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Tantai X, Wen Z, Tuo S, Ran Q, Li C, Li Y, Yuan J, Wang J, Li L, Dai S. Associations of Serum Vitamin D with Sarcopenia in Patients with Chronic Liver Disease: A Population-Based Cross-Sectional Study. Calcif Tissue Int 2025; 116:69. [PMID: 40325227 DOI: 10.1007/s00223-025-01376-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 04/15/2025] [Indexed: 05/07/2025]
Abstract
The association between vitamin D and sarcopenia in patients with chronic liver disease (CLD) has yet to be conclusively established, particularly in Western populations. We investigated the association between serum 25(OH)D levels and sarcopenia in adult CLD patients in the USA. We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey III. Weighted logistic regression was used to determine the association between sarcopenia and serum 25(OH)D in participants with CLD. CLD was defined as chronic hepatitis B or C, non-alcoholic fatty liver disease, alcohol-related liver disease, and other liver diseases. A serum 25(OH)D level of less than 75 nmol/L was defined as vitamin D insufficiency. This study included 1402 participants with CLD. The serum 25(OH)D concentration was significantly lower in the sarcopenia group (45.3 nmol/l) compared to the non-sarcopenia group (50.6 nmol/l). The prevalence of vitamin D insufficiency was as high as 91.3% in participants with CLD, and the proportion of vitamin D insufficiency was higher in those with sarcopenia. In the full multivariate model, each 10-nmol/L increase in 25(OH)D concentration was significantly associated with a decreased risk of sarcopenia (OR 0.89; 95%CI 0.79-0.99). Conversely, participants with insufficient vitamin D levels had a significantly increased risk of sarcopenia (OR, 2.07; 95% CI 1.08-4.00). Subgroup analyses suggested a sex difference in the association between vitamin D levels and sarcopenia, with a significant association only observed in females. Restricted cubic spline curves indicated a linear inverse association between serum 25(OH)D concentration and risk of sarcopenia in all participants and in females. Low serum 25(OH)D levels were significantly associated with an increased risk of sarcopenia in individuals with CLD, with the observed gender differences in this association warranting further validation in future studies.
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Affiliation(s)
- Xinxing Tantai
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhang Wen
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Shuyue Tuo
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Qiuju Ran
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Chan Li
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yong Li
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jia Yuan
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jinhai Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Lu Li
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China.
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| | - Shejiao Dai
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, 710004, Shaanxi Province, China.
- Clinical Research Center for Gastrointestinal Diseases of Shaanxi Province, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
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Jiao H, Wang H, Li J, Yang Z, Sun C. The Molecular Pathogenesis of Sarcopenia/Frailty in Cirrhosis. Semin Liver Dis 2025. [PMID: 40239708 DOI: 10.1055/a-2564-7551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
Cirrhosis is an important cause of morbidity and death in patients with chronic liver disease. It can be divided into compensatory and decompensated stages. During the decompensation period, complications such as esophageal and gastric varices hemorrhage, hepatic encephalopathy, infection, and hepatorenal syndrome are often incurred, which has a high mortality rate and leverages huge economic burden on society, healthcare resources, and individuals. Sarcopenia and frailty are common in patients with cirrhosis. The pathogenesis of sarcopenia and frailty in the context of cirrhosis is complicated and multifactorial, including overwhelming systemic inflammation, imbalance of muscle protein metabolism, malnutrition, endocrine and metabolic dysfunctions, intestinal microecological disorders, lack of physical exercise, and other aspects. Notably, accumulating evidence implicates that many patients experience sarcopenia/frailty even before the onset of liver cirrhosis. In this regard, the magnitude of liver fibrosis is closely linked to the progression of sarcopenia with reciprocal impact. In conclusion, this review article will shed light on the pathogenesis of cirrhosis complicated with sarcopenia/frailty, aimed at facilitating early diagnosis and effective management.
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Affiliation(s)
- Huanli Jiao
- Department of Health Management, Tianjin Hospital, Hexi District, Tianjin, People's Republic of China
| | - Han Wang
- Department of Health Management, Tianjin Hospital, Hexi District, Tianjin, People's Republic of China
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
| | - Ziyi Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, People's Republic of China
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Díaz-Ruíz R, Poca M, Román E, Cuyàs B, Bañares I, Morales Á, Hernández Martínez-Esparza E, Panadero R, Velasco C, Rapado-Castro M, Bretón I, Bañares R, Soriano G, García-Martínez R. Treatment of Vitamin D Deficiency in Decompensated Patients with Cirrhosis Is Associated with Improvement in Frailty. Med Sci (Basel) 2025; 13:30. [PMID: 40137450 PMCID: PMC11943887 DOI: 10.3390/medsci13010030] [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] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 02/17/2025] [Accepted: 03/10/2025] [Indexed: 03/27/2025] Open
Abstract
Background/aim: Frailty is increasingly recognized as a relevant prognostic factor in patients with cirrhosis, regardless of liver failure. Vitamin D deficiency is frequent in these patients and has been related to frailty and sarcopenia, but the impact of its supplementation on frailty in cirrhosis is unknown. The aim was to evaluate the effect of vitamin D supplementation on frailty in patients with decompensated cirrhosis and vitamin D deficiency or insufficiency. Methods: We included patients with cirrhosis who had vitamin D deficiency or insufficiency following their hospitalization for acute decompensation. Vitamin D was supplemented according to current recommendations, as were other micronutrients if necessary. Patients were followed for one year to evaluate changes at 6 and 12 months in frailty (Fried frailty index), health-related quality of life (SF-36, CLDQ) and mood (HADS). Body composition was assessed by DXA at baseline and at 12 months. Results: We included 39 patients, 27 of whom reached the 6-month follow-up. Serum vitamin D increased at 6 and 12 months (p < 0.001 compared to baseline). Fried frailty index improved at the 6-month visit (p = 0.004), and handgrip strength improved at 6 (p = 0.001) and 12 (p = 0.002) months, similarly in women and men. At 12 months, we observed an increase in body mass index, right arm lean mass and total fat mass. Conclusions: A multifactorial nutritional intervention, especially vitamin D supplementation after discharge in decompensated, vitamin D-deficient patients with cirrhosis, was associated with an improvement in frailty, muscular strength and lean muscle mass. However, the increase in fat mass strengthens the recommendation for diet, exercise and weight supervision.
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Affiliation(s)
- Raquel Díaz-Ruíz
- Department of Gastroenterology, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, CIBERehd, 28007 Madrid, Spain; (R.D.-R.); (R.B.)
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain; (I.B.); (R.P.); (M.R.-C.)
| | - Maria Poca
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR Sant Pau), Universitat Autònoma de Barcelona, CIBERehd, 08025 Barcelona, Spain; (M.P.); (E.R.); (B.C.)
| | - Eva Román
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR Sant Pau), Universitat Autònoma de Barcelona, CIBERehd, 08025 Barcelona, Spain; (M.P.); (E.R.); (B.C.)
- University Nursing School EUI-Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08025 Barcelona, Spain;
| | - Berta Cuyàs
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR Sant Pau), Universitat Autònoma de Barcelona, CIBERehd, 08025 Barcelona, Spain; (M.P.); (E.R.); (B.C.)
| | - Irene Bañares
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain; (I.B.); (R.P.); (M.R.-C.)
| | - Ángela Morales
- Unidad de Nutrición Clínica y Dietética, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain; (Á.M.); (C.V.); (I.B.)
| | - Elvira Hernández Martínez-Esparza
- University Nursing School EUI-Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08025 Barcelona, Spain;
| | - Rocío Panadero
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain; (I.B.); (R.P.); (M.R.-C.)
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, CIBERSAM, ISCIII, School of Medicine, Universidad Complutense, 28007 Madrid, Spain
| | - Cristina Velasco
- Unidad de Nutrición Clínica y Dietética, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain; (Á.M.); (C.V.); (I.B.)
| | - Marta Rapado-Castro
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain; (I.B.); (R.P.); (M.R.-C.)
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, CIBERSAM, ISCIII, School of Medicine, Universidad Complutense, 28007 Madrid, Spain
- Department of Psychiatry, The University of Melbourne, Melbourne, VIC 3010, Australia
| | - Irene Bretón
- Unidad de Nutrición Clínica y Dietética, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain; (Á.M.); (C.V.); (I.B.)
| | - Rafael Bañares
- Department of Gastroenterology, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, CIBERehd, 28007 Madrid, Spain; (R.D.-R.); (R.B.)
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain; (I.B.); (R.P.); (M.R.-C.)
| | - German Soriano
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Sant Pau (IR Sant Pau), Universitat Autònoma de Barcelona, CIBERehd, 08025 Barcelona, Spain; (M.P.); (E.R.); (B.C.)
| | - Rita García-Martínez
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain; (I.B.); (R.P.); (M.R.-C.)
