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Zhang F, Liu L, Li W. Correlation of sarcopenia with progression of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: a study from two cohorts in China and the United States. Nutr J 2025; 24:6. [PMID: 39810142 PMCID: PMC11730808 DOI: 10.1186/s12937-025-01081-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 01/08/2025] [Indexed: 01/16/2025] Open
Abstract
OBJECTIVE The objective of this study was to investigate the association between sarcopenia and liver fibrosis in patients aged 18-59 years with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential of sarcopenia as a risk factor for the progression of liver fibrosis. METHODS The study included 821 patients with MASLD in the US cohort and 3,405 patients with MASLD in the Chinese cohort. Liver controlled attenuation parameters (CAP) and liver stiffness measurements (LSM) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the extent of hepatic steatosis and fibrosis. Sarcopenia was assessed by measuring appendicular skeletal muscle mass (ASM) and calculating ASMI. To analyze the relationship between sarcopenia, ASMI, and liver fibrosis, logistic regression models, multivariate-adjusted models, and restricted cubic spline (RCS) models were employed, with stratification and interaction analyses. RESULTS The results demonstrated that patients with sarcopenia exhibited a markedly elevated risk of significant liver fibrosis, advanced liver fibrosis, and cirrhosis compared to those without sarcopenia in both cohorts. After adjusting for confounding variables, sarcopenia was identified as an independent risk factor for the progression of liver fibrosis in patients with MASLD. A significant negative correlation was observed between ASMI and the severity of liver fibrosis, with a progressive reduction in the risk of liver fibrosis associated with increasing ASMI. Additionally, a non-linear feature was evident in some liver fibrosis indicators. Subgroup analysis further corroborated the finding that the harmful effect of sarcopenia on liver fibrosis was consistent across all identified subgroups. CONCLUSION Sarcopenia may be associated with the progression of liver fibrosis in patients with MASLD. Monitoring ASMI may assist in identifying individuals at an elevated risk of liver fibrosis in MASLD patients.
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Affiliation(s)
- Fan Zhang
- Department of Endocrinology, Changzhou Third People's Hospital, Changzhou, 213001, China
- Department of Clinical Nutrition, Changzhou Third People's Hospital, Changzhou, 213001, China
- Changzhou Clinical College, Xuzhou Medical University, Changzhou, 213001, China
| | - Longgen Liu
- Department of Liver Diseases, Changzhou Third People's Hospital, Changzhou, 213001, China
- Changzhou Clinical College, Xuzhou Medical University, Changzhou, 213001, China
| | - Wenjian Li
- Department of Urology, Changzhou Third People's Hospital, Changzhou, 213001, China.
- Changzhou Clinical College, Xuzhou Medical University, Changzhou, 213001, China.
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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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3
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Chan WK, Wong VWS, Adams LA, Nguyen MH. MAFLD in adults: non-invasive tests for diagnosis and monitoring of MAFLD. Hepatol Int 2024; 18:909-921. [PMID: 38913148 DOI: 10.1007/s12072-024-10661-x] [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: 12/16/2023] [Accepted: 02/13/2024] [Indexed: 06/25/2024]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of a metabolic syndrome and is highly prevalent in the general population. There has been significant progress in non-invasive tests for MAFLD, from the diagnosis of fatty liver and monitoring of liver fat content in response to intervention, to evaluation of liver fibrosis and its change over time, and from risk stratification of patients within the context of clinical care pathways, to prognostication. Various non-invasive tests have also been developed to assess for fibrotic metabolic dysfunction-associated steatohepatitis, which has emerged as an important diagnostic goal, particularly in the context of clinical trials. Non-invasive tests can be used to diagnose clinically significant portal hypertension so that intervention can be administered to reduce the risk of decompensation. Furthermore, the use of risk stratification algorithms can identify at-risk patients for hepatocellular carcinoma surveillance. Beyond the liver, various tests that evaluate cardiovascular disease risk, assess sarcopenia and measure patient reported outcomes, can be utilized to improve the care of patients with MAFLD. This review provides an up-to-date overview of these non-invasive tests and the limitations of liver biopsy in the management of patients with MAFLD.
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Affiliation(s)
- Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Leon A Adams
- Medical School, University of Western Australia, Perth, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
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Henin G, Loumaye A, Deldicque L, Leclercq IA, Lanthier N. Unlocking liver health: Can tackling myosteatosis spark remission in metabolic dysfunction-associated steatotic liver disease? Liver Int 2024; 44:1781-1796. [PMID: 38623714 DOI: 10.1111/liv.15938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/12/2024] [Accepted: 04/02/2024] [Indexed: 04/17/2024]
Abstract
Myosteatosis is highly prevalent in metabolic dysfunction-associated steatotic liver disease (MASLD) and could reciprocally impact liver function. Decreasing muscle fat could be indirectly hepatoprotective in MASLD. We conducted a review to identify interventions reducing myosteatosis and their impact on liver function. Non-pharmacological interventions included diet (caloric restriction or lipid enrichment), bariatric surgery and physical activity. Caloric restriction in humans achieving a mean weight loss of 3% only reduces muscle fat. Lipid-enriched diet increases liver fat in human with no impact on muscle fat, except sphingomyelin-enriched diet which reduces both lipid contents exclusively in pre-clinical studies. Bariatric surgery, hybrid training (resistance exercise and electric stimulation) or whole-body vibration in human decrease both liver and muscle fat. Physical activity impacts both phenotypes by reducing local and systemic inflammation, enhancing insulin sensitivity and modulating the expression of key mediators of the muscle-liver-adipose tissue axis. The combination of diet and physical activity acts synergistically in liver, muscle and white adipose tissue, and further decrease muscle and liver fat. Several pharmacological interventions (patchouli alcohol, KBP-089, 2,4-dinitrophenol methyl ether, adipoRon and atglistatin) and food supplementation (vitamin D or resveratrol) improve liver and muscle phenotypes in pre-clinical studies by increasing fatty acid oxidation and anti-inflammatory properties. These interventions are effective in reducing myosteatosis in MASLD while addressing the liver disease itself. This review supports that disturbances in inter-organ crosstalk are key pathophysiological mechanisms involved in MASLD and myosteatosis pathogenesis. Focusing on the skeletal muscle might offer new therapeutic strategies to treat MASLD by modulating the interactions between liver and muscles.
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Affiliation(s)
- Guillaume Henin
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Audrey Loumaye
- Service d'Endocrinologie, Diabétologie et Nutrition, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | | | - Isabelle A Leclercq
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Nicolas Lanthier
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
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Thakral N, Desalegn H, Diaz LA, Cabrera D, Loomba R, Arrese M, Arab JP. A Precision Medicine Guided Approach to the Utilization of Biomarkers in MASLD. Semin Liver Dis 2024; 44:273-286. [PMID: 38991536 DOI: 10.1055/a-2364-2928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
The new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes a positive diagnosis based on cardiometabolic risk factors. This definition is not only less stigmatizing but also allows for subclassification and stratification, thereby addressing the heterogeneity of what was historically referred to as nonalcoholic fatty liver disease. The heterogeneity within this spectrum is influenced by several factors which include but are not limited to demographic/dietary factors, the amount of alcohol use and drinking patterns, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The net effect of this dynamic and intricate system-level interaction is reflected in the phenotypic presentation of MASLD. Therefore, the application of precision medicine in this scenario aims at complex phenotyping with consequent individual risk prediction, development of individualized preventive strategies, and improvements in the clinical trial designs. In this review, we aim to highlight the importance of precision medicine approaches in MASLD, including the use of novel biomarkers of disease, and its subsequent utilization in future study designs.
