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Isakov V. Metabolic dysfunction-associated steatotic liver disease: A story of muscle and mass. World J Gastroenterol 2025; 31:105346. [DOI: 10.3748/wjg.v31.i20.105346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 04/13/2025] [Accepted: 05/09/2025] [Indexed: 05/28/2025] Open
Abstract
Skeletal muscle alterations (SMA) are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting disease progression and outcomes. Sarcopenia is common in patients with MASLD, with a prevalence ranging from 20% to 40% depending on the population and diagnostic criteria used. In advanced stages, such as metabolic dysfunction-associated steatohepatitis and fibrosis, its prevalence is even higher. Sarcopenia exacerbates insulin resistance, systemic inflammation, and oxidative stress, all of which worsen MASLD. It is an independent risk factor for fibrosis progression and poor outcomes including mortality. Myosteatosis refers to the abnormal accumulation of fat within muscle tissue, leading to decreased muscle quality. Myosteatosis is prevalent (> 30%) in patients with MASLD, especially those with obesity or type 2 diabetes, although this can vary with the imaging techniques used. It reduces muscle strength and metabolic efficiency, further contributing to insulin resistance and is usually associated with advanced liver disease, cardiovascular complications, and lower levels of physical activity. Altered muscle metabolism, which includes mitochondrial dysfunction and impaired amino acid metabolism, has been reported in metabolic syndromes, including MASLD, although its actual prevalence is unknown. Altered muscle metabolism limits glucose uptake and oxidation, worsening hyperglycemia and lipotoxicity. Reduced muscle perfusion and oxygenation due to endothelial dysfunction and systemic metabolic alterations are common in MASLD associated with comorbidities, such as obesity, hypertension, and atherosclerosis. It decreases the muscle capacity for aerobic metabolism, leading to fatigue and reduced physical activity in patients with MASLD, aggravating metabolic dysfunction. Various SMA in MASLD worsen insulin resistance and hepatic fat accumulation, may accelerate progression to fibrosis and cirrhosis, and increase the risk of cardiovascular disease and mortality. Management strategies for SMA include resistance training, aerobic exercise, and nutritional support (e.g., high-protein diets, vitamin D, and omega-3 fatty acids), which are essential for mitigating skeletal muscle loss and improving outcomes. However, pharmacological agents that target the muscle and liver (such as glucagon-like peptide-1 receptor agonists) show promise but have not yet been approved for the treatment of MASLD.
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Affiliation(s)
- Vasily Isakov
- Department of Gastroenterology and Hepatology, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow 115446, Russia
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Zhan C, Quan Z, Huang X, Bu J, Li S. Causal relationships of circulating amino acids with sarcopenia-related traits: A bidirectional Mendelian randomization study. Clin Nutr 2025; 47:258-264. [PMID: 40073510 DOI: 10.1016/j.clnu.2025.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 01/26/2025] [Accepted: 02/16/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND AND AIM Recent studies have indicated a correlation between certain Amino acids (AAs) and sarcopenia. However, the exact causal relationship among these associations is still unclear. This study aims to elucidate the causal relationships between 20 types of AAs and the phenotypic characteristics associated with sarcopenia through Mendelian randomization (MR) analysis. METHODS AND RESULTS This MR study employed single nucleotide polymorphisms (SNPs) that were significantly associated with both AAs and the traits of sarcopenia as instrumental variables (IVs). The main method for estimating causal effects was the inverse-variance weighted (IVW) approach. To ensure the robustness of the findings, additional methods such as weighted median, weighted mode, and MR Egger regression were used. Sensitivity analyses included heterogeneity and pleiotropy tests. In this research, we discovered potential causal relationships between AAs and traits associated with sarcopenia. We not only found that AAs previously studied, such as Glutamine, Tyrosine, Glycine, and branched-chain amino acids, play positive roles in muscle metabolism. Additionally, our study identified the role of AAs previously neglected or not considered in earlier research, such as Alanine, Lysine, Cysteine, and Methionine, which exert potential effects on muscle metabolism and offer considerable research potential and value. CONCLUSIONS This MR study clarified the reciprocal effects between circulating levels of AAs and sarcopenia-related traits. These results indicate that AAs may be used as biomarkers for diagnosing sarcopenia or as intervention targets for its treatment in clinical practice.
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Affiliation(s)
- Chenyang Zhan
- Department of General Surgery, Chengdu Second People's Hospital, Chengdu 610041, China; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, China.
| | - Zongjie Quan
- Department of General Surgery, Chengdu Second People's Hospital, Chengdu 610041, China; School of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, China.
| | - Xiujin Huang
- Department of General Surgery, Chengdu Second People's Hospital, Chengdu 610041, China; School of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, China.
| | - Jun Bu
- Department of General Surgery, Chengdu Second People's Hospital, Chengdu 610041, China.
| | - Sheng Li
- Department of General Surgery, Chengdu Second People's Hospital, Chengdu 610041, China; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, China.
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Wei WX, Mao ZF, Chen ML, Meng L. The impact of chronic diseases and lifestyle on sarcopenia risk in older adults: a population-based longitudinal study. Front Med (Lausanne) 2025; 12:1500915. [PMID: 40078393 PMCID: PMC11897525 DOI: 10.3389/fmed.2025.1500915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
Background Sarcopenia, characterized by the gradual decline of muscle mass and strength, seriously affects the health and mobility of older adults. The purpose of this study is to investigate the risk factors for sarcopenia, particularly the relationship between chronic diseases and lifestyle factors in individuals aged 60 and over. Methods This study used data from the Longitudinal Study on Health and Retirement in China (CHARLS) collected in 2011 and 2015. All eligible participants were classified according to the standards established by the Asian Sarcopenia Working Group in 2019. The evaluation of sarcopenia was based on a comprehensive score across five dimensions: strength, assistance in walking, rise from a chair, climb stairs, and falls. A multivariate logistic regression model was employed to explore the risk factors for sarcopenia. Results The risk of sarcopenia is significantly influenced by multiple factors. Key findings include the association between past drinking and an increased risk of sarcopenia (HR = 2.198, 95% CI: 1.072-4.560, p < 0.05), indicating that individuals with a history of drinking have more than twice the risk of sarcopenia compared to non-drinkers. Chronic diseases such as stroke were also associated with a significantly elevated risk (HR = 3.137, 95% CI: 1.128-8.721, p < 0.05). Conversely, participation in social activities significantly reduced the risk of sarcopenia (HR = 0.482, 95% CI: 0.265-0.876, p < 0.05). A three-piece spline regression model revealed a nonlinear relationship between physical activity and the risk of sarcopenia, characterized by an initial decline in risk followed by an increase as physical activity levels rose. Moderate-intensity physical activity reduced the risk of sarcopenia by approximately 35% (HR ≈ 0.65). However, high-intensity physical activity led to a rebound in risk, increasing the likelihood of sarcopenia relative to moderate activity. Similarly, adequate sleep duration was associated with a reduced risk of sarcopenia, whereas excessive sleep counteracted this benefit. Conclusion The findings underscore the critical role of lifestyle modifications and balanced physical activity in mitigating the risk of sarcopenia among older adults. Implementing targeted interventions for high-risk groups is essential to reduce the incidence of sarcopenia.
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Malik A, Javaid S, Malik MI, Qureshi S. Relationship between sarcopenia and metabolic dysfunction-associated steatotic liver disease (MASLD): A systematic review and meta-analysis. Ann Hepatol 2024; 29:101544. [PMID: 39214253 DOI: 10.1016/j.aohep.2024.101544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 05/13/2024] [Accepted: 06/17/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION AND OBJECTIVES Metabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease. Identifying MASLD risk factors could help early intervention and reduce the burden of the disease. Previous studies investigated the association between sarcopenia and NAFLD. Several trials were published after the last meta-analysis with indecisive results. This is an updated meta-analysis which aims to assess the association between sarcopenia, MASLD, and MASLD-related fibrosis. MATERIALS AND METHODS Relevant trials published on PubMed, Web of Science, Scopus, and Cochrane Library databases until October 2022 were included. We included studies in which skeletal mass index (SMI) or sarcopenia was compared between patients with and without NAFLD now MASLD. Also, studies comparing fibrosis between MASLD patients with and without sarcopenia were included. Data were pooled as odds ratios (ORs) and 95 % confidence intervals (CIs) using Review Manager Software. RESULTS A total of 25 studies were included. The incidence of sarcopenia was significantly higher in MASLD than controls (OR, 1.25; 95 % CI, 1.08-1.44; P = 0.003). SMI odds showed no significant difference between MASLD patients and controls (OR, 1.02; 95 % CI, 0.91-1.15; P = 0.7). MASLD patients with sarcopenia had higher odds of fibrosis than MASLD patients without sarcopenia (OR, 1.49; 95 % CI, 1.03-2.14; P = 0.03). CONCLUSIONS Sarcopenia increased MASLD's probability and was associated with a higher probability of liver fibrosis in MASLD patients. However, SMI had no predictive value of MASLD occurrence.
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Affiliation(s)
- Adnan Malik
- Mountain Vista Medical Center, Mesa Arizona, USA.
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Warner JD, Blake GM, Garrett JW, Lee MH, Nelson LW, Summers RM, Pickhardt PJ. Correlation of HbA1c levels with CT-based body composition biomarkers in diabetes mellitus and metabolic syndrome. Sci Rep 2024; 14:21875. [PMID: 39300115 DOI: 10.1038/s41598-024-72702-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 09/10/2024] [Indexed: 09/22/2024] Open
Abstract
Diabetes mellitus and metabolic syndrome are closely linked with visceral body composition, but clinical assessment is limited to external measurements and laboratory values including hemoglobin A1c (HbA1c). Modern deep learning and AI algorithms allow automated extraction of biomarkers for organ size, density, and body composition from routine computed tomography (CT) exams. Comparing visceral CT biomarkers across groups with differing glycemic control revealed significant, progressive CT biomarker changes with increasing HbA1c. For example, in the unenhanced female cohort, mean changes between normal and poorly-controlled diabetes showed: 53% increase in visceral adipose tissue area, 22% increase in kidney volume, 24% increase in liver volume, 6% decrease in liver density (hepatic steatosis), 16% increase in skeletal muscle area, and 21% decrease in skeletal muscle density (myosteatosis) (all p < 0.001). The multisystem changes of metabolic syndrome can be objectively and retrospectively measured using automated CT biomarkers, with implications for diabetes, metabolic syndrome, and GLP-1 agonists.
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Affiliation(s)
- Joshua D Warner
- The Departments of Radiology and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Glen M Blake
- School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, SE1 7EH, UK
| | - John W Garrett
- The Departments of Radiology and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Matthew H Lee
- The Departments of Radiology and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Leslie W Nelson
- The Departments of Radiology and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Ronald M Summers
- Imaging Biomarkers and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, MD, USA
| | - Perry J Pickhardt
- The Departments of Radiology and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI, 53792-3252, USA.
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Li X, He J, Sun Q. The prevalence and effects of sarcopenia in patients with metabolic dysfunction-associated steatotic liver disease (MASLD): A systematic review and meta-analysis. Clin Nutr 2024; 43:2005-2016. [PMID: 39053329 DOI: 10.1016/j.clnu.2024.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 07/07/2024] [Accepted: 07/09/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND AND AIMS Sarcopenia is a common complication in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prevalence and its impact on the survival of sarcopenia in patients with MASLD is unknown. In this study, we aimed to assess the prevalence and effects of sarcopenia in patients with MASLD. METHODS Systematic review and meta-analysis of full texts of relevant studies were searched from inception until June 12, 2024 in five databases (PubMed, Cochrane Library, Embase, Web of Science, and the China National Knowledge Infrastructure). Next, we assessed the prevalence of sarcopenia in MASLD, and calculated the ORs and HRs between sarcopenia and MASLD based on the adjusted data from individual studies. Statistical analyses were performed using Stata 11.0. RESULTS Of the 2984 records considered, 29 studies recruiting 63,330 patients were included. The pooled prevalence of sarcopenia in patients with MASLD was 23.5% overall (95% CI; 19.1%-27.9%, I2 = 99.6%), and was higher in Asian patients, male, cross-sectional studies, when BIA were employed to measure muscle mass, one criterion of diagnosis sarcopenia, MASLD was diagnosed employing MRI, and moderate-quality studies. Sarcopenia was associated with MASLD patients (adjusted odds ratio [aOR] 2.08, 95% CI 1.58-2.74, I2 = 93.6%) with similar findings in subgroups stratified by age, study design, methods for measuring muscle mass, assessment method to detect sarcopenia, and study quality. The association between all-cause mortality further supports the association between sarcopenia and poor prognosis with MASLD (aHR 1.59, 95% CI 1.33-1.91, I2 = 0%). CONCLUSIONS Sarcopenia was strongly associated with MASLD progression and was a risk factor not only for MASLD pathogenesis but was also markedly correlated with MASLD-associated mortality.