- Department of Internal Medicine, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, CIBERehd, 28007 Madrid, Spain
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Koyano K, Atsukawa M, Tsubota A, Kondo C, Miwa T, Namisaki T, Hiraoka A, Toyoda H, Tada T, Kobayashi Y, Kawata K, Matsuura K, Mikami S, Kawabe N, Oikawa T, Suzuki K, Kawano T, Okubo T, Arai T, Tani J, Morishita A, Iwasa M, Ishikawa T, Ikegami T, Tanaka Y, Shimizu M, Yoshiji H, Iwakiri K. Association Between Laboratory Values and Covert Hepatic Encephalopathy in Patients with Liver Cirrhosis: A Multicenter, Retrospective Study. J Clin Med 2025; 14:1858. [PMID: 40142666 PMCID: PMC11942637 DOI: 10.3390/jcm14061858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/24/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objective: Recently, there has been an increasing need to implement the diagnosis of the presence of covert hepatic encephalopathy (CHE) in patients with cirrhosis. The aim of this study was to identify novel factors associated with CHE in clinical practice. Methods: This retrospective study enrolled a total of 402 patients with cirrhosis at 17 institutions. The Stroop test was performed to diagnose CHE at each center. Results: The patients comprised 233 males and 169 females, with a median age of 69 (IQR, 61-75) years. The median albumin and 25(OH)D3 levels were 3.9 (3.5-4.3) g/dL and 15.4 (11.0-21.0) ng/mL, respectively. This cohort included 181 patients with esophageal varices (EV). Multivariate analysis revealed that low 25(OH)D3 (p < 0.05) and EV (p < 0.05) were independent risk factors for CHE. When limited to only laboratory factors, low albumin (p < 0.01) and low 25(OH)D3 (p < 0.05) were independent factors for CHE. The optimal cut-off values of albumin and 25(OH)D3 for predicting CHE were 3.7 g/dL and 16.5 ng/mL, respectively. The prevalence of CHE was 59.2% for 25(OH)D3 < 16.5 ng/mL and EV, 53.8% for albumin < 3.7 g/dL and 25(OH)D3 < 16.5 ng/mL, and 66.7% for albumin < 3.7 g/dL, EV, and 25(OH)D3 < 16.5 ng/mL. Conclusions: Low 25(OH)D3 and albumin levels, and the EV were positively associated with CHE in patients with cirrhosis. Specifically, the prevalence of CHE increased with a decrease in 25(OH)D3 levels. Patients with such risk factors should be actively and carefully examined for the presence of CHE.
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Affiliation(s)
- Kaori Koyano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (A.T.); (T.O.)
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan (M.S.)
| | - Tadashi Namisaki
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan; (T.N.); (H.Y.)
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama 790-0024, Japan;
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Gifu 503-8502, Japan;
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji 670-8540, Japan;
| | - Yuji Kobayashi
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan; (Y.K.); (T.I.)
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu 431-3125, Japan;
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 464-0083, Japan;
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda 278-0005, Japan;
| | - Naoto Kawabe
- Department of Gastroenterology and Hepatology, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan;
| | - Tsunekazu Oikawa
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (A.T.); (T.O.)
| | - Kenta Suzuki
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Tadamichi Kawano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Tomomi Okubo
- Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai 270-1694, Japan;
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
| | - Joji Tani
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa 761-0793, Japan; (J.T.); (A.M.)
| | - Asahiro Morishita
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa 761-0793, Japan; (J.T.); (A.M.)
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu 514-8507, Japan;
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan; (Y.K.); (T.I.)
| | - Tadashi Ikegami
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki 300-0332, Japan;
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8555, Japan;
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan (M.S.)
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan; (T.N.); (H.Y.)
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8602, Japan; (K.K.); (C.K.); (K.S.); (T.K.); (T.A.); (K.I.)
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Hager A, Mazurak, Dajani K, Dunichand-Hoedl A, Shapiro AMJ, Bigam D, Anderson B, Kneteman N, Montano-Loza AJ, Noga M, Gavreau C, Dziwenkocox C, Yap J, Gilmour SM, Mager DR. The assessment of myopenia and muscle biopsy in pediatric patients with liver disease awaiting liver transplantation-A cross-sectional analysis. Liver Transpl 2025; 31:277-286. [PMID: 39586016 DOI: 10.1097/lvt.0000000000000520] [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: 06/18/2024] [Accepted: 10/08/2024] [Indexed: 11/27/2024]
Abstract
Little is known about the skeletal muscle characteristics (fiber type proportion and size, location of nuclei, presence of fat infiltration) in children with liver disease with radiologically determined myopenia (low muscle mass). During liver transplantation (LTx) surgery, biopsies from the rectus abdominis muscle were collected. Muscle fiber types (I, I/IIA, IIA, IIA/X, IIX) and cross-sectional area index (µm/m 2 ) were determined using immunofluorescence staining. Triacylglycerol and phospholipid content of muscle was determined using gas chromatography. Myopenia was defined using study-specific cutoffs (skeletal muscle index <-2 SD) from age-sex-matched healthy control scans. Myopenia was prevalent in 41% of children. Children also had a high prevalence of high muscle adiposity (37%). Children with myopenia were older (8.4 vs. 0.7 y; p <0.001), had smaller total (median 595 vs. 844 µm/m 2 ; p =0.04) and hybrid IIA/X (612±143 vs. 993±341 µm/m 2 ; p =0.04) muscle fiber size index, lower prevalence of type I fibers (53% vs. 64%; p =0.01) and higher prevalence of type IIA/X hybrid fibers (median 7.5% vs. 0%; p =0.04). Children with myopenia also had a higher prevalence of elevated triacylglycerol content (>75 percentile) within the muscle compared to children without myopenia (36% vs. 0%; p =0.009). Percent of muscle fibers with centralized nuclei was not different between groups. In conclusion, children with myopenia experience differences in skeletal muscle biological characteristics when compared to children without myopenia at LTx, and these findings may have implications for dietary and exercise rehabilitation pre-LTx and post-LTx.
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Affiliation(s)
- Amber Hager
- Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, Canada
| | - Mazurak
- Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, Canada
| | - Khaled Dajani
- Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - Abha Dunichand-Hoedl
- Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, Canada
| | - A M James Shapiro
- Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - David Bigam
- Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - Blaire Anderson
- Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - Norm Kneteman
- Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Michelle Noga
- Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
| | - Cynthia Gavreau
- Transplant Services, Stollery Children's Hospital, Alberta Health Services, Edmonton, Alberta, Canada
| | - Cindy Dziwenkocox
- Transplant Services, Stollery Children's Hospital, Alberta Health Services, Edmonton, Alberta, Canada
| | - Jason Yap
- Division of Pediatric Gastroenterology & Nutrition/Transplant Services, Department of Pediatrics, The Stollery Children's Hospital, Alberta Health Services, Edmonton, Alberta, Canada
| | - Susan M Gilmour
- Division of Pediatric Gastroenterology & Nutrition/Transplant Services, Department of Pediatrics, The Stollery Children's Hospital, Alberta Health Services, Edmonton, Alberta, Canada
| | - Diana R Mager
- Department of Agricultural, Food & Nutritional Sciences, University of Alberta, Edmonton, Canada
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
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6
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Sobhrakhshankhah E, Farahmand M, Hasan Rashedi M, Shahinfar H, Shab-Bidar S, Dinari S, Doustmohammadian A. Efficacy of different nutrition interventions on sarcopenia in patients with cirrhosis: a systematic review and network meta-analysis. BMC Nutr 2025; 11:39. [PMID: 39940017 DOI: 10.1186/s40795-025-01028-y] [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: 10/31/2024] [Accepted: 02/05/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND & AIMS Sarcopenia, characterized by the loss of muscle mass and strength, is a significant concern in cirrhotic patients. Nutritional interventions have been explored for its management, but the comparative efficacy of these interventions remains unclear. This study synthesizes current evidence to evaluate the effectiveness of nutritional interventions for sarcopenia in cirrhosis. METHODS Data sources included Scopus, PubMed, Web of Science Core Collection, and Cochrane Library up to Dec 2024. Eligible trials compared different nutritional interventions against control diets, placebos, or each other. A Bayesian network meta-analysis was performed to combine direct and indirect evidence. Effect sizes were calculated as mean differences (MD) with 95% confidence intervals (CIs). Intervention rankings were assessed using P-score, and evidence quality was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS A total of 14 randomized controlled trials (RCTs) involving 1,437 patients met the inclusion criteria. For improving muscle mass (MAMC), post-paracentesis intravenous nutritional support combined with an oral nutritional protocol (Treat A) showed the greatest effect compared to high-calorie, high-protein diets (HCHP) (MD: 2.78 cm, 95% CI: 1.15 to 4.40, low certainty), and oral nutritional protocol (Treat B) (MD of 3.41 cm, 95% CI: 2.12, 4.69). For muscle strength, the HINT diet (MD: 8.01 kg, 95% CI: 7.64 to 8.37, low certainty) and the HCHP (MD: 5 kg, 95% CI: 3.90 to 6.10, low certainty) were more effective than control diets. HCHP also demonstrated greater handgrip improvement than the HINT diet (MD: 3.00 kg, 95% CI: 1.84, 4.16; low certainty evidence). BCAA combined with vitamin D (2000 IU once a day) significantly improved skeletal muscle index (SMI) compared to both BCAA (MD: 0.72 kg/m2, 95% CI: 0.11 to 1.34; low certainty evidence) and placebo (MD: 0.25 kg/m2, 95% CI: -0.05 to 0.05; very low certainty evidence). BCAA supplementation effectively improved handgrip strength compared to placebo (MD: 2.36 kg, 95% CI: 1.85, 2.88; low certainty evidence). CONCLUSIONS Post-paracentesis intravenous nutritional support combined with an oral nutritional protocol effectively improves muscle mass, while high-calorie, high-protein diets enhance handgrip strength. BCAA supplementation alone or with vitamin D has been shown to effectively enhance muscle strength and muscle mass. However, these findings should be interpreted cautiously due to low evidence certainty.