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Affiliation(s)
- Nimish Thakral
- Division of Gastroenterology and Hepatology, University of Kentucky, Lexington, Kentucky
| | - Hailemichael Desalegn
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Daniel Cabrera
- Centro de Investigación e Innovación Biomédica (CiiB), Universidad de los Andes, Santiago, Chile
- Escuela de Medicina, Facultad de Ciencias Medicas, Universidad Bernardo O'Higgins, Santiago, Chile
| | - Rohit Loomba
- Division of Gastroenterology and Hepatology, MASLD Research Center, University of California San Diego, San Diego, California
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia
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Reichelt S, Merle U, Klauss M, Kahlert C, Lurje G, Mehrabi A, Czigany Z. Shining a spotlight on sarcopenia and myosteatosis in liver disease and liver transplantation: Potentially modifiable risk factors with major clinical impact. Liver Int 2024; 44:1483-1512. [PMID: 38554051 DOI: 10.1111/liv.15917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 03/07/2024] [Accepted: 03/17/2024] [Indexed: 04/01/2024]
Abstract
Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.
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Affiliation(s)
- Sophie Reichelt
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital of Bonn, Bonn, Germany
| | - Uta Merle
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Miriam Klauss
- Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christoph Kahlert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Georg Lurje
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Zoltan Czigany
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
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Wong R, Yuan LY. Sarcopenia and metabolic dysfunction associated steatotic liver disease: Time to address both. World J Hepatol 2024; 16:871-877. [PMID: 38948439 PMCID: PMC11212657 DOI: 10.4254/wjh.v16.i6.871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 06/20/2024] Open
Abstract
Sarcopenia and metabolic dysfunction associated steatotic liver disease (MASLD) are closely intertwined. Sarcopenia, traditionally a disease of the older adult and chronic disease population, has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD. They share similar risk factors of insulin resistance and physical inactivity. Given similar pathophysiology along the liver-muscle axis, sarcopenia has been studied as a risk factor for MASLD, and vice versa. Current research suggests a bidirectional relationship. Given the chronicity of MASLD as a chronic inflammatory liver disease, it can break down muscle mass and lead to sarcopenia, while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver. However, for the longest time, a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes. A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study. However, no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet. Future studies are needed to reach a consensus and reduce diagnostic variation. With similar pathophysiology and shared risk factors between the two diseases, future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.
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Affiliation(s)
- Rochelle Wong
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, United States.
| | - Li-Yun Yuan
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, United States
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8
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Giri S, Anirvan P, Angadi S, Singh A, Lavekar A. Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease. World J Gastrointest Pathophysiol 2024; 15:91100. [PMID: 38682026 PMCID: PMC11045355 DOI: 10.4291/wjgp.v15.i1.91100] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/09/2024] [Accepted: 04/01/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. AIM To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD. METHODS We conducted a comprehensive search for relevant studies in MEDLINE, Embase, and Scopus from their inception to June 2023. We included studies that focused on patients with NAFLD, reported the prevalence of sarcopenia as the primary outcome, and examined secondary outcomes, such as liver fibrosis and other adverse events. We also used the Newcastle-Ottawa scale for quality assessment. RESULTS Of the 29 studies included, the prevalence of sarcopenia in NAFLD varied widely (1.6% to 63.0%), with 20 studies reporting a prevalence of more than 10.0%. Substantial heterogeneity was noted in the measurement modalities for sarcopenia. Sarcopenia was associated with a higher risk of advanced fibrosis (odd ratio: 1.97, 95% confidence interval: 1.44-2.70). Increased odds were consistently observed in fibrosis assessment through biopsy, NAFLD fibrosis score/body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes (BARD) score, and transient elastography, whereas the fibrosis-4 score showed no such association. Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis, insulin resistance, cardiovascular risks, and mortality. CONCLUSION This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients. The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings. This review demonstrates the multidimensional impact of sarcopenia on NAFLD, indicating its importance beyond liver-related events to include cardiovascular risks, mortality, and metabolic complications.
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Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar 751024, Odisha, India
| | - Prajna Anirvan
- Department of Gastroenterology, Kalinga Gastroenterology Foundation, Cuttack, 753001, Odisha, India
| | - Sumaswi Angadi
- Department of Gastroenterology, Nizam’s Institute of Medical Sciences, Hyderabad 500082, Telangana, India
| | - Ankita Singh
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai 400012, Maharashtra, India
| | - Anurag Lavekar
- Department of Gastroenterology, Sagar Hospital, Bengaluru 560041, Karnataka, India
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9
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Kamiliou A, Lekakis V, Chrysavgis L, Cholongitas E. Prevalence and impact on the outcome of myosteatosis in patients with cirrhosis: a systematic review and meta-analysis. Hepatol Int 2024; 18:688-699. [PMID: 38329701 PMCID: PMC11014812 DOI: 10.1007/s12072-023-10632-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 12/18/2023] [Indexed: 02/09/2024]
Abstract
BACKGROUND Myosteatosis in cirrhotic patients has been evaluated in limited studies with conflicting results and no systematic review or meta-analysis have been performed in this setting. METHODS We searched for all articles published until June 2023 to evaluate the prevalence of myosteatosis in cirrhosis and chronic liver disease. RESULTS Seventeen studies focused on cirrhosis and five studies in patients with chronic liver disease were included: the overall pooled prevalence of myosteatosis was 46% [95% Confidence Interval (CI) 36-57%] and 33% (95% CI 15-59%), respectively (p = 0.35). Among the studies with cirrhosis, the prevalence of myosteatosis was higher in those using the body mass index-based definition of myosteatosis (56%), than gender-based (36%) or other criteria (21%) (p < 0.01); was higher in women than in men (61% vs 45%), in Child-Pugh class C than A or B (57% vs 49% vs 50%), in non-alcoholic fatty liver disease (NAFLD)- than viral-associated cirrhosis (57% vs 43%), but these differences were not statistically significant (p > 0.05). Cirrhotic patients with myosteatosis, compared to those without myosteatosis, had more frequently a previous history of hepatic encephalopathy (32% vs 15%, p = 0.04), less frequently a previous history of variceal bleeding (46% vs 65%, p < 0.01), were more likely to suffer from diabetes mellitus (27% vs 18%, p < 0.01), while they had higher mortality rates (40% vs 14%, p = 0.02). CONCLUSION Myosteatosis is highly prevalent in patients with cirrhosis, particularly in those with NAFLD-associated cirrhosis. Myosteatosis is associated with hepatic encephalopathy, while it seems to have a negative impact on the outcome.
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Affiliation(s)
- Aikaterini Kamiliou
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527, Athens, Greece
| | - Vasileios Lekakis
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527, Athens, Greece
| | - Lampros Chrysavgis
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527, Athens, Greece.
