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Zhou L, Li B, Wang Z, Ao X, Wang X, Zheng Y, He Y, Fan X, Yang L. Association of sarcopenia assessed by CT/MRI with treatment response and clinical outcomes in noncirrhotic primary biliary cholangitis patients. Eur J Radiol 2025; 187:112094. [PMID: 40220738 DOI: 10.1016/j.ejrad.2025.112094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 01/26/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025]
Abstract
BACKGROUND AND OBJECTIVE Sarcopenia is a common complication in patients with cirrhosis. However, research on sarcopenia in patients with noncirrhotic primary biliary cholangitis (PBC) is limited. This study aimed to investigate the prevalence of sarcopenia and the associations between concomitant sarcopenia and the biochemical response to ursodeoxycholic acid (UDCA) treatment and clinical outcomes in patients with noncirrhotic PBC. METHODS This retrospective study enrolled consecutive patients whose baseline visits occurred between January 2009 and December 2023. Sarcopenia was assessed via pretreatment CT or MRI at the mid-L3 level through the skeletal muscle index (SMI). Baseline characteristics, response rate after UDCA administration, liver-related events were compared. And baseline liver and plasma C-reactive protein (CRP) and IL-6 levels in a subset of patients were also evaluated. RESULTS A total of 164 patients were included and sarcopenia was identified in 66 (40.2 %) patients. The median duration of follow-up was 4.75 (1.71, 6.40) years. The PBC patients with sarcopenia had a lower biochemical response rate (45.9 % vs. 65.9 %; P = 0.014) after 12 months of UDCA treatment and a higher incidence of liver-related events (24.2 % vs. 11.2 %, P = 0.027) during follow-up. Furthermore, higher levels of baseline CRP and IL-6 in the plasma and liver were also observed(P < 0.05). CONCLUSIONS Sarcopenia was highly prevalent in patients with noncirrhotic PBC. Concomitant sarcopenia may adversely affect the biochemical response to UDCA treatment and the occurrence of liver-related adverse events in PBC patients without cirrhosis.
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Affiliation(s)
- Leyu Zhou
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, People's Republic of China
| | - Bo Li
- Department of Radiology, West China Hospital, Sichuan University, People's Republic of China
| | - Zhetao Wang
- Department of Radiology, West China Hospital, Sichuan University, People's Republic of China
| | - Xiaoyan Ao
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, People's Republic of China
| | - Xianglin Wang
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, People's Republic of China
| | - Yanyi Zheng
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, People's Republic of China
| | - Yazhou He
- Department of Epidemiology and Medical Statistics, Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, People's Republic of China
| | - Xiaoli Fan
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, People's Republic of China.
| | - Li Yang
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, People's Republic of China.
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Marjot T, Armstrong MJ, Stine JG. Skeletal muscle and MASLD: Mechanistic and clinical insights. Hepatol Commun 2025; 9:e0711. [PMID: 40408301 DOI: 10.1097/hc9.0000000000000711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Accepted: 03/17/2025] [Indexed: 05/25/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is intrinsically linked with widespread metabolic perturbations, including within skeletal muscle. Indeed, MASLD is associated with a range of skeletal muscle abnormalities, including insulin resistance, myosteatosis, and sarcopenia, which all converge on the liver to drive disease progression and adverse patient outcomes. This review explores the mechanistic links between skeletal muscle and MASLD, including the role of abnormal glycemic control, systemic inflammation, and disordered myokine signaling. In turn, we discuss how intrinsic liver pathology can feed back to further exacerbate poor skeletal muscle health. Given the central importance of skeletal muscle in MASLD pathogenesis, it offers clinicians an opportunity to intervene for therapeutic benefit. We, therefore, summarize the role of nutrition and physical activity on skeletal muscle mass, quality, and metabolic function and discuss the knock-on effect this has on the liver. An awareness of these treatment strategies is particularly important in the era of effective pharmacological and surgical weight loss interventions, which can be associated with the development of sarcopenia. Finally, we highlight a number of promising drug agents in the clinical trial pipeline that specifically target skeletal muscle in an attempt to improve metabolic and physical functioning.
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Affiliation(s)
- Thomas Marjot
- Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Radcliffe Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK
- Translational Gastroenterology and Liver Unit (TGLU), Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - Matthew J Armstrong
- Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
- Birmingham NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - Jonathan G Stine
- Department of Medicine, Division of Gastroenterology and Hepatology, Penn State Health-Milton S. Hershey Medical Centre, Hershey, Pennsylvania, USA
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Arasteh B, Hamzehzadeh S, Toutounchi KS, Nikniaz Z, Amini L, Alizadeh L. Association of ultrasound signs of sarcopenia with serum ferritin levels and hepatic indices like NFS and FIB-4 in NAFLD patients. BMC Gastroenterol 2025; 25:261. [PMID: 40234765 PMCID: PMC12001710 DOI: 10.1186/s12876-025-03773-7] [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: 07/02/2024] [Accepted: 03/10/2025] [Indexed: 04/17/2025] Open
Abstract
INTRODUCTION Non-alcoholic fatty liver disease is one of the most common chronic diseases all around the world, which significantly correlates with metabolic disorders and inflammatory cycles. Sarcopenia is a decrease in the mass of skeletal muscles interacting with factors such as inflammatory processes and chronic diseases. It can also lead to the aggravation of chronic diseases. METHOD The study population was randomly selected and entered into the research based on exclusion and inclusion criteria. Non-alcoholic fatty liver disease was confirmed in all members of the study population by ultrasound. Patients' serum ferritin level was assessed, and their NFS and Fib 4 scores were calculated. Sarcopenia was diagnosed by measuring the thickness of the rectus femoris by ultrasonography. The correlation between these variables was evaluated and analyzed by statistical software. RESULTS According to statistical analysis, there is a significant association between the serum ferritin level and sarcopenia (P-value < 0.001). Besides, there is a significant association between NFS, Fib4, and sarcopenia (P-value = 0.024, 0.000). CONCLUSION This research's results reflect the correlation between serum ferritin and sarcopenia; however, it cannot conclude a cause-and-effect relationship between these variables.
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Affiliation(s)
- Bahar Arasteh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Hamzehzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
| | | | - Zeinab Nikniaz
- Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Amini
- Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Alizadeh
- Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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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: 6] [Impact Index Per Article: 6.0] [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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Aggarwal K, Singh B, Goel A, Agrawal DK, Bansal S, Kanagala SG, Anamika F, Gupta A, Jain R. Complex dichotomous links of nonalcoholic fatty liver disease and inflammatory bowel disease: exploring risks, mechanisms, and management modalities. Intest Res 2024; 22:414-427. [PMID: 38835139 PMCID: PMC11534450 DOI: 10.5217/ir.2024.00001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 04/04/2024] [Accepted: 04/15/2024] [Indexed: 06/06/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has been shown to be linked to inflammatory bowel disease (IBD) due to established risk factors such as obesity, age, and type 2 diabetes in numerous studies. However, alternative research suggests that factors related to IBD, such as disease activity, duration, and drug-induced toxicity, can contribute to NAFLD. Recent research findings suggest IBD relapses are correlated with dysbiosis, mucosal damage, and an increase in cytokines. In contrast, remission periods are characterized by reduced metabolic risk factors. There is a dichotomy evident in the associations between NAFLD and IBD during relapses and remissions. This warrants a nuanced understanding of the diverse influences on disease manifestation and progression. It is possible to provide a holistic approach to care for patients with IBD by emphasizing the interdependence between metabolic and inflammatory disorders.
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Affiliation(s)
- Kanishk Aggarwal
- Department of Medicine, Dayanand Medical College, Ludhiana, India
| | - Bhupinder Singh
- Department of Medicine, Government Medical College Amritsar, Amritsar, India
| | - Abhishek Goel
- Department of Medicine, Cape Fear Valley Medical Center, Fayetteville, NC, USA
| | | | - Sourav Bansal
- Department of Medicine, Government Medical College Amritsar, Amritsar, India
| | | | - Fnu Anamika
- Department of Medicine, University College of Medical Sciences, New Delhi, India
| | | | - Rohit Jain
- Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
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Demirci S, Sezer S, Erdoğan K, Abdulsalam AJ, Kara Ö, Kara M. Strong association between sarcopenic obesity and non-alcoholic fatty liver disease: An observational study with ISarcoPRM algorithm. Clin Res Hepatol Gastroenterol 2024; 48:102412. [PMID: 38964606 DOI: 10.1016/j.clinre.2024.102412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 06/19/2024] [Accepted: 07/01/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND In recent times, sarcopenia and non-alcoholic fatty liver disease (NAFLD) have garnered widespread attention in public health. Nevertheless, the relationship between sarcopenia and NAFLD remains uncertain. This study investigated the association between NAFLD and sarcopenia in the elderly population. METHODS In this cross-sectional study, 1099 adults aged 60 and older participated. The participants were classified based on their body composition, and the International Society of Physical and Rehabilitation Medicine's diagnostic algorithm (ISarcoPRM) was utilized to diagnose sarcopenia, while the fatty liver index was utilized to diagnose NAFLD. Binary logistic regression analysis determined the correlation between NAFLD and sarcopenia. RESULTS Of the 1099 participants, 213 (58.2 %) males and 480 (65.5 %) females were afflicted with NAFLD. After adjusting for other clinical factors, exercise was found to decrease the likelihood of NAFLD in females (but not in males) by approximately 70 % [relative risk (RR): 0.312, 95 % confidence interval (CI): 0.182-0.547]. In addition, sarcopenia was not discerned as a risk factor for NAFLD in either gender (both p > 0.05). However, obesity increased the likelihood of NAFLD in males by 27.5 (95 % CI: 10.4-73.1) and in females by 28.1 (95 % CI: 17.1-46.4), and sarcopenic obesity increased the likelihood of NAFLD by 49.5 (95 % CI: 11.1-219.1) in males and 35.5 (95 % CI: 18.5-68.2) in females (all p < 0.001). CONCLUSION Our study suggests that sarcopenia is not a risk factor for NAFLD in non-obese elderly subjects. However, a strong association was observed between obesity, especially sarcopenic obesity, and NAFLD. Regular physical activity seems protective for NAFLD in older females.