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Affiliation(s)
- Xiaoyan Li
- School of Nursing, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang, China
| | - Jie He
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan, China; Clinical Medical College of Chengdu Medical College, Chengdu 610500, Sichuan, China
| | - Qiuhua Sun
- School of Nursing, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang, China.
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Yang Y, Chi L, Hsiao YC, Lu K. Sex-specific effects of gut microbiome on shaping bile acid metabolism. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.27.601003. [PMID: 38979196 PMCID: PMC11230406 DOI: 10.1101/2024.06.27.601003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations between sex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sexspecific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum. Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes.
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Affiliation(s)
- Yifei Yang
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
| | - Liang Chi
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
| | - Yun-Chung Hsiao
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
| | - Kun Lu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
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Swan J, Szabó Z, Peters J, Kummu O, Kemppi A, Rahtu-Korpela L, Konzack A, Hakkola J, Pasternack A, Ritvos O, Kerkelä R, Magga J. Inhibition of activin receptor 2 signalling ameliorates metabolic dysfunction-associated steatotic liver disease in western diet/L-NAME induced cardiometabolic disease. Biomed Pharmacother 2024; 175:116683. [PMID: 38705130 DOI: 10.1016/j.biopha.2024.116683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 04/19/2024] [Accepted: 04/29/2024] [Indexed: 05/07/2024] Open
Abstract
OBJECTIVE Blockade of activin 2 receptor (ACVR2) signaling has been shown to improve insulin sensitivity and aid in weight loss. Inhibition of ACVR2 signaling restores cardiac function in multiple heart failure models. However, its potential in the treatment of obesity-related cardiometabolic disease remains unknown. Here, we investigated targeting ACVR2 signaling in cardiometabolic disease manifested with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS Mice were fed a high-fat, high-sugar diet combined with the administration of nitric oxide synthase inhibitor L-NAME in drinking water, which causes hypertensive stress. For the last eight weeks, the mice were treated with the soluble ACVR2B decoy receptor (sACVR2B-Fc). RESULTS sACVR2B-Fc protected against the development of comorbidities associated with cardiometabolic disease. This was most pronounced in the liver where ACVR2 blockade attenuated the development of MASLD including cessation of pro-fibrotic activation. It also significantly reduced total plasma cholesterol levels, impeded brown adipose tissue whitening, and improved cardiac diastolic function. In vitro, ACVR2 ligands activin A, activin B and GDF11 induced profibrotic signaling and the proliferation of human cardiac fibroblasts. CONCLUSIONS Blockade of ACVR2B exerts broad beneficial effects for therapy of cardiometabolic disease. By reducing obesity, ameliorating cardiovascular deterioration and restraining MASLD, blockade of ACVR2B signaling proves a potential target in MASLD and its comorbidities.
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Affiliation(s)
- Julia Swan
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland; Biocenter Oulu, University of Oulu, Aapistie 5, Oulu 90220, Finland.
| | - Zoltán Szabó
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Juliana Peters
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Outi Kummu
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland; Biocenter Oulu, University of Oulu, Aapistie 5, Oulu 90220, Finland; Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Anna Kemppi
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Lea Rahtu-Korpela
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Anja Konzack
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland; Biocenter Oulu, University of Oulu, Aapistie 5, Oulu 90220, Finland; Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Jukka Hakkola
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland; Biocenter Oulu, University of Oulu, Aapistie 5, Oulu 90220, Finland; Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Arja Pasternack
- Department of Physiology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, Helsinki 00014, Finland
| | - Olli Ritvos
- Department of Physiology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, Helsinki 00014, Finland
| | - Risto Kerkelä
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland; Biocenter Oulu, University of Oulu, Aapistie 5, Oulu 90220, Finland; Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, Aapistie 5, Oulu 90220, Finland
| | - Johanna Magga
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, Aapistie 5, Oulu 90220, Finland; Biocenter Oulu, University of Oulu, Aapistie 5, Oulu 90220, Finland.
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Viswanath A, Fouda S, Fernandez CJ, Pappachan JM. Metabolic-associated fatty liver disease and sarcopenia: A double whammy. World J Hepatol 2024; 16:152-163. [PMID: 38495287 PMCID: PMC10941748 DOI: 10.4254/wjh.v16.i2.152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 12/26/2023] [Accepted: 01/17/2024] [Indexed: 02/27/2024] Open
Abstract
The prevalence of metabolic-associated fatty liver disease (MAFLD) has increased substantially in recent years because of the global obesity pandemic. MAFLD, now recognized as the number one cause of chronic liver disease in the world, not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnoea, lipid disorders and sarcopenia. Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies. Sarcopenia can be either part of the disease process that results in MAFLD (e.g., obesity or adiposity) or a consequence of MAFLD, especially in the advanced stages such as fibrosis and cirrhosis. Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors. Therefore, it is crucial to thoroughly understand how we deal with these diseases, especially when they coexist. We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.
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Affiliation(s)
- Aditya Viswanath
- School of Medicine, Leicester University, Leicester LE1 7RH, United Kingdom
| | - Sherouk Fouda
- School of Health and Biomedical Sciences, Rmit University, Melbourne VIC, Australia
| | - Cornelius James Fernandez
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, United Kingdom
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom.
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Atabieke F, Li XJ, Aierken A, Li J, Zhang Y, Aizezi Y, Gao HL, Zhang ZQ. Association between frailty and hepatic fibrosis in NAFLD among middle-aged and older adults: results from NHANES 2017-2020. Front Public Health 2024; 12:1330221. [PMID: 38389936 PMCID: PMC10883311 DOI: 10.3389/fpubh.2024.1330221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 01/29/2024] [Indexed: 02/24/2024] Open
Abstract
Background Although previous studies found that frailty is prevalent in NAFLD patients with advanced liver fibrosis and cirrhosis, studies examining the relationship are spare. Aim Our study aspires to investigate the potential correlation between the Frailty Index (FI) and hepatic fibrosis among middle-aged and older adults with NAFLD. Methods Data from the 2017-2020.03 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 2,383 participants aged 50 years and older included. The quantification of frailty was executed employing a 49-item frailty index. The recognition of hepatic steatosis and fibrosis was accomplished through the utilization of the controlling attenuation parameter (CAP) and transient elastography (TE). The relationship between the FI and hepatic fibrosis were investigated employing univariable and multivariable-adjusted logistic regression analyses. A subgroup analysis was conducted, dividing the subjects based on gender, Body Mass Index (BMI), and the presence of hyperlipidemia. Results The findings demonstrated a positive correlation between the FI and significant hepatic fibrosis in NAFLD, even after using multivariate logistic regression models adjusting for potential confounding factors (OR = 1.022, 95% CI, 1.004-1.041) and in tertiles (Q3vs Q1: OR = 2.004, 95% CI, 1.162-3.455). In the subgroup analysis, the correlation was more statistically significant in male (OR = 1.046, 95% CI, 1.022-1.071), under/normal weight (OR = 1.077, 95% CI, 1.009-1.150), overweight (OR = 1.040, 95% CI, 1.010-1.071), and subjects without hyperlipidemia (OR = 1.054, 95% CI, 1.012-1.097). The area under the Receiver Operating Characteristic (ROC) curve for the FI in assessing the existence of substantial fibrosis in NAFLD was 0.612 (95% CI, 0.596-0.628). Conclusion This study demonstrated a positive correlation between significant hepatic fibrosis and frailty, particularly among males aged 50 years and older, who were non-obese and did not have hyperlipidemia with NAFLD. Additional studies are required to further validate these findings.
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Affiliation(s)
- Falide Atabieke
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Xiu-Juan Li
- Department of Pathophysiology, School of Basic Medical Sciences Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Ailikamu Aierken
- Xinjiang Medical University School of Clinical Medicine, Children's Hospital of the Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Jian Li
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Yu Zhang
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Yierzhati Aizezi
- Center of Critical Care Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Hong-Liang Gao
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Zhi-Qiang Zhang
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
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Zhong L, Liu J, Xia M, Zhang Y, Liu S, Tan G. Effect of sarcopenia on survival in patients after pancreatic surgery: a systematic review and meta-analysis. Front Nutr 2024; 10:1315097. [PMID: 38260056 PMCID: PMC10800600 DOI: 10.3389/fnut.2023.1315097] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/12/2023] [Indexed: 01/24/2024] Open
Abstract
Background Numerous studies have reported sarcopenia to be associated with unfavorable outcomes in patients who have undergone pancreatectomy. Therefore, in this meta-analysis, we examined the relationship between sarcopenia and survival after pancreatic surgery. Methods PubMed, Embase, and Cochrane Library were searched for studies that examined the association between sarcopenia and survival after pancreatic surgery from the inception of the database until June 1, 2023. Hazard ratio (HR) for overall survival (OS) and/or progression-free survival (PFS) of sarcopenia and pancreatic surgery were extracted from the selected studies and random or fixed-effect models were used to summarize the data according to the heterogeneity. Publication bias was assessed using Egger's linear regression test and a funnel plot. Results Sixteen studies met the inclusion criteria. For 13 aggregated univariate and 16 multivariate estimates, sarcopenia was associated with decreased OS (univariate analysis: HR 1.69, 95% CI 1.48-1.93; multivariate analysis: HR 1.69; 95% CI 1.39-2.05, I2 = 77.4%). Furthermore, sarcopenia was significantly associated with poor PFS of pancreatic resection (Change to univariate analysis: HR 1.74, 95% CI 1.47-2.05; multivariate analysis: HR 1.54; 95% CI 1.23-1.93, I2 = 63%). Conclusion Sarcopenia may be a significant prognostic factor for a shortened survival following pancreatectomy since it is linked to an elevated risk of mortality. Further studies are required to understand how sarcopenia affects long-term results after pancreatic resection.Systematic review registrationRegistration ID: CRD42023438208 https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
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Affiliation(s)
- Lei Zhong
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jifeng Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Mingquan Xia
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yunshu Zhang
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shuo Liu
- Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Guang Tan
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Falvo C, Crowley D, Benson E, Hall MN, Schwarz B, Bohrnsen E, Ruiz-Aravena M, Hebner M, Ma W, Schountz T, Rynda-Apple A, Plowright RK. Diet-induced changes in metabolism influence immune response and viral shedding dynamics in Jamaican fruit bats. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.12.01.569121. [PMID: 38077027 PMCID: PMC10705527 DOI: 10.1101/2023.12.01.569121] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
Land-use change may drive viral spillover from bats into humans, partly through dietary shifts caused by decreased availability of native foods and increased availability of cultivated foods. We manipulated diets of Jamaican fruit bats to investigate whether diet influences shedding of a virus they naturally host. To reflect dietary changes experienced by wild bats during periods of nutritional stress, bats were fed either standard or putative suboptimal diets which were deprived of protein (suboptimal-sugar) and/or supplemented with fat (suboptimal-fat). Upon H18N11 influenza A-virus infection, bats fed the suboptimal-sugar diet shed the most viral RNA for the longest period, but bats fed the suboptimal-fat diet shed the least viral RNA for the shortest period. Unlike mice and humans, bats fed the suboptimal-fat diet displayed higher pre-infection levels of metabolic markers associated with gut health. Diet-driven heterogeneity in viral shedding may influence population-level viral dynamics in wild bats and alter risk of shedding and spillover to humans.