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Affiliation(s)
- Elham Sobhrakhshankhah
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Farahmand
- Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Minoo Hasan Rashedi
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Shahinfar
- Nutritional Health Research Center, School of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Sakineh Shab-Bidar
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Saghar Dinari
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Internal Medicine, School of Medicine, Firoozgar General Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Azam Doustmohammadian
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Miwa T, Hanai T, Hirata S, Nishimura K, Sahashi Y, Unome S, Imai K, Shirakami Y, Suetsugu A, Takai K, Shimizu M. Vitamin D deficiency stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis: A retrospective cohort study. Clin Nutr ESPEN 2024; 63:267-273. [PMID: 38972037 DOI: 10.1016/j.clnesp.2024.06.055] [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: 02/21/2024] [Revised: 06/05/2024] [Accepted: 06/28/2024] [Indexed: 07/09/2024]
Abstract
BACKGROUNDS & AIMS This study aimed to investigate the association between vitamin D deficiency and covert hepatic encephalopathy (CHE), overt hepatic encephalopathy (OHE) occurrence, and mortality in patients with cirrhosis. METHODS This retrospective study reviewed 679 patients with cirrhosis. Vitamin D deficiency was defined as serum 25-hydorxyvitamin D (25-OHD) levels < 20 ng/mL. The associations between 25-OHD and CHE, OHE occurrence, and mortality were assessed using logistic regression, Fine-Gray competing risk regression, and Cox proportional hazards regression models, respectively. RESULTS Of 428 eligible patients, 75% had vitamin D deficiency and 23% had CHE. The prevalence of CHE was higher in patients with vitamin D deficiency than in those without vitamin D deficiency (28% vs. 13%, p = 0.002). During the median follow-up period of 2.3 years, 14% of the patients developed OHE and 27% died. Patients with vitamin D deficiency had a higher incidence of OHE (p = 0.002) and mortality (p = 0.006) than those without vitamin D deficiency. After adjustment for potential covariates, multivariate analyses showed that 25-OHE was associated with CHE (odds ratio, 0.95; 95% confidence interval [CI], 0.91-0.99; p = 0.023), OHE occurrence (sub-distribution hazard ratio, 0.92; 95% CI, 0.86-0.98; p = 0.013) and mortality (hazard ratio, 0.96; 95% CI, 0.93-0.99; p = 0.020) in patients with cirrhosis. CONCLUSIONS Vitamin D deficiency is highly prevalent and is associated with CHE, OHE, and mortality in patients with cirrhosis. Evaluation of vitamin D is essential to predict the outcomes of patients with cirrhosis.
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Affiliation(s)
- Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan.
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan; Center for Nutrition Support and Infection Control, Gifu University Hospital, Gifu, Japan.
| | - Sachiyo Hirata
- Center for Nutrition Support and Infection Control, Gifu University Hospital, Gifu, Japan.
| | - Kayoko Nishimura
- Center for Nutrition Support and Infection Control, Gifu University Hospital, Gifu, Japan.
| | - Yuki Sahashi
- Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
| | - Shinji Unome
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan.
| | - Kenji Imai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan.
| | - Yohei Shirakami
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan.
| | - Atsushi Suetsugu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan.
| | - Koji Takai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan; Division for Regional Cancer Control, Graduate School of Medicine, Gifu University, Gifu, Japan.
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu, Japan.
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8
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Zhang F, Li W. Vitamin D and Sarcopenia in the Senior People: A Review of Mechanisms and Comprehensive Prevention and Treatment Strategies. Ther Clin Risk Manag 2024; 20:577-595. [PMID: 39253031 PMCID: PMC11382659 DOI: 10.2147/tcrm.s471191] [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: 03/28/2024] [Accepted: 08/31/2024] [Indexed: 09/11/2024] Open
Abstract
This article reviews the mechanisms and prevention strategies associated with vitamin D and sarcopenia in older adults. As a geriatric syndrome, sarcopenia is defined by a notable decline in skeletal muscle mass and strength, which increases the risk of adverse health outcomes such as falls and fractures. Vitamin D, an essential fat-soluble vitamin, is pivotal in skeletal muscle health. It affects muscle function through various mechanisms, including regulating calcium and phosphorus metabolism, promoting muscle protein synthesis, and modulation of muscle cell proliferation and differentiation. A deficiency in vitamin D has been identified as a significant risk factor for the development of sarcopenia in older adults. Many studies have demonstrated that low serum vitamin D levels are significantly associated with an increased risk of sarcopenia. While there is inconsistency in the findings, most studies support the importance of vitamin D in maintaining skeletal muscle health. Vitamin D influences the onset and progression of sarcopenia through various pathways, including the promotion of muscle protein synthesis, the regulation of mitochondrial function, and the modulation of immune and inflammatory responses. Regarding the prevention and treatment of sarcopenia, a combination of nutritional, exercise, and pharmacological interventions is recommended. Further research should be conducted to elucidate the molecular mechanism of vitamin D in sarcopenia, to study genes related to sarcopenia, to perform large-scale clinical trials, to investigate special populations, and to examine the combined application of vitamin D with other nutrients or drugs. A comprehensive investigation of the interconnection between vitamin D and sarcopenia will furnish a novel scientific foundation and productive strategies for preventing and treating sarcopenia. This, in turn, will enhance the senior people's quality of life and health.
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Affiliation(s)
- Fan Zhang
- Department of Endocrinology, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People's Republic of China
- Department of Clinical Nutrition, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People's Republic of China
| | - Wenjian Li
- Department of Urology, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People's Republic of China
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9
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Herrmann M, Rodriguez-Blanco G, Balasso M, Sobolewska K, Semeraro MD, Alonso N, Herrmann W. The role of bile acid metabolism in bone and muscle: from analytics to mechanisms. Crit Rev Clin Lab Sci 2024; 61:510-528. [PMID: 38488591 DOI: 10.1080/10408363.2024.2323132] [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: 12/06/2023] [Revised: 02/09/2024] [Accepted: 02/21/2024] [Indexed: 08/25/2024]
Abstract
Osteoporosis and sarcopenia are both common age-related disorders that are associated with increased morbidity and mortality. Bone and muscle are metabolically very active tissues that require large amounts of energy. Bile acids (BAs), a group of liver-derived steroid compounds, are primarily known as emulsifiers that facilitate the resorption of dietary fat and lipids. In addition, they have pleiotropic metabolic functions in lipoprotein and glucose metabolism, inflammation, and intestinal bacterial growth. Through these effects, they are related to metabolic diseases, such as diabetes, hypertriglyceridemia, atherosclerosis, and nonalcoholic steatohepatitis. BAs mediate their metabolic effects through receptor dependent and receptor-independent mechanisms. Emerging evidence suggests that BAs are also involved in bone and muscle metabolism. Under normal circumstances, BAs support bone health by shifting the delicate equilibrium of bone turnover toward bone formation. In contrast, low or excessive amounts of BAs promote bone resorption. In cholestatic liver disease, BAs accumulate in the liver, reach toxic concentrations in the circulation, and thus may contribute to bone loss and muscle wasting. In addition, the measurement of BAs is in rapid evolution with modern mass spectrometry techniques that allow for the detection of a continuously growing number of BAs. This review provides a comprehensive overview of the biochemistry, physiology and measurement of bile acids. Furthermore, it summarizes the existing literature regarding their role in bone and muscle.