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Affiliation(s)
- Selim Demirci
- Department of Internal Medicine, Divisions of Gastroenterology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkiye.
| | - Semih Sezer
- Department of Internal Medicine, Divisions of Gastroenterology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkiye
| | - Kübra Erdoğan
- Department of Internal Medicine, Divisions of Geriatric Medicine, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkiye
| | - Ahmad J Abdulsalam
- Department of Physical and Rehabilitation Medicine,Hacettepe University Medical School, Ankara, Turkiye
| | - Özgür Kara
- Department of Internal Medicine, Divisions of Geriatric Medicine, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkiye
| | - Murat Kara
- Department of Physical and Rehabilitation Medicine,Hacettepe University Medical School, Ankara, Turkiye
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Sandireddy R, Sakthivel S, Gupta P, Behari J, Tripathi M, Singh BK. Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases. Front Cell Dev Biol 2024; 12:1433857. [PMID: 39086662 PMCID: PMC11289778 DOI: 10.3389/fcell.2024.1433857] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 07/01/2024] [Indexed: 08/02/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common liver disorder worldwide, with an estimated global prevalence of more than 31%. Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide a comprehensive analysis of the extrahepatic manifestations of MASH, focusing on chronic diseases related to the cardiovascular, muscular, and renal systems. A systematic review of published studies and literature was conducted to summarize the findings related to the systemic impacts of MASLD and MASH. The review focused on the association of MASLD and MASH with metabolic comorbidities, cardiovascular mortality, sarcopenia, and chronic kidney disease. Mechanistic insights into the concept of lipotoxic inflammatory "spill over" from the MASH-affected liver were also explored. MASLD and MASH are highly associated (50%-80%) with other metabolic comorbidities such as impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, and hypertension. Furthermore, more than 90% of obese patients with type 2 diabetes have MASH. Data suggest that in middle-aged individuals (especially those aged 45-54), MASLD is an independent risk factor for cardiovascular mortality, sarcopenia, and chronic kidney disease. The concept of lipotoxic inflammatory "spill over" from the MASH-affected liver plays a crucial role in mediating the systemic pathological effects observed. Understanding the multifaceted impact of MASH on the heart, muscle, and kidney is crucial for early detection and risk stratification. This knowledge is also timely for implementing comprehensive disease management strategies addressing multi-organ involvement in MASH pathogenesis.
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Affiliation(s)
| | | | | | | | - Madhulika Tripathi
- Cardiovascular and Metabolic Disorders Research Program, Duke-NUS Medical School, Singapore, Singapore
| | - Brijesh Kumar Singh
- Cardiovascular and Metabolic Disorders Research Program, Duke-NUS Medical School, Singapore, Singapore
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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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Deng C, Ou Q, Ou X, Pan D. Association between non-alcoholic fatty liver disease and risk of sarcopenia: a systematic review and meta-analysis. BMJ Open 2024; 14:e078933. [PMID: 38719326 PMCID: PMC11086578 DOI: 10.1136/bmjopen-2023-078933] [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: 08/16/2023] [Accepted: 03/07/2024] [Indexed: 05/12/2024] Open
Abstract
OBJECTIVES To determine the association of non-alcoholic fatty liver disease (NAFLD) with the incidence of sarcopenia. DESIGN Systematic review and meta-analysis of observational clinical studies. SETTING AND PARTICIPANTS Adults with NAFLD. METHODS Databases such as PubMed, Embase, Cochrane and Web of Science were searched for eligible studies published from the inception of each database up to 4 April 2023. All cross-sectional studies on the association between NAFLD and sarcopenia were included in this study. The quality of the included studies and risk of bias was assessed using the Agency for Healthcare Research and Quality checklist. STATA V.15.1 software was used for statistical analysis. RESULTS Of the 1524 retrieved articles, 24 were included in this review, involving 88 609 participants. Our findings showed that the prevalence of sarcopenia was higher in the NAFLD group than in the control group (pooled OR 1.74, 95% CI 1.39 to 2.17). In a subgroup analysis by region, patients with NAFLD showed an increased risk of sarcopenia (pooled OR 1.97, 95% CI 1.54 to 2.51) in the Asian group, whereas patients with NAFLD had no statistically significant association with the risk of sarcopenia in the American and European groups, with a pooled OR of 1.31 (95% CI 0.71 to 2.40) for the American group and a pooled OR of 0.99 (95% CI 0.21 to 4.69) for the European group. Similar results were observed in the sensitivity analysis, and no evidence of publication bias was observed. CONCLUSIONS AND IMPLICATIONS The current study indicated a significant positive correlation between NAFLD and sarcopenia, which may be affected by regional factors. This study provides the correlation basis for the relationship between NAFLD and sarcopenia and helps to find the quality strategy of sarcopenia targeting NAFLD.
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Affiliation(s)
- Chao Deng
- Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital Central South University, Changsha, Hunan, China
| | - Qifeng Ou
- Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital Central South University, Changsha, Hunan, China
| | - Xuee Ou
- Changsha County Xingsha Hospital, Changsha City, Hunan Province, China
| | - Ding Pan
- Department of Orthopedics, Hand and Microsurgery, Xiangya Hospital Central South University, Changsha, Hunan, China
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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: 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: 12/21/2023] [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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Xu M, Lin Y, Yang N, Li J, Li L, Ding H, Xu C. Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2024; 70:e20230963. [PMID: 38451586 PMCID: PMC10914329 DOI: 10.1590/1806-9282.20230963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/07/2023] [Indexed: 03/08/2024]
Abstract
OBJECTIVE The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.
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Affiliation(s)
- Miao Xu
- Zhejiang University School of Medicine, The First Affiliated
Hospital, Zhejiang Provincial Clinical Research Center for Digestive Diseases,
Department of Gastroenterology – Hangzhou, China
- The First Affiliated Hospital of Ningbo University, Department of
Endocrinology and Metabolism – Ningbo, China
| | - Yi Lin
- University of Nottingham, Faculty of Humanities and Social Sciences,
Center for Health Economics – Ningbo, China
| | - Naibin Yang
- The First Affiliated Hospital of Ningbo University, Metabolic
(Dysfunction)-Associated Fatty Liver Disease Research Center, Department of
Hepatology – Ningbo, China
| | - Jialin Li
- The First Affiliated Hospital of Ningbo University, Department of
Endocrinology and Metabolism – Ningbo, China
| | - Li Li
- The First Affiliated Hospital of Ningbo University, Department of
Endocrinology and Metabolism – Ningbo, China
| | - Huiqing Ding
- The First Affiliated Hospital of Ningbo University, Department of
Obstetrics and Gynecology – Ningbo, China
| | - Chengfu Xu
- Zhejiang University School of Medicine, The First Affiliated
Hospital, Zhejiang Provincial Clinical Research Center for Digestive Diseases,
Department of Gastroenterology – Hangzhou, China
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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: 7] [Impact Index Per Article: 7.0] [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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14
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Yuan J, Zhang J, Luo Q, Peng L. Effects of nonalcoholic fatty liver disease on sarcopenia: evidence from genetic methods. Sci Rep 2024; 14:2709. [PMID: 38302636 PMCID: PMC10834579 DOI: 10.1038/s41598-024-53112-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 01/28/2024] [Indexed: 02/03/2024] Open
Abstract
With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.
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Affiliation(s)
- Jiaqin Yuan
- Department of Orthopedics, The Second People's Hospital of Yibin, Sichuan, China
| | - Jinglin Zhang
- Department of Occupational Diseases, Yibin Center for Disease Control and Prevention, Sichuan, China
| | - Qiang Luo
- Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, China.
| | - Lipeng Peng
- Department of Orthopedics, The Second People's Hospital of Yibin, Sichuan, China.
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15
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Ferenc K, Jarmakiewicz-Czaja S, Filip R. What Does Sarcopenia Have to Do with Nonalcoholic Fatty Liver Disease? Life (Basel) 2023; 14:37. [PMID: 38255652 PMCID: PMC10820621 DOI: 10.3390/life14010037] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/11/2023] [Accepted: 12/16/2023] [Indexed: 01/24/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. As the second stage of developing steatosis, nonalcoholic hepatitis (NASH) carries the risk of fibrosis, cirrhosis, and hepatocellular carcinoma. Sarcopenia is defined as a condition characterized by a decrease in muscle mass and functional decline. Both NAFLD and sarcopenia are global problems. The pathophysiological mechanisms that link the two entities of the disease are insulin resistance, inflammation, nutritional deficiencies, impairment of myostatin and adiponectin, or physical inactivity. Furthermore, disorders of the gut-liver axis appear to induce the process of developing NAFLD and sarcopenia. The correlations between NAFLD and sarcopenia appear to be bidirectional, so the main objective of the review was to determine the cause-and-effect relationship between the two diseases.