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13
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Igudesman D, Mucinski J, Harrison S, Cawthon PM, Linge J, Goodpaster BH, Cummings SR, Hepple RT, Jurczak MJ, Kritchevsky SB, Marcinek D, Coen PM, Corbin KD. Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness with Liver Fat Among Older Adults. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.10.24.23297480. [PMID: 37961367 PMCID: PMC10635187 DOI: 10.1101/2023.10.24.23297480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Background Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults. Methods We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D 3 -creatine dilution), muscle fat infiltration (MRI), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO 2 peak) with liver fat among older adults. Linear regression models adjusted for age, gender, technician (respirometry only), daily minutes of moderate to vigorous physical activity, and prediabetes/diabetes status tested main effects and interactions of each independent variable with waist circumference (high: women-≥88 cm, men-≥102 cm) and gender. Results Among older adults aged 75 (IQR 73, 79 years; 59.8% women), muscle mass and liver fat were not associated overall but were positively associated among participants with a high waist circumference (β: 25.2; 95%CI 11.7, 40.4; p =.0002; N=362). Muscle fat infiltration and liver fat were positively associated (β: 15.2; 95%CI 6.8, 24.3; p =.0003; N=378). Carbohydrate-supported maximum oxidative phosphorylation and VO 2 peak (adjusted β: -12.9; 95%CI -20.3, -4.8; p =0.003; N=361) were inversely associated with liver fat; adjustment attenuated the estimate for maximum oxidative phosphorylation although the point estimate remained negative (β: -4.0; 95%CI -11.6, 4.2; p =0.32; N=321). Conclusions Skeletal muscle-related characteristics are metabolically relevant factors linked to liver fat in older adults. Future research should confirm our results to determine whether trials targeting mechanisms common to liver and muscle fat accumulation are warranted.
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Harring M, Golabi P, Paik JM, Shah D, Racila A, Cable R, Srishord M, Younossi ZM. Sarcopenia Among Patients With Nonalcoholic Fatty Liver Disease (NAFLD) Is Associated With Advanced Fibrosis. Clin Gastroenterol Hepatol 2023; 21:2876-2888.e5. [PMID: 36848980 DOI: 10.1016/j.cgh.2023.02.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 01/30/2023] [Accepted: 02/13/2023] [Indexed: 03/01/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) and sarcopenia can be associated with advanced liver disease. Our aim was to assess the association between sarcopenia and the risk of fibrosis among patients with NAFLD. METHODS We used the National Health and Nutrition Examination Survey (2017-2018). NAFLD was defined by transient elastography without other causes of liver disease or excessive alcohol use. Significant fibrosis (SF) and advanced fibrosis (AF) were defined by liver stiffness greater than 8.0 kPa and greater than 13.1 kPa, respectively. Sarcopenia was defined using the Foundation for the National Institutes of Health definition. RESULTS Of the total cohort (N = 2422), 18.9% had sarcopenia, 9.8% had obese sarcopenia, 43.6% had NAFLD, 7.0% had SF, and 2.0% had AF. Moreover, 50.1% had neither sarcopenia nor NAFLD, 6.3% had sarcopenia without NAFLD, 31.1% had NAFLD without sarcopenia, and 12.5% had NAFLD with sarcopenia. Compared with individuals without NAFLD or sarcopenia, individuals with sarcopenic NAFLD had higher rates of SF (18.3% vs 3.2%) and AF (7.1% vs 0.2%). In the absence of sarcopenia, compared with individuals without NAFLD, individuals with NAFLD have a significantly increased risk of SF (odds ratio, 2.18; 95% CI, 0.92-5.19). In the presence of sarcopenia, NAFLD was associated with an increased risk of SF (odds ratio, 11.27; 95% CI, 2.79-45.56). This increase was independent of metabolic components. The proportion of SF that is attributable to the interaction of NAFLD and sarcopenia was 55% (attributable proportion, 0.55; 95% CI, 0.36-0.74). Increased leisure time physical activity was associated with a lower risk of sarcopenia. CONCLUSIONS Patients with sarcopenic NAFLD are at risk for SF and AF. Increased physical activity and a healthy diet targeted to improve sarcopenic NAFLD could reduce the risk of significant fibrosis.
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Affiliation(s)
- Michael Harring
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia
| | - Pegah Golabi
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - James M Paik
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Dipam Shah
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia
| | - Andrei Racila
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Rebecca Cable
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Manirath Srishord
- Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Zobair M Younossi
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
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15
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Polyzos SA, Vachliotis ID, Mantzoros CS. Sarcopenia, sarcopenic obesity and nonalcoholic fatty liver disease. Metabolism 2023; 147:155676. [PMID: 37544590 DOI: 10.1016/j.metabol.2023.155676] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/29/2023] [Accepted: 08/01/2023] [Indexed: 08/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), sarcopenia and sarcopenic obesity (SO) are highly prevalent conditions that may coexist, especially in the aging population, without any approved pharmacologic treatment for all of them. There are multiple pathophysiologic mechanisms suggested to explain an association between NAFLD and sarcopenia or SO, including alterations in the adipokines, cytokines, hepatokines and myokines, which may interplay with other factors, such as aging, diet and physical inactivity. In clinical terms, most observational studies support an association between NAFLD and sarcopenia or SO; importantly, there are few cohort studies indicating higher mortality in patients with NAFLD and sarcopenia. Their association also bears some treatment considerations: for example, pioglitazone or vitamin E, suggested as off label treatment for selected patients with nonalcoholic steatohepatitis, may be recommended in the coexistence of sarcopenia or SO, since limited evidence did not show adverse effects of them on sarcopenia and abdominal obesity. In this review, evidence linking sarcopenia and SO with NAFLD is summarized, with a special focus on clinical data. A synopsis of the major pathophysiological links between NAFLD and sarcopenia/SO is initially presented, followed by selected clinical studies and, finally, treatment considerations in patients with NAFLD and sarcopenia or SO are discussed.
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Affiliation(s)
- Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Ilias D Vachliotis
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christos S Mantzoros
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Internal Medicine, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
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16
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Weiler N, Bojunga J. Ernährung bei fortgeschrittener Leberzirrhose und perioperativ bei Lebertransplantation. DIE GASTROENTEROLOGIE 2023; 18:308-316. [DOI: 10.1007/s11377-023-00706-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/16/2023] [Indexed: 01/04/2025]
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17
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Yamamoto S, Honma K, Fujii M, Kakimoto M, Kirihara S, Nakayama H, Kitamori K, Sato I, Hirohata S, Watanabe S. SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet develop disease-induced sarcopenia as nonalcoholic steatohepatitis progresses. Ann Anat 2023; 249:152104. [PMID: 37209870 DOI: 10.1016/j.aanat.2023.152104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 03/07/2023] [Accepted: 05/10/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND Secondary sarcopenia develops as a result of a bedridden state and illnesses, such as cachexia, liver disease, and diabetes. However, there is a lack of animal models to investigate the underlying mechanisms and potential treatments for secondary sarcopenia. Recently, secondary sarcopenia has been associated with the prognosis of nonalcoholic steatohepatitis. This study aimed to investigate whether stroke-prone spontaneously hypertensive rat 5 (SHRSP5/Dmcr) which developed severe nonalcoholic steatohepatitis by a high-fat and high-cholesterol (HFC; containing 2% cholic acid) diet is a useful model of secondary sarcopenia. METHODS SHRSP5/Dmcr rats were divided into 6 groups fed with a Stroke-Prone (SP: normal chow) or HFC diets for different periods (4, 12, and 20 weeks), and WKY/Izm rats were divided into 2 groups fed an SP or HFC diet. Body weight, food intake, and muscle force were measured weekly for all rats. After the end of the diet period, skeletal muscle strength evoked by electrical stimulation was recorded, blood was collected, and organ weight was measured. The sera were used for biochemical analysis and the organs were used for histopathological analysis. RESULTS SHRSP5/Dmcr rats fed an HFC diet developed nonalcoholic steatohepatitis, and their skeletal muscles, especially fast muscles, showed atrophy, indicating that muscle atrophy is aggravated by the progression of nonalcoholic steatohepatitis. In contrast, WKY/Izm rats fed an HFC diet did not exhibit sarcopenia. CONCLUSIONS This study suggests that SHRSP5/Dmcr rats could be a useful novel model for investigate the mechanism of secondary sarcopenia disorder associated with nonalcoholic steatohepatitis.
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Affiliation(s)
- Shusei Yamamoto
- Faculty of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan; Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
| | - Koki Honma
- Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
| | - Moe Fujii
- Department of Medical Technology, Ehime Prefectural University of Health Sciences, 543, Takoda, Tobe-cho, Iyo-gun, Ehime 791-2101, Japan.
| | - Mai Kakimoto
- Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
| | - Sora Kirihara
- Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
| | - Hinako Nakayama
- Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
| | - Kazuya Kitamori
- College of Human Life and Environment, Kinjo Gakuin University, 2-1723, Omori, Moriyama-ku, Nagoya-shi, Aichi 463-8521, Japan.
| | - Ikumi Sato
- Faculty of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan; Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
| | - Satoshi Hirohata
- Faculty of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
| | - Shogo Watanabe
- Faculty of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity but around 10% to 20% of patients with NAFLD have normal body mass index, a condition referred to as lean or nonobese NAFLD. Although lean patients more often have milder liver disease, a proportion may nonetheless develop steatohepatitis and advanced liver fibrosis. Both genetic and environmental factors contribute to the development of NAFLD. Noninvasive tests have similarly good accuracy as initial assessments for lean NAFLD. Future studies should determine the most appropriate treatment in this special population.
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Affiliation(s)
- Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Vincent Wong
- Department of Medicine and Therapeutics, Medical Data Analytics Center, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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Kountouras J, Papaefthymiou A, Polyzos SA, Kazakos E, Tzilves D, Touloumtzi M, Chatzopoulos D, Tzitiridou-Chatzopoulou M, Liatsos C, Zavos C, Kavaliotis J, Kulaksiz H, Doulberis M. Letter: higher severe outcomes among Helicobacter pylori-related lean patients with non-alcoholic fatty liver disease and metabolic comorbidities. Aliment Pharmacol Ther 2023; 57:1186-1187. [PMID: 37094305 DOI: 10.1111/apt.17484] [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: 04/26/2023]
Affiliation(s)
- Jannis Kountouras
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Apostolis Papaefthymiou
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, UK
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Evangelos Kazakos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- Midwifery Department, School of Healthcare Sciences, University of West Macedonia, Kozani, Macedonia, Greece
| | - Dimitrios Tzilves
- Gastroenterology Department, Theageneio Hospital, Thessaloniki, Macedonia, Greece
| | - Maria Touloumtzi
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Dimitrios Chatzopoulos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Maria Tzitiridou-Chatzopoulou
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- Midwifery Department, School of Healthcare Sciences, University of West Macedonia, Kozani, Macedonia, Greece
| | - Christos Liatsos
- Department of Gastroenterology, General Military Hospital of Athens, Attiki, Greece
| | - Christos Zavos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - John Kavaliotis
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Hasan Kulaksiz
- Gastroklinik, Private Gastroenterological Practice, Horgen, Switzerland
| | - Michael Doulberis
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
- Gastroklinik, Private Gastroenterological Practice, Horgen, Switzerland
- Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland
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20
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Yuan S, Larsson SC. Epidemiology of sarcopenia: Prevalence, risk factors, and consequences. Metabolism 2023:155533. [PMID: 36907247 DOI: 10.1016/j.metabol.2023.155533] [Citation(s) in RCA: 325] [Impact Index Per Article: 162.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/21/2023] [Accepted: 03/04/2023] [Indexed: 03/14/2023]
Abstract
Sarcopenia is a geriatric condition featured by a progressive loss of muscle mass and function and associated with various adverse health outcomes. In this review, we aimed to summarize the epidemiological features of sarcopenia as well as consequences and risk factors of the disease. We performed a systematic review of meta-analysis on sarcopenia to collect data. The prevalence of sarcopenia varied between studies and depending on definition used. Sarcopenia was estimated to influence 10 %-16 % of the elderly worldwide. The prevalence of sarcopenia was higher among patients compared to general populations. The prevalence of sarcopenia ranged from 18 % in diabetic patients to 66 % in patients with unresectable esophageal cancer. Sarcopenia is associated with a high risk of a wide range of adverse health outcomes, including poor overall and disease-progression free survival rate, postoperative complications, and longer hospitalization in patients with different medical situations as well as falls and fracture, metabolic disorders, cognitive impairment, and mortality in general populations. Physical inactivity, malnutrition, smoking, extreme sleep duration, and diabetes were associated with an increased risk of sarcopenia. However, these associations were mainly based on non-cohort observational studies and need confirmation. High-quality cohort, omics, and Mendelian randomization studies are needed to deeply understand the etiological basis of sarcopenia.