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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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Cernea S. NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic-Metabolic Interplay. Life (Basel) 2024; 14:272. [PMID: 38398781 PMCID: PMC10890557 DOI: 10.3390/life14020272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/13/2024] [Accepted: 02/14/2024] [Indexed: 02/25/2024] Open
Abstract
The bidirectional relationship between type 2 diabetes and (non-alcoholic fatty liver disease) NAFLD is indicated by the higher prevalence and worse disease course of one condition in the presence of the other, but also by apparent beneficial effects observed in one, when the other is improved. This is partly explained by their belonging to a multisystemic disease that includes components of the metabolic syndrome and shared pathogenetic mechanisms. Throughout the progression of NAFLD to more advanced stages, complex systemic and local metabolic derangements are involved. During fibrogenesis, a significant metabolic reprogramming occurs in the hepatic stellate cells, hepatocytes, and immune cells, engaging carbohydrate and lipid pathways to support the high-energy-requiring processes. The natural history of NAFLD evolves in a variable and dynamic manner, probably due to the interaction of a variable number of modifiable (diet, physical exercise, microbiota composition, etc.) and non-modifiable (genetics, age, ethnicity, etc.) risk factors that may intervene concomitantly, or subsequently/intermittently in time. This may influence the risk (and rate) of fibrosis progression/regression. The recognition and control of the factors that determine a rapid progression of fibrosis (or its regression) are critical, as the fibrosis stages are associated with the risk of liver-related and all-cause mortality.
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Affiliation(s)
- Simona Cernea
- Department M3, Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu Mureş, Romania; or
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, 540136 Târgu Mureş, Romania
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12
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Henin G, Loumaye A, Leclercq IA, Lanthier N. Myosteatosis: Diagnosis, pathophysiology and consequences in metabolic dysfunction-associated steatotic liver disease. JHEP Rep 2024; 6:100963. [PMID: 38322420 PMCID: PMC10844870 DOI: 10.1016/j.jhepr.2023.100963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 10/27/2023] [Accepted: 10/27/2023] [Indexed: 02/08/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of multisystemic complications, including muscle changes such as sarcopenia and myosteatosis that can reciprocally affect liver function. We conducted a systematic review to highlight innovative assessment tools, pathophysiological mechanisms and metabolic consequences related to myosteatosis in MASLD, based on original articles screened from PUBMED, EMBASE and COCHRANE databases. Forty-six original manuscripts (14 pre-clinical and 32 clinical studies) were included. Microscopy (8/14) and tissue lipid extraction (8/14) are the two main assessment techniques used to measure muscle lipid content in pre-clinical studies. In clinical studies, imaging is the most used assessment tool and included CT (14/32), MRI (12/32) and ultrasound (4/32). Assessed muscles varied across studies but mainly included paravertebral (4/14 in pre-clinical; 13/32 in clinical studies) and lower limb muscles (10/14 in preclinical; 13/32 in clinical studies). Myosteatosis is already highly prevalent in non-cirrhotic stages of MASLD and correlates with disease activity when using muscle density assessed by CT. Numerous pathophysiological mechanisms were found and included: high-fat and high-fructose diet, dysregulation in fatty acid transport and ketogenesis, endocrine disorders and impaired microRNA122 pathway signalling. In this review we also uncover several potential consequences of myosteatosis in MASLD, such as insulin resistance, MASLD progression from steatosis to metabolic steatohepatitis and loss of muscle strength. In conclusion, data on myosteatosis in MASLD are already available. Screening for myosteatosis could be highly relevant in the context of MASLD, considering its correlation with MASLD activity as well as its related consequences.
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Affiliation(s)
- Guillaume Henin
- Service d’Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Audrey Loumaye
- Service d’Endocrinologie, Diabétologie et Nutrition, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Isabelle A. Leclercq
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Nicolas Lanthier
- Service d’Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
- Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium
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Zhou T, Ye J, Luo L, Wang W, Feng S, Dong Z, Zhuo S, Zhong B. Restoring skeletal muscle mass as an independent determinant of liver fat deposition improvement in MAFLD. Skelet Muscle 2023; 13:23. [PMID: 38115119 PMCID: PMC10731792 DOI: 10.1186/s13395-023-00333-z] [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: 05/29/2023] [Accepted: 11/30/2023] [Indexed: 12/21/2023] Open
Abstract
AIMS Cross-sectional studies have demonstrated the association of skeletal muscle mass with metabolic-associated fatty liver disease (MAFLD), while longitudinal data are scarce. We aimed to explore the impact of changes in relative skeletal muscle mass on the MAFLD treatment response. METHODS MAFLD patients undergoing magnetic resonance imaging-based proton density fat fraction for liver fat content (LFC) assessments and bioelectrical impedance analysis before and after treatment (orlistat, meal replacement, lifestyle modifications) were enrolled. Appendicular muscle mass (ASM) was adjusted by weight (ASM/W). RESULTS Overall, 256 participants were recruited and divided into two groups: with an ASM/W increase (n=166) and without an ASM/W increase (n=90). There was a great reduction in LFC in the group with an ASM/W increase (16.9% versus 8.2%, P < 0.001). However, the change in LFC in the group without an ASM/W increase showed no significant difference (12.5% versus 15.0%, P > 0.05). △ASM/W Follow-up-Baseline [odds ratio (OR)=1.48, 95% confidence interval (CI) 1.05-2.07, P = 0.024] and △total fat mass (OR=1.45, 95% CI 1.12-1.87, P = 0.004) were independent predictors for steatosis improvement (relative reduction of LFC ≥ 30%). The subgroup analysis showed that, despite without weight loss, decrease in HOMA-IR (OR=6.21, 95% CI 1.28-30.13, P=0.023), △total fat mass Baseline -Follow-up (OR=3.48, 95% CI 1.95-6.21, P <0.001 and △ASM/W Follow-up-Baseline (OR=2.13, 95% CI 1.12-4.05, P=0.022) independently predicted steatosis improvement. CONCLUSIONS ASM/W increase and loss of total fat mass benefit the resolution of liver steatosis, independent of weight loss for MAFLD.
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Affiliation(s)
- Ting Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Ling Luo
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Zhi Dong
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Shuyu Zhuo
- Department of Nutrition, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, Guangdong, China.
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China.
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14
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Bai J, Xu M, Peng F, Gong J, Song X, Li Y. A nomogram based on psoas muscle index predicting long-term cirrhosis incidence in non-cirrhotic patients with HBV-related acute‑on‑chronic liver failure. Sci Rep 2023; 13:21265. [PMID: 38040786 PMCID: PMC10692120 DOI: 10.1038/s41598-023-47463-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 11/14/2023] [Indexed: 12/03/2023] Open
Abstract
There is a lack of scoring system to predict the occurrence of cirrhosis in individuals with acute-on-chronic liver failure (ACLF) in the absence of cirrhosis. The goal of this study was to develop a psoas muscle index (PMI)-based nomogram for cirrhosis risk in non-cirrhotic patients with HBV-related ACLF. We included 274 non-cirrhotic HBV-ACLF patients who were randomly assigned to training and validation groups. Logistic analyses were performed to identify risk factors for cirrhosis. A nomogram was then constructed. The predictive performance of the nomogram was assessed using the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA). During the 360-day follow-up, 44.5% (122/274) of non-cirrhotic HBV-ACLF patients developed cirrhosis. A higher PMI at the L3 level was correlated with a decreased risk of long-term cirrhosis occurrence (OR 0.677, 95% CI 0.518-0.885, P = 0.004). The nomogram incorporating PMI, age, neutrophil-to-lymphocyte ratio (NLR), and international normalized ratio (INR), indicated satisfactory predictive performance for cirrhosis risk stratification in ACLF population. The nomograms had an AUROC of 0.812 (95% CI 0.747-0.866) and 0.824 (95% CI 0.730-0.896) in the training and validation cohorts, respectively. The calibration curves displayed excellent predictive accuracy of the nomogram in both sets. In both cohorts, the DCA verified the nomogram's clinical efficacy. In non-cirrhotic HBV-ACLF patients, a greater PMI appears to protect against long-term cirrhosis occurrence. Strong predictive performance has been demonstrated by PMI-based nomograms in assessing the likelihood of 1-year cirrhosis in those with HBV-ACLF.