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Affiliation(s)
- Katarzyna Ferenc
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
| | | | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland;
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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16
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Altajar S, Wang N, Rosenthaler MP, Murabito JM, Long MT. NAFLD Associates with Sarcopenia Defined by Muscle Mass and Slow Walking Speed: A Cross-Sectional Analysis from the Framingham Heart Study. J Clin Med 2023; 12:7523. [PMID: 38137592 PMCID: PMC10743412 DOI: 10.3390/jcm12247523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/30/2023] [Accepted: 12/02/2023] [Indexed: 12/24/2023] Open
Abstract
Sarcopenia is associated with NAFLD. It is unknown if the association is explained by shared risk factors. Our study sought to investigate the association between liver fat and sarcopenia in our cohort. Liver fat was measured on CT between 2008 and 2011. We excluded heavy alcohol use and missing covariates. Muscle mass in a subset (n = 485) was measured by 24 h urinary creatinine. Physical function was defined by h strength and walking speed. Sarcopenia was defined as low muscle mass and/or low physical function. We created multivariable-adjusted regression models to evaluate cross-sectional associations between liver fat and low muscle mass, grip strength, and walking speed. The prevalence of hepatic steatosis was 30% (n = 1073; 58.1% women; mean age 65.8 ± 8.6 years). There was a significant positive association between liver fat and muscle mass in linear regression models. The association was not significant after adjusting for BMI. The odds of sarcopenia increased by 28% for each SD in liver fat (OR 1.28; 95% CI 1.02, 1.60) and persisted after accounting for confounders in multivariable-adjusted models (OR 1.30, 95% CI 1.02, 1.67). Further studies are needed to determine if there is a causal relationship between liver fat and sarcopenia and whether treatment of sarcopenia improves liver fat.
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Affiliation(s)
- Sarah Altajar
- Division of Gastroenterology and Hepatology, University of Miami Health System, Miami, FL 33136, USA;
| | - Na Wang
- Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, MA 02118, USA;
| | - Max P. Rosenthaler
- Department of Internal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA;
| | - Joanne M. Murabito
- Department of Internal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA;
| | - Michelle T. Long
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA;
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Maurotti S, Pujia R, Mazza E, Pileggi MF, Arturi F, Tarsitano MG, Montalcini T, Pujia A, Ferro Y. Low Relative Handgrip Strength Is Associated with a High Risk of Non-Alcoholic Fatty Liver Disease in Italian Adults: A Retrospective Cohort Study. APPLIED SCIENCES 2023; 13:12489. [DOI: 10.3390/app132212489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) and the presence of low muscle mass (sarcopenia) represent noteworthy health issues. Handgrip strength, a muscle function indicator, is vital for sarcopenia diagnosis. We investigated the link between handgrip strength and hepatic steatosis in Italian adults. Methods: We retrospectively assessed 388 adults (≥50 years), measuring muscle function and hepatic steatosis using a dynamometer and transient elastography. We divided participants into handgrip strength tertiles. Results: 207 had NAFLD. The lowest handgrip strength tertile had a higher NAFLD prevalence (64% vs. 46%, p = 0.02). Tertiles I and II exhibited increased odds of NAFLD in comparison to tertile III, with an odds ratio of 5.30 (95% confidence interval: 2.24–12.57, p < 0.001) and 2.56 (95% confidence interval: 1.17–5.59, p = 0.01), respectively. rHGS predicted NAFLD with an AUC of 0.41 (SE = 0.029, p = 0.003). An rHGS of 1.22 achieved 18% sensitivity and 80% specificity for hepatic steatosis prediction. Conclusion: Low handgrip strength is linked to an increased susceptibility to NAFLD among the Italian population, implying its potential utility in the identification of risk for hepatic steatosis.
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Affiliation(s)
- Samantha Maurotti
- Department of Clinical and Experimental Medicine, University Magna Græcia, 88100 Catanzaro, Italy
| | - Roberta Pujia
- Department of Medical and Surgical Science, University Magna Græcia, 88100 Catanzaro, Italy
| | - Elisa Mazza
- Department of Medical and Surgical Science, University Magna Græcia, 88100 Catanzaro, Italy
| | | | - Franco Arturi
- Department of Medical and Surgical Science, University Magna Græcia, 88100 Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Græcia, 88100 Catanzaro, Italy
| | - Maria Grazia Tarsitano
- Department of Medical and Surgical Science, University Magna Græcia, 88100 Catanzaro, Italy
| | - Tiziana Montalcini
- Department of Clinical and Experimental Medicine, University Magna Græcia, 88100 Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Græcia, 88100 Catanzaro, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Science, University Magna Græcia, 88100 Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Græcia, 88100 Catanzaro, Italy
| | - Yvelise Ferro
- Department of Medical and Surgical Science, University Magna Græcia, 88100 Catanzaro, Italy
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18
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Zhao Q, Yin Y, Deng Y. Metabolic associated fatty liver disease and sarcopenia additively increase mortality: a real-world study. Nutr Diabetes 2023; 13:21. [PMID: 37968264 PMCID: PMC10651884 DOI: 10.1038/s41387-023-00250-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 10/31/2023] [Accepted: 11/02/2023] [Indexed: 11/17/2023] Open
Abstract
BACKGROUND AND AIMS Sarcopenia is associated with worse prognosis for non-alcoholic fatty liver disease (NAFLD). However, disease progression in the MAFLD-related sarcopenia is largely unknown. We aimed to clarify the relationship between MAFLD and/or sarcopenia with mortality and liver fibrosis in the real world. METHODS A total of 13,692 individuals were selected from the third National Health and Nutrition Examination Surveys and linked mortality until December 2019. MAFLD is diagnosed based on a radiologically diagnosed hepatic steatosis and the presence of any one of the following three conditions: overweight/obesity, diabetes mellitus (DM), or metabolic dysregulation. Sarcopenia is defined by weight-adjusted skeletal muscle mass. RESULTS The mean age was 43.7 ± 15.97 years, and 47.3% of the individuals were male. MAFLD was diagnosed in 4207/13,692 (30.73%) participants, and the proportion of sarcopenic was 19.42% amongst subjects with MAFLD. The mean follow-up duration was of 23.7 ± 7.62 years. MAFLD (aHR 1.152, 95% CI 1.070-1.241) and sarcopenia (aHR 1.123, 95% CI 1.042-1.210) were related to increased all-cause mortality in MAFLD after adjustment for age, sex, race, marital status, education, and smoking. Stratified analysis revealed that MAFLD and sarcopenia additively increased the risk of mortality (aHR 1.247, 95% CI 1.132-1.373) and liver fibrosis (aOR 2.296, 95% CI 1.718-3.069 assessed by NFS score >0.676; aOR 2.218, 95% CI 1.788-2.752 assessed by FIB-4 score >1.3) in fully adjusted models (P < 0.001 for all). CONCLUSION Sarcopenia in individuals with MAFLD portends increased mortality and significant liver fibrosis. Novel therapeutic strategies targeting at increasing skeletal muscle mass should be explored for patients with MAFLD.
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Affiliation(s)
- Qianwen Zhao
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610200, China
| | - Yifan Yin
- Department of Nephrology, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, 82#Qinglong Street, Qingyang District, Chengdu, 610031, China
| | - Yunlei Deng
- Department of Nephrology, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, 82#Qinglong Street, Qingyang District, Chengdu, 610031, China.
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19
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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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20
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Zhao X, Shi X, Gu H, Zhou W, Zhang Q. Association between handgrip strength, nonalcoholic fatty liver disease, advanced hepatic fibrosis and its modifiers: Evidence from the NHANES database of the USA. J Gastroenterol Hepatol 2023; 38:1734-1742. [PMID: 36805682 DOI: 10.1111/jgh.16150] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/08/2023] [Accepted: 02/15/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND AND AIM Nonalcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis (AHF) have been associated with sarcopenia. However, modifiers of this association have been less studied. METHODS This study used data from the NHANES database 2011-2014 of the USA. Adults aged 18 years or older, had complete information of handgrip strength test and NAFLD and AHF status were eligible for inclusion. NAFLD was defined using the Fatty Liver Index (FLI). AHF was defined using the NAFLD fibrosis score (NFS). Univariate and multivariate logistic regression were performed to determine the associations between the study variables and prevalent NAFLD and AHF. RESULTS A total of 19 931 participants were selected from the 2011-2014 NHANES database. The multivariate analysis showed that stronger grip strength was significantly and independently associated with decreased odds for NAFLD (tertile 2: adjusted odd ratio [aOR]: 0.41, 95% confidence interval [CI]: 0.29-0.59; tertile 3: aOR: 0.11, 95% CI: 0.05-0.24) and AHF (tertile 2: aOR: 0.66, 95% CI: 0.46-0.94; tertile 3: aOR: 0.28, 95% CI: 0.12-0.63). In stratified analyses, strongest grip strength was significantly associated with reduced odds for NAFLD regardless of age, body mass index, and having diabetes or not. Strongest grip strength was associated with reduced odds for NAFLD in individuals who had moderate to ideal physical activity (aOR: 0.31). CONCLUSIONS Grip strength has an inverse association with prevalent NAFLD and AHF in the US population, which appears to be modified by physical activity level. Future prospective cohort studies are needed to clarify the role of physical activity in modifying the risks.
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Affiliation(s)
- Xiaohong Zhao
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
- Key Laboratory of Diagnosis and Treatment of Aging and Physic-Chemical Injury Diseases of Zhejiang Province, Zhejiang, China
| | - Xuexue Shi
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Haifeng Gu
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Wenjing Zhou
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Qin Zhang
- Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
- Key Laboratory of Diagnosis and Treatment of Aging and Physic-Chemical Injury Diseases of Zhejiang Province, Zhejiang, China
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21
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Harring M, Golabi P, Paik JM, Shah D, Racila A, Cable R, Srishord M, Younossi ZM. Sarcopenia Among Patients With Nonalcoholic Fatty Liver Disease (NAFLD) Is Associated With Advanced Fibrosis. Clin Gastroenterol Hepatol 2023; 21:2876-2888.e5. [PMID: 36848980 DOI: 10.1016/j.cgh.2023.02.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 01/30/2023] [Accepted: 02/13/2023] [Indexed: 03/01/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) and sarcopenia can be associated with advanced liver disease. Our aim was to assess the association between sarcopenia and the risk of fibrosis among patients with NAFLD. METHODS We used the National Health and Nutrition Examination Survey (2017-2018). NAFLD was defined by transient elastography without other causes of liver disease or excessive alcohol use. Significant fibrosis (SF) and advanced fibrosis (AF) were defined by liver stiffness greater than 8.0 kPa and greater than 13.1 kPa, respectively. Sarcopenia was defined using the Foundation for the National Institutes of Health definition. RESULTS Of the total cohort (N = 2422), 18.9% had sarcopenia, 9.8% had obese sarcopenia, 43.6% had NAFLD, 7.0% had SF, and 2.0% had AF. Moreover, 50.1% had neither sarcopenia nor NAFLD, 6.3% had sarcopenia without NAFLD, 31.1% had NAFLD without sarcopenia, and 12.5% had NAFLD with sarcopenia. Compared with individuals without NAFLD or sarcopenia, individuals with sarcopenic NAFLD had higher rates of SF (18.3% vs 3.2%) and AF (7.1% vs 0.2%). In the absence of sarcopenia, compared with individuals without NAFLD, individuals with NAFLD have a significantly increased risk of SF (odds ratio, 2.18; 95% CI, 0.92-5.19). In the presence of sarcopenia, NAFLD was associated with an increased risk of SF (odds ratio, 11.27; 95% CI, 2.79-45.56). This increase was independent of metabolic components. The proportion of SF that is attributable to the interaction of NAFLD and sarcopenia was 55% (attributable proportion, 0.55; 95% CI, 0.36-0.74). Increased leisure time physical activity was associated with a lower risk of sarcopenia. CONCLUSIONS Patients with sarcopenic NAFLD are at risk for SF and AF. Increased physical activity and a healthy diet targeted to improve sarcopenic NAFLD could reduce the risk of significant fibrosis.