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Affiliation(s)
- Markus Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Giovanny Rodriguez-Blanco
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Marco Balasso
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Katarzyna Sobolewska
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Maria Donatella Semeraro
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Nerea Alonso
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Wolfgang Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
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10
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Onishi Y, Akasaka H, Hatta K, Terashima K, Yoshida S, Yasunobe Y, Fujimoto T, Isaka M, Godai K, Kido M, Kabayama M, Sugimoto K, Masui Y, Matsumoto K, Yasumoto S, Ogawa M, Nakagawa T, Arai Y, Ishizaki T, Gondo Y, Ikebe K, Kamide K, Yamamoto K. Association between serum vitamin D levels and skeletal muscle indices in an older Japanese population: The SONIC study. Geriatr Gerontol Int 2024; 24:898-903. [PMID: 39091107 DOI: 10.1111/ggi.14951] [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: 01/31/2024] [Revised: 06/28/2024] [Accepted: 07/16/2024] [Indexed: 08/04/2024]
Abstract
AIM Vitamin D (VD) affects skeletal muscles. The high prevalence of VD deficiency in Japan may lead to decreased skeletal muscle mass and strength, increasing the prevalence of sarcopenia. Therefore, we aimed to investigate the association between serum VD levels and skeletal muscle indices in a Japanese community-dwelling older population. METHODS We extracted data from the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. We analyzed the data for participants in the 70s and 90s age groups. Skeletal mass index (SMI) using bioimpedance analysis, grip strength, walking speed, and serum VD levels using 25-hydroxyvitamin D [25(OH)D] were measured. RESULTS We analyzed the data of 310 participants in their 70s and 48 in their 90s. Mean serum 25(OH)D levels were 21.6 ± 5.0 ng/mL in the 70s group and 23.4 ± 9.1 ng/mL in the 90s group. In the 70s group, serum 25(OH)D levels correlated with SMI (r = 0.21, P < 0.0001) and grip strength (r = 0.30, P < 0.0001). Serum 25(OH)D levels were independently associated with SMI after adjusting for sex, body mass index, and serum albumin levels. In the 90s group, serum 25(OH)D levels were correlated with SMI (r = 0.29, P = 0.049) and grip strength (r = 0.34, P = 0.018). However, the multivariate analysis showed no independent association between SMI, grip strength, and serum 25(OH)D levels. CONCLUSION In a cross-sectional analysis of an older population, serum VD levels were associated with SMI and grip strength, and this association was more pronounced in the 70s group than in the 90s group. Our results suggest that serum VD levels maintain skeletal muscle mass and grip strength. Geriatr Gerontol Int 2024; 24: 898-903.
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Affiliation(s)
- Yuri Onishi
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroshi Akasaka
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kodai Hatta
- Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Ken Terashima
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Shino Yoshida
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yukiko Yasunobe
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Taku Fujimoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
| | - Masaaki Isaka
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
- Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kayo Godai
- Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan
| | - Michiko Kido
- Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan
| | - Mai Kabayama
- Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ken Sugimoto
- Department of General Geriatric Medicine, Kawasaki Medical School, Kurashiki, Japan
| | - Yukie Masui
- Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
| | | | - Saori Yasumoto
- Graduate School of Human Sciences, Osaka University, Suita, Japan
| | - Madoka Ogawa
- Graduate School of Human Sciences, Osaka University, Suita, Japan
| | - Takeshi Nakagawa
- Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan
| | - Yasumichi Arai
- Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan
| | | | - Yasuyuki Gondo
- Graduate School of Human Sciences, Osaka University, Suita, Japan
| | - Kazunori Ikebe
- Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry, Suita, Japan
| | - Kei Kamide
- Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan
| | - Koichi Yamamoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan
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11
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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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12
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Okubo T, Atsukawa M, Tsubota A, Ono H, Kawano T, Yoshida Y, Arai T, Hayama K, Itokawa N, Kondo C, Iwakiri K. Low vitamin D levels accelerates muscle mass loss in patients with chronic liver disease. PLoS One 2024; 19:e0299313. [PMID: 38530830 DOI: 10.1371/journal.pone.0299313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 02/08/2024] [Indexed: 03/28/2024] Open
Abstract
Sarcopenia frequently and progressively occurs in patients with chronic liver disease. This study aimed to clarify the relationship between vitamin D levels and muscle mass loss. A total of 166 patients with chronic liver disease were enrolled in this study. Skeletal muscle mass index (SMI) was measured by bioelectrical impedance analysis at baseline and after 1 year. The rate of change in SMI from baseline after 1 year was calculated: ΔSMI (%) = [(1-year SMI - baseline SMI) / baseline SMI] × 100. Muscle mass loss was defined as ΔSMI ≤ -2%. The median 25-hydroxyvitamin D was 15.2 (11.2-19.3) ng/mL. The median SMI were 6.8 (5.9-7.8) kg/m2 at baseline and 6.7 (5.9-7.6) kg/m2 after 1 year. The median ΔSMI was -1.23% (-2.21% to 1.61%). Multivariate analysis identified low 25-hydroxyvitamin D as an independent factor associated with muscle mass loss. The optimal cut-off value of 25-hydroxyvitamin D to predict muscle mass loss was 12.7 ng/mL. Muscle mass loss was found in 56.4% v.s. 18.0% of patients with 25-hydroxyvitamin D < 12.7 vs. ≥ 12.7 ng/mL, respectively (p = 9.01 × 10-7); with the highest incidence in patients with non-alcoholic fatty liver disease (NAFLD). Specifically, patients with NAFLD and 25-hydroxyvitamin D < 12.7 ng/mL had a significantly higher incidence of muscle mass loss than those with ≥ 12.7 ng/mL (p = 1.23 × 10-3). Low vitamin D levels are associated with muscle mass loss after 1 year in patients with chronic liver disease, especially NAFLD.
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Affiliation(s)
- Tomomi Okubo
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Akihito Tsubota
- Project Research Units, Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroki Ono
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Tadamichi Kawano
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Yuji Yoshida
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Korenobou Hayama
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Norio Itokawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Chisa Kondo
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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13
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Wu M, Wang J, Zhou W, Wang M, Hu C, Zhou M, Jiao K, Li Z. Vitamin D inhibits tamoxifen-induced non-alcoholic fatty liver disease through a nonclassical estrogen receptor/liver X receptor pathway. Chem Biol Interact 2024; 389:110865. [PMID: 38191086 DOI: 10.1016/j.cbi.2024.110865] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 12/20/2023] [Accepted: 01/05/2024] [Indexed: 01/10/2024]
Abstract
Non-alcoholic Fatty Liver Disease (NAFLD) is one of the common side effects of tamoxifen treatment for estrogen receptor-positive breast cancer, and is representative of disorders of energy metabolism. Fatty liver is induced after tamoxifen (TAM) inhibition of estrogen receptor activity, but the exact mechanism is not clear. This study investigated the effects and mechanisms of TAM-induced steatosis in the liver. The effects and mechanisms of TAM on hepatocyte lipid metabolism were assessed using C57BL/6 female mice and human hepatoma cells. TAM promoted fat accumulation in the liver by upregulation of Srebp-1c expression. Regarding the molecular mechanism, TAM promoted the recruitment of the auxiliary transcriptional activator, p300, and dissociated the auxiliary transcriptional repressor, nuclear receptor corepressor (NCOR), of the complexes, which led to enhancement of Srebp-1c transcription and an increase of triglyceride (TG) synthesis. Vitamin D (VD), a common fat-soluble vitamin, can decrease TAM-induced NAFLD by promoting p300 dissociation and NCOR recruitment. Tamoxifen promoted the recruitment and dissociation of co-transcription factors on the LXR/ER/RXR receptor complex, leading to a disorder of liver lipid metabolism. VD interfered with TAM-induced liver lipid metabolism disorders by reversing this process.
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Affiliation(s)
- Maoxuan Wu
- Nantong Center for Disease Control and Prevention, Nantong, 226000, China
| | - Jie Wang
- The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Wanqing Zhou
- The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Mengting Wang
- The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Chunyan Hu
- The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Ming Zhou
- The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
| | - Kailin Jiao
- Department of Nutrition, The Second Affiliated Hospital, Air Force Medical University, Xi'an, 710038, China.
| | - Zhong Li
- The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
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14
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Colosimo S, Bertoli S, Saffioti F. Use of Branched-Chain Amino Acids as a Potential Treatment for Improving Nutrition-Related Outcomes in Advanced Chronic Liver Disease. Nutrients 2023; 15:4190. [PMID: 37836474 PMCID: PMC10574343 DOI: 10.3390/nu15194190] [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: 09/02/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 10/15/2023] Open
Abstract
Advanced chronic liver disease (ACLD) represents a complex and multifactorial clinical entity characterized by liver dysfunction and associated complications. In recent years, the significance of nutritional status in ACLD prognosis has gained considerable attention. This review article delves into the multifactorial pathogenesis of malnutrition in ACLD and its profound consequences for health outcomes. We explore the clinical implications of secondary sarcopenia in ACLD and highlight the critical relevance of frailty in both decompensated and compensated ACLD. A specific focus of this review revolves around branched-chain amino acids (BCAAs) and their pivotal role in managing liver disease. We dissect the intricate relationship between low Fischer's ratio and BCAA metabolism in ACLD, shedding light on the molecular mechanisms involved. Furthermore, we critically evaluate the existing evidence regarding the effects of BCAA supplementation on outcomes in ACLD patients, examining their potential to ameliorate the nutritional deficiencies and associated complications in this population.