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Affiliation(s)
- Jie Bai
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Manman Xu
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Fengling Peng
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junwei Gong
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaodong Song
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Yongguo Li
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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15
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Zhou T, Ye J, Lin Y, Wang W, Feng S, Zhuo S, Zhong B. Impact of skeletal muscle mass evaluating methods on severity of metabolic associated fatty liver disease in non-elderly adults. Br J Nutr 2023; 130:1373-1384. [PMID: 36896599 PMCID: PMC10511683 DOI: 10.1017/s0007114523000399] [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: 09/28/2022] [Revised: 01/18/2023] [Accepted: 02/01/2023] [Indexed: 03/11/2023]
Abstract
The study aimed to explore the relationships of skeletal muscle mass with disease severity in metabolic-associated fatty liver disease (MAFLD) patients with different methods. Consecutive subjects undergoing bioelectrical impedance analysis were included. The steatosis grade and liver fibrosis were evaluated by MRI-derived proton density fat fraction and two-dimensional shear wave elastography. The appendicular skeletal muscle mass (ASM) was adjusted by height2 (ASM/H2), weight (ASM/W) and BMI (ASM/BMI). Overall, 2223 subjects (50·5 %, MAFLD; 46·9 %, male) were included, with the mean age 37·4 ± 10·6 years. In multivariate logistic regression analysis, the subjects with the lowest quartile (Q1) of ASM/W or ASM/BMI had higher risk ratios for MAFLD (OR (95 % CI) in male: 2·57 (1·35, 4·89), 2·11(1·22, 3·64); in female: 4·85 (2·33, 10·01), 4·81 (2·52, 9·16), all P < 0·05, all for Q1 v. Q4). The MAFLD patients with lower quartiles of ASM/W had the higher risk OR for insulin resistance (IR), both in male and female (2·14 (1·16, 3·97), 4·26 (1·29, 14·02) for Q4 v. Q1, both P < 0·05). While the significant OR were not observed when ASM/H2 and ASM/BMI were used. There were significant dose-dependent associations between decreased ASM/W as well as ASM/BMI and moderate-severe steatosis (2·85(1·54, 5·29), 1·90(1·09, 3·31), both P < 0·05) in male MAFLD patients. In conclusion, ASM/W is superior to ASM/H2 and ASM/BMI in predicting the degree of MAFLD. A lower ASM/W is associated with IR and moderate-severe steatosis in non-elderly male MAFLD.
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Affiliation(s)
- Ting Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou510080, People’s Republic of China
| | - Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou510080, People’s Republic of China
| | - Yansong Lin
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou510080, People’s Republic of China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, Guangdong510080, People’s Republic of China
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, Guangdong510080, People’s Republic of China
| | - Shuyu Zhuo
- Department of Nutrition, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, Guangdong510080, People’s Republic of China
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou510080, People’s Republic of China
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16
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Kim HK, Bae SJ, Lee MJ, Kim EH, Park H, Kim HS, Cho YK, Jung CH, Lee WJ, Choe J. Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity. Clin Mol Hepatol 2023; 29:987-1001. [PMID: 37403320 PMCID: PMC10577332 DOI: 10.3350/cmh.2023.0035] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 06/30/2023] [Accepted: 07/05/2023] [Indexed: 07/06/2023] Open
Abstract
BACKGROUND/AIMS To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis. METHODS This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography. RESULTS Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19-1.67, P<0.001; women: OR=1.59, 95% CI 1.40-1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02-1.50, P=0,028; women: OR=1.23, 95% CI 1.04-1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43-4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44-4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53-6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51-6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors. CONCLUSION In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.
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Affiliation(s)
- Hong-Kyu Kim
- Subdivision of Endocrinology and Metabolism, Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea
| | - Sung-Jin Bae
- Subdivision of Endocrinology and Metabolism, Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea
| | - Min Jung Lee
- Subdivision of Endocrinology and Metabolism, Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea
| | - Eun Hee Kim
- Subdivision of Endocrinology and Metabolism, Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea
| | - Hana Park
- Subdivision of Gastroenterology and Hepatology, Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea
| | - Hwi Seung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Korea
| | - Yun Kyung Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Korea
| | - Chang Hee Jung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Korea
| | - Woo Je Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Korea
| | - Jaewon Choe
- Subdivision of Gastroenterology and Hepatology, Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea
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17
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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: 5] [Impact Index Per Article: 2.5] [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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18
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Akambase JA, Prieto JE, Mattos AZ, Mattos AA, Carrera E, Díaz-Ferrer J, Gallardo P, Curia A, Ballerga EG, Tovo CV, Balderramo D, Debes JD. Epidemiology and risk factors for histopathologic characteristics of non-alcoholic fatty liver disease in South America. Aliment Pharmacol Ther 2023; 58:526-536. [PMID: 37349900 DOI: 10.1111/apt.17615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 06/02/2023] [Accepted: 06/02/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND The burden of non-alcoholic fatty liver disease (NAFLD) in South America is among the highest in the world. However, the epidemiology and risk factors for NAFLD are insufficiently described in the region. AIM To explore the associations between clinical characteristics and histopathological features of NAFLD METHODS: This was a descriptive study of 2722 patients with NAFLD from 8 medical centres across 5 South American countries. We collected clinical, biochemical and histopathological data using a templated chart. Fibrosis was assessed by elastography or fibrosis scores and confirmed with biopsy when available. We examined associations between histopathological features and clinical characteristics with logistic regression models. Models were adjusted for country, age and sex. RESULTS The median age was 53 years (IQR: 41-62), and 63% were women. Subjects from Brazil had the highest body mass index at 42 kg/m2 . Sixty-seven percent had dyslipidemia, 46% had obesity, 30% had hypertension, 17% had type 2 diabetes mellitus (T2DM) and 34% had metabolic syndrome. Biopsy reports were available for 948 (35%), of which 58% showed fibrosis, 91% steatosis and 65% inflammation; 25% showed significant fibrosis and 27% severe steatosis. Metabolic syndrome, T2DM and hypertension were significantly associated with significant fibrosis (OR = 1.94, p < 0.001; OR = 2.93, p < 0.001 and OR = 1.60, p = 0.003, respectively), severe steatosis (OR = 2.05, p < 0.001; OR = 1.91, p = 0.001 and OR = 2.17, p < 0.001, respectively) and liver inflammation (OR = 1.66, p = 0.007; OR = 2.00, p = 0.002; OR = 1.62, p = 0.001, respectively). CONCLUSIONS In the largest NAFLD cohort study to date from South America, metabolic syndrome, hypertension and T2DM were independently associated with significant fibrosis, severe steatosis, and inflammation. The prevalence of T2DM was lower than the reported global prevalence.