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Affiliation(s)
- Michael Harring
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia
| | - Pegah Golabi
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - James M Paik
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Dipam Shah
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia
| | - Andrei Racila
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Rebecca Cable
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Manirath Srishord
- Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Zobair M Younossi
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; Inova Medicine, Inova Health System, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
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22
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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: 35] [Impact Index Per Article: 17.5] [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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23
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Fouda S, Jeeyavudeen MS, Pappachan JM, Jayanthi V. Pathobiology of Metabolic-Associated Fatty Liver Disease. Endocrinol Metab Clin North Am 2023; 52:405-416. [PMID: 37495333 DOI: 10.1016/j.ecl.2023.01.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/10/2023]
Abstract
Metabolic-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is highly associated with the metabolic syndrome. Given its high heterogeneity in patients along with unpredictable clinical outcomes, MAFLD is difficult to diagnose and manage. MAFLD is associated with obesity, diabetes, metabolic derangements, lipid disorders, cardiovascular disorders, sleep apnea, sarcopenia, gut dysbiosis, and sex hormone-related disorders. Identification of risk factors is imperative in understanding disease heterogeneity and clinical presentation to reliably diagnose and manage patients. The complexity of MAFLD pathobiology is discussed in this review in relation to its association with common metabolic and nonmetabolic disorders.
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Affiliation(s)
- Sherouk Fouda
- School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria VIC3001, Australia
| | | | - Joseph M Pappachan
- Department of Endocrinology & Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Preston PR2 9HT, UK; Manchester Metropolitan University, M15 6BH, UK.
| | - Venkataraman Jayanthi
- Department of Hepatology, Sriramachandra Institute of Higher Education & Research, Chennai 600116, India
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24
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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: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [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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Affiliation(s)
| | | | | | - Li Zhang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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25
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Musio A, Perazza F, Leoni L, Stefanini B, Dajti E, Menozzi R, Petroni ML, Colecchia A, Ravaioli F. Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease. Int J Mol Sci 2023; 24:7517. [PMID: 37108675 PMCID: PMC10139188 DOI: 10.3390/ijms24087517] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.
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Affiliation(s)
- Alessandra Musio
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Federica Perazza
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Laura Leoni
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy;
| | - Bernardo Stefanini
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Elton Dajti
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Renata Menozzi
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy;
| | - Maria Letizia Petroni
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy;
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.M.); (F.P.); (L.L.); (B.S.); (E.D.); (M.L.P.)
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy;
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26
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Kim HS, 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;47:104-17). Diabetes Metab J 2023; 47:304-305. [PMID: 36944454 PMCID: PMC10040624 DOI: 10.4093/dmj.2023.0058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/17/2023] Open
Affiliation(s)
- Hwi Seung Kim
- Department of Internal Medicine, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, 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
- Chang Hee Jung https://orcid.org/0000-0003-4043-2396 Department of Internal Medicine, 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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27
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Kim D, Dennis BB, Wijarnpreecha K, Cholankeril G, Ahmed A. Muscle strength in non-alcoholic fatty liver disease and all-cause and cause-specific mortality. Liver Int 2023; 43:513-516. [PMID: 36520009 DOI: 10.1111/liv.15498] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/09/2022] [Accepted: 12/10/2022] [Indexed: 01/22/2023]
Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Brittany B Dennis
- British Columbia Centre on Substance Use, University of British Columbia, Vancouver, British Columbia, Canada
| | - Karn Wijarnpreecha
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Banner University Medical Center, Phoenix, Arizona, USA
| | - George Cholankeril
- Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
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28
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Choe HJ, Lee H, Lee D, Kwak SH, Koo BK. Different effects of low muscle mass on the risk of non-alcoholic fatty liver disease and hepatic fibrosis in a prospective cohort. J Cachexia Sarcopenia Muscle 2023; 14:260-269. [PMID: 36403577 PMCID: PMC9891951 DOI: 10.1002/jcsm.13125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 07/26/2022] [Accepted: 10/25/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and sarcopenia share insulin resistance as a common pathophysiology and have overlapping clinical manifestation of metabolic derangement; hence, it is difficult to differentiate the independent effect of sarcopenia on the development of NAFLD from concomitant metabolic disorders. Using a community-based prospective cohort study, the contributions of low muscle mass and genetic risk factors to the development of NAFLD and NAFLD-related hepatic fibrosis were investigated in the Korean population. METHODS This prospective community-based cohort study included 40-70-year-old adults, followed up biennially from 2001-2002 to 2017-2018. NAFLD was defined as a hepatic steatosis index of ≥36, and hepatic fibrosis was defined based on the fibrosis-4 index. Sex-specific quartiles of body mass index (BMI)-adjusted muscle mass were calculated (muscle mass/BMI), and low muscle mass was defined as the lowest quartile (Q1). Cox proportional hazard models for incident NAFLD or hepatic fibrosis incorporating age, sex, BMI of ≥25 kg/m2 , metabolic syndrome and PNPLA3 and TM6SF2 risk alleles were used to assess the independent determinants for incident NAFLD and hepatic fibrosis among individuals with NAFLD at baseline. RESULTS Among the 4038 participants without NAFLD at baseline (mean age, 51.5 ± 8.8 years), 920 (22.8%) developed NAFLD during the 12-year follow-up period. As muscle mass decreased, the risk of NAFLD increased even after adjustment for age, sex, obesity, metabolic syndrome and PNPLA3 and TM6SF2 risk alleles [hazard ratio (HR) per quartile, 1.18, 95% confidence interval (CI), 1.11-1.27, P < 0.001]. TM6SF2 also affected the risk of NAFLD development [HR 1.19, (95% CI, 1.00-1.40), P = 0.044]. Of the 1176 patients with NAFLD but without hepatic fibrosis at baseline, the incident of hepatic fibrosis was found in 51.8%, 44.7%, 42.6% and 41.0% in Q1, Q2, Q3 and Q4 of BMI-adjusted muscle mass, respectively, during the follow-up period (P for trend = 0.006). However, this trend lost its statistical significance when adjusted for confounders. The PNPLA3 risk variant, but not the TM6SF2 genotype, was an independent risk factor for developing hepatic fibrosis among patients with NAFLD (HR 1.17, 95% CI 1.04-1.32, P = 0.010). CONCLUSIONS Both lower muscle mass index and genetic risk variants are important contributors to the development of NAFLD. In patients already diagnosed with NAFLD, however, PNPLA3 confers a greater risk for hepatic fibrosis progression than lower muscle mass.
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Affiliation(s)
- Hun Jee Choe
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Hyunsuk Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - DongHo Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Soo-Heon Kwak
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Bo Kyung Koo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea
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29
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Konyn P, Ahmed A, Kim D. Causes and risk profiles of mortality among individuals with nonalcoholic fatty liver disease. Clin Mol Hepatol 2023; 29:S43-S57. [PMID: 36417893 PMCID: PMC10029952 DOI: 10.3350/cmh.2022.0351] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/17/2022] [Accepted: 11/17/2022] [Indexed: 11/24/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and worldwide. Though nonalcoholic fatty liver per se may not be independently associated with an increased risk for all-cause mortality, it is associated with a number of harmful metabolic risk factors, such as type 2 diabetes mellitus, hyperlipidemia, obesity, a sedentary lifestyle, and an unhealthy diet. The fibrosis stage is a predictor of all-cause mortality in NAFLD. Mortality in individuals with NAFLD has been steadily increasing, and the most common cause-specific mortality for NAFLD is cardiovascular disease, followed by extra-hepatic cancer, liver-related mortality, and diabetes. High-risk profiles for mortality in NAFLD include PNPLA3 I148M polymorphism, low thyroid function and hypothyroidism, and sarcopenia. Achieving weight loss through adherence to a high-quality diet and sufficient physical activity is the most important predictor of improvement in NAFLD severity and the benefit of survival. Given the increasing health burden of NAFLD, future studies with more long-term mortality data may demonstrate an independent association between NAFLD and mortality.
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Affiliation(s)
- Peter Konyn
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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30
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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: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Sarcopenia and nonalcoholic fatty liver disease (NAFLD) are common health problems related to aging. Despite the differences in their diagnostic methods, several cross-sectional and longitudinal studies have revealed the close link between sarcopenia and NAFLD. Sarcopenia and NAFLD are linked by several shared pathogenetic mechanisms, including insulin resistance, hormonal imbalance, systemic inflammation, myostatin and adiponectin dysregulation, nutritional deficiencies, and physical inactivity, thus implicating a bidirectional relationship between sarcopenia and NAFLD. However, there is not sufficient data to support a direct causal relationship between sarcopenia and NAFLD. Moreover, it is currently difficult to conclude whether sarcopenia is a risk factor for nonalcoholic steatohepatitis (NASH) or is a consequence of NASH. Therefore, this review intends to touch on the shared common mechanisms and the bidirectional relationship between sarcopenia and NAFLD.
