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Liu A, Sun Y, Qi X, Zhou Y, Zhou J, Li Z, Wu X, Zou Z, Lv X, Li H, Li Y. Nonlinear association between liver fat content and lumbar bone mineral density in overweight and obese individuals: evidence from a large-scale health screening data in China. Endocrine 2025; 88:446-456. [PMID: 39869295 PMCID: PMC12069136 DOI: 10.1007/s12020-025-04168-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/14/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND The impact of fatty liver disease on lumbar bone mineral density (BMD) represents an intriguing area of study, particularly in light of established research linking obesity to bone metabolism. However, there remains limited investigation into the correlation between quantifying liver fat content (LFC) and lumbar BMD among overweight and obese populations, particularly within the Chinese demographic. This study aims to accurately quantify LFC and investigate its association with lumbar BMD in overweight or obese individuals. METHODS This cross-sectional study was conducted at the Health Management Center of Henan Provincial People's Hospital from January 2019 to February 2023, involving 6996 participants with a body mass index (BMI) of 24 kg/m² or higher. LFC and lumbar BMD were assessed using computed tomography. The study utilized one-way ANOVA, subgroup analysis, multifactor regression analysis, smooth curve fitting, and threshold and saturation effect analysis to explore the relationship between LFC and lumbar BMD. Furthermore, inflammatory cell analysis was included to investigate the potential mediating role of inflammatory cells in the association between LFC and lumbar BMD. RESULTS After adjusting for confounding variables, multivariate regression analysis revealed a significant negative association between LFC and lumbar BMD (β = -0.323, 95% CI: -0.464 to -0.183, P < 0.001). Particularly, participants in the highest baseline LFC quartile (Q4 group) exhibited a more pronounced negative impact on lumbar BMD compared to those in the lowest quartile (Q1 group) (β = -5.026, 95% CI: -7.040 to -3.012, P < 0.001). Threshold saturation effect analysis identified a turning point in the LFC-BMD relationship (K = 5.4). Below this point, LFC showed a positive correlation with lumbar BMD (β = 0.962, 95% CI: 0.016-1.907, P < 0.05), whereas above it, LFC was significantly negatively correlated with lumbar BMD (β = -0.405, 95% CI: -0.558 to -0.253, P < 0.001). Additionally, mediation analysis indicated that leukocytes and monocytes potentially mediated the association between LFC and lumbar BMD, with mediation ratios of -5.78 and -6.68%, respectively. CONCLUSION Among individuals categorized as overweight or obese, elevated levels of LFC were associated with reduced lumbar BMD, particularly noticeable above a threshold of 5.4%. Additionally, various types of inflammatory cells are presumed to exert a substantial mediating influence on the correlation between LFC and lumbar BMD.
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Affiliation(s)
- Ao Liu
- Department of Medical Imaging, People's Hospital of Zhengzhou University, #7 Wei Wu Road, Zhengzhou, 450003, China
| | - Yongbing Sun
- Department of Medical Imaging, People's Hospital of Zhengzhou University, #7 Wei Wu Road, Zhengzhou, 450003, China
| | - Xin Qi
- Department of Medical Imaging, Henan Provincial People's Hospital, Xinxiang Medical College, Zhengzhou, 450003, China
| | - Yang Zhou
- Department of Medical Imaging, People's Hospital of Zhengzhou University, #7 Wei Wu Road, Zhengzhou, 450003, China
| | - Jing Zhou
- Department of Health Management, Chronic Health Management Laboratory, Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Zhonglin Li
- Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Xiaoling Wu
- Department of Nuclear Medicine, Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Zhi Zou
- Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Xue Lv
- Department of Health Management, Chronic Health Management Laboratory, Henan Provincial People's Hospital, Zhengzhou, 450003, China
| | - Hao Li
- Department of Health Management, Fuwai Central China Cardiovascular Hospital, #1 Fuwai Avenue, Zhengzhou, 451464, China
| | - Yongli Li
- Department of Health Management, Chronic Health Management Laboratory, Henan Provincial People's Hospital, Zhengzhou, 450003, China.
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Goyal A, Kubihal S, Gupta Y, Shalimar, Kandasamy D, Kalaivani M, Tandon N. Bone mass, microarchitecture and turnover among young Indian women with non-alcoholic fatty liver disease. Endocrine 2024; 86:790-799. [PMID: 38914745 DOI: 10.1007/s12020-024-03934-w] [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: 04/17/2024] [Accepted: 06/14/2024] [Indexed: 06/26/2024]
Abstract
PURPOSE To evaluate comprehensive bone health among young Indian women, including bone mass, microarchitecture, and turnover, in relation to their non-alcoholic fatty liver disease (NAFLD) status. METHODS This cross-sectional study (May 2018-November 2019) recruited women with a history of gestational diabetes mellitus (GDM) and normoglycemia in their index pregnancy, who were at least 6 months postpartum. All participants underwent abdominal ultrasonography for determination of NAFLD status (grades 2 and 3: severe NAFLD) and transient elastography (FibroScan) for hepatic fibrosis (LSM >6 kPa). Bone mass was assessed by DXA, bone microarchitecture with trabecular bone score {TBS} (low TBS ≤ 1.310) and bone turnover with markers of bone formation (osteocalcin and P1NP), and resorption (CTX). RESULTS Bone mineral density (BMD) at femoral neck (p = 0.026) and total hip (p = 0.007) was significantly higher among women with NAFLD (n = 170) compared to those without (n = 124). There was no significant difference in bone turnover markers between the two groups. The presence of NAFLD [adjusted OR: 1.82 (1.07, 3.11)] was associated with low TBS, with a greater strength of association among women with severe NAFLD [adjusted OR: 2.97 (1.12, 7.88)]. However, these associations were attenuated and no longer significant after additionally adjusting for BMI. Women with NAFLD and hepatic fibrosis manifested significantly higher BMD at lumbar spine, femoral neck, and total hip (p < 0.001 for all) and significantly lower bone turnover markers (osteocalcin, p = 0.009 and CTX, p = 0.029), however, the association with low TBS was not observed. CONCLUSION Among young Indian women, NAFLD is associated with increased bone mass and impaired bone microarchitecture, and hepatic fibrosis with increased bone mass and reduced bone turnover.