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Affiliation(s)
- Joseph A Akambase
- Division of Epidemiology and Community Health, School of Medicine, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
- Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA
| | - Jhon E Prieto
- Centro de Enfermedades Hepáticas y Digestivas, Bogotá, Colombia
| | - Angelo Z Mattos
- Graduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Angelo A Mattos
- Graduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Enrique Carrera
- Departamento de Gastroenterología y Hepatología, Hospital Eugenio Espejo, Quito, Ecuador
| | - Javier Díaz-Ferrer
- Department of Gastroenterology, Hospital Nacional Edgardo Rebagliati Martins, HNERM, Lima, Peru
| | | | - Andrea Curia
- División Gastroenterology, Hospital de Clínicas José de San Martín - UBA, Buenos Aires, Argentina
| | - Esteban G Ballerga
- División Gastroenterology, Hospital de Clínicas José de San Martín - UBA, Buenos Aires, Argentina
| | - Cristiane V Tovo
- Graduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Domingo Balderramo
- Departamento de Gastroenterología, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Jose D Debes
- Division of Epidemiology and Community Health, School of Medicine, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
- Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA
- Department of Medicine, University of MInnesota, Minneapolis, United States
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19
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Chen M, Cao Y, Ji G, Zhang L. Lean nonalcoholic fatty liver disease and sarcopenia. Front Endocrinol (Lausanne) 2023; 14:1217249. [PMID: 37424859 PMCID: PMC10327437 DOI: 10.3389/fendo.2023.1217249] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 06/13/2023] [Indexed: 07/11/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. The risk factor for NAFLD is often considered to be obesity, but it can also occur in people with lean type, which is defined as lean NAFLD. Lean NAFLD is commonly associated with sarcopenia, a progressive loss of muscle quantity and quality. The pathological features of lean NAFLD such as visceral obesity, insulin resistance, and metabolic inflammation are inducers of sarcopenia, whereas loss of muscle mass and function further exacerbates ectopic fat accumulation and lean NAFLD. Therefore, we discussed the association of sarcopenia and lean NAFLD, summarized the underlying pathological mechanisms, and proposed potential strategies to reduce the risks of lean NAFLD and sarcopenia in this review.
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20
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Hsieh YC, Joo SK, Koo BK, Lin HC, Lee DH, Chang MS, Park JH, So YH, Kim W. Myosteatosis, but not Sarcopenia, Predisposes NAFLD Subjects to Early Steatohepatitis and Fibrosis Progression. Clin Gastroenterol Hepatol 2023; 21:388-397.e10. [PMID: 35101634 DOI: 10.1016/j.cgh.2022.01.020] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 01/13/2022] [Accepted: 01/17/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Sarcopenia and myosteatosis are associated with advanced nonalcoholic fatty liver disease (NAFLD). However, muscle alterations in early stage NAFLD remain unclear. METHODS Patients with nonalcoholic fatty liver (NAFL) or early nonalcoholic steatohepatitis (NASH) without significant fibrosis were selected from a prospective biopsy-proven NAFLD cohort (N = 338). The skeletal muscle index and mean muscle attenuation (MA) were measured using abdominal fat computed tomography at the third lumbar vertebra level. Severe myosteatosis was defined as the lowest quartile of sex-stratified MA values. RESULTS Patients with early NASH (n = 87) had lower MA (45.61 ± 6.45 vs 47.48 ± 5.85 HU; P = .028) than patients with NAFL (n = 251) but a similar skeletal muscle index. Patients with more severe lobular inflammation and hepatocellular ballooning had lower MA (P = .003 and P = .041, respectively). The severe myosteatosis prevalence was higher in early NASH than in NAFL (33.3% vs 21.1%; P = .029). Patients with severe myosteatosis were more likely to have early NASH in multivariable analysis adjusted for age, sex, and metabolic factors (odds ratio, 2.45; 95% confidence interval (CI), 1.24-4.86), which was maintained after adjustment for visceral fat amount (odds ratio, 2.44; 95% CI, 1.22-4.89). During a median 29-month follow-up, 170 patients underwent repeated transient elastography. Fibrosis progression-an increase in liver stiffness measurement >2 kPa or second liver stiffness measurement ≥7 kPa-was found in 28 and 31 individuals. Severe myosteatosis was significantly associated with fibrosis progression after adjustment for various confounders (hazard ratio, 2.49; 95% CI, 1.15-5.40 and hazard ratio, 2.09; 95% CI, 1.01-4.34 for different fibrosis progression definitions). CONCLUSIONS Severe myosteatosis is significantly associated with early NASH and fibrosis progression in early stage NAFLD.
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Affiliation(s)
- Yun-Cheng Hsieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Sae Kyung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Bo Kyung Koo
- Division of Endocrinology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Dong Hyeon Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Mee Soo Chang
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Jeong Hwan Park
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Young Ho So
- Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea.
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21
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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: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [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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22
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Guo W, Zhao X, Cheng D, Liang X, Miao M, Li X, Lu J, Xu N, Hu S, Zhang Q. Muscle Fat Content Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Chinese Adults. J Nutr Health Aging 2023; 27:960-965. [PMID: 37997716 DOI: 10.1007/s12603-023-2015-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 10/09/2023] [Indexed: 11/25/2023]
Abstract
OBJECTIVES Several studies have linked myosteatosis with nonalcoholic fatty liver disease (NAFLD) in individuals with obesity. The clinical significance of myosteatosis in individuals with NAFLD in the general population has not been well investigated. Here, we wanted to explore and compare the associations of NAFLD and liver fibrosis with muscle fat content and skeletal muscle mass (SMM) in a relatively large general population in China. METHODS We retrospectively included all participants who underwent abdominal CT scans in our health promotion center between April 2021 and October 2021. Muscle fat content was assessed by abdomen quantitative computed tomography (QCT) scans, and SMM was evaluated by bioelectrical impedance. NAFLD was assessed by ultrasonography. The NAFLD fibrosis score (NFS) and Fibrosis-4 Index (FIB-4) score were calculated to assess liver fibrosis. RESULTS Compared with participants without NAFLD, patients with NAFLD showed significantly increased intermuscular adipose tissue (IMAT%) (7.40±3.37% vs. 6.76±2.66%, P <0.01). According to a multiple logistic regression model, IMAT% (OR=1.091, 95% CI 1.030-1.155, P=0.003) was only independently correlated with NAFLD in obese participants. Mediation analysis showed that BMI mediated the association between IMAT% and NAFLD. In participants with NAFLD, increased IMAT% was independently associated with an increased intermediate to high risk of advanced fibrosis assessed by the NFS or FIB-4 score after adjusting for multiple potential confounders. However, SMM was only independently correlated with an intermediate to high risk for advanced fibrosis evaluated by the NFS and not by the FIB-4 score. CONCLUSION Increased muscle fat content is positively correlated with NAFLD and intermediate to high risk for advanced fibrosis in the general Chinese population.