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Affiliation(s)
- Sae Kyung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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31
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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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32
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Han E, Lee YH, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Lee BW, Kang ES, Cha BS, Kim SU. Fibrotic Burden Determines Cardiovascular Risk among Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease. Gut Liver 2022; 16:786-797. [PMID: 35321955 PMCID: PMC9474484 DOI: 10.5009/gnl210290] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/10/2021] [Accepted: 10/21/2021] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND/AIMS Metabolic dysfunction associated fatty liver disease (MAFLD) has recently been introduced to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We explored whether fibrotic burden determines the risk of atherosclerotic cardiovascular disease (ASCVD) among subjects with MAFLD. METHODS We recruited 9,444 participants from the Korea National Health and Nutrition Examination Survey (2008 to 2011). Liver fibrosis was identified using the fibrosis-4 (FIB-4) index and NAFLD fibrosis score. The 10-year ASCVD risk score (>10%) was used to determine a high probability ASCVD risk. For sensitivity analysis, propensity score matching was assessed to subjects with aged 40 to 75 years free from ASCVD. RESULTS The prevalence of MAFLD was 38.0% (n=3,592). The ASCVD risk scores stratified in quartile were positively correlated to MAFLD and FIB-4 defined-significant liver fibrosis (p for trend <0.001). Individuals with both MAFLD and FIB-4 defined-significant liver fibrosis had a greater chance of high probability ASCVD risk (odds ratio [OR]=2.40; p<0.001) than those without MAFLD. The impact of MAFLD on high probability ASCVD risk was greater than that of significant liver fibrosis (OR=4.72 for MAFLD vs OR=1.88 for FIB-4 defined-significant liver fibrosis; all p<0.001). Among participants with MAFLD, low muscle mass enhanced the risk of significant liver fibrosis (OR=1.56 to 2.43; p<0.001). When NAFLD fibrosis score was applied to define significant liver fibrosis, similar findings were observed. CONCLUSIONS Individuals with MAFLD had a substantial ASCVD risk compared to those without MAFLD. Accompanying significant liver fibrosis further enhanced the risk of ASCVD among subjects with MAFLD.
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Affiliation(s)
- Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Yong-ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Byung-Wan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Bong-Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Fatty Hepatocytes Induce Skeletal Muscle Atrophy In Vitro: A New 3D Platform to Study the Protective Effect of Albumin in Non-Alcoholic Fatty Liver. Biomedicines 2022; 10:biomedicines10050958. [PMID: 35625696 PMCID: PMC9139027 DOI: 10.3390/biomedicines10050958] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/13/2022] [Accepted: 04/19/2022] [Indexed: 02/04/2023] Open
Abstract
The liver neutralizes endogenous and exogenous toxins and metabolites, being metabolically interconnected with many organs. Numerous clinical and experimental studies show a strong association between Non-alcoholic fatty liver disease (NAFLD) and loss of skeletal muscle mass known as sarcopenia. Liver transplantation solves the hepatic-related insufficiencies, but it is unable to revert sarcopenia. Knowing the mechanism(s) by which different organs communicate with each other is crucial to improve the drug development that still relies on the two-dimensional models. However, those models fail to mimic the pathological features of the disease. Here, both liver and skeletal muscle cells were encapsulated in gelatin methacryloyl and carboxymethylcellulose to recreate the disease’s phenotype in vitro. The 3D hepatocytes were challenged with non-esterified fatty acids (NEFAs) inducing features of Non-alcoholic fatty liver (NAFL) such as lipid accumulation, metabolic activity impairment and apoptosis. The 3D skeletal muscle tissues incubated with supernatant from fatty hepatocytes displayed loss of maturation and atrophy. This study demonstrates the connection between the liver and the skeletal muscle in NAFL, narrowing down the players for potential treatments. The tool herein presented was employed as a customizable 3D in vitro platform to assess the protective effect of albumin on both hepatocytes and myotubes.
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Koo BK, Lim S. Metabolic Syndrome and Metabolic Dysfunction‐Associated Fatty Liver Disease. CLINICAL OBESITY IN ADULTS AND CHILDREN 2022:159-177. [DOI: 10.1002/9781119695257.ch13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Lee S, Kim KW, Lee J, Park T, Koo K, Song GW, Lee SG. Visceral Fat Area Is an Independent Risk Factor for Overweight or Obese Nonalcoholic Fatty Liver Disease in Potential Living Liver Donors. Transplant Proc 2022; 54:702-705. [PMID: 35256204 DOI: 10.1016/j.transproceed.2021.10.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/30/2021] [Accepted: 10/27/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND The present study aimed to evaluate the correlation between hepatic steatosis (HS), determined by biopsy, and visceral adiposity, measured by computed tomography (CT), in overweight or obese potential living liver donors, and to investigate the risk factors for overweight or obese nonalcoholic fatty liver disease (NAFLD). METHODS This retrospective study included 375 overweight or obese (body mass index ≥23 kg/m2) potential living liver donors (mean age, 30.4 ± 9.5 years; 273 men) who underwent liver biopsies and abdominal CT examinations in 2017 and 2018. Anthropometry, laboratory parameters, body composition, and HS were assessed. Correlations were analyzed using Pearson's correlation coefficient, and logistic regression was used to identify independent predictors of overweight or obese NAFLD. RESULTS Visceral fat area (VFA) was positively correlated with the degree of HS in men (r = 0.307; P < .001) and women (r = 0.387; P < .001). Multivariable logistic regression analysis showed that alanine aminotransferase (odds ratio [OR], 1.017; 95% confidence interval [CI], 1.001-1.033; P = .033) and VFA (OR, 1.015; 95% CI, 1.008-1.022; P < .001) were independent risk factors for overweight or obese NAFLD in men, and VFA (OR, 1.029; 95% CI, 1.011-1.047; P = .002) was an independent risk factor for overweight or obese NAFLD in women. CONCLUSION Visceral adiposity was positively correlated with the degree of HS in overweight or obese potential living liver donors. Additionally, visceral adiposity may be an independent risk factor for overweight or obese NAFLD in potential living liver donors.
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Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyoung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Jeongjin Lee
- School of Computer Science and Engineering, Soongsil University, Seoul, Republic of Korea
| | - Taeyong Park
- School of Computer Science and Engineering, Soongsil University, Seoul, Republic of Korea
| | - Kyoyeong Koo
- School of Computer Science and Engineering, Soongsil University, Seoul, Republic of Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Cespiati A, Meroni M, Lombardi R, Oberti G, Dongiovanni P, Fracanzani AL. Impact of Sarcopenia and Myosteatosis in Non-Cirrhotic Stages of Liver Diseases: Similarities and Differences across Aetiologies and Possible Therapeutic Strategies. Biomedicines 2022; 10:biomedicines10010182. [PMID: 35052859 PMCID: PMC8773740 DOI: 10.3390/biomedicines10010182] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/13/2022] [Accepted: 01/14/2022] [Indexed: 12/15/2022] Open
Abstract
Sarcopenia is defined as a loss of muscle strength, mass and function and it is a predictor of mortality. Sarcopenia is not only a geriatric disease, but it is related to several chronic conditions, including liver diseases in both its early and advanced stages. Despite the increasing number of studies exploring the role of sarcopenia in the early stages of chronic liver disease (CLD), its prevalence and the relationship between these two clinical entities are still controversial. Myosteatosis is characterized by fat accumulation in the muscles and it is related to advanced liver disease, although its role in the early stages is still under researched. Therefore, in this narrative review, we firstly aimed to evaluate the prevalence and the pathogenetic mechanisms underlying sarcopenia and myosteatosis in the early stage of CLD across different aetiologies (mainly non-alcoholic fatty liver disease, alcohol-related liver disease and viral hepatitis). Secondly, due to the increasing prevalence of sarcopenia worldwide, we aimed to revise the current and the future therapeutic approaches for the management of sarcopenia in CLD.
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Affiliation(s)
- Annalisa Cespiati
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, Via F Sforza 35, 20122 Milan, Italy; (A.C.); (M.M.); (G.O.); (P.D.); (A.L.F.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
| | - Marica Meroni
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, Via F Sforza 35, 20122 Milan, Italy; (A.C.); (M.M.); (G.O.); (P.D.); (A.L.F.)
| | - Rosa Lombardi
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, Via F Sforza 35, 20122 Milan, Italy; (A.C.); (M.M.); (G.O.); (P.D.); (A.L.F.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
- Correspondence: ; Tel.: +39-02-5503-4192; Fax: +39-02-5503-3509
| | - Giovanna Oberti
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, Via F Sforza 35, 20122 Milan, Italy; (A.C.); (M.M.); (G.O.); (P.D.); (A.L.F.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
| | - Paola Dongiovanni
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, Via F Sforza 35, 20122 Milan, Italy; (A.C.); (M.M.); (G.O.); (P.D.); (A.L.F.)
| | - Anna Ludovica Fracanzani
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, Via F Sforza 35, 20122 Milan, Italy; (A.C.); (M.M.); (G.O.); (P.D.); (A.L.F.)