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Affiliation(s)
- Santo Colosimo
- School of Nutrition Science, University of Milan, 20133 Milan, Italy
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, 20133 Milan, Italy
| | - Simona Bertoli
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, 20133 Milan, Italy
- Laboratory of Clinical Studies on Obesity, Istituto Auxologico Italiano IRCCS, 20145 Milan, Italy
| | - Francesca Saffioti
- Oxford Liver Unit, Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK;
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Yang C, Dai Y, Li Z, Peng Y, Zhang L, Jia H. Relationship of Serum 25-Hydroxyvitamin D Levels With Sarcopenia and Body Composition in Community-Dwelling Older Adults: A Paired Case-Control Study. J Am Med Dir Assoc 2023:S1525-8610(23)00550-9. [PMID: 37423260 DOI: 10.1016/j.jamda.2023.06.004] [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] [Received: 01/25/2023] [Revised: 06/01/2023] [Accepted: 06/02/2023] [Indexed: 07/11/2023]
Abstract
OBJECTIVE Sarcopenia is a leading health problem among older adults. However, few studies have explored the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels, sarcopenia, and body composition in older Chinese individuals. The aim of this study was to investigate the relationship of serum 25(OH)D levels with sarcopenia, sarcopenia indices, and body composition in community-dwelling older Chinese adults. DESIGN Paired case-control study. SETTING AND PARTICIPANTS This case-control study enrolled 66 older adults newly diagnosed with sarcopenia (sarcopenia group) and 66 older adults without sarcopenia (non-sarcopenia group) after screening in the community. METHODS The definition of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 criteria. Serum levels of 25(OH)D were measured using an enzyme-linked immunosorbent assay. Conditional logistic regression analysis was performed to estimate odds ratios (ORs) and 95% CIs. Spearman's correlation was used to examine the correlations among sarcopenia indices, body composition, and serum 25(OH)D. RESULTS Serum 25(OH)D levels were significantly lower in the sarcopenia group (29.08 ± 15.11 ng/mL) than in the non-sarcopenia group (36.28 ± 14.68 ng/mL) (P < .05). Vitamin D deficiency was associated with an increased risk of sarcopenia (OR, 7.749; 95% CI, 1.955-30.714). Serum 25(OH)D levels in men were positively correlated with skeletal muscle mass index (SMI) (r = 0.450; P < .001) and negatively correlated with gait speed (r = -0.282; P = .032). Serum 25(OH)D levels in women were positively correlated with SMI (r = 0.286; P < .001), skeletal muscle mass (r = 0.395; P < .001), and fat-free mass (r = 0.412; P < .001). CONCLUSIONS AND IMPLICATIONS Serum 25(OH)D levels were lower in older adults with sarcopenia than those in adults without sarcopenia. Vitamin D deficiency was associated with increased risk of sarcopenia, and serum 25(OH)D levels were positively correlated with SMI.
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Affiliation(s)
- Chan Yang
- School of Public Health, Southwest Medical University, Luzhou, Sichuan Province, China
| | - Yanyan Dai
- School of Public Health, Southwest Medical University, Luzhou, Sichuan Province, China
| | - Zetian Li
- School of Public Health, Southwest Medical University, Luzhou, Sichuan Province, China
| | - Yating Peng
- School of Public Health, Southwest Medical University, Luzhou, Sichuan Province, China
| | - Liangchuan Zhang
- School of Public Health, Southwest Medical University, Luzhou, Sichuan Province, China
| | - Hong Jia
- School of Public Health, Southwest Medical University, Luzhou, Sichuan Province, China; Collaborating Center of the National Institute of Health Data Sciences of China, Southwest Medical University, Luzhou, Sichuan Province, China.
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Mazeaud S, Zupo R, Couret A, Panza F, Sardone R, Castellana F. Prevalence of Sarcopenia in Liver Cirrhosis: A Systematic Review and Meta-Analysis. Clin Transl Gastroenterol 2023; 14:e00584. [PMID: 37011140 PMCID: PMC10371322 DOI: 10.14309/ctg.0000000000000584] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 02/24/2023] [Indexed: 04/05/2023] Open
Abstract
INTRODUCTION Chronic liver disease is often combined with a morbidity burden that strongly affects the functional domain. In liver cirrhosis (LC), qualitative and quantitative muscle wasting, known as sarcopenia, poses an added clinical burden, together with comorbidities and a poor quality of life. METHODS We conducted a systematic review and meta-analysis of the prevalence of sarcopenia in LC. The literature was screened through 6 electronic databases from the study's inception to January 2023. No exclusion criteria were applied to language, operative tools for diagnosing sarcopenia, population age, general health status, country, and study setting (cohort or cross-sectional). Two independent researchers applied the inclusion criteria in parallel to evaluate the eligibility of the 44 retrieved articles; only 36 met the eligibility requirements. RESULTS The total sample (N = 8,821) was slightly dominated by men (N = 4,941). The cross-sectional design predominated over the longitudinal, and the hospital setting was prevalent. The pooled prevalence of sarcopenia across the selected studies was 33% (95% confidence interval [CI] 0.32-0.34), with high heterogeneity ( I2 = 96%). A further meta-analysis using the Child-Pugh (CP) score to stage LC was conducted on 24 entries, and the results showed that for the LC populations classified with the CP-A, CP-B, and CP-C staging, respectively, the overall mean prevalence was 33% (95% CI 0.31-0.35), 36% (95% CI 0.34-0.39) and 46% (95% CI 0.43-0.50). The risk of bias was moderate. In LC, 1 in 3 patients suffers sarcopenia. DISCUSSION Poor management of muscle mass loss plays a role in the prognosis of death and quality of life of patients with LC. Clinicians in the field are recommended, when screening for sarcopenia, to pay close attention by carefully assessing body composition as part of the monitoring scheme.
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Affiliation(s)
- Simon Mazeaud
- Clermont Auvergne University, CRNH, AME2P, Clermont-Ferrand, France
| | - Roberta Zupo
- Department of Interdisciplinary Medicine, University “Aldo Moro”, Bari, Italy
| | - Alexis Couret
- Clermont Auvergne University, CRNH, AME2P, Clermont-Ferrand, France
- Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Francesco Panza
- Department of Translational Biomedicine and Neuroscience (DiBrain), University “Aldo Moro,” Bari, Italy
| | | | - Fabio Castellana
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology IRCCS Saverio De Bellis, Research Hospital, Bari, Italy
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17
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Shi L, Zhou L, Han M, Zhang Y, Zhang Y, Yuan XX, Lu HP, Wang Y, Yang XL, Liu C, Wang J, Liang P, Liu SA, Liu XJ, Cheng J, Lin SM. Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF β1/Smad3 and NF-κB signaling pathways. World J Gastroenterol 2023; 29:2798-2817. [PMID: 37274069 PMCID: PMC10237113 DOI: 10.3748/wjg.v29.i18.2798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 03/08/2023] [Accepted: 04/10/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Hepatic fibrosis is a serious condition, and the development of hepatic fibrosis can lead to a series of complications. However, the pathogenesis of hepatic fibrosis remains unclear, and effective therapy options are still lacking. Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1 (NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis, but its role in diseases including hepatic fibrosis remains undefined. Therefore, additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.
AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.
METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups, comprising the normal, fibrosis, and calcitriol treatment groups, and liver fibrosis was modeled by carbon tetrachloride (CCl4). To evaluate the level of hepatic fibrosis in every group, serological and pathological examinations of the liver were conducted. TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells. NS3TP1, α-smooth muscle actin (α-SMA), collagen I, and collagen III in every group were examined using a Western blot and real-time quantitative polymerase chain reaction. The activity of the transforming growth factor beta 1 (TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected. The statistical analysis of the data was performed using the Student’s t test.
RESULTS NS3TP1 promoted the activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways, as evidenced by the presence of α-SMA, collagen I, collagen III, p-smad3, and p-p65 in LX-2 cells, which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference. The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression, as shown by the luciferase assay. NS3TP1 inhibited the apoptosis of HSCs. Moreover, both Smad3 and p65 could bind to NS3TP1, and p65 increased the promoter activity of NS3TP1, while NS3TP1 increased the promoter activity of TGFβ1 receptor I, as indicated by coimmunoprecipitation and luciferase assay results. Both in vivo and in vitro, treatment with calcitriol dramatically reduced the expression of NS3TP1. Calcitriol therapy-controlled HSCs activation, proliferation, and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice. Furthermore, calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.
CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique, prospective therapeutic target in hepatic fibrosis.
