1
|
Machado-Silva L, Terra C, Campos CF, Lanzoni V, Miguez M, Perazzo H, Gomes MB, Perez RM. The use of simple tests to predict biopsy-proven steatohepatitis in people with type 2 diabetes. Eur J Gastroenterol Hepatol 2025; 37:320-326. [PMID: 39919007 DOI: 10.1097/meg.0000000000002890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
BACKGROUND/AIMS Metabolic-associated steatotic liver disease (MASLD) has become the most common chronic liver disease, especially in people with type 2 diabetes mellitus (T2DM). Liver biopsy remains the gold standard method for diagnosis of MASLD subtypes, but prevalences may be under or overestimated when biopsy is performed with selection bias. The aims of this study were to define prevalence of MASLD subtypes by liver biopsy in T2DM participants not selected by abnormal exams, determine variables associated with metabolic-associated steatohepatitis (MASH), and analyze performance of aminotransferases and abdominal ultrasound in diagnosis. METHODS T2DM participants from 18 to 70 years were considered for enrollment. Of the 396 participants, 85 were included and submitted to clinical, laboratory examinations, and ultrasound. Eighty-three performed liver biopsy evaluated by two independent pathologists. Factors independently associated to MASH and significant fibrosis were assessed by hierarchical multivariate logistic regression. RESULTS Prevalence of MASLD was 92% (50% simple steatosis, 42% MASH) and kappa = 0.78. Steatosis was mild in 76% of participants with simple steatosis and severe in 65% of MASH (P < 0.001). Presence of MASH or fibrosis was associated with BMI and alanine aminotransferase (ALT) [threshold of 33.5 mg/dl in predicting MASH (area under the curve = 0.82, P = 0.001)]. CONCLUSION Prevalence of MASLD by liver biopsy in T2DM regardless of ultrasound or ALT elevation is almost 100%, with 42% of MASH. MASH was associated to severe steatosis on histology. BMI and ALT were independently associated with MASH and ALT close to the upper limit of normal gave the best cutoff point for MASH detection.
Collapse
Affiliation(s)
- Lilian Machado-Silva
- Medical Division, Gastroenterology Unit, Air Force Central Hospital (HCA), Brazilian Air Force (FAB)
| | - Carlos Terra
- Department of Internal Medicine, Liver Unit, Pedro Ernesto University Hospital, State University of Rio de Janeiro
- Department of Internal Medicine, Liver Unit, Lagoa Federal Hospital
| | | | - Valeria Lanzoni
- Department of Pathology, Federal University of São Paulo, São Paulo
| | - Marcio Miguez
- Department of Internal Medicine, Radiology Unit, Pedro Ernesto University Hospital, State University of Rio de Janeiro
| | - Hugo Perazzo
- Laboratory of STI and HIV, Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ)
| | - Marilia Brito Gomes
- Department of Internal Medicine, Diabetes Unit, Pedro Ernesto University Hospital, State University of Rio de Janeiro
| | - Renata M Perez
- Department of Internal Medicine, School of Medicine, Federal University of Rio de Janeiro (UFRJ)
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
| |
Collapse
|
2
|
Choque Vargas C, Cáceres F, Landeira G, Perez S, Marchi L, Ruffillo G, Tevez S, Puga-Tejada M, Fassio E. Cardiovascular events and incident diabetes in 220 patients with MASLD according to basal liver fibrosis: a 10-year follow-up historic cohort. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00490. [PMID: 39975992 DOI: 10.1097/meg.0000000000002943] [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: 02/21/2025]
Abstract
AIM The aim of this study is to analyze association between liver fibrosis with CVE, incident diabetes, and cirrhosis complications. METHODS Historic cohort of biopsy-proven MASLD patients, divided into two groups: F0-F2 vs F3-F4 fibrosis. Baseline data included metabolic traits and liver function tests. Patients were contacted and scheduled for laboratory analysis and elastography. Endpoints were (a) CVE, defined as any of acute myocardial infarction, coronary stenting, ischemic cardiopathy, and stroke; (b) incident diabetes; (c) cirrhosis complications. Baseline data were collected at the time of liver biopsy, while follow-up data were recovered through personal interview or medical records. A stepwise logistic regression determined predictive variables for each endpoint. RESULTS Study population included 220 patients with median age 53 years, and 145 were women; baseline fibrosis was F0-F2 in 165 patients and F3-F4 in 55 patients; median follow-up was 9.9 years. A higher percentage of F3-F4 patients had CVE (29.4%) than F0-F2 ones (13.1%) (hazard ratio 2.42; 95% CI: 1.26-4.6; P = 0.008). Incident diabetes occurred in 53.3% of F3-F4 and 20.2% of F0-F2 cohort (hazard ratio 3.04; 95% CI: 1.99-4.86; P < 0.001); cirrhosis complications occurred in 9/55 F3-F4 patients and in 1/165 F0-F2 ones (hazard ratio 26.3; 95% CI: 3.3-208.3; P = 0.002). Multivariate analysis confirmed liver fibrosis as an independent predictor of incident diabetes and cirrhosis complications. CVE were associated with baseline diabetes and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. CONCLUSION In a cohort of 220 MASLD patients followed for 9.9 years, baseline F3-F4 was associated with incident diabetes and cirrhosis complications. AST/ALT ratio and diabetes were associated with CVE.
Collapse
Affiliation(s)
- Cinthia Choque Vargas
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Francisco Cáceres
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Graciela Landeira
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Soledad Perez
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Laura Marchi
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Gabriela Ruffillo
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Silvina Tevez
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Miguel Puga-Tejada
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
- División de Investigación Médica & Bioestadística, Instituto Ecuatoriano de Enfermedades Digestivas, Guayaquil, Ecuador
| | - Eduardo Fassio
- Sección Hígado, Vías Biliares y Páncreas, Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| |
Collapse
|
3
|
Michalopoulou E, Thymis J, Lampsas S, Pavlidis G, Katogiannis K, Vlachomitros D, Katsanaki E, Kostelli G, Pililis S, Pliouta L, Kountouri A, Papanikolaou IS, Lambadiari V, Ikonomidis I. The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment. J Clin Med 2025; 14:428. [PMID: 39860434 PMCID: PMC11765821 DOI: 10.3390/jcm14020428] [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: 11/29/2024] [Revised: 12/30/2024] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and it is not only the keystone precursor of eventual liver-related morbidity, but it also places patients at considerably higher cardiovascular risk, which is still a leading cause of death in these patients. The most important common underlying pathophysiological mechanisms in these diseases are primarily related to insulin resistance, chronic inflammation and oxidative stress. The presence of MASLD with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) elevates the risk for poor outcomes, thus this review highlights a method to the therapeutic approaches. Given the intertwined nature of MASLD, T2DM, and CVD, there is an urgent need for therapeutic strategies that address all three conditions. Although lifestyle changes are important as treatment, medication plays a crucial role in managing hyperglycemia, enhancing liver function and lowering cardiovascular risk. The onset and progression of MASLD should be addressed through a multifaceted therapeutic approach, targeting inflammatory, immune, metabolic, oxidative stress, hormonal and gutaxis pathways, alongside the treatment strategies for T2DM. In this review, we discuss the effects of antidiabetic drugs with an impact on both liver outcomes and cardiovascular risk in patients affected by MASLD, T2DM and CDV.
