4A3J1, Canada
| | - Philip Wong
- Department of Medicine, McGill University Health Centre, Montreal H4A3J1, Canada
| | - Tianyan Chen
- Department of Medicine, McGill University Health Centre, Montreal H4A3J1, Canada
| | - Giada Sebastiani
- Department of Medicine, McGill University Health Centre, Montreal H4A3J1, Canada
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45
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Spinosa M, Stine JG. Nonalcoholic Fatty Liver Disease-Evidence for a Thrombophilic State? Curr Pharm Des 2020; 26:1036-1044. [PMID: 32003679 DOI: 10.2174/1381612826666200131101553] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 12/16/2019] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease is the leading cause of liver disease worldwide. It has expansive extrahepatic morbidity and mortality including increased rates of both cardiovascular disease and venous thromboembolism. Derangements in primary, secondary and tertiary hemostasis are found in nonalcoholic fatty liver disease independent of those ascribed to end-stage liver disease. The abnormalities across all stages of hemostasis explain the increased rates of clinically relevant thrombotic events, including pulmonary embolism, deep vein thrombosis and portal vein thrombosis, which on an epidemiologic basis appears to be independent of obesity and other traditional venous thromboembolic risk factors. However, given the complex interaction between obesity, body composition and nonalcoholic fatty liver disease and the potential for exercise to benefit all three, more research is needed to further define the role of each in contributing to the prohemostatic state of nonalcoholic fatty liver disease in order to improve patient oriented outcomes.
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Affiliation(s)
- Margaret Spinosa
- Department of Medicine, Pennsylvania State University Milton S. Hershey Medical Center, PA 17033, United States
| | - Jonathan G Stine
- Division of Gastroenterology & Hepatology, Department of Medicine, Pennsylvania State University Milton S. Hershey Medical Center, United States.,Department of Public Health Sciences, Pennsylvania State University Milton S. Hershey Medical Center, PA 17033, United States
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Chiu LS, Pedley A, Massaro J, Benjamin EJ, Mitchell GF, McManus DD, Aragam J, Vasan RS, Cheng S, Long MT. The association of non-alcoholic fatty liver disease and cardiac structure and function-Framingham Heart Study. Liver Int 2020; 40:2445-2454. [PMID: 32654390 PMCID: PMC7669676 DOI: 10.1111/liv.14600] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 06/29/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease confers increased risk for cardiovascular disease, including heart failure (HF), for reasons that remain unclear. Possible pathways could involve an association of liver fat with cardiac structural or functional abnormalities even after accounting for body size. METHODS We analysed N = 2356 Framingham Heart Study participants (age 52 ± 12 years, 52% women) who underwent echocardiography and standardized computed tomography measures of liver fat. RESULTS In cross-sectional multivariable regression models adjusted for age, gender, cohort and cardiovascular risk factors, liver fat was positively associated with left ventricular (LV) mass (β = 1.45; 95% confidence interval (CI): 0.01, 2.88), LV wall thickness (β = 0.01; 95% CI: 0.00, 0.02), mass volume ratio (β = 0.02; 95% CI 0.01, 0.03), mitral peak velocity (E) (β = 0.83; 95% CI 0.31, 1.36) and LV filling pressure (E/e' ratio) (β = 0.16; 95% CI 0.09, 0.23); and inversely associated with global systolic longitudinal strain (β = 0.20, 95% CI 0.07, 0.33), diastolic annular velocity (e') (β = -0.12; 95% CI - 0.22, -0.03), and E/A ratio (β = -0.01; 95% CI - 0.02, -0.00). After additional adjustment for body mass index (BMI), statistical significance was attenuated for all associations except for that of greater liver fat with increased LV filling pressure, a possible precursor to HF (β = 0.11; 95% CI 0.03, 0.18). CONCLUSION Increased liver fat was associated with multiple subclinical cardiac dysfunction measures, with most of associations mediated by obesity. Interestingly, the association of liver fat and LV filling pressure was only partially mediated by BMI, suggesting a possible direct effect of liver fat on LV filling pressure. Further confirmatory studies are needed.