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
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Ghoshal UC, Sachdeva S, Ghoshal U, Misra A, Puri AS, Pratap N, Shah A, Rahman MM, Gwee KA, Tan VPY, Ahmed T, Lee YY, Ramakrishna BS, Talukdar R, Rana SV, Sinha SK, Chen M, Kim N, Holtmann G. Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association. Indian J Gastroenterol 2022; 41:483-507. [PMID: 36214973 PMCID: PMC9549446 DOI: 10.1007/s12664-022-01292-x] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/02/2022] [Indexed: 02/04/2023]
Abstract
In the clinical setting, small intestinal bacterial overgrowth (SIBO) is a frequent, but under-diagnosed entity. SIBO is linked to various gastrointestinal (GI) and non-GI disorders with potentially significant morbidity. The optimal management of SIBO is undefined while there is a lack of published consensus guidelines. Against this background, under the auspices of the Indian Neurogastroenterology and Motility Association (INMA), formerly known as the Indian Motility and Functional Diseases Association (IMFDA), experts from the Asian-Pacific region with extensive research and clinical experience in the field of gut dysbiosis including SIBO developed this evidence-based practice guideline for the management of SIBO utilizing a modified Delphi process based upon 37 consensus statements, involving an electronic voting process as well as face-to-face meetings and review of relevant supporting literature. These statements include 6 statements on definition and epidemiology; 11 on etiopathogenesis and pathophysiology; 5 on clinical manifestations, differential diagnosis, and predictors; and 15 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservations was 80% or higher, the statement was regarded as accepted. The members of the consensus team consider that this guideline would be valuable to inform clinical practice, teaching, and research on SIBO in the Asian-Pacific region as well as in other countries.
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Affiliation(s)
- Uday C. Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | - Sanjeev Sachdeva
- Department of Gastroenterology, G B Pant Hospital, New Delhi, 110 002 India
| | - Ujjala Ghoshal
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | - Asha Misra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | | | | | - Ayesha Shah
- University of Queensland, Faculty of Medicine, and Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Brisbane, Queensland, Australia
| | - M. Masudur Rahman
- Sheikh Russel National Gastroliver Institute and Hospital, Dhaka, Bangladesh
| | - Kok Ann Gwee
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ,Stomach, Liver and Bowel Centre, Gleneagles Hospital, Singapore, Singapore
| | - Victoria P Y Tan
- Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Tahmeed Ahmed
- International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia ,GI Function and Motility Unit, Hospital Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - B S Ramakrishna
- SIMS Institute of Gastroenterology, Hepatology, and Transplantation, SRM Institutes for Medical Science, Chennai, 600 026 India
| | - Rupjyoti Talukdar
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, 500 082 India
| | - S V Rana
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, 249 203 India
| | - Saroj K Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012 India
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Gerald Holtmann
- University of Queensland, Faculty of Medicine, and Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Brisbane, Queensland, Australia
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Pivtorak K, Fedzhaga I, Pivtorak N, Vozniuk L, Klekot O. FAT AND MUSCLE COMPONENTS OF BODY WEIGHT AND THEIR RELATIONSHIP WITH THE CONCENTRATION OF SERUM ADIPOKINES IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2022; 75:1289-1294. [PMID: 35758445 DOI: 10.36740/wlek202205210] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
OBJECTIVE The aim: Identify differences in indexes of body fat and muscle masses, as well as blood adipokines in patients with nonalcoholic fatty liver disease, from gender-appropriate healthy men and women. PATIENTS AND METHODS Materials and methods: 135 patients with non-alcoholic fatty liver disease with normal, overweight and obesity and 20 almost healthy individuals for the control group were examined. Verification of the diagnosis was performed in accordance with the recommendations of the unified clinical protocol. An anthropometric examination of patients was performed according to the method, which included the determination of 48 anthropometric parameters. The formulas determined the absolute amount of adipose and muscle tissue. Levels of adipokines (leptin and adiponectin) were determined by enzyme-linked immunosorbent assay. RESULTS Results: According to Matiegka, body fat was 30.2-35.2% higher, and muscle body weight was 17.4-29.1% lower in patients with non-alcoholic fatty liver disease compared to healthy people. The concentration of leptin in the serum of patients with nonalcoholic fatty liver disease was statistically significantly higher (2.05-3.78 times) compared with almost healthy individuals. At the same time, the indicators of adiponectin concentration (1.54-1.92 times) and log A / L index (1.16-1.32 times) were lower. Correlations between changes in muscle mass and adipokines concentration have been established. CONCLUSION Conclusions: In addition to the known increase in body fat in non-alcoholic fatty liver disease, there has been established a significant decrease in muscle mass. A direct correlation between adiponectin concentration and an inverse correlation between leptin levels and muscle mass in patients with nonalcoholic fatty liver disease was found.
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Affiliation(s)
| | - Iryna Fedzhaga
- NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSIA, UKRAINE
| | - Natalya Pivtorak
- NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSIA, UKRAINE
| | - Larysa Vozniuk
- NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSIA, UKRAINE
| | - Olexandra Klekot
- NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSIA, UKRAINE
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Mikami K, Endo T, Sawada N, Igarashi G, Kimura M, Hasegawa T, Iino C, Sawada K, Ando M, Sugimura Y, Mikami T, Nakaji S, Matsuzaka M, Sakuraba H, Fukuda S. Association of serum creatinine-to-cystatin C ratio with skeletal muscle mass and strength in nonalcoholic fatty liver disease in the Iwaki Health Promotion Project. J Clin Biochem Nutr 2022; 70:273-282. [PMID: 35692671 PMCID: PMC9130064 DOI: 10.3164/jcbn.21-61] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 09/01/2021] [Indexed: 12/11/2022] Open
Abstract
We evaluated the feasibility of using serum creatinine-to-cystatin C ratio in the assessments of muscle mass and strength in nonalcoholic fatty liver disease. In a community-based cross-sectional study, skeletal muscle mass and handgrip strength were assessed in 641 Japanese adults. Low skeletal muscle mass index and low handgrip strength were defined as indicated in the sarcopenia diagnostic criteria of the Japan Society of Hepatology. Nonalcoholic fatty liver disease was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. The creatinine-to-cystatin C ratio was useful for identifying the participants with low skeletal muscle mass index, with an area under the receiver-operating characteristic curve of 0.84 [95% confidence interval (CI), 0.77–0.91] in men and 0.72 in women (95% CI, 0.65–0.78), and those with low handgrip strength, with an area under the receiver-operating characteristic curve of 0.96 (95% CI, 0.93–0.99) in men and 0.79 (95% CI, 0.66–0.92) in women. Moreover, the creatinine-to-cystatin C ratio correlated with skeletal muscle mass index (r = 0.511, p<0.001) and handgrip strength (r = 0.657, p<0.001), whereas it did not correlate with exacerbation of hepatic steatosis. In this study, creatinine-to-cystatin C ratio correlated with muscle mass and strength in nonalcoholic fatty liver disease regardless of hepatic steatosis.
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Affiliation(s)
- Kenichiro Mikami
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Tetsu Endo
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Naoya Sawada
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Go Igarashi
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Masayo Kimura
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Takuma Hasegawa
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Chikara Iino
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Kaori Sawada
- Department of Diet and Health Science, Hirosaki University Graduate School of Medicine
| | - Masataka Ando
- Department of Diet and Health Science, Hirosaki University Graduate School of Medicine
| | - Yoshikuni Sugimura
- Department of Microbial Flora and Health Science, Hirosaki University Graduate School of Medicine
| | - Tatsuya Mikami
- Innovation Center for Health Promotion, Hirosaki University Graduate School of Medicine
| | - Shigeyuki Nakaji
- Department of Social Medicine, Hirosaki University Graduate School of Medicine
| | | | - Hirotake Sakuraba
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
| | - Shinsaku Fukuda
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine
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Lee S, Kim KW, Lee J, Park T, Khang S, Jeong H, Song GW, Lee SG. Visceral adiposity as a risk factor for lean non-alcoholic fatty liver disease in potential living liver donors. J Gastroenterol Hepatol 2021; 36:3212-3218. [PMID: 34169561 DOI: 10.1111/jgh.15597] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 06/01/2021] [Accepted: 06/19/2021] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND AIM This study aimed to investigate the relationship between hepatic steatosis (HS) evaluated by biopsy and visceral adiposity assessed by computed tomography in lean living liver donor candidates and to determine the risk factors for lean non-alcoholic fatty liver disease (NAFLD). METHODS This retrospective study included 250 lean (body mass index, < 23 kg/m2 ) potential living liver donors (mean age, 31.1 ± 8.6 years; 141 men) who had undergone liver biopsy and abdominal computed tomography between 2017 and 2018. Anthropometry, laboratory parameters, body composition, and the degree of HS were evaluated. Logistic regression was used to identify independent predictors of lean NAFLD. RESULTS The visceral fat area (VFA) was significantly correlated with the degree of HS in men (r = 0.408; P < 0.001) and women (r = 0.360; P < 0.001). The subcutaneous fat area was significantly correlated with the degree of HS in men (r = 0.398; P < 0.001), but not in women. The skeletal muscle area did not correlate with the degree of HS in either men or women. In the multivariable logistic regression analysis, the VFA (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.013-1.044; P < 0.001) and subcutaneous fat area (OR, 1.016; 95% CI, 1.004-1.028; P = 0.009) were independent risk factors for lean NAFLD in men, and the VFA (OR, 1.036; 95% CI, 1.013-1.059; P = 0.002) was an independent risk factor for lean NAFLD in women. CONCLUSIONS The severity of non-alcoholic fatty liver was positively correlated with visceral fat accumulation in a lean Asian population. Visceral adiposity may be a risk factor for lean NAFLD in potential living liver donors.