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Affiliation(s)
- Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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21
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Linge J, Nasr P, Sanyal AJ, Dahlqvist Leinhard O, Ekstedt M. Adverse muscle composition is a significant risk factor for all-cause mortality in NAFLD. JHEP Rep 2023; 5:100663. [PMID: 36818816 PMCID: PMC9929853 DOI: 10.1016/j.jhepr.2022.100663] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 11/27/2022] [Indexed: 12/26/2022] Open
Abstract
Background & Aims Adverse muscle composition (MC) (i.e., low muscle volume and high muscle fat) has previously been linked to poor functional performance and comorbidities in non-alcoholic fatty liver disease (NAFLD). In this study we aimed to investigate associations of all-cause mortality with liver fat, NAFLD, and MC in the UK Biobank imaging study. Methods Magnetic resonance images of 40,174 participants were analyzed for liver proton density fat fraction (PDFF), thigh fat-free muscle volume (FFMV) z-score, and muscle fat infiltration (MFI) using the AMRA® Researcher. Participants with NAFLD were sex-, age-, and BMI-matched to participants without NAFLD with low alcohol consumption. Adverse MC was identified using previously published cut-offs. All-cause mortality was investigated using Cox regression. Models within NAFLD were crude and subsequently adjusted for sex, age, BMI (M1), hand grip strength, physical activity, smoking, alcohol (M2), and previous cancer, coronary heart disease, type 2 diabetes (M3). Results A total of 5,069 participants had NAFLD. During a mean (±SD) follow-up of 3.9 (±1.4) years, 150 out of the 10,138 participants (53% men, age 64.4 [±7.6] years, BMI 29.7 [±4.4] kg/m2) died. In the matched dataset, neither NAFLD nor liver PDFF were associated with all-cause mortality, while all MC variables achieved significance. Within NAFLD, adverse MC, MFI and FFMV z-score were significantly associated with all-cause mortality and remained so in M1 and M2 (crude hazard ratios [HRs] 2.84, 95% CI 1.70-4.75, p <0.001; 1.15, 95% CI 1.07-1.24, p <0.001; 0.70, 95% CI 0.55-0.88, p <0.001). In M3, the relationship was attenuated for adverse MC and FFMV z-score (adjusted HRs 1.72, 95% CI 1.00-2.98, p = 0.051; 0.77, 95% CI 0.58-1.02, p = 0.069) but remained significant for MFI (adjusted HR 1.13, 95% CI 1.01-1.26, p = 0.026). Conclusions Neither NAFLD nor liver PDFF was predictive of all-cause mortality. Adverse MC was a strong predictor of all-cause mortality in individuals with NAFLD. Impact and implications Individuals with fatty liver disease and poor muscle health more often suffer from poor functional performance and comorbidities. This study shows that they are also at a higher risk of dying. The study results indicate that measuring muscle health (the patient's muscle volume and how much fat they have in their muscles) could help in the early detection of high-risk patients and enable targeted preventative care.
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Affiliation(s)
- Jennifer Linge
- AMRA Medical AB, Linköping, Sweden
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Corresponding author. Address: Badhusgatan 5, 58 222 Linköping, Sweden. Tel.: +46 72 399 70 29..
| | - Patrik Nasr
- Department of Gastroenterology and Hepatology, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Arun J. Sanyal
- Stravitz-Sanyal Institute of Liver Disease and Metabolic Health, Department of Internal Medicine, VCU School of Medicine, Richmond, VA, USA
| | - Olof Dahlqvist Leinhard
- AMRA Medical AB, Linköping, Sweden
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
| | - Mattias Ekstedt
- Department of Gastroenterology and Hepatology, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
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Cho Y, Park HS, Huh BW, Lee YH, Seo SH, Seo DH, Ahn SH, Hong S, Kim SH. Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus. Diabetes Metab J 2023; 47:232-241. [PMID: 36653888 PMCID: PMC10040622 DOI: 10.4093/dmj.2021.0355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/18/2022] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis. RESULTS Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients. CONCLUSION NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.
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Affiliation(s)
- Yongin Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Hye-Sun Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Wook Huh
- Huh’s Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Yong-ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seong Ha Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Da Hea Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seong Hee Ahn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seongbin Hong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - So Hun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
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23
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Matsumoto Y, Fujii H, Harima M, Okamura H, Yukawa-Muto Y, Odagiri N, Motoyama H, Kotani K, Kozuka R, Kawamura E, Hagihara A, Uchida-Kobayashi S, Enomoto M, Yasui Y, Habu D, Kawada N. Severity of Liver Fibrosis Is Associated with the Japanese Diet Pattern and Skeletal Muscle Mass in Patients with Nonalcoholic Fatty Liver Disease. Nutrients 2023; 15:nu15051175. [PMID: 36904174 PMCID: PMC10005291 DOI: 10.3390/nu15051175] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 02/20/2023] [Accepted: 02/24/2023] [Indexed: 03/02/2023] Open
Abstract
It is not fully clear as to which dietary patterns are associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in Asia. We conducted a cross-sectional study of 136 consecutively recruited patients with NAFLD (49% female, median age 60 years). Severity of liver fibrosis was assessed using the Agile 3+ score, a recently proposed system based on vibration-controlled transient elastography. Dietary status was assessed using the 12-component modified Japanese diet pattern index (mJDI12). Skeletal muscle mass was assessed by bioelectrical impedance. Factors associated with intermediate-high-risk Agile 3+ scores and skeletal muscle mass (75th percentile or higher) were analyzed by multivariable logistic regression. After adjustment for confounders, such as age and sex, the mJDI12 (OR: 0.77; 95% CI: 0.61, 0.99) and skeletal muscle mass (75th percentile or higher) (OR: 0.23; 95% CI: 0.07, 0.77) were significantly associated with intermediate-high-risk Agile 3+ scores. Soybeans and soybean foods were significantly associated with skeletal muscle mass (75th percentile or higher) (OR: 1.02; 95% CI: 1.00, 1.04). In conclusion, the Japanese diet pattern was associated with the severity of liver fibrosis in Japanese patients with NAFLD. Skeletal muscle mass was also associated with the severity of liver fibrosis, and intake of soybeans and soybean foods.
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Affiliation(s)
- Yoshinari Matsumoto
- Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, 3-7-30 Habikino, Habikino-shi, Osaka 583-8555, Japan
| | - Hideki Fujii
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
- Correspondence: ; Tel.: +81-6-6645-3905
| | - Mika Harima
- Nutrition Department, Osaka Metropolitan University Hospital, 1-5-7 Asahimachi, Abeno-ku, Osaka 545-8586, Japan
| | - Haruna Okamura
- Nutrition Department, Osaka Metropolitan University Hospital, 1-5-7 Asahimachi, Abeno-ku, Osaka 545-8586, Japan
| | - Yoshimi Yukawa-Muto
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Naoshi Odagiri
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Hiroyuki Motoyama
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Kohei Kotani
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Ritsuzo Kozuka
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Etsushi Kawamura
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Atsushi Hagihara
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Sawako Uchida-Kobayashi
- Department of Premier Preventive Medicine, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
| | - Yoko Yasui
- Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, 3-7-30 Habikino, Habikino-shi, Osaka 583-8555, Japan
| | - Daiki Habu
- Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, 3-7-30 Habikino, Habikino-shi, Osaka 583-8555, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
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24
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Iwaki M, Kobayashi T, Nogami A, Saito S, Nakajima A, Yoneda M. Impact of Sarcopenia on Non-Alcoholic Fatty Liver Disease. Nutrients 2023; 15:nu15040891. [PMID: 36839249 PMCID: PMC9965462 DOI: 10.3390/nu15040891] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023] Open
Abstract
With the increasing incidence of non-alcoholic fatty liver disease (NAFLD) and the aging of the population, sarcopenia is attracting attention as one of the pathological conditions involved in the development and progression of NAFLD. In NAFLD, sarcopenia is closely associated with insulin resistance and results from the atrophy of skeletal muscle, an insulin target organ. In addition, inflammatory cytokines that promote skeletal muscle protein breakdown, low adiponectin levels leading to decreased insulin sensitivity, and hyperleptinemia are also involved in NAFLD pathogenesis. The presence of sarcopenia is a prognostic factor and increases the risk of mortality in patients with cirrhosis and post-treatment liver cancer. Sarcopenia, the presence of which mainly occurs due to decreased muscle mass, combined with increased visceral fat, can lead to sarcopenia-associated obesity, which increases the risk of NASH, liver fibrosis, and cardiovascular disease. In order to treat sarcopenia, it is necessary to properly evaluate sarcopenia status. Patients with high BMI, as in sarcopenic obesity, may improve with caloric restriction. However, inadequate oral intake may lead to further loss of muscle mass. Aerobic and resistance exercise should also be used appropriately.
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25
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Joo SK, Kim W. Interaction between sarcopenia and nonalcoholic fatty liver disease. Clin Mol Hepatol 2023; 29:S68-S78. [PMID: 36472051 PMCID: PMC10029947 DOI: 10.3350/cmh.2022.0358] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Sarcopenia and nonalcoholic fatty liver disease (NAFLD) are common health problems related to aging. Despite the differences in their diagnostic methods, several cross-sectional and longitudinal studies have revealed the close link between sarcopenia and NAFLD. Sarcopenia and NAFLD are linked by several shared pathogenetic mechanisms, including insulin resistance, hormonal imbalance, systemic inflammation, myostatin and adiponectin dysregulation, nutritional deficiencies, and physical inactivity, thus implicating a bidirectional relationship between sarcopenia and NAFLD. However, there is not sufficient data to support a direct causal relationship between sarcopenia and NAFLD. Moreover, it is currently difficult to conclude whether sarcopenia is a risk factor for nonalcoholic steatohepatitis (NASH) or is a consequence of NASH. Therefore, this review intends to touch on the shared common mechanisms and the bidirectional relationship between sarcopenia and NAFLD.
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Affiliation(s)
- Sae Kyung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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26
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Sachan A, Mandavdhare HS. EUS versus MRCP in patients with intermediate risk of choledocholithiasis: clinical and statistical viewpoint. Gut 2023; 72:209-210. [PMID: 35260445 DOI: 10.1136/gutjnl-2022-327239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 02/26/2022] [Indexed: 02/04/2023]
Affiliation(s)
- Anurag Sachan
- Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Harshal S Mandavdhare
- Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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27
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Van Dongen C, Paik JM, Harring M, Younossi Y, Price JK, Kabbara K, Golabi P, Younossi ZM. Sarcopenia, healthy living, and mortality in patients with chronic liver diseases. Hepatol Commun 2022; 6:3140-3153. [PMID: 35950286 PMCID: PMC9592796 DOI: 10.1002/hep4.2061] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 06/01/2022] [Accepted: 07/02/2022] [Indexed: 12/14/2022] Open
Abstract
Chronic liver diseases (CLDs) are associated with increased morbidity and mortality. Sarcopenia is an important complication of CLD that can be impacted by several modifiable risk factors. Our aim was to assess the associations between healthy living, sarcopenia, and long-term outcomes among patients with CLD. We used the Third National Health and Nutrition Examination Survey data with National Death Index-linked mortality files. We used the American Heart Association's Life's Simple 7 (LS7) metrics as surrogates of healthy living. The study included 12,032 subjects (34.9% CLDs [0.5% hepatitis B virus (HBV), 1.8% hepatitis C virus (HCV), 5.7% alcohol-associated liver disease (ALD), 26.9% nonalcoholic fatty liver disease (NAFLD)] and 65.1% controls). Prevalence of sarcopenia was higher among NAFLD than other CLDs and the controls (40.7% in NAFLD, 27.2% in ALD, 22.4% in HCV, 16.8% in HBV, and 18.5% in controls; p < 0.001). Among NAFLD and ALD, patients with sarcopenia were less likely to meet ideal LS7 metrics than those without sarcopenia. During 27 years of follow-up, among 4 patients with CLDs and the controls, all-cause cumulative mortality was highest among patients with HCV (35.2%), followed by ALD (34.7%) and NAFLD (29.6%). The presence of sarcopenia was associated with higher risk of all-cause mortality only among subjects with NAFLD (hazard ratio [HR] 1.24; 95% confidence interval [CI] 1.01-1.54; p = 0.04). Among subjects with NAFLD, presence of sarcopenia was associated with higher risk of cardiovascular-specific (HR 2.28 [1.71-3.05; p < 0.01]), cancer-specific (HR 1.90 [1.37-2.65]; p < 0.01), diabetes-specific (HR 6.42 [2.87-14.36]; p < 0.01), and liver-specific mortality (HR 2.49 [1.08-5.76]; p = 0.04). The multivariable model showed that component of LS7 metrics that provided the strongest protection against sarcopenia were ideal body mass index, ideal blood pressure, ideal physical activity, and ideal glycemic control among subjects with NAFLD subjects. Conclusions: Among subjects with NAFLD, sarcopenia is associated with a higher risk of all-cause mortality and liver mortality. Attainment of ideal LS7 metrics provides protection against sarcopenia in NAFLD.