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Affiliation(s)
- W Guo
- Qun Zhang, M.D., Department of Health Promotion Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, China, 210029. E-mail: , ORCID: 0000-0003-2208-7998; Shuang Hu, M.D., Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, China, 210008, E-mail:
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23
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Kim HS, Lee J, Kim EH, Lee MJ, Bae IY, Lee WJ, Park JY, Kim HK, Jung CH. Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography. Diabetes Metab J 2023; 47:104-117. [PMID: 36727165 PMCID: PMC9925154 DOI: 10.4093/dmj.2022.0081] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 06/29/2022] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population. METHODS Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores. RESULTS According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all). CONCLUSION A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.
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Affiliation(s)
- Hwi Seung Kim
- Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea
| | - Jiwoo Lee
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Eun Hee Kim
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min Jung Lee
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Young Bae
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Korea
| | - Joong-Yeol Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Korea
| | - Hong-Kyu Kim
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Corresponding authors: Hong-Kyu Kim https://orcid.org/0000-0002-7606-3521 Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea E-mail:
| | - Chang Hee Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Korea
- Corresponding authors: Hong-Kyu Kim https://orcid.org/0000-0002-7606-3521 Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea E-mail:
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24
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Sinn DH, Kang D, Kang M, Guallar E, Hong YS, Lee KH, Park J, Cho J, Gwak GY. Nonalcoholic fatty liver disease and accelerated loss of skeletal muscle mass: A longitudinal cohort study. Hepatology 2022; 76:1746-1754. [PMID: 35588190 DOI: 10.1002/hep.32578] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 05/09/2022] [Accepted: 05/13/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Whether subjects with NAFLD are at increased risk of sarcopenia is not well established. APPROACH AND RESULTS This is a cohort study of 52,815 men and women of 20 years of age or older who underwent at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging. Bioelectrical impedance analysis was used to calculate appendicular skeletal muscle mass (ASM). NAFLD was assessed by ultrasonography, and its severity was assessed by the NAFLD fibrosis score (NFS). We estimated the 5-year change in ASM comparing participants with and without NAFLD at baseline using mixed linear models. The 5-year change in ASM in participants without and with NAFLD was -225.2 g (95% CI -232.3, -218.0) and -281.3 g (95% CI -292.0, -270.6), respectively (p < 0.001). In multivariable adjusted analysis, the difference in 5-year change in ASM comparing participants with and without NAFLD was -39.9 g (95% CI -53.1, -26.8). When participants with NAFLD were further divided by NAFLD severity, ASM loss was much faster in participants with NAFLD with intermediate to high NFS than in those with low NFS. CONCLUSIONS Participants with NAFLD were at increased risk of sarcopenia, indicated by faster loss of skeletal muscle mass. Patients with NAFLD may need screening and early intervention to mitigate skeletal muscle mass loss.
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Affiliation(s)
- Dong Hyun Sinn
- Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea.,Department of Clinical Research Design and Evaluation, The Samsung Advanced Institute for Health Sciences & Technology (SAIHST)Sungkyunkwan UniversitySeoulSouth Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, The Samsung Advanced Institute for Health Sciences & Technology (SAIHST)Sungkyunkwan UniversitySeoulSouth Korea
| | - Mira Kang
- Center for Health Promotion, Samsung Medical CenterSungkyunkwan UniversitySeoulSouth Korea
| | - Eliseo Guallar
- Center for Clinical Epidemiology, Samsung Medical CenterSungkyunkwan UniversitySeoulSouth Korea.,Department of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology and Clinical ResearchJohns Hopkins Medical InstitutionsBaltimoreMarylandUSA
| | - Yun Soo Hong
- Department of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology and Clinical ResearchJohns Hopkins Medical InstitutionsBaltimoreMarylandUSA
| | - Kyung Hyun Lee
- Department of Digital Health, SAIHSTSungkyunkwan UniversitySeoulSouth Korea
| | - Jiyeon Park
- Research Institute for Future Medicine, Samsung Medical CenterSungkyunkwan UniversitySeoulSouth Korea
| | - Juhee Cho
- Department of Clinical Research Design and Evaluation, The Samsung Advanced Institute for Health Sciences & Technology (SAIHST)Sungkyunkwan UniversitySeoulSouth Korea.,Center for Clinical Epidemiology, Samsung Medical CenterSungkyunkwan UniversitySeoulSouth Korea.,Department of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology and Clinical ResearchJohns Hopkins Medical InstitutionsBaltimoreMarylandUSA
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
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25
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Hari A. Ultrasound-Based Diagnostic Methods: Possible Use in Fatty Liver Disease Area. Diagnostics (Basel) 2022; 12:diagnostics12112822. [PMID: 36428882 PMCID: PMC9689357 DOI: 10.3390/diagnostics12112822] [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: 10/02/2022] [Revised: 11/11/2022] [Accepted: 11/14/2022] [Indexed: 11/19/2022] Open
Abstract
Liver steatosis is a chronic liver disease that is becoming one of the most important global health problems, due to its direct connection with metabolic syndrome, its significant impact on patients' socioeconomic status and frailty, and the occurrence of advanced chronic liver disease. In recent years, there has been rapid technological progress in the ultrasound-based diagnostics field that can help us to quantitatively assess liver steatosis, including continuous attenuation parameters in A and B ultrasound modes, backscatter coefficients (e.g., speed of sound) and ultrasound envelope statistic parametric imaging. The methods used in this field are widely available, have favorable time and financial profiles, and are well accepted by patients. Less is known about their reliability in defining the presence and degree of liver steatosis. Numerous study reports have shown the methods' favorable negative and positive predictive values in comparison with reference investigations (liver biopsy and MRI). Important research has also evaluated the role of these methods in diagnosing and monitoring non-alcoholic fatty liver disease (NAFLD). Since NAFLD is becoming the dominant global cause of liver cirrhosis, and due to the close but complex interplay of liver steatosis with the coexistence of liver fibrosis, knowledge regarding NAFLD's influence on the progression of liver fibrosis is of crucial importance. Study findings, therefore, indicate the possibility of using these same diagnostic methods to evaluate the impact of NAFLD on the patient's liver fibrosis progression risk, metabolic risk factors, cardiovascular complications, and the occurrence of hepatocellular carcinoma. The mentioned areas are particularly important in light of the fact that most of the known chronic liver disease etiologies are increasingly intertwined with the simultaneous presence of NAFLD.