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Affiliation(s)
- Laura S. Chiu
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
| | | | - Joseph Massaro
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Department of Mathematics and Statistics, Boston University, Boston, MA, United States
| | - Emelia J. Benjamin
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | | | - David D. McManus
- Cardiology Division, Department of Medicine and the Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worchester, MA
| | - Jayashri Aragam
- Cardiovascular Division, VA Boston Healthcare System, West Roxbury, MA,Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - Ramachandran S. Vasan
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA.,Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA,Department of Epidemiology, Boston University School of Public Health, Boston, MA,Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston Medical Center, Boston, MA
| | - Susan Cheng
- Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Michelle T. Long
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA
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Joaquim M, Escobar-Henriques M. Role of Mitofusins and Mitophagy in Life or Death Decisions. Front Cell Dev Biol 2020; 8:572182. [PMID: 33072754 PMCID: PMC7539839 DOI: 10.3389/fcell.2020.572182] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 09/03/2020] [Indexed: 12/12/2022] Open
Abstract
Mitochondria entail an incredible dynamism in their morphology, impacting death signaling and selective elimination of the damaged organelles. In turn, by recycling the superfluous or malfunctioning mitochondria, mostly prevalent during aging, mitophagy contributes to maintain a healthy mitochondrial network. Mitofusins locate at the outer mitochondrial membrane and control the plastic behavior of mitochondria, by mediating fusion events. Besides deciding on mitochondrial interconnectivity, mitofusin 2 regulates physical contacts between mitochondria and the endoplasmic reticulum, but also serves as a decisive docking platform for mitophagy and apoptosis effectors. Thus, mitofusins integrate multiple bidirectional inputs from and into mitochondria and ensure proper energetic and metabolic cellular performance. Here, we review the role of mitofusins and mitophagy at the cross-road between life and apoptotic death decisions. Furthermore, we highlight the impact of this interplay on disease, focusing on how mitofusin 2 and mitophagy affect non-alcoholic fatty liver disease.
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Affiliation(s)
- Mariana Joaquim
- Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
| | - Mafalda Escobar-Henriques
- Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
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48
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Harris SE, Poolman TM, Arvaniti A, Cox RD, Gathercole LL, Tomlinson JW. The American lifestyle-induced obesity syndrome diet in male and female rodents recapitulates the clinical and transcriptomic features of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2020; 319:G345-G360. [PMID: 32755310 PMCID: PMC7509261 DOI: 10.1152/ajpgi.00055.2020] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the progression to nonalcoholic steatohepatitis (NASH) and increased risk of hepatocellular carcinoma remain poorly understood. Additionally, there is increasing recognition of the extrahepatic manifestations associated with NAFLD and NASH. We demonstrate that intervention with the American lifestyle-induced obesity syndrome (ALIOS) diet in male and female mice recapitulates many of the clinical and transcriptomic features of human NAFLD and NASH. Male and female C57BL/6N mice were fed either normal chow (NC) or ALIOS from 11 to 52 wk and underwent comprehensive metabolic analysis throughout the duration of the study. From 26 wk, ALIOS-fed mice developed features of hepatic steatosis, inflammation, and fibrosis. ALIOS-fed mice also had an increased incidence of hepatic tumors at 52 wk compared with those fed NC. Hepatic transcriptomic analysis revealed alterations in multiple genes associated with inflammation and tissue repair in ALIOS-fed mice. Ingenuity Pathway Analysis confirmed dysregulation of metabolic pathways as well as those associated with liver disease and cancer. In parallel the development of a robust hepatic phenotype, ALIOS-fed mice displayed many of the extrahepatic manifestations of NAFLD, including hyperlipidemia, increased fat mass, sarcopenia, and insulin resistance. The ALIOS diet in mice recapitulates many of the clinical features of NAFLD and, therefore, represents a robust and reproducible model for investigating the pathogenesis of NAFLD and its progression.NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) affects 30% of the general population and can progress to nonalcoholic steatohepatitis (NASH) and potentially hepatocellular carcinoma. Preclinical models rely on mouse models that often display hepatic characteristics of NAFLD but rarely progress to NASH and seldom depict the multisystem effects of the disease. We have conducted comprehensive metabolic analysis of both male and female mice consuming a Western diet of trans fats and sugar, focusing on both their hepatic phenotype and extrahepatic manifestations.
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Affiliation(s)
- Shelley E. Harris
- 1Oxford Centre for Diabetes, Endocrinology and Metabolism, National Institute for Health Research Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Toryn M. Poolman
- 1Oxford Centre for Diabetes, Endocrinology and Metabolism, National Institute for Health Research Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Anastasia Arvaniti
- 1Oxford Centre for Diabetes, Endocrinology and Metabolism, National Institute for Health Research Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom,2Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, United Kingdom
| | - Roger D. Cox
- 3Mammalian Genetics Unit, Medical Research Council Harwell Institute, Oxford, United Kingdom
| | - Laura L. Gathercole
- 1Oxford Centre for Diabetes, Endocrinology and Metabolism, National Institute for Health Research Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom,2Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, United Kingdom
| | - Jeremy W. Tomlinson
- 1Oxford Centre for Diabetes, Endocrinology and Metabolism, National Institute for Health Research Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
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Benmassaoud A, Deschenes M, Chen T, Ghali P, Sebastiani G. Optimizing patients with non-alcoholic fatty liver disease pre-transplant. CANADIAN LIVER JOURNAL 2020; 3:237-250. [PMID: 35992526 PMCID: PMC9202706 DOI: 10.3138/canlivj-2019-0025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 11/17/2019] [Indexed: 06/01/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Non-alcoholic steatohepatitis (NASH), which is the progressive counterpart of the disease, is becoming the leading indication for liver transplantation in North America. Owing to the lack of symptoms, NASH is often an incidental diagnosis, resulting in a significant proportion of patients being diagnosed when advanced liver disease has already developed. NAFLD has recently been characterized as the hepatic manifestation of metabolic syndrome. Consequently, it is a multisystem disease that often co-exists with several other conditions, such as obesity, diabetes, cardiovascular diseases, and extra-hepatic malignancy, which have an impact on selection of transplant recipients. The complexity of diagnostic approach, need for multidisciplinary clinical management, and lack of a specific treatment further complicate the picture of this extremely prevalent liver condition. NAFLD patients with advanced liver disease should be considered for early referral to liver transplant clinics for careful metabolic and cardiovascular risk stratification because they have worse survival rates after liver transplantation than other patients with chronic liver disease. Early referral will also facilitate optimization of metabolic comorbidities before proceeding with transplantation. This review provides an overview of strategies to identify patients with advanced NAFLD, with an emphasis on the management of associated comorbidities and optimal timing of pre-transplant evaluation. Other topics that have been shown to affect recipient optimization, such as the role of lifestyle changes and bariatric surgery in the management of obesity, as well as sarcopenia in decompensated NASH-related cirrhosis, are addressed.