Collapse
Affiliation(s)
- Eleni Michalopoulou
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| | - John Thymis
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| | - Stamatios Lampsas
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (S.L.); (S.P.); (L.P.); (A.K.); (V.L.)
| | - George Pavlidis
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| | - Konstantinos Katogiannis
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| | - Dimitrios Vlachomitros
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| | - Eleni Katsanaki
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| | - Gavriella Kostelli
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| | - Sotirios Pililis
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (S.L.); (S.P.); (L.P.); (A.K.); (V.L.)
| | - Loukia Pliouta
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (S.L.); (S.P.); (L.P.); (A.K.); (V.L.)
| | - Aikaterini Kountouri
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (S.L.); (S.P.); (L.P.); (A.K.); (V.L.)
| | - Ioannis S. Papanikolaou
- Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Attikon University Hospital, Rimini 1, Chaidari, 12462 Athens, Greece;
| | - Vaia Lambadiari
- Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (S.L.); (S.P.); (L.P.); (A.K.); (V.L.)
| | - Ignatios Ikonomidis
- 2nd Cardiology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12462 Athens, Greece; (E.M.); (J.T.); (G.P.); (K.K.); (D.V.); (E.K.); (G.K.)
| |
Collapse
|
4
|
Yu H, Su X, Tao W, Sun W, Zhang X, Han Q, Zhao Z, Zhang Y, Chen X, Liu X, Jia D, Fang L, Li L. Prevalence and characteristics of liver steatosis and fibrosis in type 2 diabetes mellitus (T2DM) patients: a cross-sectional study in populations of eastern China. BMJ Open 2024; 14:e087550. [PMID: 39672583 PMCID: PMC11647396 DOI: 10.1136/bmjopen-2024-087550] [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: 04/12/2024] [Accepted: 11/22/2024] [Indexed: 12/15/2024] Open
Abstract
OBJECTIVES To describe the prevalence, clinical characteristics and risk factors of liver steatosis and fibrosis in type 2 diabetes mellitus (T2DM) patients in eastern China. DESIGN A cross-sectional, multicentre study based on an ongoing cohort study. SETTING 16 clinics in eastern China, including primary clinics to tertiary hospitals. PARTICIPANTS 1816 patients with T2DM diagnosis who met the inclusion criteria were recruited into the study. INTERVENTION Participants underwent elastography examination. MAIN OUTCOME MEASURES Descriptive analysis was performed to calculate the prevalence and characteristics of liver steatosis and fibrosis. The correlated factors were analysed using single- and multivariate logistic regression analysis. RESULTS The prevalence of liver steatosis in T2DM patients is 69.7%, with 46% moderate to severe steatosis. 34.6% and 6.7% of the patients were detected with liver fibrosis and cirrhosis. Steatosis patients were younger, had higher body mass index (BMI), higher levels of insulin resistance and more severe lipid metabolism disorders. Similar trends of differences were observed in patients with fibrosis. Female gender (OR=0.574, 95% CI 0.381 to 0.865), BMI (OR=1.491, 95% CI 1.375 to 1.616), disease duration, inflammation and serum lipid profile markers were risk factors of steatosis, while BMI (OR=1.204, 95% CI 1.137 to 1.275) and female gender (OR=0.672, 95% CI 0.470 to 0.961) were still the most significant predictors of liver fibrosis. CONCLUSIONS The prevalence of liver steatosis and fibrosis were high in patients with T2DM. Liver steatosis and fibrosis in these patients appeared to be more associated with lipid metabolism disorders and insulin resistance rather than glucose levels. TRIAL REGISTRATION NUMBER Clinical trial: NCT05597709.
Collapse
Affiliation(s)
- Hekai Yu
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Xianghui Su
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, Xinjiang, China
| | - Wenxuan Tao
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Weixia Sun
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Xiaoyan Zhang
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
| | - Qing Han
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
| | - Zhuoxiao Zhao
- Nanjing Gaochun Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Yan Zhang
- Department of Endocrinology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xiaoqian Chen
- Department of Endocrinology, Nanjing Central Hospital, Nanjing, Jiangsu, China
| | - Xinliang Liu
- Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China
| | - Dianrong Jia
- Department of Endocrinology, Taizhou Jiangyan Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu, China
| | - Li Fang
- Nanjing Gaochun Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Ling Li
- Department of Endocrinology, School of Medicine, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China
| |
Collapse
|
5
|
Huang N, Su X, Yu T, Wu X, Lu B, Sun W, Yao L, Wang M, Wang Y, Wu W, Liu Y, Yang T, Gao R, Miao C, Li L. Serum 25-hydroxy vitamin D level is associated with elastography-detected liver fibrosis in patients with type 2 diabetes mellitus in China. Front Endocrinol (Lausanne) 2024; 15:1420088. [PMID: 39698035 PMCID: PMC11653015 DOI: 10.3389/fendo.2024.1420088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 10/28/2024] [Indexed: 12/20/2024] Open
Abstract
Objective In this cross-sectional study including patients with type 2 diabetes mellitus (T2DM) we aimed to explore the relationship between serum 25-hydroxy vitamin (25(OH)D) level and liver steatosis and fibrosis in the Chinese population. Methods Patients visiting 16 clinical centers with T2DM were recruited. Their liver steatosis and fibrosis status were then assessed using elastography. Factors associated with steatosis and fibrosis were explored using regression analysis. Correlations between serum 25(OH)D levels and other patient characteristics were analyzed using linear regression. Results In total, 1,513 patients with T2DM were included in the study. The prevalence of steatosis and fibrosis was 69.7%, and 34.6%, separately. A lower level of 25(OH)D was detected in patients with liver steatosis compared to those without, although it was not an independent predictor of this condition. However, 25(OH)D level was independently associated with liver fibrosis even when adjusted for age, sex, body mass index, hemoglobin A1c, insulin, and homeostatic model assessment of insulin resistance (OR = 0.964 [0.935-0.993], P = 0.015). When patients were separated into subgroups by sex, a correlation between 25(OH)D and fibrosis was identified in the male group (OR = 0.969 [0.940-0.998], P = 0.038). Conclusions In conclusion, this multi-center, cross-sectional study in patients with T2DM showed that serum 25-hydroxy vitamin D level was strongly associated with liver fibrosis and this relationship was more pronounced in male patients. Clinical trial registration https://clinicaltrials.gov/ct2/show/, identifier NCT05597709.
Collapse
Affiliation(s)
- Nan Huang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Xianghui Su
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Ting Yu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiaodong Wu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Bing Lu
- Department of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, China
| | - Weixia Sun
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Liqin Yao
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, China
| | - Maoyun Wang
- Department of Endocrinology, Baoying Hospital of Traditional Chinese Medicine, Yangzhou, China
| | - Yao Wang
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, China
| | - Wenxuan Wu
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, China
| | - Yingzhao Liu
- Department of Endocrinology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Ting Yang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Ruidong Gao
- Department of Endocrinology, Baoying Hospital of Traditional Chinese Medicine, Yangzhou, China
| | - Congqing Miao
- Department of Endocrinology, Jiangdu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| |
Collapse
|
6
|
Gancheva S, Roden M, Castera L. Diabetes as a risk factor for MASH progression. Diabetes Res Clin Pract 2024; 217:111846. [PMID: 39245423 DOI: 10.1016/j.diabres.2024.111846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 09/10/2024]
Abstract
Non-alcoholic (now: metabolic) steatohepatitis (MASH) is the progressive inflammatory form of metabolic dysfunction-associated steatotic liver disease (MASLD), which often coexists and mutually interacts with type 2 diabetes (T2D), resulting in worse hepatic and cardiovascular outcomes. Understanding the intricate mechanisms of diabetes-related MASH progression is crucial for effective therapeutic strategies. This review delineates the multifaceted pathways involved in this interplay and explores potential therapeutic implications. The synergy between adipose tissue, gut microbiota, and hepatic alterations plays a pivotal role in disease progression. Adipose tissue dysfunction, particularly in the visceral depot, coupled with dysbiosis in the gut microbiota, exacerbates hepatic injury and insulin resistance. Hepatic lipid accumulation, oxidative stress, and endoplasmic reticulum stress further potentiate inflammation and fibrosis, contributing to disease severity. Dietary modification with weight reduction and exercise prove crucial in managing T2D-related MASH. Additionally, various well-known but also novel anti-hyperglycemic medications exhibit potential in reducing liver lipid content and, in some cases, improving MASH histology. Therapies targeting incretin receptors show promise in managing T2D-related MASH, while thyroid hormone receptor-β agonism has proven effective as a treatment of MASH and fibrosis.
Collapse
Affiliation(s)
- Sofiya Gancheva
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich-Heine University, Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, München-Neuherberg, Germany
| | - Michael Roden
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich-Heine University, Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, München-Neuherberg, Germany.
| | - Laurent Castera
- Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; Université Paris-Cité, INSERM UMR 1149, Centre de Recherche sur l'Inflammation Paris, Montmartre, Paris, France.
| |
Collapse
|
7
|
Xu W, Zhang D, Ma Y, Gaspar RC, Kahn M, Nasiri A, Murray S, Samuel VT, Shulman GI. Ceramide synthesis inhibitors prevent lipid-induced insulin resistance through the DAG-PKCε-insulin receptor T1150 phosphorylation pathway. Cell Rep 2024; 43:114746. [PMID: 39302831 DOI: 10.1016/j.celrep.2024.114746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 07/22/2024] [Accepted: 08/28/2024] [Indexed: 09/22/2024] Open
Abstract
Inhibition of the ceramide synthetic pathway with myriocin or an antisense oligonucleotide (ASO) targeting dihydroceramide desaturase (DES1) both improved hepatic insulin sensitivity in rats fed either a saturated or unsaturated fat diet and was associated with reductions in both hepatic ceramide and plasma membrane (PM)-sn-1,2-diacylglycerol (DAG) content. The insulin sensitizing effects of myriocin and Des1 ASO were abrogated by acute treatment with an ASO against DGAT2, which increased hepatic PM-sn-1,2-DAG but not hepatic C16 ceramide content. Increased PM-sn-1,2-DAG content was associated with protein kinase C (PKC)ε activation, increased insulin receptor (INSR)T1150 phosphorylation leading to reduced insulin-stimulated INSRY1152/AktS473 phosphorylation, and impaired insulin-mediated suppression of endogenous glucose production. These results demonstrate that inhibition of de novo ceramide synthesis by either myriocin treatment or DES1 knockdown protects against lipid-induced hepatic insulin resistance through a C16 ceramide-independent mechanism and that they mediate their effects to protect from lipid-induced hepatic insulin resistance via the PM-sn-1,2-DAG-PKCε-INSRT1150 phosphorylation pathway.