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Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kyoung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeongjin Lee
- School of Computer Science and Engineering, Soongsil University, Seoul, Korea
| | - Taeyong Park
- School of Computer Science and Engineering, Soongsil University, Seoul, Korea
| | - Seungwoo Khang
- School of Computer Science and Engineering, Soongsil University, Seoul, Korea
| | - Heeryeol Jeong
- School of Computer Science and Engineering, Soongsil University, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Hanna DJ, Jamieson ST, Lee CS, Pluskota CA, Bressler NJ, Benotti PN, Khurana S, Rolston DDK, Still CD. "Bioelectrical impedance analysis in managing sarcopenic obesity in NAFLD". Obes Sci Pract 2021; 7:629-645. [PMID: 34631140 PMCID: PMC8488453 DOI: 10.1002/osp4.509] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 02/02/2021] [Accepted: 02/11/2021] [Indexed: 11/08/2022] Open
Abstract
INTRODUCTION Sarcopenic obesity and its association with nonalcoholic fatty liver disease (NAFLD) is under-recognized by many healthcare providers in Western medicine due to the lack of awareness and diagnostic guidelines. The result is delayed recognition and treatment, which leads to further health deterioration and increased healthcare costs. Sarcopenic obesity is characterized by the presence of increased fat mass in combination with muscle catabolism related to chronic inflammation and/or inactivity. Previous research has recommended evaluating body composition and physical function performance to adequately diagnose sarcopenic obesity. Body composition analysis can be performed by imaging applications through magnetic resonance imaging, computed tomography, and dual-energy x-ray absorptiometry. Due to the cost of each device and radiation exposure for patients as evidenced in all three modalities, bioelectrical impedance analysis offers a noninvasive approach capable of providing quick and reliable estimates of lean body and fat mass. METHODS AND RESULTS This review analyzes the current evidence-based literature, indicating a lower skeletal muscle mass and increased visceral adipose tissue correlation to the advancement of fibrosis in fatty liver disease. CONCLUSION Given the substantial promising research conducted in predominantly Asian populations regarding body tissue distribution and NAFLD, additional prospective research is needed to extend these findings in Western populations.
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Affiliation(s)
- David J. Hanna
- Obesity InstituteGeisinger Health SystemDanvillePennsylvaniaUSA
- Department of Gastroenterology and HepatologyGeisinger Health SystemDanvillePennsylvaniaUSA
| | | | | | | | | | | | - Sandeep Khurana
- Department of Gastroenterology and HepatologyGeisinger Health SystemDanvillePennsylvaniaUSA
| | - David D. K. Rolston
- Obesity InstituteGeisinger Health SystemDanvillePennsylvaniaUSA
- Department of Internal MedicineGeisinger Health SystemDanvillePennsylvaniaUSA
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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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Kim D, Wijarnpreecha K, Sandhu KK, Cholankeril G, Ahmed A. Sarcopenia in nonalcoholic fatty liver disease and all-cause and cause-specific mortality in the United States. Liver Int 2021; 41:1832-1840. [PMID: 33641244 DOI: 10.1111/liv.14852] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 02/03/2021] [Accepted: 02/20/2021] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) has been associated with sarcopenia. However, mortality in the setting of NAFLD-related sarcopenia remains undefined. We aim to determine the all-cause and cause-specific mortality from sarcopenia among adults with NAFLD in the USA. METHODS 11 065 individuals in the Third National Health and Nutrition Examination Survey were studied and linked mortality through 2015 was analysed. NAFLD was diagnosed based on presence of ultrasonographic hepatic steatosis without other known liver diseases. Sarcopenia was defined as skeletal muscle index determined by bioelectrical impedance analysis. The Cox proportional hazard model was used to assess all-cause mortality and cause-specific mortality, and hazard ratio (HR) adjusted for known risk factors. RESULTS During a median follow-up of 23 years or more, sarcopenia was associated with increased all-cause mortality (HR 1.27, 95% confidence interval [CI] 1.11-1.44). Only in individuals with NAFLD, sarcopenia was associated with a higher risk for all-cause mortality, while this association was absent in those without NAFLD. Individuals with both sarcopenia and NAFLD had a higher risk for all-cause mortality (HR 1.28 95% CI 1.06-1.55) compared with those without sarcopenia and NAFLD. Furthermore, sarcopenia was associated with a higher risk for cancer- and diabetes-related mortality among those with NAFLD. This association was not noted in those without NAFLD. CONCLUSION In this nationally representative sample of US adults, sarcopenia was associated with a higher risk for all-cause, cancer- and diabetes-related mortality in individuals with NAFLD.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | | | - George Cholankeril
- Division of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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44
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Differences among Three Skeletal Muscle Mass Indices in Predicting Non-Alcoholic Fatty Liver Disease: Korean Nationwide Population-Based Study. Life (Basel) 2021; 11:life11080751. [PMID: 34440495 PMCID: PMC8401633 DOI: 10.3390/life11080751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/16/2021] [Accepted: 07/25/2021] [Indexed: 02/06/2023] Open
Abstract
Recent studies have investigated the relationship between sarcopenia and non-alcoholic fatty liver disease (NAFLD); however, there is no unified definition of sarcopenia. Thus, we aimed to investigate the differences among three skeletal muscle mass indices (SMI) in predicting NAFLD. This study included 8133 adults from the 2008–2010 Korea National Health and Nutrition Survey. SMI was calculated as appendicular skeletal muscle mass divided by height-square (hSMI), weight (wSMI), or body mass index (bSMI). The presence of NAFLD was defined by using the NAFLD-liver fat score. On the receiver operating characteristic curve analysis, the predictive power of wSMI for NAFLD was significantly higher than those of hSMI and bSMI in men (wSMI vs. hSMI, p = 0.003; wSMI vs. bSMI, p < 0.001). In women, the predictive power of hSMI was only significantly higher than that of bSMI (p = 0.023), and other predictive powers were not significantly different. In addition, hSMI was correlated with insulin resistance and NAFLD-liver fat score in the opposite direction to wSMI and bSMI in both men and women. Among the three definitions of SMI, wSMI showed the highest diagnostic performance for predicting NAFLD in men, suggesting the importance of defining sarcopenia for its association with specific diseases.
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Lim S, Kim JW, Targher G. Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease. Trends Endocrinol Metab 2021; 32:500-514. [PMID: 33975804 DOI: 10.1016/j.tem.2021.04.008] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/15/2021] [Accepted: 04/15/2021] [Indexed: 02/08/2023]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition characterized by hepatic fat accumulation combined with underlying metabolic dysregulation. Having evolved from the previous term of nonalcoholic fatty liver disease (NAFLD), the term MAFLD more closely implicates the presence of overweight/obesity, type 2 diabetes, or metabolic dysregulation as essential pathogenic factors, leading to better identification of individuals with this metabolic liver disease. Low-grade inflammation, increased oxidative stress, mitochondrial dysfunction, and intestinal dysbiosis are also involved in its pathogenesis. MAFLD is not only associated with liver-related complications, but also with adverse cardiometabolic outcomes. Further studies are needed to assess whether the newly proposed definition of MAFLD is more accurate than the NAFLD in predicting the adverse liver-related and extrahepatic outcomes.
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Affiliation(s)
- Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea.
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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46
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Lee JH, Lee HS, Lee BK, Kwon YJ, Lee JW. Relationship between Muscle Mass and Non-Alcoholic Fatty Liver Disease. BIOLOGY 2021; 10:biology10020122. [PMID: 33562473 PMCID: PMC7915258 DOI: 10.3390/biology10020122] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 01/27/2021] [Accepted: 01/29/2021] [Indexed: 12/18/2022]
Abstract
Simple Summary Sarcopenia and non-alcoholic fatty liver disease share common pathological and physiological mechanisms that can co-occur with aging. Low skeletal muscle mass index and non-alcoholic fatty liver disease were related, regardless of abdominal obesity. Maintenance of muscle mass should be emphasized for prevention of non-alcoholic fatty liver disease. Management of fatty liver also could be an important strategy to preserve muscle mass. Abstract Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass <0.789 in men and <0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs = 1.21, 95% CIs = 1.05–1.40). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs = 1.56, 95% CIs = 1.38–1.78). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.
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Affiliation(s)
- Jun-Hyuk Lee
- Department of Medicine, Graduate School of Yonsei University College of Medicine, Seoul 03722, Korea;
- Department of Family Medicine, Yonsei University College of Medicine, Yongin Severance Hospital, Yongin 16995, Korea
| | - Hye-Sun Lee
- Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul 06273, Korea;
| | - Byoung-Kwon Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul 06273, Korea;
| | - Yu-Jin Kwon
- Department of Family Medicine, Yonsei University College of Medicine, Yongin Severance Hospital, Yongin 16995, Korea
- Correspondence: (Y.-J.K.); (J.-W.L.); Tel.: +82-31-5189-8777 (Y.-J.K.); +82-2-2019-3480 (J.-W.L.)
| | - Ji-Won Lee
- Department of Family Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul 06273, Korea
- Correspondence: (Y.-J.K.); (J.-W.L.); Tel.: +82-31-5189-8777 (Y.-J.K.); +82-2-2019-3480 (J.-W.L.)