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Affiliation(s)
- Catherine Van Dongen
- Betty and Guy Beatty Center for Integrated Research, Inova Health SystemFalls ChurchVirginiaUSA
| | - James M. Paik
- Betty and Guy Beatty Center for Integrated Research, Inova Health SystemFalls ChurchVirginiaUSA
- Center for Liver Disease, Department of MedicineInova Fairfax Medical CampusFalls ChurchVirginiaUSA
| | - Michael Harring
- Center for Liver Disease, Department of MedicineInova Fairfax Medical CampusFalls ChurchVirginiaUSA
| | - Youssef Younossi
- Center for Outcomes Research in Liver DiseasesWashingtonDistrict of ColumbiaUSA
| | - Jillian K. Price
- Betty and Guy Beatty Center for Integrated Research, Inova Health SystemFalls ChurchVirginiaUSA
| | - Khaled Kabbara
- Center for Liver Disease, Department of MedicineInova Fairfax Medical CampusFalls ChurchVirginiaUSA
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health SystemFalls ChurchVirginiaUSA
- Center for Liver Disease, Department of MedicineInova Fairfax Medical CampusFalls ChurchVirginiaUSA
- Inova Medicine, Inova Health SystemFalls ChurchVirginiaUSA
| | - Zobair M. Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health SystemFalls ChurchVirginiaUSA
- Center for Liver Disease, Department of MedicineInova Fairfax Medical CampusFalls ChurchVirginiaUSA
- Inova Medicine, Inova Health SystemFalls ChurchVirginiaUSA
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28
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Almeida NS, Rocha R, de Souza CA, da Cruz ACS, Ribeiro BDR, Vieira LV, Daltro C, Silva R, Sarno M, Cotrim HP. Prevalence of sarcopenia using different methods in patients with non-alcoholic fatty liver disease. World J Hepatol 2022; 14:1643-1651. [PMID: 36157861 PMCID: PMC9453470 DOI: 10.4254/wjh.v14.i8.1643] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/11/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Sarcopenia is a clinical condition associated with several liver diseases and it includes non-alcoholic fatty liver disease (NAFLD) in its broad spectrum as steatosis, steatohepatitis and fibrosis. However, the criteria to define sarcopenia are diverse, and even those established in consensus have been discussed regarding their performance in making an accurate diagnosis. AIM To evaluate the prevalence of sarcopenia, using different methods, in patients with NAFLD, and its association with clinical-anthropometric parameters. METHODS This was an observational study of outpatients with NAFLD. Sarcopenia was defined by the European Working Group Consensus on Sarcopenia in Older People of 2010 (EWGSOP1) and 2018 (EWGSOP2). The skeletal muscle index was used to estimate muscle mass, handgrip strength was assessed using the dynamometer and physical performance by walking a distance of four meters at usual walking speed. The non-invasive fibrosis scores, fibrosis-4 (FIB-4) index and Aspartate aminotransferase to platelet ratio index (APRI), were used to assess the absence and presence of fibrosis. RESULTS Fifty-seven individuals with NAFLD were evaluated, the mean age (SD) was 52.7 (11.3) years and 75.4% were female. Fibrosis assessed by FIB-4 and APRI was observed in 3.7% and 16.6% of patients with NAFLD, respectively. The diagnosis of sarcopenia was identified only by EWGSOP1 in 3.5% of NAFLD patients, and the prevalence of probable/pre-sarcopenia was higher using the EWGSOP2 consensus at 26.3%, when compared to 1.8% with EWGSOP1. Sarcopenia defined by EWGSOP1, was associated with grade I steatosis, but without overweight (P < 0.05). An association between sarcopenia and fibrosis was not observed (P > 0.05). EWGSOP2 showed a greater number of patients with probable sarcopenia, and who were overweight (12 (80.0%)), with a higher degree of steatosis [11 (73.3%) and presence of fibrosis (1 (6.7%), FIB-4 and 3 (20.0%), APRI] compared to EWGSOP1 [1 (100%), 0 (0.0%), 0 (0.0%), FIB-4 and 0 (0.0%), APRI, respectively]. CONCLUSION The present study showed that sarcopenia in NAFLD was not predominant in patients without fibrosis, by both diagnostic methods. In addition, the prevalence of probable sarcopenia also depends on the method applied.
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Affiliation(s)
- Naiade Silveira Almeida
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
| | - Raquel Rocha
- Departamento de Ciência da Nutrição, Escola de Nutrição, Universidade Federal da Bahia, Salvador 40110-060, Brazil.
| | - Claudineia Almeida de Souza
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
| | - Ana Carolina Sirelli da Cruz
- Departamento de Ciência da Nutrição, Escola de Nutrição, Universidade Federal da Bahia, Salvador 40110-060, Brazil
| | - Bruna Dos Reis Ribeiro
- Departamento de Ciência da Nutrição, Escola de Nutrição, Universidade Federal da Bahia, Salvador 40110-060, Brazil
| | - Luiza Valois Vieira
- Departamento de Ciência da Nutrição, Escola de Nutrição, Universidade Federal da Bahia, Salvador 40110-060, Brazil
| | - Carla Daltro
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
- Departamento de Ciência da Nutrição, Escola de Nutrição, Universidade Federal da Bahia, Salvador 40110-060, Brazil
| | - Rafael Silva
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
- Caliper Clínica e Escola de Imagem, Salvador 41810-012, Brazil
| | - Manoel Sarno
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
- Caliper Clínica e Escola de Imagem, Salvador 41810-012, Brazil
| | - Helma Pinchemel Cotrim
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
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29
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Non-alcoholic fatty liver disease-related fibrosis and sarcopenia: An altered liver-muscle crosstalk leading to increased mortality risk. Ageing Res Rev 2022; 80:101696. [PMID: 35843589 DOI: 10.1016/j.arr.2022.101696] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/11/2022] [Accepted: 07/13/2022] [Indexed: 11/22/2022]
Abstract
In the last few decades, the loss of skeletal muscle mass and function, known as sarcopenia, has significantly increased in prevalence, becoming a major global public health concern. On the other hand, the prevalence of non-alcoholic fatty liver disease (NAFLD) has also reached pandemic proportions, constituting the leading cause of hepatic fibrosis worldwide. Remarkably, while sarcopenia and NAFLD-related fibrosis are independently associated with all-cause mortality, the combination of both conditions entails a greater risk for all-cause and cardiac-specific mortality. Interestingly, both sarcopenia and NAFLD-related fibrosis share common pathophysiological pathways, including insulin resistance, chronic inflammation, hyperammonemia, alterations in the regulation of myokines, sex hormones and growth hormone/insulin-like growth factor-1 signaling, which may explain reciprocal connections between these two disorders. Additional contributing factors, such as the gut microbiome, may also play a role in this relationship. In skeletal muscle, phosphatidylinositol 3-kinase/Akt and myostatin signaling are the central anabolic and catabolic pathways, respectively, and the imbalance between them can lead to muscle wasting in patients with NAFLD-related fibrosis. In this review, we summarize the bidirectional influence between NAFLD-related fibrosis and sarcopenia, highlighting the main potential mechanisms involved in this complex crosstalk, and we discuss the synergistic effects of both conditions in overall and cardiovascular mortality.
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30
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Karakousis ND, Chrysavgis L, Chatzigeorgiou A, Papatheodoridis G, Cholongitas E. Frailty in metabolic syndrome, focusing on nonalcoholic fatty liver disease. Ann Gastroenterol 2022; 35:234-242. [PMID: 35599934 PMCID: PMC9062844 DOI: 10.20524/aog.2022.0705] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 02/07/2022] [Indexed: 11/11/2022] Open
Abstract
In recent years, frailty has been increasingly recognized among researchers of distinct medical specialties worldwide. Frailty comprises a complex of multisystemic physiological decline, reduced physiologic reserve, and vulnerability to stressors. Frail people tend to have a shorter lifespan and greater disability, morbidity and mortality. In the field of hepatology, frailty is identified in nearly 50% of patients who have cirrhosis of any cause. The most predominant cause of chronic liver disease is nonalcoholic fatty liver disease (NAFLD), considered as the hepatic manifestation of the metabolic syndrome (MetS). Although it is viewed as a benign disease, it may progress to nonalcoholic steatohepatitis (NASH), characterized by the additional emergence of inflammation and hepatocyte ballooning, with or without fibrosis. During the progression of NAFLD to NASH and liver cirrhosis, NAFLD patients present sarcopenia along with lower skeletal muscle strength and function. Moreover, aging and the increased prevalence of comorbidities further exacerbate their physical performance. The aforementioned features are strongly associated with the frailty phenotype, implying that the latter could be associated with both MetS and NAFLD. Although it is a relatively new topic of research interest, in this review we aim to provide a synopsis of the current literature dealing with the interplay between frailty and MetS, and to shed more light on the association between NAFLD and frailty. Finally, we discuss the potential pathophysiological mechanisms linking the distinct features of MetS and NAFLD with aspects of the frailty phenotype.
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Affiliation(s)
- Nikolaos D. Karakousis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, “Laiko” General Hospital of Athens, Greece (Nikolaos D. Karakousis, George Papatheodoridis)
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece (Nikolaos D. Karakousis, Lampros Chrysavgis, Antonios Chatzigeorgiou)
| | - Lampros Chrysavgis
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece (Nikolaos D. Karakousis, Lampros Chrysavgis, Antonios Chatzigeorgiou)
| | - Antonios Chatzigeorgiou
- Department of Physiology, Medical School of National and Kapodistrian University of Athens, Athens, Greece (Nikolaos D. Karakousis, Lampros Chrysavgis, Antonios Chatzigeorgiou)
- Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (Antonios Chatzigeorgiou)
| | - George Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, “Laiko” General Hospital of Athens, Greece (Nikolaos D. Karakousis, George Papatheodoridis)
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, “Laiko” General Hospital of Athens, Athens, Greece (Evangelos Cholongitas)
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31
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Kouvari M, Polyzos SA, Chrysohoou C, Skoumas J, Pitsavos CS, Panagiotakos DB, Mantzoros CS. Skeletal Muscle Mass and Abdominal Obesity are Independent Predictors of Hepatic Steatosis and Interact to Predict Ten-Year Cardiovascular Disease Incidence: Data from the ATTICA Cohort Study. Clin Nutr 2022; 41:1281-1289. [DOI: 10.1016/j.clnu.2022.03.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 02/28/2022] [Accepted: 03/20/2022] [Indexed: 11/03/2022]
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32
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Fang D, Tang W, Zhao X, Sun H, Gu T, Bi Y. Gender differences in the association of body composition and biopsy-proved nonalcoholic steatohepatitis. Hepatol Int 2022; 16:337-347. [PMID: 35201574 DOI: 10.1007/s12072-021-10265-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/20/2021] [Indexed: 11/04/2022]
Abstract
BACKGROUND AND AIM Body composition was associated with nonalcoholic steatohepatitis (NASH), but results were controversial probably due to gender differences. Hence, we aim to explore the association of body composition and NASH in males and females. METHODS We conducted a cross-sectional analysis of obese subjects undergone liver biopsy. According to NASH Clinical Research Network system, subjects were categorized as Normal Control (NC), non-NASH or NASH. Body composition was accessed by dual-energy X-ray absorptiometry. RESULTS This study enrolled 336 subjects (mean age 32.0 years, mean BMI 39.15 kg/m2, female, 64.0%). Males have lower relative muscle mass (RMM 55.21 ± 4.07%) and females have higher android to gynoid ratio (AGR, 0.82 ± 0.21) in NASH when compared with non-NASH (RMM 57.49 ± 4.75%; AGR 0.7 ± 0.15) and NC (RMM 58.69 ± 4.09%; AGR 0.66 ± 0.19, p < 0.05 for each). After adjusting for confounding factors, low RMM was the independent risk factor for NASH in males (odds ratio [OR] 0.550; 95% confidence interval [CI] 0.312-0.970), high AGR was the independent risk factor for NASH in females (OR 1.694; 95% CI 1.073-2.674). Further, RMM in males and AGR in females, respectively, was associated with liver steatosis and activity, but not with fibrosis. ROC curve revealed that the optimal cutoff value of RMM was 58.09% in males and AGR was 0.92 in females for predicting NASH. CONCLUSIONS We firstly revealed that low RMM and high AGR were the independent risk factors for NASH in males and females, respectively, indicating that sex-specific interventions for improving body composition may reduce the risk of NASH in obese subjects.