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Affiliation(s)
- Amine Benmassaoud
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marc Deschenes
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Tianyan Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Peter Ghali
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Gastroenterology, Department of Medicine, University of Florida, Jacksonville, Florida, USA
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
- Chronic Viral Illness Service, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
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50
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Monserrat-Mesquida M, Quetglas-Llabrés M, Abbate M, Montemayor S, Mascaró CM, Casares M, Tejada S, Abete I, Zulet MA, Tur JA, Martínez JA, Sureda A. Oxidative Stress and Pro-Inflammatory Status in Patients with Non-Alcoholic Fatty Liver Disease. Antioxidants (Basel) 2020; 9:E759. [PMID: 32824349 PMCID: PMC7463614 DOI: 10.3390/antiox9080759] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/06/2020] [Accepted: 08/13/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation, especially triglycerides, in hepatocytes. If the pathology is not properly treated, it can progress to nonalcoholic steatohepatitis (NASH) and continue to fibrosis, cirrhosis or hepatocarcinoma. OBJECTIVE The aim of the current research was to identify the plasma biomarkers of liver damage, oxidative stress and inflammation that facilitate the early diagnosis of the disease and control its progression. METHODS Antioxidant and inflammatory biomarkers were measured in the plasma of patients diagnosed with NAFLD (n = 100 adults; 40-60 years old) living in the Balearic Islands, Spain. Patients were classified according to the intrahepatic fat content (IFC) measured by magnetic resonance imaging (MRI). RESULTS Circulating glucose, glycosylated haemoglobin, triglycerides, low-density lipoprotein-cholesterol, aspartate aminotransferase and alanine aminotransferase were higher in patients with an IFC ≥ 2 of NAFLD in comparison to patients with an IFC of 0 and 1. The plasma levels of catalase, irisin, interleukin-6, malondialdehyde, and cytokeratin 18 were higher in stage ≥2 subjects, whereas the resolvin D1 levels were lower. No differences were observed in xanthine oxidase, myeloperoxidase, protein carbonyl and fibroblast growth factor 21 depending on liver status. CONCLUSION The current available data show that the severity of NAFLD is associated with an increase in oxidative stress and proinflammatory status. It may be also useful as diagnostic purpose in clinical practice.
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Affiliation(s)
- Margalida Monserrat-Mesquida
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; (I.A.); (M.A.Z.); (J.A.M.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
| | - Magdalena Quetglas-Llabrés
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
| | - Manuela Abbate
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
| | - Sofía Montemayor
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
| | - Catalina M. Mascaró
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
| | - Miguel Casares
- Radiodiagnosis Service, Red Asistencial Juaneda, 07011 Palma de Mallorca, Spain;
| | - Silvia Tejada
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; (I.A.); (M.A.Z.); (J.A.M.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
- Laboratory of Neurophysiology, University of the Balearic Islands, 07122 Palma de Mallorca, Spain
| | - Itziar Abete
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; (I.A.); (M.A.Z.); (J.A.M.)
- Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
| | - Maria Angeles Zulet
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; (I.A.); (M.A.Z.); (J.A.M.)
- Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
| | - Josep A. Tur
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; (I.A.); (M.A.Z.); (J.A.M.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
| | - J. Alfredo Martínez
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; (I.A.); (M.A.Z.); (J.A.M.)
- Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
- Cardiometabolics Precision Nutrition Program, IMDEA Food, CEI UAM-CSIC, 28049 Madrid, Spain
| | - Antoni Sureda
- Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands and Health Research Institute of Balearic Islands (IdISBa), 07122 Palma de Mallorca, Spain; (M.M.-M.); (M.Q.-L.); (M.A.); (S.M.); (C.M.M.); (S.T.); (A.S.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; (I.A.); (M.A.Z.); (J.A.M.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain
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