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Affiliation(s)
- Andrej Hari
- Oddelek za Bolezni Prebavil, Splošna Bolnišnica Celje, Oblakova Cesta 3, 3000 Celje, Slovenia
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26
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Pichon C, Nachit M, Gillard J, Vande Velde G, Lanthier N, Leclercq IA. Impact of L-ornithine L-aspartate on non-alcoholic steatohepatitis-associated hyperammonemia and muscle alterations. Front Nutr 2022; 9:1051157. [PMID: 36466421 PMCID: PMC9709200 DOI: 10.3389/fnut.2022.1051157] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 10/31/2022] [Indexed: 12/13/2023] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world. Progression toward non-alcoholic steatohepatitis (NASH) is associated with alterations of skeletal muscle. One plausible mechanism for altered muscle compartment in liver disease is changes in ammonia metabolism. In the present study, we explored the hypothesis that NASH-associated hyperammonemia drives muscle changes as well as liver disease progression. MATERIALS AND METHODS In Alms1-mutant mice (foz/foz) fed a 60% fat diet (HFD) for 12 weeks; we investigated hepatic and muscular ammonia detoxification efficiency. We then tested the effect of an 8 week-long supplementation with L-ornithine L-aspartate (LOLA), a known ammonia-lowering treatment, given after either 4 or 12 weeks of HFD for a preventive or a curative intervention, respectively. We monitored body composition, liver and muscle state by micro computed tomography (micro-CT) as well as muscle strength by four-limb grip test. RESULTS According to previous studies, 12 weeks of HFD induced NASH in all foz/foz mice. Increase of hepatic ammonia production and alterations of urea cycle efficiency were observed, leading to hyperammonemia. Concomitantly mice developed marked myosteatosis. First signs of myopenia occurred after 20 weeks of diet. Early LOLA treatment given during NASH development, but not its administration in a curative regimen, efficiently prevented myosteatosis and muscle quality, but barely impacted liver disease or, surprisingly, ammonia detoxification. CONCLUSION Our study confirms the perturbation of hepatic ammonia detoxification pathways in NASH. Results from the interventional experiments suggest a direct beneficial impact of LOLA on skeletal muscle during NASH development, though it does not improve ammonia metabolism or liver disease.
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Affiliation(s)
- Camille Pichon
- Laboratory of Hepato-Gastroenterology (GAEN), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
| | - Maxime Nachit
- Laboratory of Hepato-Gastroenterology (GAEN), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
| | - Justine Gillard
- Laboratory of Hepato-Gastroenterology (GAEN), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
| | - Greetje Vande Velde
- Department of Imaging and Pathology, Molecular Small Animal Imaging Center, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Nicolas Lanthier
- Laboratory of Hepato-Gastroenterology (GAEN), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
- Service d’Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, Brussels, Belgium
| | - Isabelle A. Leclercq
- Laboratory of Hepato-Gastroenterology (GAEN), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
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27
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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: 26] [Impact Index Per Article: 8.7] [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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28
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Li G, Tang LJ, Zhu PW, Huang OY, Rios RS, Zheng KI, Chen SD, Ma HL, Targher G, Byrne CD, Pan XY, Zheng MH. PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease. J Clin Transl Hepatol 2022; 10:439-448. [PMID: 35836754 PMCID: PMC9240254 DOI: 10.14218/jcth.2021.00286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/11/2021] [Accepted: 09/22/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism. METHODS The variant of PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest. RESULTS The distribution of PNPLA3 genotypes was CC: 27.5%, CG: 48.2%, and GG: 24.3%. Higher VFA was associated with greater risk of having SF (adjusted-odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02-1.04, p<0.05), independent of potential confounders. Among subjects with the same VFA level, the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not. Stratified analysis showed that PNPLA3 rs738409 significantly influenced the association between VFA and SF. VFA remained significantly associated with SF only among the rs738409 G-allele carriers (adjusted-OR: 1.05; 95% CI: 1.03-1.08 for the GG group; and adjusted-OR:1.03; 95% CI: 1.01-1.04 for the GC group). There was a significant interaction between VFA and PNPLA3 rs738409 genotype (P interaction =0.004). CONCLUSIONS PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD. Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF.
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Affiliation(s)
- Gang Li
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Liang-Jie Tang
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Pei-Wu Zhu
- Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ou-Yang Huang
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Rafael S. Rios
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Kenneth I. Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Sui-Dan Chen
- Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hong-Lei Ma
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Christopher D. Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Xiao-Yan Pan
- Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, Zhejiang, China
- Correspondence to: Ming-Hua Zheng, NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, Zhejiang 325000, China. ORCID: https://orcid.org/0000-0003-4984-2631. Tel: +86-577-55579611, Fax: +86-577-55578522, E-mail:
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29
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Guo W, Zhao X, Miao M, Liang X, Li X, Qin P, Lu J, Zhu W, Wu J, Zhu C, Xu N, Zhang Q. Association Between Skeletal Muscle Mass and Severity of Steatosis and Fibrosis in Non-alcoholic Fatty Liver Disease. Front Nutr 2022; 9:883015. [PMID: 35558748 PMCID: PMC9087584 DOI: 10.3389/fnut.2022.883015] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/04/2022] [Indexed: 12/18/2022] Open
Abstract
Background Sarcopenia is known to be the risk factor of non-alcoholic fatty liver disease (NAFLD). However, studies evaluating the association of skeletal muscle mass (SMM) with liver fibrosis by transient elastography are limited. Here, we investigated the association of SMM with hepatic steatosis and fibrosis assessed in Chinese adults. Methods Patients who underwent liver ultrasonography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University between January 2020 to June 2021 were enrolled. We used transient elastography to evaluate the degree of hepatic fat and liver stiffness. Appendicular skeletal muscle mass was determined by bioelectrical impedance and was adjusted for body weight to derive the skeletal muscle mass index (SMI). Results Of 3,602 finally enrolled individuals, 1,830 had NAFLD and 1,772 did not have NAFLD. SMI gradually decreased as the severity of hepatic steatosis increased (40.47 ± 3.94% vs. 39.89 ± 3.57% vs. 39.22 ± 3.46% vs. 37.81 ± 2.84%, P < 0.001). Individuals with F3-F4 and F2 liver fibrosis groups had significantly lower SMI than individuals with F0-F1 stages (37.51 ± 3.19% vs. 38.06 ± 3.51% vs. 39.36 ± 3.38%, P < 0.001). As the SMI increased, the percentages of subjects with mild and severe NAFLD, and the percentages of subjects in F2 and F3-F4 stage were gradually decreased. SMI was independently associated with the severity of hepatic steatosis and fibrosis by logistic regression analysis. Moreover, decreased SMI was an independent risk factor for NAFLD and fibrosis. Conclusion SMI is closely associated with liver fat content and liver fibrosis in Chinese adults with NAFLD.
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Affiliation(s)
- Wen Guo
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xin Zhao
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Mengyuan Miao
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xiuru Liang
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xiaona Li
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Pei Qin
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Jing Lu
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Wenfang Zhu
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Juan Wu
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Chen Zhu
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Nianzhen Xu
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Qun Zhang
- Department of Health Promotion Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
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30
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Nawrot M, Peschard S, Lestavel S, Staels B. Intestine-liver crosstalk in Type 2 Diabetes and non-alcoholic fatty liver disease. Metabolism 2021; 123:154844. [PMID: 34343577 DOI: 10.1016/j.metabol.2021.154844] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/28/2021] [Accepted: 07/29/2021] [Indexed: 02/08/2023]
Abstract
Type 2 diabetes (T2D) and Non-Alcoholic Fatty Liver Disease (NAFLD) are pathologies whose prevalence continues to increase worldwide. Both diseases are precipitated by an excessive caloric intake, which promotes insulin resistance and fatty liver. The role of the intestine and its crosstalk with the liver in the development of these metabolic diseases is receiving increasing attention. Alterations in diet-intestinal microbiota interactions lead to the dysregulation of intestinal functions, resulting in altered metabolite and energy substrate production and increased intestinal permeability. Connected through the portal circulation, these changes in intestinal functions impact the liver and other metabolic organs, such as visceral adipose tissue, hence participating in the development of insulin resistance, and worsening T2D and NAFLD. Thus, targeting the intestine may be an efficient therapeutic approach to cure T2D and NAFLD. In this review, we will first introduce the signaling pathways linking T2D and NAFLD. Next, we will address the role of the gut-liver crosstalk in the development of T2D and NAFLD, with a particular focus on the gut microbiota and the molecular pathways behind the increased intestinal permeability and inflammation. Finally, we will summarize the therapeutic strategies which target the gut and its functions and are currently used or under development to treat T2D and NAFLD.