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Affiliation(s)
- Da Fang
- Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Wenjuan Tang
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoyu Zhao
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Haixiang Sun
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Tianwei Gu
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
| | - Yan Bi
- Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. .,Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
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Qiong L, Jie Z, Zhong Z, Wen S, Jun Z, Liping L, Jinkui C. Detection of hepatocellular carcinoma in a population at risk: iodine-enhanced multidetector CT and/or gadoxetic acid-enhanced 3.0 T MRI. BMJ Open 2022; 12:e058461. [PMID: 35177466 PMCID: PMC8860074 DOI: 10.1136/bmjopen-2021-058461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE To evaluate the diagnostic performance of iodine-enhanced multidetector CT and gadoxetic acid-enhanced 3.0 Tesla (T) MRI for detection of hepatocellular carcinoma of patients. DESIGN Retrospective, multicentre cohort study. SETTING The Gong'an County People's Hospital, Gong'an County, China and the First People's Hospital of Jingzhou City, China. PARTICIPANTS Reports of CT, MRI and liver biopsies/histopathology data of a total of 815 patients who at risk were reviewed. PRIMARY AND SECONDARY OUTCOME MEASURES The lesions that possessed detection in the plain scan phase, enhanced arterial phase and/or enhanced portal phase of CT images and the lesions that possessed enhancements in the plain scan phase, enhanced arterial phase, enhanced portal phase and/or hepatobiliary phases of MRI were considered hepatocellular carcinoma. The decision of hepatocellular carcinoma was made based on the current Liver Imaging and Data Reporting System for diagnosing hepatocellular carcinoma. RESULTS True positive hepatocellular carcinoma (563 vs 521, p=0.0314), true negative hepatocellular carcinoma (122 vs 91, p=0.0275), false positive hepatocellular carcinoma (88 vs 123, p=0.0121), false negative hepatocellular carcinoma (42 vs 80, p=0.0005), specificity (58.10 vs 42.52, p=0.0478) and negative clinical utility (0.1 vs 0.073, p=0.0386) were superior for gadoxetic acid-enhanced 3.0 T MRI than those of iodine-enhanced multidetector CT. Sensitivity and accuracy for gadoxetic acid-enhanced 3.0 T MRI were 93.06% and 77.40 %, respectively, and those for iodine-enhanced multidetector CT were 86.69% and 75.09 %, respectively. Likelihood to detect hepatocellular carcinoma for gadoxetic acid-enhanced 3.0 T MRI was 0-0.894 diagnostic confidence/lesion, and that for iodine-enhanced multidetector CT was 0-0.887 diagnostic confidence/lesion. CONCLUSION Gadoxetic acid-enhanced 3.0 T MRI facilitates the confidence of initiation of treatment of hepatocellular carcinoma. LEVEL OF EVIDENCE III. TECHNICAL EFFICACY STAGE 4.
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Affiliation(s)
- Lan Qiong
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Zhao Jie
- Department of Rehabilitation, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Zheng Zhong
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Sheng Wen
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Zhao Jun
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Lu Liping
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Cheng Jinkui
- Department of Ophthalmology, The First People's Hospital of Jingzhou, Jingzhou, Hubei, China
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Hong J, Shin WK, Lee JW, Lee SY, Kim Y. Associations of Serum Vitamin D Level with Sarcopenia, Non-Alcoholic Fatty Liver Disease (NAFLD), and Sarcopenia in NAFLD Among People Aged 50 Years and Older: The Korea National Health and Nutrition Examination Survey IV-V. Metab Syndr Relat Disord 2022; 20:210-218. [PMID: 35100057 DOI: 10.1089/met.2021.0106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: The role of serum 25-hydroxyvitamin D [25(OH)D] levels in the development of sarcopenia in non-alcoholic fatty liver disease (NAFLD) remains controversial. We investigated the association between vitamin D levels, occurrence of sarcopenia, NAFLD, and sarcopenia in NAFLD in adults aged >50 years. Methods: This study used data pertaining to 5396 adults aged >50 years (1870 men and 3526 women) from the 2008-2011 Korea National Health and Nutrition Examination Survey. Appendicular skeletal muscle mass adjusted by weight (ASM/Wt) was used to diagnose sarcopenia, and NAFLD was diagnosed using the NAFLD fat score. Results: The lowest quintile of serum 25(OH)D level (4.85-15.26 ng/mL) was associated with an increased occurrence of sarcopenia [odds ratio (OR) 2.65; 95% confidence interval (CI) 1.64-4.27], NAFLD (OR 1.82; 95% CI 1.19-2.96), and sarcopenia in NAFLD (OR 2.25; 95% CI 1.26-4.03) in men. In women, sarcopenia (OR 1.80; 95% CI 1.29-2.51) was also significantly associated with serum vitamin D levels, whereas high levels of vitamin D were not significantly related to NAFLD. Conclusions: Serum vitamin D levels are associated with sarcopenia, NAFLD, and sarcopenia in NAFLD. Vitamin D level can be a useful marker of sarcopenia and NAFLD, especially in men.
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Affiliation(s)
- Jihye Hong
- Department of Human Ecology, Graduate School, Korea University, Seoul, Korea
| | - Woo-Kyoung Shin
- Department of Preventive Medicine, College of Medicine, Seoul National University, Seoul, Korea
| | - Jung Woo Lee
- Department of Human Ecology, Graduate School, Korea University, Seoul, Korea
| | - Seung-Yeon Lee
- Department of Nutritional Sciences, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA
| | - Yookyung Kim
- Department of Human Ecology, Graduate School, Korea University, Seoul, Korea
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Zambon Azevedo V, Silaghi CA, Maurel T, Silaghi H, Ratziu V, Pais R. Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease. Front Nutr 2022; 8:774030. [PMID: 35111794 PMCID: PMC8802760 DOI: 10.3389/fnut.2021.774030] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the "sarcopenic NAFLD phenotype." This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.
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Affiliation(s)
- Vittoria Zambon Azevedo
- Doctoral School Physiology, Physiopathology and Therapeutics 394, Sorbonne Université, Paris, France
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Thomas Maurel
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
| | - Horatiu Silaghi
- Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Vlad Ratziu
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
| | - Raluca Pais
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS 938, Paris, France
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Pivtorak KV, Marchuk OV. NON-ALCOHOLIC FATTY LIVER DISEASE AND SARCOPENIA. BULLETIN OF PROBLEMS BIOLOGY AND MEDICINE 2022. [DOI: 10.29254/2077-4214-2022-3-166-79-86] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Danielsson O, Nissinen MJ, Jula A, Salomaa V, Männistö S, Lundqvist A, Perola M, Åberg F. Waist and hip circumference are independently associated with the risk of liver disease in population-based studies. Liver Int 2021; 41:2903-2913. [PMID: 34510711 DOI: 10.1111/liv.15053] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/30/2021] [Accepted: 09/04/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS While several anthropometric measures predict liver disease, the waist-hip ratio (WHR) has shown superiority in previous studies. We analysed independent and joint associations of waist circumference (WC) and hip circumference (HC) with liver disease and liver-related risk factors. METHODS Cross-sectional study (n = 6619) and longitudinal cohort (n = 40 923) comprised individuals from Health 2000 and FINRISK 1992-2012 studies. Prevalent and viral liver diseases were excluded. Longitudinal cohort was linked with national healthcare registers for severe incident liver disease. Linear regression and Cox proportional hazards models were used to analyse anthropometric, lifestyle, metabolic and bioimpedance-related parameters; liver enzymes; and 59 liver-related genetic risk variants. RESULTS WC and HC showed independent and opposite associations with both liver enzymes and incident liver disease among men (HR for liver disease: WC, 1.07, 95% CI 1.03-1.11; HC, 0.96, 95% CI 0.92-0.99; P-range .04 to <.001) and women (HR for liver diseases: WC, 1.06, 95% CI 1.02-1.10; HC, 0.93, 95% CI 0.89-0.98; P-range .005 to .004). HC modified associations between WC and liver enzymes, and between WC and incident liver disease, particularly among men. Liver enzymes and risk of liver disease increased with increasing WC, more so among individuals with high WHR compared to with low WHR. WC and HC jointly reflected both body fat distribution and muscle mass, which was largely mirrored by WHR. CONCLUSIONS WC and HC exhibit independent and joint associations with liver disease, which are largely reflected by WHR. Both body fat distribution and muscle mass contribute to these anthropometric measures.
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Affiliation(s)
- Oscar Danielsson
- Clinic of Gastroenterology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
| | - Markku J Nissinen
- Clinic of Gastroenterology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
| | - Antti Jula
- Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Veikko Salomaa
- Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Satu Männistö
- Finnish Institute for Health and Welfare, Helsinki, Finland
| | | | - Markus Perola
- Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Fredrik Åberg
- Transplantation and Liver Surgery, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
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Forlano R, Harlow C, Mullish BH, Thursz MR, Manousou P, Yee M. Binge-eating disorder is associated with an unfavorable body mass composition in patients with non-alcoholic fatty liver disease. Int J Eat Disord 2021; 54:2025-2030. [PMID: 34272900 DOI: 10.1002/eat.23584] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 07/08/2021] [Accepted: 07/09/2021] [Indexed: 12/14/2022]
Abstract
The interaction between eating disorders and non-alcoholic fatty liver disease (NAFLD) remains unexplored, especially with regards to binge-eating disorder (BED). Our team conducted a service evaluation project in order to assess risk factors for the presence of BED among patients with NAFLD and the impact of BED on body mass composition. The overall prevalence of patients screening positive to BED Screener-7 (BEDS-7) was 28.4%, while a previous diagnosis of depression and marital status (as single or separated) were independently associated with positive BED. Furthermore, patients with positive BEDS-7 had higher BMI, with greater visceral component and overall lower muscle mass. There was no difference in terms of liver disease severity as assessed by noninvasive markers of fibrosis. However, as body mass composition and sarcopenia have been shown to be associated to disease progression in patients with NAFLD, further studies are required to ascertain the long-term impact of BED in these patients. Moreover, further work is warranted to identify to implement multidisciplinary approach within clinical psychology for the management of patients with BED, who may be particularly challenging in terms of achieving lifestyle modifications. As a hepatology community, we should address NAFLD with a more holistic approach.
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Affiliation(s)
- Roberta Forlano
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Christopher Harlow
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Benjamin H Mullish
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Mark R Thursz
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Pinelopi Manousou
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Michael Yee
- Section of Endocrinology and Metabolic Medicine, St Mary's Hospital, Imperial College NHS Trust, London, UK
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Miele L, Perna A, Dajko M, Zocco MA, De Magistris A, Nicoletti TF, Biolato M, Marrone G, Liguori A, Maccora D, Valenza V, Rossi S, Riso V, Di Natale D, Gasbarrini A, Grieco A, Silvestri G. Clinical characteristics of metabolic associated fatty liver disease (MAFLD) in subjects with myotonic dystrophy type 1 (DM1). Dig Liver Dis 2021; 53:1451-1457. [PMID: 33436321 DOI: 10.1016/j.dld.2020.12.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 12/14/2020] [Accepted: 12/15/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated with insulin resistance, and its association with metabolically associated fatty liver disease (MAFLD) has never been explored in prospective studies. The aim of this study was to assess the clinical features of MAFLD in DM1 patients. METHODS We investigated the prevalence and the diagnostic features of MAFLD in a cohort of 29 outpatient fully characterized DM1 patients; afterward, we compared the selected cohort of DM1-MAFLD individuals with a propensity-matched cohort of non-DM1-MAFLD RESULTS: 13/29 (44.83%) DM1 patients received a clinical diagnosis of MAFLD. Compared to DM1 patients with normal liver, DM1-MAFLD individuals showed a higher male prevalence (p = 0.008), BMI (p = 0.014), HOMA score (p = 0.012), and GGT levels (p = 0.050). The statistical comparison showed that the DM1-MAFLD group had a more severe MAFLD according to the FIB4 score than non-DM1-MAFLD patients. This association of a more severe form of liver disease with DM1 remained significant after logistic regression analysis (OR: 6.12, 95% CI 1.44- 26.55).