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Affiliation(s)
- Alpesh Goyal
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Suraj Kubihal
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Yashdeep Gupta
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Mani Kalaivani
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Nikhil Tandon
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
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Al Ghaithi F, Waly MI, Al-Farsi Y, Al Mukhaini Z, Al Balushi R, Almashrafi A. Biochemical and nutritional determinants of non-alcoholic fatty liver disease in Omani adult patients: a case-control study. INTERNATIONAL JOURNAL OF NUTRITION, PHARMACOLOGY, NEUROLOGICAL DISEASES 2024; 14:407-415. [DOI: 10.4103/ijnpnd.ijnpnd_57_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 08/05/2024] [Indexed: 01/03/2025]
Abstract
Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is a risk factor for atherosclerosis, diabetes, kidney disease, and liver cirrhosis. Limited research exists on the biochemical and nutritional elements influencing NAFLD among adult patients in Oman. Objective: This study aimed to characterize the biochemical parameters and nutritional factors of Omani adults diagnosed with NAFLD at the Diwan Polyclinic in Muscat, Oman. Methods: This retrospective case–control study included 104 participants (52 cases and 52 controls) who have 2 or more risk factors for NAFLD and were referred to the Radiology department from January 2021 to January 2022 for abdominal ultrasound after Internal Medicine consultations. A validated scale, incorporating a semi-quantitative food frequency questionnaire, was employed. Results: The study revealed a significantly higher risk of NAFLD among men (69%) compared to women (31%). A common characteristic among participants was a prior diabetes diagnosis, 61.5% of the case group and 65% of the control group. While average liver enzyme levels were within the normal range for both groups, alanine transaminase levels were notably elevated in the case group. The case group exhibited a significantly higher average caloric intake than the control group. Conclusion: NAFLD is significantly more common among men. Alanine transaminase is significantly high in NAFLD group, which might be considered as a biochemical marker for NAFLD, but further investigations are needed. Moreover, high daily caloric intake is directly related to NAFLD.
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Affiliation(s)
| | - Mostafa I. Waly
- Food Science and Nutrition Department, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
| | - Yahya Al-Farsi
- Family Medicine and Public Health, College of Medicine and Health Sciences, Sultan Qaboos University, Oman
| | | | - Ruqaiya Al Balushi
- Food Science and Nutrition Department, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
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Saeki C, Saito M, Tsubota A. Association of chronic liver disease with bone diseases and muscle weakness. J Bone Miner Metab 2024; 42:399-412. [PMID: 38302761 DOI: 10.1007/s00774-023-01488-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 11/16/2023] [Indexed: 02/03/2024]
Abstract
The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies.
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Affiliation(s)
- Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Mitsuru Saito
- Department of Orthopedic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
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Khanmohammadi S, Kuchay MS. Effects of Metabolic Dysfunction-Associated Steatotic Liver Disease on Bone Density and Fragility Fractures: Associations and Mechanisms. J Obes Metab Syndr 2024; 33:108-120. [PMID: 38740429 PMCID: PMC11224928 DOI: 10.7570/jomes24004] [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: 01/24/2024] [Revised: 02/23/2024] [Accepted: 02/27/2024] [Indexed: 05/16/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has profound adverse effects on bone health and homeostasis. MASLD appears to be associated with changes in bone mineral density (BMD) and fracture rate. However, the data are ambiguous and conflicting. Although several studies have shown that children and adolescents with MASLD have decreased BMD, the data on the prevalence of fragility fractures among children are scarce. In adults, increasing evidence suggests that MASLD decreases BMD and increases the risk of fragility fractures, which appears to be due to deterioration of bone architecture in addition to a decrease in BMD. Effects of MASLD on bone health may also be age- and race-specific. MASLD does not seem to increase fracture risk in children and adolescents but increases the risk of fractures in elderly men, especially those of Asian origin. From a mechanistic perspective, bone remodeling is a continuous process between osteoblasts (bone-forming) and osteoclasts (bone-resorbing), with any imbalance resulting in metabolic bone disease. In individuals with MASLD, loss of anabolic insulin receptor signaling (insulin resistance) in osteoblasts and increased receptor activator of nuclear factor κB (RANK)/RANK ligand signaling in osteoclasts (proinflammatory cytokines) swings the pendulum toward accelerated bone loss. These processes are further complicated by the concomitant presence of obesity, type 2 diabetes mellitus, or sarcopenia in individuals with MASLD. This study reviews the current literature associated with the effects of MASLD on BMD and fragility fractures in children/adolescents and adults. This review also discusses the pathomechanisms that link MASLD with changes in BMD and fragility fractures.
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Affiliation(s)
- Shaghayegh Khanmohammadi
- Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Shafi Kuchay
- Division of Endocrinology and Diabetes, Medanta The Medicity Hospital, Gurugram, India
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Chondrogianni ME, Kyrou I, Androutsakos T, Flessa CM, Menenakos E, Chatha KK, Aranan Y, Papavassiliou AG, Kassi E, Randeva HS. Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe. Front Endocrinol (Lausanne) 2024; 15:1344376. [PMID: 38524631 PMCID: PMC10957571 DOI: 10.3389/fendo.2024.1344376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 01/05/2024] [Indexed: 03/26/2024] Open
Abstract
Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.