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47
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Nachit M, De Rudder M, Thissen JP, Schakman O, Bouzin C, Horsmans Y, Vande Velde G, Leclercq IA. Myosteatosis rather than sarcopenia associates with non-alcoholic steatohepatitis in non-alcoholic fatty liver disease preclinical models. J Cachexia Sarcopenia Muscle 2021; 12:144-158. [PMID: 33244884 PMCID: PMC7890270 DOI: 10.1002/jcsm.12646] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 09/29/2020] [Accepted: 10/12/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver (NAFL) disease (NAFLD) is the most common chronic liver disease in the world. While most subjects have 'inert' NAFL, a subset will progress to non-alcoholic steatohepatitis (NASH) and its life-threatening complications. A substantial body of literature supports that a low muscle mass, low strength, and/or muscle fatty infiltration (myosteatosis) are associated with NAFLD severity. Here, we evaluated the muscle compartment in NASH preclinical models to decipher the kinetics of muscle alterations in relation with liver disease progression. METHODS We developed and validated a micro-computed tomography-based methodology to prospectively study skeletal muscle mass and density in muscle and liver (i.e. reflecting fatty infiltration) in a high-throughput and non-invasive manner in three preclinical NAFLD/NASH rodent models: fat aussie (FOZ) mice fed a high-fat diet (FOZ HF), wild-type (WT) mice fed a high-fat high-fructose diet (WT HFF), and WT mice fed a high-fat diet (WT HF). We compared them with WT mice fed a normal diet (WT ND) used as controls. RESULTS -FOZ HF with fibrosing NASH had sarcopenia characterized by a reduced muscle strength when compared with WT HF and WT HFF with early NASH and WT ND controls (165.2 ± 5.2 g vs. 237.4 ± 11.7 g, 256 ± 5.7 g, and 242.9 ± 9.3 g, respectively, P 60; 0.001). Muscle mass or strength was not lower in FOZ HF, WT HF, and WT HFF with early NASH than in controls. Myosteatosis was present in FOZ HF with fibrosing NASH, but also in FOZ HF, WT HF, and WT HFF with early NASH (muscle density = 0.50 ± 0.02, 0.62 ± 0.02, 0.70 ± 0.05, and 0.75 ± 0.03, respectively, with P 60; 0.001 when compared with respective controls). Myosteatosis degree was strongly correlated with NAFLD activity score (r = -0.87, n = 67, P 60; 0.001). In multivariate analysis, the association between myosteatosis and NASH was independent from homeostatic model assessment of insulin resistance and visceral fat area (P 60; 0.05). Myosteatosis degree powerfully discriminated NASH from benign NAFL and normal liver (area under the receiver operating characteristic = 0.96, n = 67, P 60; 0.001). CONCLUSIONS Taken together, our data support that there is no sarcopenia in obese mice with early NASH. In contrast, the severity of myosteatosis reflects on hepatocellular damage and inflammation during early NASH development. This observation prompts us to exploit myosteatosis as a novel non-invasive marker of NASH.
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Affiliation(s)
- Maxime Nachit
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium.,Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Maxime De Rudder
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium
| | - Jean-Paul Thissen
- Pole of Endocrinology, Diabetes and Nutrition, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium
| | | | | | - Yves Horsmans
- Service d'Hépato-Gastro-Entérologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Greetje Vande Velde
- Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.,Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Leuven, Belgium
| | - Isabelle Anne Leclercq
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium
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Chakravarthy MV, Siddiqui MS, Forsgren MF, Sanyal AJ. Harnessing Muscle-Liver Crosstalk to Treat Nonalcoholic Steatohepatitis. Front Endocrinol (Lausanne) 2020; 11:592373. [PMID: 33424768 PMCID: PMC7786290 DOI: 10.3389/fendo.2020.592373] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 11/16/2020] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions, affecting an estimated one-quarter of the world's adult population. Multiple organ systems have been implicated in the pathophysiology of NAFLD; however, the role of skeletal muscle has until recently been largely overlooked. A growing body of evidence places skeletal muscle-via its impact on insulin resistance and systemic inflammation-and the muscle-liver axis at the center of the NAFLD pathogenic cascade. Population-based studies suggest that sarcopenia is an effect-modifier across the NAFLD spectrum in that it is tightly linked to an increased risk of non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), and advanced liver fibrosis, all independent of obesity and insulin resistance. Longitudinal studies suggest that increases in skeletal muscle mass over time may both reduce the incidence of NAFLD and improve preexisting NAFLD. Adverse muscle composition, comprising both low muscle volume and high muscle fat infiltration (myosteatosis), is highly prevalent in patients with NAFLD. The risk of functional disability conferred by low muscle volume in NAFLD is further exacerbated by the presence of myosteatosis, which is twice as common in NAFLD as in other chronic liver diseases. Crosstalk between muscle and liver is influenced by several factors, including obesity, physical inactivity, ectopic fat deposition, oxidative stress, and proinflammatory mediators. In this perspective review, we discuss key pathophysiological processes driving sarcopenia in NAFLD: anabolic resistance, insulin resistance, metabolic inflexibility and systemic inflammation. Interventions that modify muscle quantity (mass), muscle quality (fat), and physical function by simultaneously engaging multiple targets and pathways implicated in muscle-liver crosstalk may be required to address the multifactorial pathogenesis of NAFLD/NASH and provide effective and durable therapies.
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Affiliation(s)
| | - Mohammad S. Siddiqui
- Department of Internal Medicine and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States
| | - Mikael F. Forsgren
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden
- AMRA Medical AB, Linköping, Sweden
| | - Arun J. Sanyal
- Department of Internal Medicine and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States
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Mikolasevic I, Pavic T, Filipec Kanizaj T, Bender DV, Domislovic V, Krznaric Z. Nonalcoholic Fatty Liver Disease and Sarcopenia: Where Do We Stand? Can J Gastroenterol Hepatol 2020; 2020:8859719. [PMID: 33204675 PMCID: PMC7652636 DOI: 10.1155/2020/8859719] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 10/04/2020] [Indexed: 12/13/2022] Open
Abstract
The link between metabolic syndrome (MetS) and sarcopenia has not been extensively studied, but it is evident that they share several common features. Crucial mechanisms involved in sarcopenia-nonalcoholic fatty liver disease (NAFLD) interplay are based on effects of insulin resistance, chronic inflammation, oxidative stress, and crosstalk between organs by secretion of cytokines (hepatokines, adipokines, and myokines). Currently, published studies confirm the association of sarcopenia with the degree of NAFLD defined by liver histology. However, prospective studies that will give us information regarding the causal effect of NAFLD and sarcopenia are still needed. Furthermore, there is a need for a patient-friendly, noninvasive, low-cost method for detection of loss of skeletal muscle mass, strength, and physical performance in the context of NAFLD. Moreover, potential treatment strategies such as physical exercise and nutritional supplementation, that are usually a part of management of sarcopenia, should also be investigated in NAFLD patients, especially given the fact that for now, we do not have a good treatment option for NAFLD. Therefore, future investigations should combine studies on NAFLD and sarcopenia in terms of physical activity and nutritional interventions such as vitamin D supplementation. This review aims to report recent evidence concerning the links between sarcopenia and NAFLD and methods to assess sarcopenia.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
- School of Medicine, Rijeka, Croatia
| | - Tajana Pavic
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia
- School of Medicine, Zagreb, Croatia
| | - Tajana Filipec Kanizaj
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
- School of Medicine, Zagreb, Croatia
| | - Darija Vranesic Bender
- University Hospital Centre Zagreb, Department of Internal Medicine, Division of Gastroenterology and Hepatology & Unit of Clinical Nutrition, Zagreb, Croatia
| | - Viktor Domislovic
- Department for Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
| | - Zeljko Krznaric
- School of Medicine, Zagreb, Croatia
- Department for Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
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50
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Contribution of sarcopenia and physical inactivity to mortality in people with non-alcoholic fatty liver disease. JHEP Rep 2020; 2:100171. [PMID: 32964202 PMCID: PMC7490851 DOI: 10.1016/j.jhepr.2020.100171] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 07/29/2020] [Accepted: 08/01/2020] [Indexed: 02/06/2023] Open
Abstract
Background & Aims Physical inactivity and sedentary lifestyle have contributed to the epidemic of obesity and non-alcoholic fatty liver disease (NAFLD). We assessed the association between physical activity, NAFLD, and sarcopenia, and their contributions to mortality. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 with Linked Mortality file (through 2015) was utilised. NAFLD was determined by the US Fatty Liver Index in the absence of secondary causes of liver disease. Sarcopenia was defined using appendicular lean mass divided by body mass index by the Foundation for the National Institutes of Health criteria. Activity level was determined using standard self-reports. Publicly available imputed dual-energy X-ray absorptiometry data sets were used. Results Of 4,611 NHANES participants (48.2% males; 72.5% White; mean age 45.9 years), NAFLD was present in 1,351 (29.3%), of whom 17.7% had sarcopenia. Of the NAFLD group, 46.3% was inactive, whilst intermediate and ideal physical activity rates were observed in 14.2% and 39.5%, respectively. Sarcopenia was significantly and inversely related to higher physical activity level, both amongst NAFLD (odds ratio [OR] = 0.45 [95% CI 0.30-0.69]) and non-NAFLD (OR = 0.51 [0.35-0.75]) groups. During a median follow-up of 13.5 years, a total of 586 subjects died, of whom 251 had NAFLD. Amongst those who died with NAFLD, 33.0% had sarcopenia and 54.3% were inactive. Compared with NAFLD without sarcopenia, NAFLD with sarcopenia was associated with a higher risk of all-cause (hazard ratio [HR] = 1.78 [1.16-2.73]), cardiac-specific (HR = 3.19 [1.17-8.74]), and cancer-specific mortality (HR = 2.12 [1.08-4.15]). Conclusions Inactivity is associated with presence of sarcopenia, whilst sarcopenia is associated with increased mortality amongst NAFLD patients. Sarcopenia should be a part of clinical assessment of patients with NAFLD. Treatment of NAFLD should include optimal management of sarcopenia. Lay summary Nonalcoholic fatty liver disease (NAFLD) and sarcopenia have similar pathophysiological profiles. Our data show that sarcopenia is associated with inactivity in subjects with NAFLD. The presence of sarcopenia in patients with NAFLD poses increased risk for all-cause and cardiac-specific mortality.
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Key Words
- ALM, appendicular lean mass
- BMI, body mass index
- CV, cardiovascular
- CVD, cardiovascular disease
- DXA, dual-energy X-ray absorptiometry
- EWGSOP2, Revised European Working Group on Sarcopenia in Older People
- FNIH, Foundation for the National Institutes of Health
- GGT, gamma glutamyltransferase
- HL, hyperlipidaemia
- HR, hazard ratio
- HTN, hypertension
- MS, metabolic syndrome
- NAFLD, non-alcoholic fatty liver disease
- NFS, NAFLD fibrosis score
- NHANES, National Health and Nutrition Examination Survey
- Non-alcoholic fatty liver disease
- Physical activity
- Sarcopenia
- T2DM, type 2 diabetes mellitus
- US FLI, Fatty Liver Index for the multi-ethnic US population
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