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Affiliation(s)
- Luca Miele
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy.
| | - Alessia Perna
- Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Marianxhela Dajko
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Maria A Zocco
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Antonio De Magistris
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Tommaso F Nicoletti
- Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Marco Biolato
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Giuseppe Marrone
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Antonio Liguori
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Daria Maccora
- Department of Radiology, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Venanzio Valenza
- Department of Radiology, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Salvatore Rossi
- Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Vittorio Riso
- Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Daniele Di Natale
- Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Antonio Grieco
- Department of Medical and Surgical Sciences. Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
| | - Gabriella Silvestri
- Department of Neuroscience, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del S. Cuore, Roma, Italy
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Nishikawa H, Asai A, Fukunishi S, Nishiguchi S, Higuchi K. Metabolic Syndrome and Sarcopenia. Nutrients 2021; 13:3519. [PMID: 34684520 PMCID: PMC8541622 DOI: 10.3390/nu13103519] [Citation(s) in RCA: 159] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/30/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
Skeletal muscle is a major organ of insulin-induced glucose metabolism. In addition, loss of muscle mass is closely linked to insulin resistance (IR) and metabolic syndrome (Met-S). Skeletal muscle loss and accumulation of intramuscular fat are associated with a variety of pathologies through a combination of factors, including oxidative stress, inflammatory cytokines, mitochondrial dysfunction, IR, and inactivity. Sarcopenia, defined by a loss of muscle mass and a decline in muscle quality and muscle function, is common in the elderly and is also often seen in patients with acute or chronic muscle-wasting diseases. The relationship between Met-S and sarcopenia has been attracting a great deal of attention these days. Persistent inflammation, fat deposition, and IR are thought to play a complex role in the association between Met-S and sarcopenia. Met-S and sarcopenia adversely affect QOL and contribute to increased frailty, weakness, dependence, and morbidity and mortality. Patients with Met-S and sarcopenia at the same time have a higher risk of several adverse health events than those with either Met-S or sarcopenia. Met-S can also be associated with sarcopenic obesity. In this review, the relationship between Met-S and sarcopenia will be outlined from the viewpoints of molecular mechanism and clinical impact.
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Affiliation(s)
- Hiroki Nishikawa
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan; (A.A.); (S.F.); (K.H.)
- Premier Departmental Research of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan
| | - Akira Asai
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan; (A.A.); (S.F.); (K.H.)
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan; (A.A.); (S.F.); (K.H.)
- Premier Departmental Research of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan
| | | | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan; (A.A.); (S.F.); (K.H.)
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Kuchay MS, Martínez-Montoro JI, Choudhary NS, Fernández-García JC, Ramos-Molina B. Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges. Biomedicines 2021; 9:biomedicines9101346. [PMID: 34680463 PMCID: PMC8533092 DOI: 10.3390/biomedicines9101346] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/23/2021] [Accepted: 09/27/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), which approximately affects a quarter of the world’s population, has become a major public health concern. Although usually associated with excess body weight, it may also affect normal-weight individuals, a condition termed as lean/non-obese NAFLD. The prevalence of lean/non-obese NAFLD is around 20% within the NAFLD population, and 5% within the general population. Recent data suggest that individuals with lean NAFLD, despite the absence of obesity, exhibit similar cardiovascular- and cancer-related mortality compared to obese NAFLD individuals and increased all-cause mortality risk. Lean and obese NAFLD individuals share several metabolic abnormalities, but present dissimilarities in genetic predisposition, body composition, gut microbiota, and susceptibility to environmental factors. Current treatment of lean NAFLD is aimed at improving overall fitness and decreasing visceral adiposity, with weight loss strategies being the cornerstone of treatment. Moreover, several drugs including PPAR agonists, SGLT2 inhibitors, or GLP-1 receptor agonists could also be useful in the management of lean NAFLD. Although there has been an increase in research regarding lean NAFLD, there are still more questions than answers. There are several potential drugs for NAFLD therapy, but clinical trials are needed to evaluate their efficacy in lean individuals.
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Affiliation(s)
- Mohammad Shafi Kuchay
- Division of Endocrinology and Diabetes, Medanta The Medicity Hospital, Gurugram 122001, Haryana, India;
| | - José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain;
| | | | - José Carlos Fernández-García
- Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain
- Correspondence: (J.C.F.-G.); (B.R.-M.)
| | - Bruno Ramos-Molina
- Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain
- Correspondence: (J.C.F.-G.); (B.R.-M.)
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Differences among Three Skeletal Muscle Mass Indices in Predicting Non-Alcoholic Fatty Liver Disease: Korean Nationwide Population-Based Study. Life (Basel) 2021; 11:life11080751. [PMID: 34440495 PMCID: PMC8401633 DOI: 10.3390/life11080751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/16/2021] [Accepted: 07/25/2021] [Indexed: 02/06/2023] Open
Abstract
Recent studies have investigated the relationship between sarcopenia and non-alcoholic fatty liver disease (NAFLD); however, there is no unified definition of sarcopenia. Thus, we aimed to investigate the differences among three skeletal muscle mass indices (SMI) in predicting NAFLD. This study included 8133 adults from the 2008–2010 Korea National Health and Nutrition Survey. SMI was calculated as appendicular skeletal muscle mass divided by height-square (hSMI), weight (wSMI), or body mass index (bSMI). The presence of NAFLD was defined by using the NAFLD-liver fat score. On the receiver operating characteristic curve analysis, the predictive power of wSMI for NAFLD was significantly higher than those of hSMI and bSMI in men (wSMI vs. hSMI, p = 0.003; wSMI vs. bSMI, p < 0.001). In women, the predictive power of hSMI was only significantly higher than that of bSMI (p = 0.023), and other predictive powers were not significantly different. In addition, hSMI was correlated with insulin resistance and NAFLD-liver fat score in the opposite direction to wSMI and bSMI in both men and women. Among the three definitions of SMI, wSMI showed the highest diagnostic performance for predicting NAFLD in men, suggesting the importance of defining sarcopenia for its association with specific diseases.
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Habig G, Smaltz C, Halegoua-DeMarzio D. Presence and Implications of Sarcopenia in Non-alcoholic Steatohepatitis. Metabolites 2021; 11:242. [PMID: 33920751 PMCID: PMC8071144 DOI: 10.3390/metabo11040242] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/09/2021] [Accepted: 04/11/2021] [Indexed: 12/11/2022] Open
Abstract
Sarcopenia, defined as the loss of muscle strength, mass, and functionality, confers a poor prognosis in the setting of cirrhosis. Given its clinical significance, a better understanding of the underlying mechanisms leading to cirrhosis, sarcopenia, and their co-occurrence may improve these patients' outcomes. Non-alcoholic steatohepatitis (NASH) shares many of the same etiologies as sarcopenia, including insulin resistance, chronic inflammation, and ectopic adipocyte deposition, which are hallmarks of metabolic syndrome (MS). NASH thus serves as a prime candidate for further exploration into the underlying pathophysiology and relationship between these three conditions. In this review, we discuss the natural history of NASH and sarcopenia, explore the interplay between these conditions in the scope of MS, and seek to better define how an assessment of muscle mass, strength, and functionality in this population is key to improved diagnosis and management of patients with sarcopenia and NASH.
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Affiliation(s)
- Gregory Habig
- Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA; (G.H.); (C.S.)
| | - Christa Smaltz
- Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA; (G.H.); (C.S.)
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA 19107, USA
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44
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Gonzalez A, Valero-Breton M, Huerta-Salgado C, Achiardi O, Simon F, Cabello-Verrugio C. Impact of exercise training on the sarcopenia criteria in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Transl Myol 2021; 31. [PMID: 33709647 PMCID: PMC8056167 DOI: 10.4081/ejtm.2021.9630] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/07/2021] [Indexed: 12/19/2022] Open
Abstract
Sarcopenia is a highly prevalent complication of non-alcoholic fatty liver disease (NAFLD). We aimed to conduct a systematic review and meta-analyses to elucidate the exercise training (ET)'s efficacy on NAFLD adult patients' sarcopenia criteria. We identified relevant randomized controlled trials (RCT) in electronic databases PubMed, CINAHL, and Scopus. We selected seven RCT from 66 screened studies. The ET programs included endurance or combined (endurance and resistance) training. No study performed resistance training alone. The physical function improved with endurance or combined training (mean differences [MD] 8.26 mL/Kg*min [95% CI 5.27 to 11.24 mL/Kg*min], p < 0.0001); Muscle mass showed no evidence of the beneficial effects of endurance or combined training (MD 1.01 Kg [95% CI -1.78 to 3.80 Kg], p = 0.48). None of the selected studies evaluated muscle strength. Endurance and combined training increase physical function criteria but do not improve muscle mass criteria on sarcopenia in NAFLD patients. These results must be interpreted with caution for the small number of patients included in the RCTs analyzed, the different characteristics of the ET carried out, the non-use of resistance training, which prevents assess its effect on sarcopenia despite the evidence that recommends it and does not assessment muscle strength criteria in RCT include. Future research should include muscle strength assessments and resistance training to evaluate the effects in this condition. Exercise training is beneficial for sarcopenia in NAFLD but is necessary more experimental evidence to define the best type of training that positively affects the three criteria of sarcopenia. PROSPERO reference number CRD42020191471.
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Affiliation(s)
- Andrea Gonzalez
- Laboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago.
| | - Mayalen Valero-Breton
- Laboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago.
| | - Camila Huerta-Salgado
- Laboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago.
| | - Oscar Achiardi
- Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso.
| | - Felipe Simon
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Universidad de Chile, Santiago, Chile; Laboratory of Integrative Physiopathology, Department of Biological Sciences, Faculty of Life Sciences. Universidad Andres Bello, Santiago.
| | - Claudio Cabello-Verrugio
- Laboratory of Muscle Pathology, Fragility and Aging, Department of Biological Sciences, Faculty of Life Sciences. Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago.
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45
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Mohammed S, Nicklas EH, Thadathil N, Selvarani R, Royce GH, Kinter M, Richardson A, Deepa SS. Role of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress. Free Radic Biol Med 2021; 164:315-328. [PMID: 33429022 PMCID: PMC8845573 DOI: 10.1016/j.freeradbiomed.2020.12.449] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/24/2020] [Accepted: 12/28/2020] [Indexed: 12/12/2022]
Abstract
Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1-/- or Sod1KO mice) have increased oxidative stress, show accelerated aging and develop spontaneous hepatocellular carcinoma (HCC) with age. Similar to humans, HCC development in Sod1KO mice progresses from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) with fibrosis, which eventually progresses to HCC. Oxidative stress plays a role in NAFLD to NASH progression, and liver inflammation is the main mechanism that drives the disease progression from NASH to fibrosis. Because necroptosis is a major source of inflammation, we tested the hypothesis that increased necroptosis in the liver plays a role in increased inflammation and fibrosis in Sod1KO mice. Phosphorylation of MLKL (P-MLKL), a well-accepted marker of necroptosis, and expression of MLKL protein were significantly increased in the livers of Sod1KO mice compared to wild type (WT) mice indicating increased necroptosis. Similarly, phosphorylation of RIPK3 and RIPK3 protein levels were also significantly increased. Markers of pro-inflammatory M1 macrophages, NLRP3 inflammasome, and transcript levels of pro-inflammatory cytokines and chemokines, e.g., TNFα, IL-6, IL-1β, and Ccl2 that are associated with human NASH, were significantly increased. Expression of antioxidant enzymes and heat shock proteins, and markers of fibrosis and oncogenic transcription factor STAT3 were also upregulated and autophagy was downregulated in the livers of Sod1KO mice. Short term treatment of Sod1KO mice with necrostatin-1s (Nec-1s), a necroptosis inhibitor, reversed these conditions. Our data show for the first time that necroptosis-mediated inflammation contributes to fibrosis in a mouse model of increased oxidative stress and accelerated aging, that also exhibits progressive HCC development.