Collapse
Affiliation(s)
- Weiwei Xu
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310003, China
| | - Dongyan Zhang
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA
| | - Yumin Ma
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Endocrinology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, China
| | - Rafael C Gaspar
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA
| | - Mario Kahn
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA
| | - Ali Nasiri
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA
| | - Sue Murray
- Ionis Pharmaceuticals, Carlsbad, CA 92010, USA
| | - Varman T Samuel
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; VA Connecticut Healthcare System, West Haven, CT 06516, USA.
| | - Gerald I Shulman
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
| |
Collapse
|
8
|
Deng D, Yang S, Yu X, Zhou R, Liu Y, Zhang H, Cui D, Feng X, Wu Y, Qi X, Su Z. Aging-induced short-chain acyl-CoA dehydrogenase promotes age-related hepatic steatosis by suppressing lipophagy. Aging Cell 2024; 23:e14256. [PMID: 38898632 PMCID: PMC11464120 DOI: 10.1111/acel.14256] [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: 01/29/2024] [Revised: 05/06/2024] [Accepted: 06/09/2024] [Indexed: 06/21/2024] Open
Abstract
Hepatic steatosis, the first step in the development of nonalcoholic fatty liver disease (NAFLD), is frequently observed in the aging population. However, the underlying molecular mechanism remains largely unknown. In this study, we first employed GSEA enrichment analysis to identify short-chain acyl-CoA dehydrogenase (SCAD), which participates in the mitochondrial β-oxidation of fatty acids and may be associated with hepatic steatosis in elderly individuals. Subsequently, we examined SCAD expression and hepatic triglyceride content in various aged humans and mice and found that triglycerides were markedly increased and that SCAD was upregulated in aged livers. Our further evidence in SCAD-ablated mice suggested that SCAD deletion was able to slow liver aging and ameliorate aging-associated fatty liver. Examination of the molecular pathways by which the deletion of SCAD attenuates steatosis revealed that the autophagic degradation of lipid droplets, which was not detected in elderly wild-type mice, was maintained in SCAD-deficient old mice. This was due to the decrease in the production of acetyl-coenzyme A (acetyl-CoA), which is abundant in the livers of old wild-type mice. In conclusion, our findings demonstrate that the suppression of SCAD may prevent age-associated hepatic steatosis by promoting lipophagy and that SCAD could be a promising therapeutic target for liver aging and associated steatosis.
Collapse
Affiliation(s)
- Dan Deng
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Shanshan Yang
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Xiaoqian Yu
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Ruixue Zhou
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Yin Liu
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Hongmei Zhang
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Daxin Cui
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Xingrong Feng
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Yanting Wu
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Xiaocun Qi
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| | - Zhiguang Su
- Molecular Medicine Research Center and National Clinical Research Center for Geriatrics, West China Hospital, and State Key Laboratory of BiotherapySichuan UniversityChengduChina
| |
Collapse
|
9
|
Ding S, Hong Q, Yao Y, Gu M, Cui J, Li W, Zhang J, Zhang C, Jiang J, Hu Y. Meta-analysis of randomized controlled trials of the effects of synbiotics, probiotics, or prebiotics in controlling glucose homeostasis in non-alcoholic fatty liver disease patients. Food Funct 2024; 15:9954-9971. [PMID: 39264166 DOI: 10.1039/d4fo02561j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
Background: Probiotics, prebiotics, and synbiotics have been suggested as a possible therapy for non-alcoholic fatty liver disease (NAFLD). However, their efficacy in improving blood glucose levels in NAFLD patients remains uncertain. Objective: The aim of this study was to assess the effects of supplementation with probiotics, prebiotics, or synbiotics on fasting blood glucose (FBG) levels in NAFLD patients. Methods: We searched PubMed, Web of Science, and Google Scholar for relevant trials published up to March 2024. Out of 3369 identified studies, 24 randomized controlled trials (RCTs) were included. Results: Probiotic, prebiotic, or synbiotic supplementation substantially reduced FBG (n = 23; standard mean difference (SMD) = -0.17; 95% confidence interval (CI): -0.30, -0.03; P = 0.02), fasting insulin levels (n = 12; SMD = -0.28; 95% CI: -0.49, -0.07; P = 0.01), and homeostatic model assessment for insulin resistance (HOMA-IR; n = 14; SMD = -0.28; 95% CI: -0.47, -0.09; P = 0.004). However, glycosylated hemoglobin (HbA1c; n = 3; SMD = -0.17; 95% CI: -0.48, 0.13; P = 0.27) was not significantly affected. The FBG-decreasing effect diminished as the body mass index (BMI) of volunteers increased in the baseline. Additionally, the number of probiotic strains and geographic region were shown to significantly affect FBG levels. Conclusion: This meta-analysis indicates that supplementation with probiotics, prebiotics, or synbiotics may aid in controlling glucose homeostasis in patients with NAFLD.
Collapse
Affiliation(s)
- Siqi Ding
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Qing Hong
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd, Shanghai, 200436, China
| | - Yuanyue Yao
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Minwen Gu
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Jie Cui
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Wenhui Li
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Jian Zhang
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Chengcheng Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jinchi Jiang
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Yonghong Hu
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| |
Collapse
|
10
|
Yeh ML, Huang JF, Dai CY, Huang CF, Yu ML, Chuang WL. Metabolic dysfunction-associated steatotic liver disease and diabetes: the cross-talk between hepatologist and diabetologist. Expert Rev Gastroenterol Hepatol 2024; 18:431-439. [PMID: 39099428 DOI: 10.1080/17474124.2024.2388790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/30/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024]
Abstract
INTRODUCTION Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (DM) are the most prevalent metabolic disorders globally. The numbers affected in both disorders are also rapidly increasing with alarming trends in children and young adults. AREAS COVERED Insulin resistance (IR) and the subsequent metabolic dysregulation are the fundamental pathogenesis pathways of the prevalent metabolic disorders. The interaction and impacts are bidirectional between MASLD and DM in terms of disease mechanisms, disease course, risks, and prognosis. There's a pressing issue for highlighting the links between MASLD and DM for both care specialists and primary care providers. The review collected the scientific evidence addressing the mutual interactions between the two disorders. The strategies for surveillance, risk stratification, and management are discussed in a practical manner. It also provides individualized viewpoints of patient care in hepatology and diabetology. EXPERT OPINION Both MASLD and DM shared similar disease mechanisms, and affected the disease development and progression in a bidirectional manner. The high prevalence and the cross-link between the two disorders raise clinical issues from awareness, screening, risk stratification, optimal referral, to appropriate management for primary care providers.