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Affiliation(s)
- Maria Eleni Chondrogianni
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Endocrine Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Kyrou
- Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, Athens, Greece
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Centre for Health & Life Sciences, Coventry University, Coventry, United Kingdom
- Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham, United Kingdom
- College of Health, Psychology and Social Care, University of Derby, Derby, United Kingdom
| | - Theodoros Androutsakos
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Christina-Maria Flessa
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Menenakos
- 5th Surgical Clinic, Department of Surgery, ‘Evgenidion Hospital’, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Kamaljit Kaur Chatha
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Department of Biochemistry and Immunology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Yekaterina Aranan
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Athanasios G. Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Endocrine Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Harpal S. Randeva
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Centre for Health & Life Sciences, Coventry University, Coventry, United Kingdom
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Su YH, Chien KL, Yang SH, Chia WT, Chen JH, Chen YC. Nonalcoholic Fatty Liver Disease Is Associated With Decreased Bone Mineral Density in Adults: A Systematic Review and Meta-Analysis. J Bone Miner Res 2023; 38:1092-1103. [PMID: 37254266 DOI: 10.1002/jbmr.4862] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 05/04/2023] [Accepted: 05/21/2023] [Indexed: 06/01/2023]
Abstract
This systematic review and meta-analysis aimed to investigate the effect of nonalcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and the risk of osteoporosis and osteoporotic fracture in adults. We searched PubMed, MEDLINE, Embase, CINAHL, Web of Science, Cochrane Library, and Scopus for observational studies published from inception to January 2023 that reported adjusted effect sizes of NAFLD on BMD, osteopenia/osteoporosis, and osteoporotic fracture. The data were synthesized using multilevel and random-effects models. A total of 19 studies were included; of these, nine (21,294 participants) evaluated the effect of NAFLD on BMD, six (133,319 participants) investigated the risk of osteoporosis, and five (227,901 participants) assessed the risk of osteoporotic fracture. This meta-analysis showed that NAFLD was associated with decreased BMD (mean difference -0.019 g/cm2 , 95% confidence interval [CI] -0.036 to -0.002, I2 = 93%) and increased risks of osteoporosis (adjusted risk ratio [RR] = 1.28, 95% CI 1.08 to 1.52, I2 = 84%) and osteoporotic fractures (adjusted RR = 1.17, 95% CI 1.00 to 1.37, I2 = 67%). Subgroup analyses revealed that NAFLD had a significantly detrimental effect on BMD in men and on the BMD of the femoral neck and total hip. Stratified analyses by ethnicity demonstrated that NAFLD was not associated with BMD, osteoporosis, or osteoporotic fracture in non-Asian populations. The publication bias of all included studies was low; however, there was considerable heterogeneity among the studies, warranting a careful interpretation of the findings. Overall, our results suggest that NAFLD is associated with decreased BMD and an increased risk of osteoporosis or osteoporotic fractures. Male sex and the BMD of the femoral neck and total hip may be potential risk factors for decreased BMD in adults with NAFLD. Additionally, ethnic disparities were observed between Asian and non-Asian populations regarding BMD and osteoporotic fractures. © 2023 American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Ying-Hao Su
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
- Department of Orthopaedic Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
| | - Shu-Hua Yang
- Department of Orthopaedic Surgery, National Taiwan University Hospital, Taipei City, Taiwan
| | - Wei-Tso Chia
- Department of Orthopaedic Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan
| | - Jen-Hau Chen
- Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Ching Chen
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
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Yeoh A, Wong R, Singal AK. The Role Bariatric Surgery and Endobariatric Therapies in Nonalcoholic Steatohepatitis. Clin Liver Dis 2023; 27:413-427. [PMID: 37024216 DOI: 10.1016/j.cld.2023.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Disease spectrum varies from steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, there are no approved medical therapies, and weight loss through lifestyle modifications remains a mainstay of therapy. Bariatric surgery is the most effective therapy for weight loss and has been shown to improve liver histology. Recently, endoscopic bariatric metabolic therapies have also emerged as effective treatments for patients with obesity and NAFLD. This review summarizes the role of bariatric surgery and endoscopic therapies in the management of patients with NAFLD.
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Affiliation(s)
- Aaron Yeoh
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Robert Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA; Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA
| | - Ashwani K Singal
- University of South Dakota Sanford School of Medicine; Avera Medical Group Liver Disease and Transplant Institute, Avera McKennan University Hospital, Clinical Research Affairs Avera Transplant Institute, 1315 South Cliff Avenue, Sioux Falls, SD 57105, USA; VA Medical Center, Sioux Falls, SD, USA.
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Vachliotis ID, Anastasilakis AD, Goulas A, Goulis DG, Polyzos SA. Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications. Diabetes Obes Metab 2022; 24:1702-1720. [PMID: 35589613 DOI: 10.1111/dom.14774] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/01/2022] [Accepted: 05/17/2022] [Indexed: 11/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and osteoporosis are two highly prevalent metabolic diseases. Increasing experimental evidence supports a pathophysiological link between NAFLD and osteoporosis. A key feature could be chronic, low-grade inflammation, which characterizes NAFLD and possibly affects bone metabolism. In this context, several factors, including but not limited to receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, osteopontin and osteocalcin, may serve as mediators. In the clinical setting, most but not all epidemiological evidence indicates that NAFLD is associated with lower bone mineral density or osteoporosis in adults. Although an association between NAFLD and osteoporosis has not yet been established, and thus remains speculative, pharmacological considerations already exist. Some of the current and emerging pharmacological options for NAFLD have shown possible anti-osteoporotic properties (eg, vitamin E, obeticholic acid, semaglutide), while others (eg, pioglitazone, canagliflozin) have been associated with increased risk of fractures and may be avoided in patients with NAFLD and concomitant osteoporosis, especially those at high fracture risk. Conversely, some anti-osteoporotic medications (denosumab) might benefit NAFLD, while others (raloxifene) might adversely affect it and, consequently, may be avoided in patients with osteoporosis and NAFLD. If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarizes the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focuses on treatment considerations derived from this potential association.