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Affiliation(s)
- Liu Shi
- Department of Infectious Disease Medicine, The First Hospital Affiliated to Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Li Zhou
- China-Japan Friendship Hospital, Department of Infectious Disease China-Japan Friendship Hospital, Beijing 100029, China
| | - Ming Han
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yu Zhang
- The Division of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yang Zhang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Xue Yuan
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Hong-Ping Lu
- Institute of Liver Diseases, Beijing Pan-Asia Tongze Institute of Biomedicine Co., Ltd, Beijing 100015, China
| | - Yun Wang
- The Division of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xue-Liang Yang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Chen Liu
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Jun Wang
- Beijing Key Laboratory of Emerging Infectious Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Pu Liang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shun-Ai Liu
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Jing Liu
- Department of Infectious Disease Medicine, The First Hospital Affiliated to Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jun Cheng
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shu-Mei Lin
- Department of Infectious Disease Medicine, The First Hospital Affiliated to Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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18
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Saeki C, Kanai T, Ueda K, Nakano M, Oikawa T, Torisu Y, Saruta M, Tsubota A. Prognostic significance of sarcopenia and severe vitamin D deficiency in patients with cirrhosis. JGH Open 2023; 7:351-357. [PMID: 37265932 PMCID: PMC10230111 DOI: 10.1002/jgh3.12900] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/21/2023] [Accepted: 03/26/2023] [Indexed: 06/03/2023]
Abstract
Background and Aim Sarcopenia and severe vitamin D deficiency are associated with malnutrition and poor prognosis. We investigated the impact of the comorbidity of Child-Pugh (CP) class B/C cirrhosis and the aforementioned complications on the prognosis of patients with cirrhosis. Methods We retrospectively evaluated 104 patients with cirrhosis. The cumulative survival rates were compared between patients with and without both or either of these disease conditions: CP class B/C and complications (sarcopenia or severe vitamin D deficiency). Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria. Severe vitamin D deficiency was defined as levels of 25-hydroxyvitamin D <10 ng/mL in serum. Results The prevalence of CP class B/C, sarcopenia, and severe vitamin D deficiency was 26.9%, 38.5%, and 24.0%, respectively. Patients with both CP class B/C and sarcopenia had significantly lower survival rates than those without both (hazard ratio [HR] = 6.101; P < 0.001) and with either condition (HR = 6.137; P = 0.001). Similarly, patients with both CP class B/C and severe vitamin D deficiency or with either condition had significantly lower survival rates than those without both conditions (HR = 8.135 or 3.189; P < 0.001 or =0.025, respectively). CP class B/C (HR = 3.354; P = 0.006) and severe vitamin D deficiency (HR = 2.445; P = 0.044) were independent prognostic factors. Conclusions The coexistence of CP class B/C and sarcopenia or severe vitamin D deficiency worsened the prognosis of patients with cirrhosis. Nutritional assessments such as sarcopenia and vitamin D status should be considered to better evaluate disease conditions and patient prognosis.
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Affiliation(s)
- Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan
- Division of Gastroenterology, Department of Internal MedicineFuji City General HospitalShizuokaJapan
| | - Tomoya Kanai
- Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan
- Division of Gastroenterology, Department of Internal MedicineFuji City General HospitalShizuokaJapan
| | - Kaoru Ueda
- Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan
- Division of Gastroenterology, Department of Internal MedicineFuji City General HospitalShizuokaJapan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan
- Division of Gastroenterology, Department of Internal MedicineFuji City General HospitalShizuokaJapan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei University School of MedicineTokyoJapan
| | - Akihito Tsubota
- Research Center for Medical ScienceThe Jikei University School of MedicineTokyoJapan
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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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Tadokoro T, Morishita A, Himoto T, Masaki T. Nutritional Support for Alcoholic Liver Disease. Nutrients 2023; 15:nu15061360. [PMID: 36986091 PMCID: PMC10059060 DOI: 10.3390/nu15061360] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/09/2023] [Accepted: 03/09/2023] [Indexed: 03/16/2023] Open
Abstract
Malnutrition is a common finding in alcohol use disorders and is associated with the prognosis of patients with alcoholic liver disease (ALD). These patients also frequently show deficiencies in vitamins and trace elements, increasing the likelihood of anemia and altered cognitive status. The etiology of malnutrition in ALD patients is multifactorial and complex and includes inadequate dietary intake, abnormal absorption and digestion, increased skeletal and visceral protein catabolism, and abnormal interactions between ethanol and lipid metabolism. Most nutritional measures derive from general chronic liver disease recommendations. Recently, many patients with ALD have been diagnosed with metabolic syndrome, which requires individualized treatment via nutritional therapy to avoid overnutrition. As ALD progresses to cirrhosis, it is frequently complicated by protein–energy malnutrition and sarcopenia. Nutritional therapy is also important in the management of ascites and hepatic encephalopathy as liver failure progresses. The purpose of the review is to summarize important nutritional therapies for the treatment of ALD.
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Affiliation(s)
- Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita 761-0793, Kagawa, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita 761-0793, Kagawa, Japan
- Correspondence: ; Tel.: +81-87-891-2156
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu 761-0123, Kagawa, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita 761-0793, Kagawa, Japan
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Tamai Y, Eguchi A, Shigefuku R, Kitamura H, Tempaku M, Sugimoto R, Kobayashi Y, Iwasa M, Takei Y, Nakagawa H. Association of lithocholic acid with skeletal muscle hypertrophy through TGR5-IGF-1 and skeletal muscle mass in cultured mouse myotubes, chronic liver disease rats and humans. eLife 2022; 11:80638. [PMID: 36206032 PMCID: PMC9545520 DOI: 10.7554/elife.80638] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/27/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Hepatic sarcopenia is one of many complications associated with chronic liver disease (CLD) and has a high mortality rate; however, the liver-muscle axis is not fully understood. Therefore, few effective treatments exist for hepatic sarcopenia, the best of which being branched-chain amino acid (BCAA) supplementation to help increase muscle mass. Our aim was to investigate the molecular mechanism(s) of hepatic sarcopenia focused on bile acid (BA) composition. Methods: The correlation between serum BA levels and psoas muscle mass index (PMI) was examined in 73 CLD patients. Gastrocnemius muscle phenotype and serum BA levels were assessed in CLD rats treated with BCAA. Mouse skeletal muscle cells (C2C12) were incubated with lithocholic acid (LCA), G-protein-coupled receptor 5 (TGR5) agonist or TGR5 antagonist to assess skeletal muscle hypertrophy. Results: In human CLD, serum LCA levels were the sole factor positively correlated with PMI and were significantly decreased in both the low muscle mass group and the deceased group. Serum LCA levels were also shown to predict patient survival. Gastrocnemius muscle weight significantly increased in CLD rats treated with BCAA via suppression of protein degradation pathways, coupled with a significant increase in serum LCA levels. LCA treated C2C12 hypertrophy occurred in a concentration-dependent manner linked with TGR5-Akt pathways based upon inhibition results via a TGR5 antagonist. Conclusions: Our results indicate LCA-mediated skeletal muscle hypertrophy via activation of TGR5-IGF1-Akt signaling pathways. In addition, serum LCA levels were associated with skeletal muscle mass in cirrhotic rats, as well as CLD patients, and predicted overall patient survival. Funding: This research was supported by JSPS KAKENHI Grant Number 22K08011 and 21H02892, and AMED under Grant Number JP21fk0210090 and JP22fk0210115. Maintaining cirrhotic rats were partially supported by Otsuka Pharmaceutical Company.
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Affiliation(s)
- Yasuyuki Tamai
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
| | - Akiko Eguchi
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
| | - Ryuta Shigefuku
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
| | - Hiroshi Kitamura
- Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan
| | - Mina Tempaku
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
| | - Ryosuke Sugimoto
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
| | - Yoshinao Kobayashi
- Center for Physical and mental health, Mie University Graduate School of Medicine, Tsu, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
| | - Yoshiyuki Takei
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology and Hepatology, Graduate school of medicine, Mie University, Tsu, Japan
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Ogushi K, Chuma M, Numata K, Nozaki A, Moriya S, Uojima H, Kondo M, Morimoto M, Maeda S. Impact of psoas muscle index assessed by a simple measurement method on tolerability and duration of continued treatment with sorafenib in hepatocellular carcinoma patients. Eur J Gastroenterol Hepatol 2022; 34:774-781. [PMID: 35102114 DOI: 10.1097/meg.0000000000002346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND In this study, we investigated the impact of simple measurement of psoas muscle index (PMI) on the tolerability of sorafenib treatment of switch from sorafenib to regorafenib. METHOD This retrospective study enrolled 109 patients with Child-Pugh A hepatocellular carcinoma (HCC) treated with sorafenib. Pretreatment PMI was calculated by measuring and multiplying the greatest anterior/posterior and transverse diameters of the psoas muscles on axial computed tomography images at the L3 vertebral level, and normalizing the sum of bilateral psoas muscle areas by the square of the height in meters. We, then, statistically analyzed the association between PMI and adverse events (AEs) to treatment, tolerability of sorafenib, time to treatment failure (TTF), and prognosis in patients stratified according to PMI. RESULT Patients were divided into high PMI (n = 41) and low PMI (n = 68) groups based on the cutoff PMI values (men: 7.04 cm2/m2; women: 4.40 cm2/m2) determined by receiver operating characteristic curve analysis to determine sorafenib tolerability. Frequencies of all types of severe AEs were higher in the low PMI group (50.0%) than in the high PMI group (29.3%; P = 0.045). The high PMI group (51.2%) had greater tolerance to sorafenib than the low PMI group (25.0%; P = 0.007). Moreover, in multivariable analysis, PMI was associated with sorafenib tolerability (odds ratio 0.26; P = 0.008) and was a prognostic factor affecting TTF (hazard ratio 1.77; P = 0.021). CONCLUSION PMI might be a predictive marker of tolerance to treatment and TTF in HCC patients receiving sorafenib treatment.