Collapse
Affiliation(s)
- Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| |
Collapse
|
11
|
Gupta VK, Sahu L, Sonwal S, Suneetha A, Kim DH, Kim J, Verma HK, Pavitra E, Raju GSR, Bhaskar L, Lee HU, Huh YS. Advances in biomedical applications of vitamin D for VDR targeted management of obesity and cancer. Biomed Pharmacother 2024; 177:117001. [PMID: 38936194 DOI: 10.1016/j.biopha.2024.117001] [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: 02/14/2024] [Revised: 06/11/2024] [Accepted: 06/17/2024] [Indexed: 06/29/2024] Open
Abstract
BACKGROUND 1,25(OH)2D3 is a fat-soluble vitamin, involved in regulating Ca2+ homeostasis in the body. Its storage in adipose tissue depends on the fat content of the body. Obesity is the result of abnormal lipid deposition due to the prolonged positive energy balance and increases the risk of several cancer types. Furthermore, it has been associated with vitamin D deficiency and defined as a low 25(OH)2D3 blood level. In addition, 1,25(OH)2D3 plays vital roles in Ca2+-Pi and glucose metabolism in the adipocytes of obese individuals and regulates the expressions of adipogenesis-associated genes in mature adipocytes. SCOPE AND APPROACH The present contribution focused on the VDR mediated mechanisms interconnecting the obese condition and cancer proliferation due to 1,25(OH)2D3-deficiency in humans. This contribution also summarizes the identification and development of molecular targets for VDR-targeted drug discovery. KEY FINDINGS AND CONCLUSIONS Several studies have revealed that cancer development in a background of 1,25(OH)2D3 deficient obesity involves the VDR gene. Moreover, 1,25(OH)2D3 is also known to influence several cellular processes, including differentiation, proliferation, and adhesion. The multifaceted physiology of obesity has improved our understanding of the cancer therapeutic targets. However, currently available anti-cancer drugs are notorious for their side effects, which have raised safety issues. Thus, there is interest in developing 1,25(OH)2D3-based therapies without any side effects.
Collapse
Affiliation(s)
- Vivek Kumar Gupta
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Lipina Sahu
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh 495009, India
| | - Sonam Sonwal
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Achanti Suneetha
- Department of Pharmaceutical Analysis, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, Andhra Pradesh 520010, India
| | - Dong Hyeon Kim
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Jigyeong Kim
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Henu Kumar Verma
- Department of Immunopathology, Institute of Lungs Health and Immunity, Comprehensive Pneumology Center, Helmholtz Zentrum, Neuherberg, Munich 85764, Germany
| | - Eluri Pavitra
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea
| | - Ganji Seeta Rama Raju
- Department of Energy and Materials Engineering, Dongguk University, Seoul 04620, Republic of Korea.
| | - Lvks Bhaskar
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh 495009, India.
| | - Hyun Uk Lee
- Division of Material Analysis and Research, Korea Basic Science Institute, Daejeon 34133, Republic of Korea.
| | - Yun Suk Huh
- NanoBio High-Tech Materials Research Center, Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea.
| |
Collapse
|
12
|
Sun L, Yue Z, Wang L. Research on the function of epigenetic regulation in the inflammation of non-alcoholic fatty liver disease. LIFE MEDICINE 2024; 3:lnae030. [PMID: 39872862 PMCID: PMC11749620 DOI: 10.1093/lifemedi/lnae030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 08/30/2024] [Indexed: 01/30/2025]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition, characterized by a spectrum that progresses from simple hepatic steatosis to nonalcoholic steatohepatitis, which may eventually lead to cirrhosis and hepatocellular carcinoma. The precise pathogenic mechanisms underlying NAFLD and its related metabolic disturbances remain elusive. Epigenetic modifications, which entail stable transcriptional changes without altering the DNA sequence, are increasingly recognized as pivotal. The principal forms of epigenetic modifications include DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. These alterations participate in the regulation of hepatic lipid metabolism, insulin resistance, mitochondrial injury, oxidative stress response, and release of inflammatory cytokines, all of which are associated with the onset and progression of NAFLD. This review discussed recent advances in understanding the potential epigenetic regulation of inflammation in NAFLD. Unraveling these epigenetic mechanisms may facilitate the identification of early diagnostic biomarkers and the development of targeted therapeutic strategies for NAFLD.
Collapse
Affiliation(s)
- Lin Sun
- Department of Hepatobiliary Surgery, Xi-Jing Hospital, Fourth Military Medical University, Changle West Road, Xincheng District, Xi’an, Shaanxi 710032, China
| | - Zhensheng Yue
- Department of Hepatobiliary Surgery, Xi-Jing Hospital, Fourth Military Medical University, Changle West Road, Xincheng District, Xi’an, Shaanxi 710032, China
- Department of Ophthalmology, Xi-Jing Hospital, Fourth Military Medical University, Changle West Road, Xincheng District, Xi’an, Shaanxi 710032, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, Xi-Jing Hospital, Fourth Military Medical University, Changle West Road, Xincheng District, Xi’an, Shaanxi 710032, China
| |
Collapse
|
13
|
Dehghani Firouzabadi M, Poopak A, Sheikhy A, Dehghani Firouzabadi F, Moosaie F, Rabizadeh S, Momtazmanesh S, Nakhjavani M, Esteghamati A. Nonalcoholic Fatty Liver Disease as a Potential Risk Factor for Cardiovascular Disease in Patients with Type 2 Diabetes: A Prospective Cohort Study. Int J Endocrinol 2024; 2024:5328965. [PMID: 38962375 PMCID: PMC11221952 DOI: 10.1155/2024/5328965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 06/11/2024] [Accepted: 06/15/2024] [Indexed: 07/05/2024] Open
Abstract
Methods and Results In this prospective cohort study, 1197 patients with type 2 diabetes (T2D) were divided into two groups (360 patients with NAFLD and 847 without NAFLD) and were followed for a median of 5 years for the incidence of CVD. Cox regression analysis was used to assess the association between NAFLD, liver enzyme level, aspartate aminotransferase to platelet ratio index (APRI), and the incidence risk of CVD and its subgroups (i.e., myocardial infarction, chronic heart disease, coronary artery bypass grafting, and percutaneous coronary intervention). There was a significant positive association between CVD incidence and NAFLD (HR = 1.488, 95% CI = 1.041-2.124, p value = 0.029). Although patients with NAFLD had higher levels of ALT and AST levels (p value = <0.001), there was no significant association between liver enzymes and the incidence risk of CVD when adjusted for different variables. Furthermore, NAFLD was associated with NAFLD APRI Q (2), APRI Q (3), and APRIQ (4) (1.365 (1.046-1.781), 1.623 (1.234-2.135), and 3.373 (2.509-4.536)), respectively. Conclusion NAFLD increased the incidence risk of CVD in T2D. However, there was no association between liver enzymes (ALT, AST, ALK-P, and GGT) and a higher incidence risk of CVD in T2D when adjusted for confounding variables.
Collapse
Affiliation(s)
- Mohammad Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Poopak
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Ali Sheikhy
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
- Department of Radiology and Imaging SciencesClinical CenterNational Institutes of Health, Bethesda, USA
| | - Fatemeh Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
- Department of Radiology and Imaging SciencesClinical CenterNational Institutes of Health, Bethesda, USA
| | - Fatemeh Moosaie
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Soghra Rabizadeh
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Sara Momtazmanesh
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
14
|
Liu H, Hao YM, Jiang S, Baihetiyaer M, Li C, Sang GY, Li Z, Du GL. Evaluation of MASLD Fibrosis, FIB-4 and APRI Score in MASLD Combined with T2DM and MACCEs Receiving SGLT2 Inhibitors Treatment. Int J Gen Med 2024; 17:2613-2625. [PMID: 38855422 PMCID: PMC11162633 DOI: 10.2147/ijgm.s460200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 05/21/2024] [Indexed: 06/11/2024] Open
Abstract
Purpose This study aims to investigate the relationship between Sodium Glucose Co-transporter-2 inhibitors (SGLT2i) treatment and fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) combined with Type 2 Diabetes Mellitus (T2DM) and Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs). Methods A case-control study was conducted, involving 280 patients with MASLD combined with T2DM treated at the First Affiliated Hospital of Xinjiang Medical University from January 2014 to October 2023. Among these patients, 135 received SGLT2i treatment. The association between the Fibrosis-4 (FIB-4) index and the occurrence of MACCEs, as well as the association between the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores and MACCEs, were evaluated. Results The FIB-4 index and APRI scores were significantly lower in the SGLT2i treatment group compared to the non-SGLT2i group (1.59 vs 1.25, P<0.001). SGLT2i treatment tended to reduce the occurrence of MACCEs compared to non-SGLT2i treatment (45.5% vs 38.5%, P=0.28). All patients who developed MACCEs in the non-SGLT2i treatment group had higher FIB-4 index (1.83 vs 1.35, P=0.003). Additionally, after SGLT2i treatment for a median duration of 22 months, patients showed significant reductions in blood glucose, APRI, and FIB-4 index. Conclusion SGLT2i treatment significantly reduces the occurrence of MACCEs and liver fibrosis in patients with MASLD combined with T2DM. The FIB-4 index may serve as a potential surrogate marker for predicting the occurrence of MACCEs.