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Affiliation(s)
- Ilias D Vachliotis
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece
| | | | - Antonis Goulas
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios G Goulis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Wester A, Hagström H. Risk of fractures and subsequent mortality in non-alcoholic fatty liver disease: A nationwide population-based cohort study. J Intern Med 2022; 292:492-500. [PMID: 35373876 PMCID: PMC9545244 DOI: 10.1111/joim.13497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Studies suggest an association between osteoporosis and non-alcoholic fatty liver disease (NAFLD), but whether patients with NAFLD are at increased risk of fractures is unknown. OBJECTIVES The aim was to determine the rate and risk of fractures and the mortality rate after fracture in patients with NAFLD compared to the general population. METHODS This was a nationwide population-based cohort study using data from the Swedish National Patient Registry on 10,678 patients with NAFLD from 1987 to 2016. Patients were matched for sex, age, and municipality with 99,176 controls from the Swedish Total Population Registry. Cox regression was used to estimate fracture rates. The risk of fractures was assessed while accounting for competing risks (death and liver transplantation). RESULTS A total of 12,312 fractures occurred during 761,176 person-years of follow-up. Patients with NAFLD (17.5 per 1000 person-years) had a slightly higher fracture rate than controls (16.1 per 1000 person-years; adjusted hazard ratio 1.11, 95% confidence interval [CI] 1.05-1.19), although the 5-year risk of fractures was similar (8.0%, 95% CI 7.4-8.6 versus 7.3%, 95% CI 7.2-7.5). Additionally, 1-year mortality after fracture was similar in NAFLD and controls. CONCLUSIONS Patients with NAFLD have a slightly higher rate of fractures but long-term risk of fractures comparable to the general population. This suggests that broad surveillance of risk factors for fractures in patients with NAFLD is not motivated.
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Affiliation(s)
- Axel Wester
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.,Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.,Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
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Liu Y, Shuai P, Liu Y, Li D. Association between non-alcoholic fatty liver disease and bone turnover markers in southwest China. J Bone Miner Metab 2022; 40:712-719. [PMID: 35639173 DOI: 10.1007/s00774-022-01340-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 05/03/2022] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is not considered only a liver disease but also associated with an increased risk of extra-hepatic diseases including bone metabolism disorders. In our study, we aim to explore the changes of several bone turnover markers (BTMs) under different fat deposition and stiffness levels of the liver. MATERIALS AND METHODS We analyzed the physical examination data of 3353 subjects from February 2018 to June 2021 in this study. The steatosis and stiffness of liver were quantitatively detected using the fat attenuation parameter (FAP) and liver stiffness measurements (LSM) of transient elastography (TE). Serum 25-hydroxyvitamin D3 (25(OH)D3), osteocalcin, carboxy-terminal collagen crosslinks (CTX), amino terminal elongation peptide of total type 1 procollagen (P1NP) were tested. Clinical and other biochemical data were also collected. RESULTS With the increasing of FAP, the levels of 25(OH)D3 and osteocalcin decreased, the difference was statistically significant. No correlation was found between LSM and all the four BTMs. Logistic regression analysis revealed that FAP ≥ 244 dB/m was negatively correlated with 25(OH)D3 (in both males and females) and osteocalcin (only in males). No correlation was found between FAP ≥ 244 dB/m and P1NP or CTX. CONCLUSION The degree of liver adipose deposition was found to be negatively associated with the serum levels of 25(OH)D3 (in both males and females) and osteocalcin (only in males) in southwest China.
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Affiliation(s)
- Ying Liu
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Ping Shuai
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Yuping Liu
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China
| | - Dongyu Li
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, Sichuan Province, China.
- Department of Health Management Center and Institute of Health Management, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, No. 32 Section 2, West 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China.
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Yadav E, Kaur RD, Sasan A, Garg S. Investigation of the influential factors for hepatic osteodystrophy in chronic liver disease: A case-control survey among the patients attending a tertiary care hospital in a rural region of Northern India. Tzu Chi Med J 2022; 35:95-102. [PMID: 36866351 PMCID: PMC9972938 DOI: 10.4103/tcmj.tcmj_27_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 03/18/2022] [Accepted: 04/28/2022] [Indexed: 11/04/2022] Open
Abstract
Objectives Hepatic osteodystrophy (HOD) is a well-recognized complication of chronic liver diseases (CLD), but the influential factors associated with this complication were studied scarcely in a rural Indian population. The study aims to evaluate the prevalence of HOD and variables that might influence it among cases diagnosed with CLD. Materials and Methods It is a cross-sectional observational design survey that was performed in a hospital among the two-hundred cases and controls with a 1:1 ratio who were age (>18 years) and gender matched in a period between April and October 2021. They were subjected to etiological workup, hematological and biochemical investigations, and Vitamin D levels. Then, dual-energy X-ray absorptiometry was used to measure the bone mineral densitometry (BMD) for whole-body, lumbar spine (LS), and hip. HOD was diagnosed according to the WHO criteria. Then, the Chi-square test and conditional logistic regression analysis were used to investigate the influential factors of HOD in CLD patients. Results The whole-body, LS-spine, and hip BMDs in CLD cases were found to be significantly lower as compared to controls. When the participants among both groups were stratified by age and gender, a significant difference in LS-spine and hip BMD was observed in elderly patients (>60 years), and in both the male and female patients. HOD was found in 70% of CLD patients. After multivariate analysis in CLD patients, we identified that being a male patient (odds ratio [OR] = 3.03), older age (OR = 3.54), duration of illness for more than 5 years (OR = 3.89), decompensated liver dysfunction with Child-Turcotte-Pugh-B and C grading (OR = 8.28), and low level of Vitamin D (OR = 18.45) were the risk factors for HOD. Conclusion This study concludes that severity of illness and lower level of Vitamin D were the main influential factors for HOD. Supplementation of Vitamin D and calcium in the patients can abate the risk of fractures in our rural communities.