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Affiliation(s)
| | | | | | | | | | - Michael Kinter
- Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, USA
| | - Arlan Richardson
- Stephenson Cancer Center, USA; Department of Biochemistry and Molecular Biology, USA; Oklahoma Center for Geroscience & Brain Aging, University of Oklahoma Health Sciences Center, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USA
| | - Sathyaseelan S Deepa
- Stephenson Cancer Center, USA; Department of Biochemistry and Molecular Biology, USA; Oklahoma Center for Geroscience & Brain Aging, University of Oklahoma Health Sciences Center, USA.
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46
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Gonzalez A, Valero-Breton M, Huerta-Salgado C, Achiardi O, Simon F, Cabello-Verrugio C. Impact of exercise training on the sarcopenia criteria in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Transl Myol 2021. [DOI: 10.4081/ejtm.2020.9630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Sarcopenia is a highly prevalent complication of non-alcoholic fatty liver disease (NAFLD). We aimed to conduct a systematic review and meta-analyses to elucidate the exercise training (ET)'s efficacy on NAFLD adult patients' sarcopenia criteria. We identified relevant randomized controlled trials (RCT) in electronic databases PubMed, CINAHL, and Scopus. We selected seven RCT from 66 screened studies. The ET programs included endurance or combined (endurance and resistance) training. No study performed resistance training alone. The physical function improved with endurance or combined training (mean differences [MD] 8.26 mL/Kg*min [95% CI 5.27 to 11.24 mL/Kg*min], p < 0.0001); Muscle mass showed no evidence of the beneficial effects of endurance or combined training (MD 1.01 Kg [95% CI -1.78 to 3.80 Kg], p = 0.48). None of the selected studies evaluated muscle strength. Endurance and combined training increase physical function criteria but do not improve muscle mass criteria on sarcopenia in NAFLD patients. These results must be interpreted with caution for the small number of patients included in the RCTs analyzed, the different characteristics of the ET carried out, the non-use of resistance training, which prevents assess its effect on sarcopenia despite the evidence that recommends it and does not assessment muscle strength criteria in RCT include. Future research should include muscle strength assessments and resistance training to evaluate the effects in this condition. Exercise training is beneficial for sarcopenia in NAFLD but is necessary more experimental evidence to define the best type of training that positively affects the three criteria of sarcopenia. PROSPERO reference number CRD42020191471.
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47
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Cheng YM, Kao JH, Wang CC. The metabolic profiles and body composition of lean metabolic associated fatty liver disease. Hepatol Int 2021; 15:405-412. [PMID: 33539004 DOI: 10.1007/s12072-021-10147-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/18/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE Metabolic associated fatty liver disease (MAFLD) is the commonest cause of chronic liver disease, which is associated with obesity and diabetes. However, it also occurs in lean individuals especially in Asian populations. METHODS The participants of Tzu Chi MAFLD cohort (TCMC) including health controls or MAFLD patients were enrolled. MAFLD was defined as fatty liver in imaging without hepatitis B virus, hepatitis C virus infection, drug, alcohol or other known causes of chronic liver disease. Lean MAFLD was defined as MAFLD in lean subjects (BMI < 23 kg/m2). RESULTS A total of 880 subjects were included for final analysis. Of 394 MAFLD patients, 65 (16.5%) patients were diagnosed as lean MAFLD. Lean MAFLD patients were elder, higher percentage of female gender, lower ALT, diastolic blood pressure, triglyceride, and waist circumference but higher HDL than non-lean MAFLD patients. Using binary regression analysis, elder age and lower waist circumference were associated with lean MAFLD. Compared with lean healthy controls, lean MAFLD patients had higher BMI, waist circumference, and percentage of hypertension. In body composition, fatty tissue index (FTI), lean tissue index (LTI) ,and total body water (TBW) were lower in lean MAFLD than non-lean MAFLD patients; but they were comparable with lean healthy controls. CONCLUSIONS The prevalence of lean MAFLD was 16.5% in this study population and it was higher in elder age, especially of female subjects. Lean MAFLD patients had different metabolic profiles compared with lean healthy controls, but different body composition compared with non-lean MAFLD patients.
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Affiliation(s)
- Yu-Ming Cheng
- Department of Gastroenterology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, 289 Jianguo Rd., Xindian area, New Taipei City, Hualien, 23142, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Chi Wang
- Department of Gastroenterology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, 289 Jianguo Rd., Xindian area, New Taipei City, Hualien, 23142, Taiwan.
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48
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Puri P, Dhiman RK, Taneja S, Tandon P, Merli M, Anand AC, Arora A, Acharya SK, Benjamin J, Chawla YK, Dadhich S, Duseja A, Eapan C, Goel A, Kalra N, Kapoor D, Kumar A, Madan K, Nagral A, Pandey G, Rao PN, Saigal S, Saraf N, Saraswat VA, Saraya A, Sarin SK, Sharma P, Shalimar, Shukla A, Sidhu SS, Singh N, Singh SP, Srivastava A, Wadhawan M. Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver. J Clin Exp Hepatol 2021; 11:97-143. [PMID: 33679050 PMCID: PMC7897902 DOI: 10.1016/j.jceh.2020.09.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.
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Key Words
- ACLF, acute on chronic liver failure
- ASM, appendicular skeletal muscle mass
- BCAA, branched chain amino acids
- BIA, bioimpedance analysis
- BMD, bone mineral densitometry
- BMI, body mass index
- CLD, chronic liver disease
- CS, corn-starch
- CT, computed tomography
- CTP, Child–Turcotte–Pugh
- DEXA, dual-energy X-ray absorptiometry
- EASL, European Association for the Study of the Liver
- ESPEN, European society for Clinical Nutrition and Metabolism
- GSD, glycogen storage disease
- HGS, hand-grip strength
- IBW, ideal body weight
- IEM, inborn error of metabolism
- INASL, Indian National Association for Study of the Liver
- L3, third lumbar
- LFI, Liver Frailty Index
- MCT, medium-chain triglyceride
- MELD, model for end-stage liver disease
- MLD, metabolic liver disease
- MRI, magnetic resonance imaging
- RDA, recommended daily allowance
- REE, NASH
- RFH-NPT, Royal Free Hospital-Nutritional Prioritizing Tool
- SMI, skeletal muscle index
- Sarcopenia
- TEE, total energy expenditure
- chronic liver disease
- cirrhosis
- malnutrition
- non-alcoholic liver disease, resting energy expenditure
- nutrition
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Radha K. Dhiman
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Puneeta Tandon
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, 00185, Italy
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Anil Arora
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Subrat K. Acharya
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, 110025, India
| | - Jaya Benjamin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Yogesh K. Chawla
- Kalinga Institute of Medical Sciences, Bhubhaneswar, 751024, Odisha, India
| | - Sunil Dadhich
- Department of Gastroenterology SN Medical College, Jodhpur, 342003, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - C.E. Eapan
- Department of Gastroenterology, Christian Medical College, Vellore, 632004, India
| | - Amit Goel
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Naveen Kalra
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad, 500004, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Kaushal Madan
- Max Smart Super Speciality Hospital, New Delhi, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital, Mumbai, 400026, India
| | - Gaurav Pandey
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Padaki N. Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, 500082, India
| | - Sanjiv Saigal
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta Hospital, Gurugram, 122001, India
| | - Vivek A. Saraswat
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences of Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | - Sandeep S. Sidhu
- Department of Gastroenterology, SPS Hospital, Ludhiana, 141001, India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110016, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, 753007, India
| | - Anshu Srivastava
- Department of Hepatobiliary Sciences, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases, BL Kapur Memorial Hospital, New Delhi, 110005, India
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Chakravarthy MV, Siddiqui MS, Forsgren MF, Sanyal AJ. Harnessing Muscle-Liver Crosstalk to Treat Nonalcoholic Steatohepatitis. Front Endocrinol (Lausanne) 2020; 11:592373. [PMID: 33424768 PMCID: PMC7786290 DOI: 10.3389/fendo.2020.592373] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 11/16/2020] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions, affecting an estimated one-quarter of the world's adult population. Multiple organ systems have been implicated in the pathophysiology of NAFLD; however, the role of skeletal muscle has until recently been largely overlooked. A growing body of evidence places skeletal muscle-via its impact on insulin resistance and systemic inflammation-and the muscle-liver axis at the center of the NAFLD pathogenic cascade. Population-based studies suggest that sarcopenia is an effect-modifier across the NAFLD spectrum in that it is tightly linked to an increased risk of non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), and advanced liver fibrosis, all independent of obesity and insulin resistance. Longitudinal studies suggest that increases in skeletal muscle mass over time may both reduce the incidence of NAFLD and improve preexisting NAFLD. Adverse muscle composition, comprising both low muscle volume and high muscle fat infiltration (myosteatosis), is highly prevalent in patients with NAFLD. The risk of functional disability conferred by low muscle volume in NAFLD is further exacerbated by the presence of myosteatosis, which is twice as common in NAFLD as in other chronic liver diseases. Crosstalk between muscle and liver is influenced by several factors, including obesity, physical inactivity, ectopic fat deposition, oxidative stress, and proinflammatory mediators. In this perspective review, we discuss key pathophysiological processes driving sarcopenia in NAFLD: anabolic resistance, insulin resistance, metabolic inflexibility and systemic inflammation. Interventions that modify muscle quantity (mass), muscle quality (fat), and physical function by simultaneously engaging multiple targets and pathways implicated in muscle-liver crosstalk may be required to address the multifactorial pathogenesis of NAFLD/NASH and provide effective and durable therapies.
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Affiliation(s)
| | - Mohammad S. Siddiqui
- Department of Internal Medicine and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States
| | - Mikael F. Forsgren
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- AMRA Medical AB, Linköping, Sweden
| | - Arun J. Sanyal
- Department of Internal Medicine and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States
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50
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Fernández-Mincone T, Contreras-Briceño F, Espinosa-Ramírez M, García-Valdés P, López-Fuenzalida A, Riquelme A, Arab JP, Cabrera D, Arrese M, Barrera F. Nonalcoholic fatty liver disease and sarcopenia: pathophysiological connections and therapeutic implications. Expert Rev Gastroenterol Hepatol 2020; 14:1141-1157. [PMID: 32811209 DOI: 10.1080/17474124.2020.1810563] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common liver diseases worldwide. Recent data suggest that loss of skeletal muscle mass and function (i.e. sarcopenia) is highly prevalent and frequently overlooked in NAFLD patients. Experimental and clinical data suggest that the relationship between NAFLD and sarcopenia is pathophysiologically complex and bi-directional and there is a growing interest in unveiling how sarcopenia could influence NAFLD development and progression. AREAS COVERED PubMed/MEDLINE was searched for articles related to concomitant occurrence of NAFLD and sarcopenia between January 2013 and April 2020. Areas covered in this review include: (1) updated sarcopenia diagnosis strategy, (2) discussion of current data on pathophysiological connections between NAFLD and sarcopenia, and (3) analysis of current and future therapeutic implications of this knowledge. EXPERT OPINION Clinical studies describe a consistent association between NAFLD and sarcopenia, although a cause-effect relation remains to be determined. Active implementation of current diagnosis algorithms and optimized treatment can prevent sarcopenia related complications in subjects with NAFLD. Pathogenic pathways implicated in this relation are multiple and complex, a better understanding of them can provide novel biomarkers and targeted therapies that will hopefully have an important impact in NAFLD management.
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Affiliation(s)
- Tiziana Fernández-Mincone
- Laboratorio de Fisiología del Ejercicio, Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Felipe Contreras-Briceño
- Laboratorio de Fisiología del Ejercicio, Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Maximiliano Espinosa-Ramírez
- Laboratorio de Fisiología del Ejercicio, Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Patricio García-Valdés
- Laboratorio de Fisiología del Ejercicio, Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Antonio López-Fuenzalida
- Laboratorio de Fisiología del Ejercicio, Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Arnoldo Riquelme
- Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile.,Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile.,Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Daniel Cabrera
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile.,Facultad de Ciencias Médicas, Universidad Bernardo O Higgins , Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile.,Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Francisco Barrera
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
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