Collapse
Affiliation(s)
- Hua Liu
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Yang-Min Hao
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Sheng Jiang
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Maiheliya Baihetiyaer
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Cheng Li
- Data Statistics and Analysis Center of Operation Management Department, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Guo-Yao Sang
- Laboratory Medicine Diagnostic Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Zhiming Li
- Department of Ultrasound, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
| | - Guo-Li Du
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China
- Bazhou People’s Hospital, Korla, Xinjiang Uygur Autonomous Region, People’s Republic of China
| |
Collapse
|
15
|
Shen TH, Wu CH, Lee YW, Chang CC. Prevalence, trends, and characteristics of metabolic dysfunction-associated steatotic liver disease among the US population aged 12-79 years. Eur J Gastroenterol Hepatol 2024; 36:636-645. [PMID: 38477858 DOI: 10.1097/meg.0000000000002741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/14/2024]
Abstract
BACKGROUND AND AIMS Clinical observation revealed an increase in metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence among adults and adolescents and young adults (AYA). However, its prevalence trend in specific subgroups and its characteristics are unclear. APPROACH AND RESULTS This cross-sectional study included adults and AYA aged 20-79 and 12-19 years, respectively, from the National Health and Nutrition Examination Survey from 1999 to 2018. MASLD was defined as US Fatty Liver Index ≥30 in adults and alanine amino transaminase elevation and obesity in AYA. Joinpoint and logistic regression were used to evaluate the MASLD prevalence trend and its associated characteristics. MASLD was diagnosed in 17 156 892 of 51 109 914 (33.6%) adults and 1 705 586 of 29 278 666 AYA (5.8%). During the study period, MASLD prevalence significantly increased from 30.8% to 37.7% ( P < 0.01) in adults and in subgroups of female participants, individuals aged 20-45 and 61-79 years, and non-Hispanic white individuals. Conversely, MASLD prevalence did not significantly change in AYA (from 5.1% to 5.2%, P = 0.139), except in the subgroup of Mexican Americans (from 8.2% to 10.8%, P = 0.01). Among adults, high MASLD prevalence was associated with male sex, Mexican American ethnicity, age >50 years, being unmarried, poverty income ratio <130, poor or fair health condition, obesity or overweight, and chronic conditions. Among AYA, high MASLD prevalence was associated with male sex, poverty income ratio <130, and education. CONCLUSION Accordingly, we concluded that health care providers should prevent and treat conditions associated with MASLD by raising awareness of the increasing trend of MASLD.
Collapse
Affiliation(s)
- Tsung-Hua Shen
- Social and Administrative Pharmacy Program, Department of Pharmaceutical Care and Health System, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA
- School of Pharmacy, College of Pharmacy, Taipei Medical University
| | - Chung-Hsuen Wu
- School of Pharmacy, College of Pharmacy, Taipei Medical University
| | - Yuan-Wen Lee
- Department of Anesthesiology, Taipei Medical University Hospital
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| |
Collapse
|
16
|
Zhou M, Hanschmann EM, Römer A, Linn T, Petry SF. The significance of glutaredoxins for diabetes mellitus and its complications. Redox Biol 2024; 71:103043. [PMID: 38377787 PMCID: PMC10891345 DOI: 10.1016/j.redox.2024.103043] [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: 12/09/2023] [Accepted: 01/13/2024] [Indexed: 02/22/2024] Open
Abstract
Diabetes mellitus is a non-communicable metabolic disease hallmarked by chronic hyperglycemia caused by beta-cell failure. Diabetic complications affect the vasculature and result in macro- and microangiopathies, which account for a significantly increased morbidity and mortality. The rising incidence and prevalence of diabetes is a major global health burden. There are no feasible strategies for beta-cell preservation available in daily clinical practice. Therefore, patients rely on antidiabetic drugs or the application of exogenous insulin. Glutaredoxins (Grxs) are ubiquitously expressed and highly conserved members of the thioredoxin family of proteins. They have specific functions in redox-mediated signal transduction, iron homeostasis and biosynthesis of iron-sulfur (FeS) proteins, and the regulation of cell proliferation, survival, and function. The involvement of Grxs in chronic diseases has been a topic of research for several decades, suggesting them as therapeutic targets. Little is known about their role in diabetes and its complications. Therefore, this review summarizes the available literature on the significance of Grxs in diabetes and its complications. In conclusion, Grxs are differentially expressed in the endocrine pancreas and in tissues affected by diabetic complications, such as the heart, the kidneys, the eye, and the vasculature. They are involved in several pathways essential for insulin signaling, metabolic inflammation, glucose and fatty acid uptake and processing, cell survival, and iron and mitochondrial metabolism. Most studies describe significant changes in glutaredoxin expression and/or activity in response to the diabetic metabolism. In general, mitigated levels of Grxs are associated with oxidative distress, cell damage, and even cell death. The induced overexpression is considered a potential part of the cellular stress-response, counteracting oxidative distress and exerting beneficial impact on cell function such as insulin secretion, cytokine expression, and enzyme activity.
Collapse
Affiliation(s)
- Mengmeng Zhou
- Clinical Research Unit, Medical Clinic and Polyclinic III, Center of Internal Medicine, Justus Liebig University, Giessen, Germany
| | - Eva-Maria Hanschmann
- Experimental and Translational Research, Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany
| | - Axel Römer
- Clinical Research Unit, Medical Clinic and Polyclinic III, Center of Internal Medicine, Justus Liebig University, Giessen, Germany
| | - Thomas Linn
- Clinical Research Unit, Medical Clinic and Polyclinic III, Center of Internal Medicine, Justus Liebig University, Giessen, Germany
| | - Sebastian Friedrich Petry
- Clinical Research Unit, Medical Clinic and Polyclinic III, Center of Internal Medicine, Justus Liebig University, Giessen, Germany.
| |
Collapse
|
17
|
Yasin A, Nguyen M, Sidhu A, Majety P, Spitz J, Asgharpour A, Siddiqui MS, Sperling LS, Quyyumi AA, Mehta A. Liver and cardiovascular disease outcomes in metabolic syndrome and diabetic populations: Bi-directional opportunities to multiply preventive strategies. Diabetes Res Clin Pract 2024; 211:111650. [PMID: 38604447 DOI: 10.1016/j.diabres.2024.111650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 03/26/2024] [Accepted: 04/01/2024] [Indexed: 04/13/2024]
Abstract
The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.
Collapse
Affiliation(s)
| | | | - Angad Sidhu
- Virginia Commonwealth University, Richmond, VA, US
| | | | - Jared Spitz
- Inova Heart and Vascular Institute, Fairfax, VA, US
| | | | | | | | - Arshed A Quyyumi
- Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia
| | - Anurag Mehta
- Virginia Commonwealth University, Richmond, VA, US.
| |
Collapse
|
18
|
Tyczyńska M, Hunek G, Szczasny M, Brachet A, Januszewski J, Forma A, Portincasa P, Flieger J, Baj J. Supplementation of Micro- and Macronutrients-A Role of Nutritional Status in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2024; 25:4916. [PMID: 38732128 PMCID: PMC11085010 DOI: 10.3390/ijms25094916] [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: 03/19/2024] [Revised: 04/28/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumulation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunctions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, insulin resistance, or diabetes, an unbalanced diet and imbalanced nutritional status should also be taken into consideration. In this narrative review, we summarized the current knowledge regarding the micro- and macronutrient status of patients suffering from NAFLD considering various diets and supplementation of chosen supplements. We aimed to summarize the knowledge indicating which nutritional impairments may be associated with the onset and progression of NAFLD at the same time evaluating the potential therapy targets that could facilitate the healing process. Except for the above-mentioned objectives, one of the most important aspects of this review was to highlight the possible strategies for taking care of NAFLD patients taking into account the challenges and opportunities associated with the micronutrient status of the patients. The current research indicates that a supplementation of chosen vitamins (e.g., vitamin A, B complex, C, or D) as well as chosen elements such as zinc may alleviate the symptoms of NAFLD. However, there is still a lack of sufficient data regarding healthy ranges of dosages; thus, further research is of high importance in this matter.
Collapse
Affiliation(s)
- Magdalena Tyczyńska
- Department of Correct, Clinical and Imaging Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland;
| | - Gabriela Hunek
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Martyna Szczasny
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
| | - Adam Brachet
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Jacek Januszewski
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (G.H.); (A.B.)