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Affiliation(s)
- Ekta Yadav
- Department of Medicine, Bhagat Phool Singh Government Medical College for Women Sonipat, Haryana, India
| | - Rupan Deep Kaur
- Department of Transfusion Medicine, Bhagat Phool Singh Government Medical College for Women, Sonipat, Haryana, India
| | - Aayushi Sasan
- Bhagat Phool Singh Government Medical College for Women, Sonipat, Haryana, India
| | - Sunny Garg
- Department of Psychiatry, Bhagat Phool Singh Government Medical College for Women, Sonipat, Haryana, India,Address for correspondence: Dr. Sunny Garg, Department of Psychiatry, Bhagat Phool Singh Government Medical College for Women, Khanpur Kalan, Sonipat - 131 305, Haryana, India. E-mail:
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13
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Xie R, Liu M. Relationship Between Non-Alcoholic Fatty Liver Disease and Degree of Hepatic Steatosis and Bone Mineral Density. Front Endocrinol (Lausanne) 2022; 13:857110. [PMID: 35360054 PMCID: PMC8964007 DOI: 10.3389/fendo.2022.857110] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 02/22/2022] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The liver and bones are both active endocrine organs that carry out several metabolic functions. However, the link between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) is still controversial. The goal of this study was to discover if there was a link between non-alcoholic fatty liver disease and bone mineral density in US persons aged 20 to 59 years of different genders and races. METHODS Using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, multivariate logistic regression models were utilized to investigate the association between NAFLD and lumbar BMD. Fitted smoothing curves and generalized additive models were also used. RESULTS The analysis included a total of 1980 adults. After controlling for various variables, we discovered that NAFLD was negatively linked with lumbar BMD. The favorable connection of NAFLD with lumbar BMD was maintained in subgroup analyses stratified by sex, race and age in men, other race and aged 20-29 years. The relationship between NAFLD and lumbar BMD in blacks and people aged 40-49 years was a U-shaped curve with the inflection point: at 236dB/m and 262dB/m. Furthermore, we discovered that liver advanced fibrosis and liver cirrhosis were independently connected with higher BMD, while no significant differences were detected in severe liver steatosis and BMD. CONCLUSIONS Our study found an independently unfavorable relationship between NAFLD and BMD in persons aged 20 to 59. We also discovered a positive link between BMD and advanced fibrosis and cirrhosis. More research is needed to back up the findings of this study and to look into the underlying issues.
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Affiliation(s)
| | - Mingjiang Liu
- Department of Hand Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
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14
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Nguyen VH, Le MH, Cheung RC, Nguyen MH. Differential Clinical Characteristics and Mortality Outcomes in Persons With NAFLD and/or MAFLD. Clin Gastroenterol Hepatol 2021; 19:2172-2181.e6. [PMID: 34033923 DOI: 10.1016/j.cgh.2021.05.029] [Citation(s) in RCA: 151] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/03/2021] [Accepted: 05/17/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) establishes new criteria for diagnosing fatty liver disease independent of alcohol intake and concomitant viral hepatitis infection. However, the long-term outcomes of patients with MAFLD are sparse. We aimed to describe the characteristics and long-term survival of persons meeting criteria for nonalcoholic fatty liver disease (NAFLD) only (non-MAFLD NAFLD), for both NAFLD and MAFLD (NAFLD-MAFLD), and for MAFLD only (non-NAFLD MAFLD). METHODS Using data from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, 2997 participants with fatty liver identified via ultrasound were categorized into 3 distinct groups: non-MAFLD NAFLD, NAFLD-MAFLD, and non-NAFLD MAFLD. RESULTS Participants in the NAFLD-MAFLD and non-NAFLD MAFLD groups were older, had more metabolic traits and higher mean liver enzymes. Nearly 8% of participants in the non-NAFLD MAFLD group had advanced fibrosis (Fibrosis-4 index >2.67), while only 1.3% and 1.9% in the NAFLD-MAFLD and non-MAFLD NAFLD groups did, respectively (P < .0001). Non-NAFLD MAFLD participants had the highest cumulative incidence of all-cause mortality (26.2%) followed by those with NAFLD-MAFLD then non-MAFLD NAFLD participants (21.1% and 10.6%, respectively; P < .0001). Similar findings were observed for cardiovascular disease-related and other-cause (noncardiovascular disease, noncancer) mortality. Non-NAFLD MAFLD was independently associated with all-cause mortality compared with non-MAFLD NAFLD (adjusted hazard ratio, 2.4; 95% confidence interval, 1.2-4.6; P = .01). CONCLUSIONS MAFLD criteria identified a significant group of people with more comorbidities and worse prognosis compared with those with NAFLD only. These criteria should be considered in the general population to identify high-risk groups for early interventions.
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Affiliation(s)
- Vy H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Michael H Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Palo Alto Veterans Affairs Health Care System, Palo Alto, California
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California.
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15
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Suzuki A, Iwata J. Amino acid metabolism and autophagy in skeletal development and homeostasis. Bone 2021; 146:115881. [PMID: 33578033 PMCID: PMC8462526 DOI: 10.1016/j.bone.2021.115881] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 12/29/2020] [Accepted: 02/06/2021] [Indexed: 02/06/2023]
Abstract
Bone is an active organ that is continuously remodeled throughout life via formation and resorption; therefore, a fine-tuned bone (re)modeling is crucial for bone homeostasis and is closely connected with energy metabolism. Amino acids are essential for various cellular functions as well as an energy source, and their synthesis and catabolism (e.g., metabolism of carbohydrates and fatty acids) are regulated through numerous enzymatic cascades. In addition, the intracellular levels of amino acids are maintained by autophagy, a cellular recycling system for proteins and organelles; under nutrient deprivation conditions, autophagy is strongly induced to compensate for cellular demands and to restore the amino acid pool. Metabolites derived from amino acids are known to be precursors of bioactive molecules such as second messengers and neurotransmitters, which control various cellular processes, including cell proliferation, differentiation, and homeostasis. Thus, amino acid metabolism and autophagy are tightly and reciprocally regulated in our bodies. This review discusses the current knowledge and potential links between bone diseases and deficiencies in amino acid metabolism and autophagy.