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Affiliation(s)
- Katsuaki Ogushi
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama
| | - Satoshi Moriya
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara
| | - Masaki Kondo
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama
- Department of Gastroenterology, Yokohama City University Hospital, Yokohama
| | - Manabu Morimoto
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Hospital, Yokohama
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Fujita M, Abe K, Kuroda H, Oikawa T, Ninomiya M, Masamune A, Okumoto K, Katsumi T, Sato W, Iijima K, Endo T, Fukuda S, Tanabe N, Numao H, Takikawa Y, Ueno Y, Ohira H. Influence of skeletal muscle volume loss during lenvatinib treatment on prognosis in unresectable hepatocellular carcinoma: a multicenter study in Tohoku, Japan. Sci Rep 2022; 12:6479. [PMID: 35444161 PMCID: PMC9021276 DOI: 10.1038/s41598-022-10514-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 04/08/2022] [Indexed: 12/27/2022] Open
Abstract
Sarcopenia is associated with poor prognosis of patients with hepatocellular carcinoma (HCC). We investigated the association of skeletal muscle volume (SMV) and its change in HCC patients taking lenvatinib. In 130 HCC patients, psoas mass index (PMI) was calculated as the left–right sum of the major × minor axis of psoas muscle at the third lumbar vertebra, divided by height squared. Patients were classified into two groups (low and normal PMI) based on indices of < 6.0 cm2/m2 for man and < 3.4 cm2/m2 for women. Change in PMI per month during the lenvatinib administration period (ΔPMI/m) was calculated; and patients were classified into two groups (severe and mild atrophy) based on the ΔPMI/m rate, as ≥ 1% or < 1%, respectively. There was no significant difference in Overall survival (OS) between the low and normal PMI groups at the start of lenvatinib administration. OS was significantly lower in the severe atrophy group than in the mild atrophy group (median; 15.2 vs. 25.6 months, P = 0.005). Multivariate analysis revealed a significant association of severe atrophy with OS (hazard ratio 1.927, P = 0.031). Progressive loss of SMV is a strong predictor of poor prognosis in HCC patients taking lenvatinib.
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Affiliation(s)
- Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.
| | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Takayoshi Oikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Masashi Ninomiya
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kazuo Okumoto
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Tomohiro Katsumi
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Wataru Sato
- Department of Gastroenterology, Akita University School of Medicine, Akita, Japan
| | - Katsunori Iijima
- Department of Gastroenterology, Akita University School of Medicine, Akita, Japan
| | - Tetsu Endo
- Department of Gastroenterology, Hirosaki University School of Medicine, Hirosaki, Japan
| | - Shinsaku Fukuda
- Department of Gastroenterology, Hirosaki University School of Medicine, Hirosaki, Japan
| | - Nobukazu Tanabe
- Department of Gastroenterology, National Hospital Organization Sendai Medical Center, Sendai, Japan
| | - Hiroshi Numao
- Department of Gastroenterology, Aomori Prefectural Central Hospital, Aomori, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
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Hong J, Shin WK, Lee JW, Lee SY, Kim Y. Associations of Serum Vitamin D Level with Sarcopenia, Non-Alcoholic Fatty Liver Disease (NAFLD), and Sarcopenia in NAFLD Among People Aged 50 Years and Older: The Korea National Health and Nutrition Examination Survey IV-V. Metab Syndr Relat Disord 2022; 20:210-218. [PMID: 35100057 DOI: 10.1089/met.2021.0106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: The role of serum 25-hydroxyvitamin D [25(OH)D] levels in the development of sarcopenia in non-alcoholic fatty liver disease (NAFLD) remains controversial. We investigated the association between vitamin D levels, occurrence of sarcopenia, NAFLD, and sarcopenia in NAFLD in adults aged >50 years. Methods: This study used data pertaining to 5396 adults aged >50 years (1870 men and 3526 women) from the 2008-2011 Korea National Health and Nutrition Examination Survey. Appendicular skeletal muscle mass adjusted by weight (ASM/Wt) was used to diagnose sarcopenia, and NAFLD was diagnosed using the NAFLD fat score. Results: The lowest quintile of serum 25(OH)D level (4.85-15.26 ng/mL) was associated with an increased occurrence of sarcopenia [odds ratio (OR) 2.65; 95% confidence interval (CI) 1.64-4.27], NAFLD (OR 1.82; 95% CI 1.19-2.96), and sarcopenia in NAFLD (OR 2.25; 95% CI 1.26-4.03) in men. In women, sarcopenia (OR 1.80; 95% CI 1.29-2.51) was also significantly associated with serum vitamin D levels, whereas high levels of vitamin D were not significantly related to NAFLD. Conclusions: Serum vitamin D levels are associated with sarcopenia, NAFLD, and sarcopenia in NAFLD. Vitamin D level can be a useful marker of sarcopenia and NAFLD, especially in men.
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Affiliation(s)
- Jihye Hong
- Department of Human Ecology, Graduate School, Korea University, Seoul, Korea
| | - Woo-Kyoung Shin
- Department of Preventive Medicine, College of Medicine, Seoul National University, Seoul, Korea
| | - Jung Woo Lee
- Department of Human Ecology, Graduate School, Korea University, Seoul, Korea
| | - Seung-Yeon Lee
- Department of Nutritional Sciences, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA
| | - Yookyung Kim
- Department of Human Ecology, Graduate School, Korea University, Seoul, Korea
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Saeki C, Tsubota A. Influencing Factors and Molecular Pathogenesis of Sarcopenia and Osteosarcopenia in Chronic Liver Disease. Life (Basel) 2021; 11:life11090899. [PMID: 34575048 PMCID: PMC8468289 DOI: 10.3390/life11090899] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/27/2021] [Accepted: 08/27/2021] [Indexed: 02/07/2023] Open
Abstract
The liver plays a pivotal role in nutrient/energy metabolism and storage, anabolic hormone regulation, ammonia detoxification, and cytokine production. Impaired liver function can cause malnutrition, hyperammonemia, and chronic inflammation, leading to an imbalance between muscle protein synthesis and proteolysis. Patients with chronic liver disease (CLD) have a high prevalence of sarcopenia, characterized by progressive loss of muscle mass and function, affecting health-related quality of life and prognosis. Recent reports have revealed that osteosarcopenia, defined as the concomitant occurrence of sarcopenia and osteoporosis, is also highly prevalent in patients with CLD. Since the differentiation and growth of muscles and bones are closely interrelated through mechanical and biochemical communication, sarcopenia and osteoporosis often progress concurrently and affect each other. Osteosarcopenia further exacerbates unfavorable health outcomes, such as vertebral fracture and frailty. Therefore, a comprehensive assessment of sarcopenia, osteoporosis, and osteosarcopenia, and an understanding of the pathogenic mechanisms involving the liver, bones, and muscles, are important for prevention and treatment. This review summarizes the molecular mechanisms of sarcopenia and osteosarcopenia elucidated to data in hopes of promoting advances in treating these musculoskeletal disorders in patients with CLD.
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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;
| | - Akihito Tsubota
- Core Research Facilities, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan
- Correspondence: ; Tel.: +81-3-3433-1111
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Yoo JI, Chung HJ, Kim BG, Jung YK, Baek KW, Song MG, Cho MC. Comparative analysis of the association between various serum vitamin D biomarkers and sarcopenia. J Clin Lab Anal 2021; 35:e23946. [PMID: 34350631 PMCID: PMC8418464 DOI: 10.1002/jcla.23946] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/27/2021] [Accepted: 07/28/2021] [Indexed: 12/16/2022] Open
Abstract
Background Vitamin D status is associated with muscle strength and maintenance of muscle fibers. However, which serum vitamin D biomarker better reflects sarcopenia remains unclear. The aim of this study was to investigate associations between various serum vitamin D biomarkers (total 25‐hydroxy vitamin D [25(OH)D], bioavailable 25(OH)D, 24,25‐dihydroxyvitamin D [24,25(OH)2D], and vitamin D metabolite ratio [VMR]) and sarcopenia. Methods The data for 83 hip fracture patients were finally included in the analysis. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria. Measurements of 24,25(OH)2D and 25(OH)D were made using solid‐phase extraction (SPE) and subsequent liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Vitamin D binding protein (VDBP) concentration was measured using an enzyme‐linked immunosorbent assay. The VMR was calculated by dividing serum 24,25(OH)2D by serum 25(OH)D and then multiplying by 100. Based on total 25(OH)D, VDBP, and albumin concentrations, bioavailable 25(OH)D concentrations were calculated using the equations from the other previous studies. Results Bioavailable 25(OH)D levels were significantly (p = 0.030) decreased in the sarcopenia group compared with the non‐sarcopenia group. Results of ROC analysis for the diagnosis of sarcopenia using serum level of bioavailable of 25(OH)D revealed that the cutoff point for bioavailable 25(OH)D was 1.70 ng/ml (AUC = 0.649, p < 0.001). In the group with a bioavailable 25(OH)D less than 1.70 ng/ml, the incidence of sarcopenia increased by 3.3 times (odds ratio: 3.33, p = 0.013). Conclusion We demonstrated that bioavailable 25(OH)D was associated with sarcopenia among the various serum vitamin D biomarkers. Bioavailable vitamin D might be helpful for assessing the risk of sarcopenia.