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Jolanta Flieger
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4A, 20-093 Lublin, Poland;
| | - Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (M.S.); (J.J.)
| |
Collapse
|
19
|
Younossi ZM, Henry L. Epidemiology of NAFLD - Focus on diabetes. Diabetes Res Clin Pract 2024; 210:111648. [PMID: 38569945 DOI: 10.1016/j.diabres.2024.111648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 04/01/2024] [Indexed: 04/05/2024]
Abstract
There is increasing appreciation of the complex interaction between nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) and insulin resistance. Not only is the prevalence of NAFLD disease high among patients with T2D, the liver disease is also more progressive. Currently, the global prevalence of NAFLD in the general population (2016-2019) is 38 %. The prevalence of T2D among those with NAFLD is approximately 23 % while the prevalence of NAFLD among those with T2D can be as high as 70 %. The prevalence of nonalcoholic steatohepatitis (NASH) is approximately 7 % in the general population and 37 % among patients with T2D. Globally, the MENA and Latin America regions of the world appear to have the highest burden of both NAFLD and T2D. Compared to those with NAFLD but without T2D, those with NAFLD and T2D are at a much higher risk for disease progression to cirrhosis and for decompensated cirrhosis, hepatocellular carcinoma, and all-cause mortality. Given that highly effective new treatments are available for T2D, high risk NAFLD with T2D should be considered for these regimens. This requires implementation of risk stratification algorithms in the primary care and endocrinology practices to identify those patients at highest risk for adverse outcomes.
Collapse
Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, United States; Center for Outcomes Research In Liver Diseases, Washington, DC, United States.
| | - Linda Henry
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, United States; Center for Outcomes Research In Liver Diseases, Washington, DC, United States
| |
Collapse
|
20
|
Crocombe D, Tsochatzis EA. Natural history of nonalcoholic fatty liver disease. METABOLIC STEATOTIC LIVER DISEASE 2024:61-75. [DOI: 10.1016/b978-0-323-99649-5.00014-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
21
|
Sahoo NR, Dalai MK, Dash DK, Sethy G. Prevalence, Metabolic Consequences of Non Alcoholic Fatty Liver Disease (NAFLD) and its Association with Microvascular Complications and Ventricular Dysfunction in Patients with Type 2 Diabetes Mellitus. MEDICAL JOURNAL OF DR. D.Y. PATIL VIDYAPEETH 2024; 17:149-155. [DOI: 10.4103/mjdrdypu.mjdrdypu_490_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 11/25/2022] [Indexed: 01/03/2025] Open
Abstract
ABSTRACT
Objective:
To study the prevalence of non-alcoholic fatty liver disease (NAFLD) and its association of with microvascular complications and ventricular dysfunction in patients with type 2 diabetes mellitus (T2DM).
Methods:
In this cross-sectional study, 100 T2DM patients were screened randomly for detection of fatty liver in ultrasonography. Patients with fatty liver (NAFLD group, n = 36) were compared with subjects without fatty liver (non-NAFLD group, n = 64). Detailed clinical, biochemical, and imaging parameters like lipid profile, LFT, fasting plasma glucose, 2-hour post-prandial plasma glucose, HbA1C, fasting insulin, spot urinary albumin/creatinine ratio, and 2-D ECHO (M-mode) were performed.
Results:
The prevalence of NAFLD was found to be 36%. NAFLD group had significantly higher BMI, WHR, blood pressure, glycemic profile, and lipid parameters compared to non-NAFLD group. HOMA IR was elevated significantly in NAFLD group (3.16 ± 1.96) compared to non-NAFLD group (1.73 ± 1.59). There was significantly higher prevalence of all the diabetes-related microvascular complications and LV diastolic dysfunction in NAFLD patients with higher odds for the occurrence of neuropathy (OR = 4.74; P = 0.001), nephropathy (OR = 3.92; P = 0.003), retinopathy (OR = 5.95; P = 0.002), and LV diastolic dysfunction (OR = 1.84; P = 0.043).
Conclusions:
NAFLD is significantly associated with various diabetes-related microvascular complications as well as LV diastolic dysfunction in T2DM patients.
Collapse
Affiliation(s)
- Nihar Ranjan Sahoo
- Department of Medicine, M.K.C.G Medical College, Berhampur, Odisha, India
| | - Motij Kumar Dalai
- Department of Gastroenterology, LTMMC, Sion Hospital, Mumbai, Maharashtra, India
| | - Deepak Kumar Dash
- Department of Endocrinology, M.K.C.G Medical College, Berhampur, Odisha, India
| | - Ganeswar Sethy
- Department of Medicine, F.M Medical College, Balasore, Odisha, India
| |
Collapse
|
22
|
Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
23
|
Ziamanesh F, Mohammadi M, Ebrahimpour S, Tabatabaei-Malazy O, Mosallanejad A, Larijani B. Unraveling the link between insulin resistance and Non-alcoholic fatty liver disease (or metabolic dysfunction-associated steatotic liver disease): A Narrative Review. J Diabetes Metab Disord 2023; 22:1083-1094. [PMID: 37975107 PMCID: PMC10638269 DOI: 10.1007/s40200-023-01293-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 08/24/2023] [Indexed: 11/19/2023]
Abstract
Objective Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a significant global health concern, representing the leading cause of chronic liver disease and posing a substantial public health challenge. NAFLD is associated with higher insulin resistance (IR) levels, a key pathophysiological mechanism contributing to its development and progression. To counter this growing trend, it is crucial to raise awareness about NAFLD and promote healthy lifestyles to mitigate the impact of this disease. Methods Relevant studies regarding IR and NAFLD published until May 30, 2023, were extracted from Google PubMed, Scopus, and Web Of Science web databases. The following keywords were used: IR, diabetes mellitus, Non-alcoholic fatty liver disease, and metabolic syndrome. Results IR leads to an accumulation of fatty acids within liver cells, resulting from increased glycolysis and decreased apolipoprotein B-100. Furthermore, the manifestations of NAFLD extend beyond liver-related morbidity and mortality, affecting multiple organs and giving rise to various non-communicable disorders such as diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, obstructive sleep apnea, and cardiovascular disease. Although lifestyle modification remains the primary treatment approach for NAFLD, alternative therapies, including pharmacological, herbal, and surgical interventions, may be considered. By implementing early and simple measures, cirrhosis, end-stage liver disease, and hepatocellular carcinoma can be prevented. Conclusions There is a clear association between NAFLD and elevated levels of IR. Several metabolic conditions, such as obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome, are closely interrelated with NAFLD and IR. Raising awareness about NAFLD and promoting a healthy lifestyle are crucial steps to reverse the impact of this disease.
Collapse
Affiliation(s)
- Fateme Ziamanesh
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Mohammadi
- Department of Clinical Pharmacy, School of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
| | - Sholeh Ebrahimpour
- Department of Clinical Pharmacy, School of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
| | - Ozra Tabatabaei-Malazy
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
24
|
Jia X, Song E, Liu Y, Chen J, Wan P, Hu Y, Ye D, Chakrabarti S, Mahajan H, George J, Yan S, Yu Y, Zhang G, Wang Y, Yang W, Wu L, Hua S, Lee CH, Li H, Jiang X, Lam KSL, Wang C, Xu A. Identification and multicentric validation of soluble CDCP1 as a robust serological biomarker for risk stratification of NASH in obese Chinese. Cell Rep Med 2023; 4:101257. [PMID: 37918406 PMCID: PMC10694619 DOI: 10.1016/j.xcrm.2023.101257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 08/15/2023] [Accepted: 10/03/2023] [Indexed: 11/04/2023]
Abstract
The definitive diagnosis of non-alcoholic steatohepatitis (NASH) currently relies on invasive and labor-intensive liver biopsy. Here, we identified soluble CUB domain-containing protein 1 (sCDCP1) as a top-ranked non-invasive biomarker for NASH using Olink-based proteomics in 238 obese individuals with liver biopsies. Both the circulating concentration and hepatic mRNA abundance of sCDCP1 were significantly elevated in patients with NASH and correlated closely with each histological feature of NASH. In the pooled multicenter validation cohort, sCDCP1 as a standalone biomarker achieved an area under the receiver operating characteristic (AUROC) of 0.838 (95% confidence interval [CI] 0.789-0.887) for diagnosing NASH, which is better than those achieved with cytokeratin-18 and other non-invasive tests. Furthermore, the C-DAG model established by the combination of sCDCP1 with diabetes, aspartate aminotransferase (AST), and gender accurately rules in and rules out both NASH and fibrotic NASH (gray zones <20%). Thus, sCDCP1-based non-invasive tests can be potentially implemented for screening and early diagnosis of NASH and for ruling out low-risk individuals to avoid unnecessary liver biopsies.