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Affiliation(s)
- Akiko Suzuki
- Department of Diagnostic & Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA; Center for Craniofacial Research, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA
| | - Junichi Iwata
- Department of Diagnostic & Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA; Center for Craniofacial Research, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
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Ma Q, Cheng X, Hou X, Yang Z, Ma D, Wang Z. Bone Marrow Fat Measured by a Chemical Shift-Encoded Sequence (IDEAL-IQ) in Patients With and Without Metabolic Syndrome. J Magn Reson Imaging 2021; 54:146-153. [PMID: 33728737 DOI: 10.1002/jmri.27548] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 01/19/2021] [Accepted: 01/19/2021] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Metabolic syndrome increases the risk of chronic diseases such as cardiovascular disease and diabetes. Metabolic syndrome also has an impact on bone mineral density. However, the relationship between metabolic syndrome and bone marrow fat is unclear. PURPOSE To determine factors associated with bone marrow fat concentration in subjects with and without metabolic syndrome. STUDY TYPE Retrospective. POPULATION One hundred and one women with metabolic syndrome (31.0 years ±5.1) and 96 female living liver transplant donors (32.0 years ±3.7). Our institutional review board approved the study. Each subject signed written informed consent. FIELD STRENGTH/SEQUENCE 3.0 T MRI system and a commercially available chemical shift-encoded 3D sequence (Iterative Decomposition of water and fat with Echo asymmetry and Least Square Estimation). ASSESSMENT Proton density fat fraction (PDFF) in liver, vertebral body, and paraspinal muscle (erector spinae) were measured from a single acquisition by a 15-year-experience orthopedic radiologist. The factors associated with PDFF were acquired. STATISTICAL TESTS The analysis of covariance test, after adjustment for body mass index and age, was used to analyze the differences between metabolic syndrome and non-metabolic syndrome groups. A stepwise multiple regression analysis was used to determine which variables were independently associated with PDFF. RESULTS Mean vertebral PDFF and alanine aminotransferase (ALT) were significantly lower in donors than subjects with metabolic syndrome (both P < 0.05). Serum vitamin D concentration, ferritin, and high-density lipoprotein (HDL) cholesterol were significantly higher in donors than subjects with metabolic syndrome (all P < 0.05). Multiple regression analysis revealed antidiabetic medicine, higher serum vitamin D concentration, lower waist circumference, lower ferritin, lower HDL, absence of metabolic syndrome, and lower ALT were significantly associated with lower vertebral PDFF (all P < 0.05). DATA CONCLUSION Multiple factors affect bone marrow fat concentration in subjects with metabolic syndrome. Serum vitamin D concentration and antidiabetic medicine are associated with low bone marrow fat, whereas waist circumference, serum ferritin, metabolic syndrome, imbalanced lipid metabolism, and abnormal liver function are associated with high bone marrow fat. LEVEL OF EVIDENCE LEVEL 3 TECHNICAL EFFICACY STAGE: 1.
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Affiliation(s)
- Qiang Ma
- Radiology Department, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Xiaoyue Cheng
- Radiology Department, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Xinmeng Hou
- Radiology Department, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Zhenghan Yang
- Radiology Department, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Daqing Ma
- Radiology Department, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Zhenchang Wang
- Radiology Department, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
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Li BT, Simon TG, Wang N, Chung RT, Corey KE, Dichtel LE, Samelson EJ, Kiel DP, Long MT. Association Between Liver Fat and Bone Density is Confounded by General and Visceral Adiposity in a Community-Based Cohort. Obesity (Silver Spring) 2021; 29:595-600. [PMID: 33528915 PMCID: PMC7904629 DOI: 10.1002/oby.23100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/27/2020] [Accepted: 11/11/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is associated with low bone mineral density (BMD); however, it is not known whether early-stage NAFLD may be associated with BMD after accounting for BMI or visceral adipose tissue (VAT). METHODS This was a cross-sectional study of 3,462 Framingham Heart Study participants who underwent computed tomographic measurement of liver fat, VAT volume, volumetric spine BMD, vertebral cross-sectional area (CSA), and vertebral compressive strength. This study excluded heavy alcohol consumers. Multivariable linear regression models were used to assess the association between NAFLD and volumetric BMD, CSA, and vertebral compressive strength after accounting for covariates, including BMI or VAT. RESULTS A total of 2,253 participants (mean age, 51.2 [SD 10.7] years; 51.1% women) were included. In multivariable-adjusted models, positive associations between NAFLD and integral BMD, trabecular BMD, and vertebral compressive strength were observed. However, results were attenuated and no longer significant after additionally adjusting for BMI or VAT. NAFLD was observed to be weakly associated with a lower vertebral CSA in adjusted models. CONCLUSIONS In a community-based cohort, the associations between NAFLD and BMD and vertebral strength were confounded by BMI and VAT. However, NAFLD was associated with a reduced vertebral CSA in adjusted models.