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Affiliation(s)
- Jun-Il Yoo
- Department of Orthopaedic Surgery, Gyeongsang National University Hospital, Jinju, Korea
| | - Hye Jin Chung
- College of Pharmacy and Research institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Korea
| | - Bo Gyu Kim
- Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Korea
| | - Youn-Kwan Jung
- Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Korea
| | - Kyung-Wan Baek
- Department of Orthopaedic Surgery, Gyeongsang National University Hospital, Jinju, Korea
| | - Myung-Geun Song
- Department of Orthopaedic Surgery, Gyeongsang National University Hospital, Jinju, Korea
| | - Min-Chul Cho
- Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea.,Institute of Health Science, Gyeongsang National University, Jinju, Korea
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27
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Li T, Xu M, Kong M, Song W, Duan Z, Chen Y. Use of skeletal muscle index as a predictor of short-term mortality in patients with acute-on-chronic liver failure. Sci Rep 2021; 11:12593. [PMID: 34131260 PMCID: PMC8206330 DOI: 10.1038/s41598-021-92087-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/04/2021] [Indexed: 02/07/2023] Open
Abstract
Sarcopenia is a well-recognized factor affecting the prognosis of chronic liver disease, but its impact on acute decompensation underlying chronic liver disease is unknown. This study evaluated the impact of sarcopenia on short-term mortality in patients with acute-on-chronic liver failure (ACLF). One hundred and seventy-one ACLF patients who underwent abdominal CT between 2015 and 2019 were retrospectively included in this study. Skeletal muscle index at the third lumbar vertebrae (L3-SMI) was used to diagnose sarcopenia.The ACLF patients in this study had a L3-SMI of 41.2 ± 8.3 cm2/m2 and sarcopenia was present in 95/171 (55.6%) patients. Body mass index (BMI), cirrhosis, and higher serum bilirubin were independently associated with sarcopenia. Following multivariate Cox regression analysis, cirrhosis (hazard ratio (HR) 2.758, 95%CI 1.323-5.750), serum bilirubin (HR 1.049, 95%CI 1.026-1.073), and international normalized ratio (INR) (HR 1.725, 95%CI 1.263-2.355) were associated with 3-month mortality (P < 0.05), whereas L3-SMI and sarcopenia were not. A subgroup analysis of the factors related to sarcopenia showed that sarcopenia was still not predictive of short-term outcome in ACLF patients. L3-SMI and sarcopenia are not associated with short-term mortality in patients with ACLF.
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Affiliation(s)
- Tongzeng Li
- Department of Infectious Disease, Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, 100069, China
| | - Manman Xu
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, 100069, China
| | - Ming Kong
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, 100069, China
| | - Wenyan Song
- Department of Radiology, Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, 100069, China
| | - Zhongping Duan
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, 100069, China
| | - Yu Chen
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, 100069, China.
- Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, 100069, China.
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28
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Effect of Vitamin D Supplementation on Skeletal Muscle Volume and Strength in Patients with Decompensated Liver Cirrhosis Undergoing Branched Chain Amino Acids Supplementation: A Prospective, Randomized, Controlled Pilot Trial. Nutrients 2021; 13:nu13061874. [PMID: 34070910 PMCID: PMC8228227 DOI: 10.3390/nu13061874] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/25/2021] [Accepted: 05/27/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Sarcopenia worsens patient prognoses in chronic liver disease. This study aimed to elucidate the effects of vitamin D supplementation on skeletal muscle volume and strength in patients with decompensated cirrhosis. METHODS Thirty-three patients were entered into the study based on the criteria and then randomly assigned to two groups: Group A (n = 17), the control group, and Group B (n = 16), those who received oral native vitamin D3 at a dose of 2000 IU once a day for 12 months. RESULTS SMI values in Group B were significantly increased at 12 months (7.64 × 10-3). The extent of changes in the SMI and grip strength in Group B were significantly greater than that in Group A at 12 months (p = 2.57 × 10-3 and 9.07 × 10-3). The median change rates in the SMI were +5.8% and the prevalence of sarcopenia was significantly decreased from 80.0% (12/15) to 33.3% (5/15; p = 2.53 × 10-2) in Group B. CONCLUSIONS Vitamin D supplementation might be an effective and safe treatment option for patients with decompensated cirrhosis to increase or restore the skeletal muscle volume and strength or prevent the muscle volume and strength losses.
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29
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Ren LK, Guo QQ, Yang Y, Liu XF, Guan HN, Chen FL, Bian X, Zhang XM, Zhang N. Structural characterization and functional properties of CNPP, a byproduct formed during CPP preparation. J Food Sci 2021; 86:1845-1860. [PMID: 33908034 DOI: 10.1111/1750-3841.15717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 02/03/2021] [Accepted: 03/06/2021] [Indexed: 11/29/2022]
Abstract
Casein nonphosphopeptide (CNPP), a byproduct formed during the preparation of casein phosphopeptide (CPP), is often discarded on a large scale. Although our previous studies have demonstrated the ameliorative effect of CNPP on muscle wasting disorders, its structure-function mechanism is still unclear. Therefore, considering the great influence of structural characteristics on function, this study aims to explain the potential mechanism by characterizing the physicochemical and functional properties of CNPP. The results of structural characterization indicated that CNPP was of low molecular weight and composed of the complete range of amino acids; it was particularly rich in leucine. Compared with casein, CNPP had a lower molecular size and total/free sulfhydryl content (reduced 2.44 and 2.02 µmol/g in CNPP, respectively). Additionally, Fourier transform infrared spectroscopic analysis revealed that enzymatic hydrolysis caused protein unfolding, and the content of β-turns and random coils reached 50.20% and 10.67%, respectively. Fluorescence-dependent detection of CNPP indicated a reduction of spectral intensity and the occurrence of a red shift. The changes in the structure of CNPP significantly affected its functional characteristics. CNPP has better solubility, foaming, and digestion properties than those of casein and whey protein. Specifically, the foam stability and emulsification properties decreased in the order of casein > CNPP > whey protein. The present study can provide a substantial basis for future application of CNPP as a functional ingredient against sarcopenia.
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Affiliation(s)
- Li-Kun Ren
- Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Engineering, Harbin University of Commerce, Harbin, China
| | - Qing-Qi Guo
- School of Forestry, Northeast Forestry University, Harbin, China
| | - Yang Yang
- Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Engineering, Harbin University of Commerce, Harbin, China
| | - Xiao-Fei Liu
- Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Engineering, Harbin University of Commerce, Harbin, China
| | - Hua-Nan Guan
- Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Engineering, Harbin University of Commerce, Harbin, China
| | - Feng-Lian Chen
- Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Engineering, Harbin University of Commerce, Harbin, China
| | - Xin Bian
- Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Engineering, Harbin University of Commerce, Harbin, China
| | | | - Na Zhang
- Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Engineering, Harbin University of Commerce, Harbin, China
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Skrzypczak D, Ratajczak AE, Szymczak-Tomczak A, Dobrowolska A, Eder P, Krela-Kaźmierczak I. A Vicious Cycle of Osteosarcopeniain Inflammatory Bowel Diseases-Aetiology, Clinical Implications and Therapeutic Perspectives. Nutrients 2021; 13:nu13020293. [PMID: 33498571 PMCID: PMC7909530 DOI: 10.3390/nu13020293] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/08/2021] [Accepted: 01/18/2021] [Indexed: 12/13/2022] Open
Abstract
Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.
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Low Serum 25-Hydroxyvitamin D Levels Are Related to Frailty and Sarcopenia in Patients with Chronic Liver Disease. Nutrients 2020; 12:nu12123810. [PMID: 33322706 PMCID: PMC7764249 DOI: 10.3390/nu12123810] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/08/2020] [Accepted: 12/11/2020] [Indexed: 02/07/2023] Open
Abstract
Low vitamin D status is related to frailty and/or sarcopenia in elderly individuals. However, these relationships are unclear in patients with chronic liver disease (CLD). This study aimed at exploring the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and frailty or sarcopenia in 231 patients with CLD. Frailty was determined based on five factors (weight loss, low physical activity, weakness, slowness, and exhaustion). Sarcopenia was diagnosed by applying the Japan Society of Hepatology criteria. The patients were classified into three groups according to baseline 25(OH)D levels: low (L), intermediate (I), and high (H) vitamin D (VD) groups. Of the 231 patients, 70 (30.3%) and 66 (28.6%) had frailty and sarcopenia, respectively. The prevalence rate of frailty and sarcopenia significantly increased stepwise with a decline in the vitamin D status. The L-VD group showed the highest prevalence rates of frailty and sarcopenia (49.1% (28/57), p < 0.001 for both), whereas the H-VD group showed the lowest prevalence rates of frailty (15.3% (9/59)) and sarcopenia (18.6% (11/59)) (p < 0.001 for both). Multivariate analysis identified serum 25(OH)D levels as a significant independent factor related to frailty and sarcopenia. Serum 25(OH)D levels significantly correlated with handgrip strength, skeletal muscle mass index, and gait speed. In conclusion, low serum vitamin D level, especially severe vitamin D deficient status, is closely related to frailty and sarcopenia in patients with CLD.
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