Collapse
Affiliation(s)
- Xi Jia
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Erfei Song
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yan Liu
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China
| | - Jiarui Chen
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Pei Wan
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Yue Hu
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Dewei Ye
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Metabolic Phenotyping in Model Animals, Guangdong Pharmaceutical University, Guangzhou, China
| | - Subrata Chakrabarti
- Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada; Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, Canada
| | - Hema Mahajan
- Institute of Clinical Pathology and Medical Research, Pathology West, NSW Health Pathology, Sydney, NSW 2145, Australia; University of Western Sydney, Sydney, NSW, Australia
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Sen Yan
- Dr. Everett Chalmers Hospital, Fredericton, NB, Canada
| | - Yongtao Yu
- Department of Gastrointestinal Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Guanghui Zhang
- Department of Gastrointestinal Surgery, Zhengzhou Second Hospital, Zhengzhou, China
| | - Yong Wang
- Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wah Yang
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Lihong Wu
- Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China
| | - Shuang Hua
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China
| | - Chi Ho Lee
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Huixin Li
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Xue Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Karen S L Lam
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Cunchuan Wang
- Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
| | - Aimin Xu
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China; Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China.
| |
Collapse
|
25
|
En Li Cho E, Ang CZ, Quek J, Fu CE, Lim LKE, Heng ZEQ, Tan DJH, Lim WH, Yong JN, Zeng R, Chee D, Nah B, Lesmana CRA, Bwa AH, Win KM, Faulkner C, Aboona MB, Lim MC, Syn N, Kulkarni AV, Suzuki H, Takahashi H, Tamaki N, Wijarnpreecha K, Huang DQ, Muthiah M, Ng CH, Loomba R. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Gut 2023; 72:2138-2148. [PMID: 37491159 DOI: 10.1136/gutjnl-2023-330110] [Citation(s) in RCA: 74] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/20/2023] [Indexed: 07/27/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM. METHODS MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies. RESULTS 156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I2=99.90%) and 31.55% (95% CI 17.12% to 50.70%, I2=97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I2=100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2-F4), while 14.95% (95% CI 11.03% to 19.95%, I2=99.00%) had advanced fibrosis (F3-F4). CONCLUSION This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD. PROSPERO REGISTRATION NUMBER CRD42022360251.
Collapse
Affiliation(s)
- Elina En Li Cho
- Department of Medicine, National University Hospital, Singapore
| | - Chong Zhe Ang
- Department of Medicine, National University Hospital, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Clarissa Elysia Fu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lincoln Kai En Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zane En Qi Heng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rebecca Zeng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Douglas Chee
- Department of Medicine, National University Hospital, Singapore
| | - Benjamin Nah
- Department of Medicine, National University Hospital, Singapore
| | | | - Aung Hlaing Bwa
- Department of Medical Research, Union of Myanmar, Naypyidaw, Myanmar
| | - Khin Maung Win
- Department of Medical Research, Union of Myanmar, Naypyidaw, Myanmar
| | - Claire Faulkner
- Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Majd B Aboona
- Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Mei Chin Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Diagnostic Imaging, National University Health System, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Anand V Kulkarni
- Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Hiroyuki Suzuki
- Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | | | - Nobuharu Tamaki
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Musashino Red Cross Hospital, Musashino, Japan
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, University of Michigan, Michigan, Michigan, USA
| | - Daniel Q Huang
- Department of Medicine, National University Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Mark Muthiah
- Department of Medicine, National University Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rohit Loomba
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| |
Collapse
|
26
|
Duan W, Shi R, Yang F, Zhou Z, Wang L, Huang Z, Zang S. FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 2023; 22:297. [PMID: 37904173 PMCID: PMC10617048 DOI: 10.1186/s12933-023-02024-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/11/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM). METHOD A total of 1424 participants were included in this study, and were firstly divided into two groups: 429 T2DM patients and 995 T2DM patients with NAFLD to assess the association of NAFLD and AMI. Then 995 T2DM co-existent NAFLD patients were categorized by NAFLD fibrosis risk to explore the association between NAFLD fibrosis risk and AMI. Immunohistochemistry staining and semi-quantitative analysis of liver FSTL3 were performed in 60 patients with NAFLD. There were 323 individuals (191 without AMI and 132 with AMI) in T2DM co-existent NAFLD patients who had serum samples, and serum FSTL3 was tested and mediation effect of FSTL3 in association of NAFLD fibrosis and AMI was performed. RESULTS First, increased NAFLD fibrosis risk was an independent risk factor for AMI in patients with T2DM and co-existent NAFLD. In addition, analysis of Gene Expression Omnibus (GEO) database and immunohistochemical staining confirmed the increased expression of FSTL3 in the liver of NAFLD patients with fibrosis. Serum FSTL3 significantly increased in patients with high NAFLD fibrosis risk and AMI, and closely associated with NAFLD fibrosis and AMI severity in T2DM patients with co-existent NAFLD. Most importantly, analysis of the level of mediation revealed that increased serum FSTL3 partially mediated the association of increased NAFLD fibrosis risk with AMI in T2DM patients with co-existent NAFLD. CONCLUSIONS NAFLD fibrosis was closely associated with AMI in T2DM patients. FSTL3 expression was enriched in the liver of NAFLD patients with significant and advanced fibrosis, and serum FSTL3 partially mediated the association of increased liver fibrosis risk with AMI in T2DM patients.
Collapse
Affiliation(s)
- Wenfei Duan
- Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, China
| | - Ruixiao Shi
- Department of Traditional Chinese Medicine, Maqiao Community Health Service Center, Minhang District, Shanghai, 20111, China
- Center of Community-Based Health Research, Fudan University, Shanghai, China
| | - Fang Yang
- Department of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China
| | - Zhoujunhao Zhou
- Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, China
| | - Lihong Wang
- Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, China
| | - Zhe Huang
- Department of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
| | - Shufei Zang
- Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, China.
| |
Collapse
|
27
|
Khoshbaten M, Maleki SH, Hadad S, Baral A, Rocha AV, Poudel L, Abdshah A. Association of nonalcoholic fatty liver disease and carotid media-intima thickness: A systematic review and a meta-analysis. Health Sci Rep 2023; 6:e1554. [PMID: 37701352 PMCID: PMC10493365 DOI: 10.1002/hsr2.1554] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 07/04/2023] [Accepted: 08/29/2023] [Indexed: 09/14/2023] Open
Abstract
Introduction The relationship between cardiovascular disorders and nonalcoholic fatty liver disease (NAFLD) has been extensively studied. To better pool this data and make a more definite conclusion, we performed a meta-analysis to evaluate the association between NAFLD and the thickness of media and intima of carotid artery (CIMT) and cardiovascular disorders. Methods We searched PubMed, Ovid, Scopus, ProQuest, Web of Science, and the Cochrane Library, and analyzed the pooled data using R studio and the "metafor" package. Results The final analysis included a total of 59 studies with 16,179 cases and 26,120 control individuals. NAFLD was shown to be associated with an increase of 0.1231 mm (20.6%) in carotid artery intima-media thickness (CIMT) (p = 0.002, 95% confidence interval [CI]: 0.0462-0.2000) in individuals with NAFLD. The prevalence of atherosclerotic plaques in the carotid arteries and the occurrence of NAFLD are significantly correlated, according to a meta-analysis based on 17 distinct studies (p = 0.001, 1.28-1.43, 95% CI, odds ratio = 1.356). Conclusion Patients with increased CIMT are considerably more likely to have NAFLD. Large prospective investigations are required to corroborate these findings and their prognostic significance, along with the effectiveness of the available interventions.