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Affiliation(s)
- Belinda T. Li
- Boston University School of Medicine, Boston, MA, USA
| | - Tracey G. Simon
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Na Wang
- Biostatistics & Epidemiology Data Analytics Center, School of Public Health, Boston University, Boston, MA, USA
| | - Raymond T. Chung
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kathleen E. Corey
- Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Laura E. Dichtel
- Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Elizabeth J. Samelson
- Hebrew SeniorLife, Hinda and Arthur Marcus Institute for Aging Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Douglas P. Kiel
- Hebrew SeniorLife, Hinda and Arthur Marcus Institute for Aging Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Michelle T. Long
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
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Prevalence of Elevated Alanine Aminotransferase by Diagnostic Criterion, Age, and Gender among Adolescents. Gastroenterol Res Pract 2020; 2020:4240380. [PMID: 32411198 PMCID: PMC7204184 DOI: 10.1155/2020/4240380] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 12/28/2019] [Indexed: 12/18/2022] Open
Abstract
Background Serum alanine aminotransferase (ALT) activity was measured not only to detect liver disease, but also to monitor overall health. The purpose of this study was to obtain the prevalence of elevated ALT levels among adolescents. Methods In a school-based cross-sectional study, a representative sample was analyzed from 9 middle and high schools in Shenzhen, China, during 2017 to 2018. Elevated ALT was defined as diagnostic criterion I (>30 U/L for boys and >19 U/L for girls) and diagnostic criterion II (>40 U/L). Results From the adolescent population, a total of 7281 students (boys, 4014, and girls, 3267) aged from 10 to 17 years were collected. The prevalence of elevated ALT was 7.11% (6.88% for boys and 7.41% for girls) by criterion I and 2.72% (3.96% for boys and 1.19% for girls) by criterion II. Based on the Shenzhen census and Chinese national census population, the adjusted prevalence of elevated ALT was 7.65% (boys 7.19% and girls 8.21%) and 6.79% (boys 6.07% and girls 7.56%) by criterion I and 2.85% (boys 4.20% and girls 1.16%) and 2.43% (boys 3.49% and girls 1.29%) by criterion II. For age, the overall trends were increasing progressively, regardless of the use of diagnostic criteria for an elevated ALT activity. Conclusions This study supplements the gap that the prevalence of elevated ALT levels differed in gender, age, and criteria among adolescents of Shenzhen. We should take the prevalence as a predictor and continue to play a warning and preventive role in preparation for further intervention.
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Ma X, Liu S, Zhang J, Dong M, Wang Y, Wang M, Xin Y. Proportion of NAFLD patients with normal ALT value in overall NAFLD patients: a systematic review and meta-analysis. BMC Gastroenterol 2020; 20:10. [PMID: 31937252 PMCID: PMC6961232 DOI: 10.1186/s12876-020-1165-z] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 01/06/2020] [Indexed: 02/06/2023] Open
Abstract
Background ALT value is often used to reflect the hepatic inflammation and injury in NAFLD patients, but many studies proved that ALT values were normal in many NAFLD patients. The aim of this study was to identify the summarized proportion of NAFLD patients with normal ALT value in the overall NAFLD patients. Methods Electronic databases PubMed, EMBASE, Ovid, and the Cochrane Library were searched for potential studies published from January 1, 2000 to September 30, 2019. Studies that have reported the number of NAFLD or NASH patients with normal and abnormal ALT value were included and analyzed. Abstracts, reviews, case reports, and letters were excluded. Results A total of 11 studies with 4084 patients were included for assessing the summarized proportion of NAFLD patients with normal ALT in overall NAFLD patients. As the results shown, the summarized proportion of NAFLD patients with normal ALT value in overall NAFLD patients was 25% (95%CI: 20–31%) which was calculated by the random-effects model. The summarized proportion of NASH patients with normal ALT value in overall NASH patients was 19% (95%CI: 13–27%). Subgroup analysis includes region, study type, diagnostic method, and group size were conducted to investigate the resource of heterogeneity in the summarized proportion of NAFLD and NASH patients with normal ALT value. Conclusions 25% NAFLD patients and 19% NASH patients possess the normal ALT value in the clinical manifestation. The value of ALT in the clinical diagnosis of NAFLD and NASH remains need be further testified.
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Affiliation(s)
- Xuefeng Ma
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, China
| | - Shousheng Liu
- Central Laboratories, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, China.,Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China
| | - Jie Zhang
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, China
| | - Mengzhen Dong
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, China
| | - Yifen Wang
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, China
| | - Mengke Wang
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, China
| | - Yongning Xin
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, China. .,Digestive Disease Key Laboratory of Qingdao, Qingdao, 266071, China.
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Association between non-alcoholic fatty liver disease and bone turnover biomarkers in post-menopausal women with type 2 diabetes. DIABETES & METABOLISM 2019; 45:347-355. [DOI: 10.1016/j.diabet.2018.10.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 10/01/2018] [Accepted: 10/02/2018] [Indexed: 02/06/2023]
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Ballestri S, Mantovani A, Nascimbeni F, Lugari S, Lonardo A. Extra-hepatic manifestations and complications of nonalcoholic fatty liver disease. Future Med Chem 2019; 11:2171-2192. [PMID: 31538528 DOI: 10.4155/fmc-2019-0003] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 05/07/2019] [Indexed: 12/14/2022] Open
Abstract
This review article aims to synthesize the evidence regarding nonalcoholic fatty liver disease (NAFLD) as a systemic disorder. We critically discuss the metabolic syndrome and its components; the cardiovascular and the endocrine system; chronic respiratory disorders; the musculoskeletal system; the skin; and extra-hepatic tumors. We conclude that, while some of these extra-hepatic conditions clearly predispose to the development of secondary forms of NAFLD (typically hypothyroidism-induced NAFLD), others result from pre-existent NAFLD (e.g., certain extra-hepatic tumors) and others (such as Type 2 Diabetes) have, with NAFLD, mutual and bidirectional associations. Analyzed data imply that NAFLD is not merely a hepatic disease. It is also and possibly more importantly, a systemic disorder requiring a special awareness, a multidisciplinary approach and a multidimensional vision.