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Affiliation(s)
- Margaux Nawrot
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
| | - Simon Peschard
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
| | - Sophie Lestavel
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
| | - Bart Staels
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France.
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31
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The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea. Life (Basel) 2021; 11:life11080848. [PMID: 34440592 PMCID: PMC8400877 DOI: 10.3390/life11080848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/12/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. Results: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38–2.78; class II, OR: 3.33, 95% CI: 1.77–6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31–2.95; class II, OR: 2.96, 95% CI: 1.51–5.78). Conclusion: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.
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Anand A, Sharma S, Saraya A. Low skeletal muscle mass and significant fibrosis in non-alcoholic fatty liver disease: Cause or effect? Liver Int 2021; 41:1160. [PMID: 33249727 DOI: 10.1111/liv.14746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 11/20/2020] [Indexed: 02/13/2023]
Affiliation(s)
- Abhinav Anand
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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Miyake T, Miyazaki M, Yoshida O, Kanzaki S, Nakaguchi H, Nakamura Y, Watanabe T, Yamamoto Y, Koizumi Y, Tokumoto Y, Hirooka M, Furukawa S, Takeshita E, Kumagi T, Ikeda Y, Abe M, Toshimitsu K, Matsuura B, Hiasa Y. Relationship between body composition and the histology of non-alcoholic fatty liver disease: a cross-sectional study. BMC Gastroenterol 2021; 21:170. [PMID: 33849437 PMCID: PMC8045325 DOI: 10.1186/s12876-021-01748-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 03/30/2021] [Indexed: 12/21/2022] Open
Abstract
Background Causes of non-alcoholic fatty liver disease and its progression include visceral fat accumulation and loss of muscle mass; however, which of the two phenomena is more critical is unclear. Therefore, we intended to examine the relationship between body composition and non-alcoholic fatty liver disease progression as indicated by fibrosis and the non-alcoholic fatty liver disease activity score. Methods This cross-sectional study comprised 149 patients (55 men; age, 20–76 years) treated for non-alcoholic fatty liver disease between December 2010 and January 2020. Body composition measurements, histological examinations of liver samples, and comprehensive blood chemistry tests were performed. The relationship between body composition and non-alcoholic fatty liver disease histology findings was analyzed using the logistic regression model. Results Fibrosis was significantly and inversely correlated with muscle mass and appendicular skeletal muscle mass and significantly and positively correlated with fat mass, fat mass/height squared, visceral fat area, and waist-hip ratio (P < 0.05). After adjustment for sex, blood chemistry measurements, and body composition indices, fibrosis remained associated with appendicular skeletal muscle mass, fat mass, fat mass/height squared, and visceral fat area (P < 0.05). Non-alcoholic fatty liver disease activity score ≥ 5 significantly correlated with fat mass and fat mass/height squared in a univariate but not multivariate analysis. Conclusions Fibrosis in non-alcoholic fatty liver disease, an indicator of unfavorable long-term outcomes, is associated with more indices of fat mass than of those of muscle mass. Hence, fat mass should be controlled to prevent non-alcoholic fatty liver disease progression. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01748-y.
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Affiliation(s)
- Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Masumi Miyazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Sayaka Kanzaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Hironobu Nakaguchi
- Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Ehime, Shitsukawa, Toon, Japan
| | - Yoshiko Nakamura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Yasunori Yamamoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Shinya Furukawa
- Health Service Center, Ehime University, Ehime, Bunkyo, Matsuyama, Japan
| | - Eiji Takeshita
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Teru Kumagi
- Post Graduate Medical Education Center, Ehime University Graduate School of Medicine, Ehime, Shitsukawa, Toon, Japan
| | - Yoshio Ikeda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan
| | - Kumiko Toshimitsu
- Nutrition Division, Ehime University Hospital, Shitsukawa, Toon, Ehime, Japan
| | - Bunzo Matsuura
- Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Ehime, Shitsukawa, Toon, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 791-0295, Shitsukawa, Toon, Ehime, Japan.
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Armandi A, Rosso C, Caviglia GP, Ribaldone DG, Bugianesi E. The Impact of Dysmetabolic Sarcopenia Among Insulin Sensitive Tissues: A Narrative Review. Front Endocrinol (Lausanne) 2021; 12:716533. [PMID: 34858322 PMCID: PMC8631324 DOI: 10.3389/fendo.2021.716533] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 10/12/2021] [Indexed: 12/25/2022] Open
Abstract
Sarcopenia is a common muscular affection among elderly individuals. More recently, it has been recognized as the skeletal muscle (SM) expression of the metabolic syndrome. The prevalence of sarcopenia is increasing along with visceral obesity, to which it is tightly associated. Nonetheless, it is a still underreported entity by clinicians, despite the worsening in disease burden and reduced patient quality of life. Recognition of sarcopenia is clinically challenging, and variability in study populations and diagnostic methods across the clinical studies makes it hard to reach a strong evidence. Impaired insulin activity in SM is responsible for the altered molecular pathways and clinical manifestations of sarcopenia, which is morphologically expressed by myosteatosis. Lipotoxicity, oxidative stress and adipose tissue-derived inflammation lead to both alterations in glucose disposal and protein synthesis in SM, with raising insulin resistance (IR) and SM atrophy. In particular, hyperleptinemia and leptin resistance interfere directly with SM activity, but also with the release of Growth Hormone from the hypohysis, leading to a lack in its anabolic effect on SM. Moreover, sarcopenia is independently associated to liver fibrosis in Non-Alcoholic Fatty Liver Disease (NAFLD), which in turn worsens SM functionality through the secretion of proinflammatory heptokines. The cross-talk between the liver and SM in the IR setting is of crucial relevance, given the high prevalence of NAFLD and the reciprocal impact of insulin-sensitive tissues on the overall disease burden. Along with the efforts of non-invasive diagnostic approaches, irisin and myostatin are two myokines currently evaluated as potential biomarkers for diagnosis and prognostication. Decreased irisin levels seem to be potentially associated to sarcopenia, whereas increased myostatin has shown to negatively impact on sarcopenia in pre-clinical studies. Gene variants in irisin have been explored with regard to the impact on the liver disease phenotype, with conflicting results. The gut-muscle axis has gain relevance with the evidence that insulin resistance-derived gut dysbiosis is responsible for increased endotoxemia and reduction in short-chain free fatty acids, directly affecting and predisposing to sarcopenia. Based on the current evidence, more efforts are needed to increase awareness and improve the management of sarcopenic patients.
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