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Affiliation(s)
- Stefano Ballestri
- Azienda USL di Modena - Ospedale di Pavullo - UOC di Medicina - Pavullo (Mo), Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes & Metabolism, Department of Medicine, University & Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Fabio Nascimbeni
- AOU di Modena - Ospedale Civile di Baggiovara, UOC di Medicina ad indirizzo Metabolico-Nutrizionistico - Modena, Italy
| | | | - Amedeo Lonardo
- AOU di Modena - Ospedale Civile di Baggiovara, UOC di Medicina ad indirizzo Metabolico-Nutrizionistico - Modena, Italy
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Samji NS, Verma R, Satapathy SK. Magnitude of Nonalcoholic Fatty Liver Disease: Western Perspective. J Clin Exp Hepatol 2019; 9:497-505. [PMID: 31516266 PMCID: PMC6728535 DOI: 10.1016/j.jceh.2019.05.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 05/07/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise worldwide, and it is estimated that this disquieting trend will continue for another 10-15 years before prevalence begins to decrease. NAFLD is the hepatic manifestation of metabolic syndrome. As obesity, diabetes, and other lifestyle-related diseases continue to rise, the spectrum of NAFLD, e.g., nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis, liver-related morbidity, and mortality, will increase in parallel. Its widespread prevalence and associated economic burden have drawn significant attention, and a multitude of pharmaceutical companies are participating in active research trying to find a "cure". Unfortunately, as of now, no targeted treatment exists to treat this condition, and therefore, emphasis has been on its prevention. The current review focuses on the epidemiology, clinical characteristics, risk factors, and clinical outcomes of NAFLD in Western countries. It is important to understand the magnitude of NAFLD and its risk factors in Western countries where the prevalence of NAFLD has now reached epidemic proportions to identify the best strategy to prevent and possibly control this epidemic.
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Affiliation(s)
- Naga S. Samji
- Tenova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
| | - Rajanshu Verma
- Tenova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN, 38139, USA
| | - Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, 11030, USA
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23
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Mantovani A, Dauriz M, Gatti D, Viapiana O, Zoppini G, Lippi G, Byrne CD, Bonnet F, Bonora E, Targher G. Systematic review with meta-analysis: non-alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density. Aliment Pharmacol Ther 2019; 49:375-388. [PMID: 30600540 DOI: 10.1111/apt.15087] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 10/29/2018] [Accepted: 11/16/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several studies have explored the effect of non-alcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and risk of osteoporotic fractures in adults. However, the extent to which NAFLD adversely affects bone health remains uncertain. AIM To provide a quantitative estimation of the magnitude of the association of NAFLD with BMD or history of osteoporotic fractures in adults. METHODS We searched PubMed, Web of Science, and Scopus using predefined keywords to identify all observational studies, published up to 31 August 2018, in which NAFLD was diagnosed by imaging or histology; BMD was measured by dual energy X-ray absorptiometry; and a self-reported history of osteoporotic fractures was collected with interviewer-assisted questionnaires. Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling. RESULTS Twelve cross-sectional or case-control studies with aggregate data on 30 041 adults of predominantly Asian ethnicity (30% with NAFLD) were included in the final analysis. No significant differences in BMD at different skeletal sites (whole body, lumbar spine, or femur) were observed between individuals with and without NAFLD. Conversely, NAFLD was associated with increased odds of osteoporotic fractures, especially in older Chinese men (n = 2 studies; random-effects odds ratio 2.10, 95% CI 1.36-3.25; I2 = 0%). Sensitivity analyses did not alter these findings. The funnel plot and Egger test did not reveal significant publication bias. CONCLUSIONS This meta-analysis suggests that imaging-defined or biopsy-proven NAFLD is associated with a self-reported history of osteoporotic fractures (principally in Chinese men), but not with low BMD, in middle-aged and elderly individuals.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Marco Dauriz
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Davide Gatti
- Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Ombretta Viapiana
- Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giacomo Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University and Azienda Ospedaliera, Universitaria Integrata of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK.,Southampton National Institute for Health Research Biomedical Research Centre, Southampton General Hospital, University Hospital Southampton, Southampton, UK
| | - Fabrice Bonnet
- Department of Endocrinology, INSERM UMR 991, University Hospital of Rennes, Rennes Cedex 9, France
| | - Enzo Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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24
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Sun Y, Dai W, Liang Y, Yang P, Yang Q, Liang M, Xia N. Relationship between nonalcoholic fatty liver disease and bone mineral density in adolescents with obesity: a meta-analysis. Diabetes Metab Syndr Obes 2019; 12:199-207. [PMID: 30787626 PMCID: PMC6363492 DOI: 10.2147/dmso.s192256] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Many studies have reported the relationship between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) among adults. However, fewer studies on this topic have been reported in adolescents. We thus conducted a meta-analysis to show the association between NAFLD and BMD in adolescents with obesity. MATERIALS AND METHODS Computer retrieval was carried out via PubMed, Embase, Cochrane Library and the Cochrane Central Register of Controlled Trials from inception to September 2018. Six published case-control studies that assessed the relationship between NAFLD and BMD were included. RESULTS The six studies included 217 obese adolescents with NAFLD and 236 controls. The meta-analysis indicated that obese children with NAFLD had a lower BMD and Z-score than the control group (weighted mean difference [WMD]-0.03, 95% CI [-0.05, -0.02], P=0.000; [WMD] -0.26, 95% CI [-0.37, -0.14], P=0.000). However, we analyzed the factor of bone mineral content, and there was no correlation between the two groups ([WMD]-55.99, 95% CI [-132.16, 20.18], P=0.150). CONCLUSION Obese children with NAFLD are more susceptible to osteoporosis than children with only obesity. Because of the limitations related to the quantity and quality of the included literature, further studies are still needed.
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Affiliation(s)
- Yue Sun
- Geriatric Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China,
| | - Weiran Dai
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Yuzhen Liang
- Department of Endocrinology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Pijian Yang
- Geriatric Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China,
| | - Qiong Yang
- Geriatric Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China,
| | - Min Liang
- Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Ning Xia
- Geriatric Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China,
- Department of Science and Technology Education, Guangxi Zhuang Autonomous Region Health Committee, Nanning, Guangxi, People's Republic of China
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