Collapse
Affiliation(s)
- Manouchehr Khoshbaten
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Sepideh H. Maleki
- Department of PathologyImam Reza Hospital, Tabriz University of Medical SciencesTabrizIran
| | - Sara Hadad
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Amrit Baral
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | - Ana V. Rocha
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | | | - Alireza Abdshah
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
- School of MedicineTehran University of Medical SciencesTehranIran
| |
Collapse
|
28
|
Jacob M, Joseph M, Idiculla J. Non-alcoholic fatty liver disease and diabetic retinopathy: Is there an association? J Family Med Prim Care 2023; 12:2028-2031. [PMID: 38024900 PMCID: PMC10657063 DOI: 10.4103/jfmpc.jfmpc_2327_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 04/30/2023] [Accepted: 05/26/2023] [Indexed: 12/01/2023] Open
Abstract
Background Studies have not proven whether an association exists between diabetic retinopathy (DR) and non-alcoholic fatty liver disease (NAFLD). The reports from various parts of the world have not used uniform criteria, and hence, results are inconclusive. Both DR and NAFLD are common conditions encountered in primary care. Methods A total of 130 patients with type 2 diabetes from the medical wards of a tertiary care hospital were enrolled. After documentation of clinical and biochemical data, they underwent ultrasonography (USG) of the abdomen and fibroscan grading of liver. Retinopathy was assessed and classified as per the Early Treatment Diabetic Retinopathy Study. Results The mean age of the patients included in the study was 46.5+/-8.8 with 55% of the participants being male and 45% female. The mean HbA1c was 7.168+/2.4. The association between DR and hepatic fibrosis was assessed by fibroscan (p 0.003) and USG (p 0.001) and was significant on univariate analysis. Multivariate analysis did not confirm this. There was no association between increasing grades of either condition. Although fibroscan and USG significantly concorded in diagnosing NAFLD, fibroscan diagnosed more cases as compared to USG (83 vs 73). Conclusion Larger studies should be conducted to conclusively determine the association in order to investigate pathogenetic factors and treatment strategies.
Collapse
Affiliation(s)
- Mathew Jacob
- Senior Resident, Department of Medicine, St. John’s Medical College, Bangalore, India
| | - Mary Joseph
- Professor, Department of Ophthalmology, St. John’s Medical College, Bangalore, India
| | - Jyothi Idiculla
- Professor, Department of Medicine, St. John’s Medical College, Bangalore, India
| |
Collapse
|
29
|
Klaric KA, Parai JL, Kepron CA, Walker AE, Milroy CM. Postmortem survey of haemoglobin A1c, non-alcoholic steatohepatitis and liver fibrosis within a general population. J Clin Pathol 2023; 76:606-611. [PMID: 35534202 DOI: 10.1136/jclinpath-2021-207998] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 04/14/2022] [Indexed: 11/04/2022]
Abstract
AIMS Non-alcoholic steatohepatitis (NASH), fatty liver disease and fibrosis are associated with diabetes mellitus and obesity. Previous autopsy series have reported prevalence of fatty liver disease to be 11%-24%. Recent studies, using imaging and serology, suggest a prevalence of 20%-35%, NASH of 5% and advanced fibrosis of 2%-3%. We examined the prevalence of NASH and liver fibrosis in a general autopsy population. METHODS A cross-sectional study of consecutive, adult, medicolegal autopsies over a 1-year period was conducted. Liver sections were scored for fibrosis, inflammation and steatosis using a modified NASH scoring system. Stepwise logistic regression was used to identify associations between NASH or moderate/severe fibrosis and several clinicopathological parameters, including postmortem haemoglobin A1c (HbA1c). RESULTS Of 376 cases, 86 (22.9%) were classified as NASH. Prevalence of diabetes mellitus, body mass index (BMI) and postmortem HbA1c were significantly higher in NASH cases (39.5%, 32.3 kg/m2 and 6.88%) than non-NASH cases (12.1%, 27.0 kg/m2 and 5.73%). Decedents with moderate/severe fibrosis (6.9%) had higher prevalence of diabetes, BMI and HbA1c (50%, 31.4 kg/m2 and 6.7%) compared with those with no/mild fibrosis (16%, 28 kg/m2 and 5.9%). HbA1c ≥7% was found to be an independent predictor of NASH (OR 5.11, 95% CI 2.61 to 9.98) and advanced fibrosis (OR 3.94, 95% CI 1.63 to 9.53). CONCLUSIONS NASH and advanced fibrosis were higher in our general adult autopsy population compared with previously published estimates. This is a large series with histological evaluation showing that HbA1c >7.0% is independently associated with NASH and advanced fibrosis.
Collapse
Affiliation(s)
- Kristina-Ana Klaric
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
| | - Jacqueline Louise Parai
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| | - Charis Anthea Kepron
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| | - Alfredo Eugene Walker
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| | - Christopher Mark Milroy
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| |
Collapse
|
30
|
Salavatizadeh M, Soltanieh S, Ataei Kachouei A, Abdollahi Fallahi Z, Kord-Varkaneh H, Poustchi H, Mansour A, Khamseh ME, Alaei-Shahmiri F, Santos HO, Hekmatdoost A. Association between dietary glycemic index and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1228072. [PMID: 37674617 PMCID: PMC10478091 DOI: 10.3389/fendo.2023.1228072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/26/2023] [Indexed: 09/08/2023] Open
Abstract
Objective Managing dietary glycemic index (GI) deserves further attention in the interplay between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). This study aimed to evaluate the relationship between dietary GI and the odds of NAFLD in patients with T2DM. Methods A cross-sectional study was carried out between April 2021 and February 2022, including 200 participants with T2DM aged 18-70 years, of which 133 had NAFLD and 67 were in the non-NAFLD group. Cardiometabolic parameters were analyzed using standard biochemical kits and dietary intake was assessed using a validated food frequency questionnaire. Binary logistic regression was applied to explore odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD according to tertiles of dietary GI. Results Highest vs. lowest tertile (< 57 vs. > 60.89) of energy-adjusted GI was not associated with the odds of having NAFLD (OR 1.25, 95% CI = 0.6-2.57; P-trend = 0.54) in the crude model. However, there was an OR of 3.24 (95% CI = 1.03-10.15) accompanied by a significant trend (P-trend = 0.04) after full control for potential confounders (age, gender, smoking status, duration of diabetes, physical activity, waist circumference, HbA1c, triglycerides, total cholesterol, dietary intake of total carbohydrates, simple carbohydrates, fat, and protein). Conclusion High dietary GI is associated with increased odds of NAFLD in subjects with T2DM. However, interventional and longitudinal cohort studies are required to confirm these findings.
Collapse
Affiliation(s)
- Marieh Salavatizadeh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Samira Soltanieh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Ataei Kachouei
- Department of Clinical Nutrition, School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Hamed Kord-Varkaneh
- Department of Nutrition and Food Hygiene, School of Medicine, Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Asieh Mansour
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad E. Khamseh
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Fariba Alaei-Shahmiri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Heitor O. Santos
- School of Medicine, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
31
|
Wang M, Zhao Y, He Y, Zhang L, Liu J, Zheng S, Bai Y. The bidirectional relationship between NAFLD and type 2 diabetes: A prospective population-based cohort study. Nutr Metab Cardiovasc Dis 2023; 33:1521-1528. [PMID: 37336719 DOI: 10.1016/j.numecd.2023.05.018] [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: 01/14/2023] [Revised: 05/06/2023] [Accepted: 05/10/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND AND AIMS To explore the bidirectional relationship between NAFLD and type 2 diabetes and the possible directions of the main effect. METHODS AND RESULTS 30 633 participants from the Jinchang cohort were enrolled. Firstly, cox proportional hazards regression model was used to assess the unidirectional causality between NAFLD and prediabetes and type 2 diabetes. Secondly, cross-lag path analysis model was conducted to estimate the bidirectional relationship between NAFLD and prediabetes and type 2 diabetes, and to determine the direction of the main effects. Finally, potential effect modifications were also considered by age, sex, hyperlipidemia, and overweight/obesity. We found that NAFLD increased the risk of prediabetes and type 2 diabetes with adjusted HR (95%CI) of 1.355(95%CI: 1.255-1.462) and 1.898(95%CI: 1.415-2.545), respectively. Prediabetes and type 2 diabetes also increased the risk of NAFLD, with adjusted HR (95%CI) of 1.245(95%CI: 1.115-1.392) and 1.592(95%CI: 1.373-1.846), respectively. Cross-lag path analysis showed that NAFLD significantly affected the incidence of prediabetes (β = 0.285, P < 0.001), while the effect on type 2 diabetes was not statistically significant. The effect of prediabetes and type 2 diabetes on the risk of NAFLD was weak, and the path coefficients were 0.076 and 0.037, respectively. Stratified analyses showed similar results. CONCLUSION This study provides evidence that there was a bidirectional causal association between NAFLD and type 2 diabetes, and the progression from NAFLD through prediabetes to type 2 diabetes may be the main pathway.
Collapse
Affiliation(s)
- Minzhen Wang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Yanan Zhao
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Yingqian He
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Lulu Zhang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Jing Liu
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Shan Zheng
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China.
| | - Yana Bai
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China.
| |
Collapse
|
32
|
Pena LC, Couto CA, Correa BHM, Ferrua LFQ, Cançado GGL, Faria LC, Mancuzo EV, Ferrari TCA. Poor cardiorespiratory fitness may be an indicator of more severe liver inflammation in non-alcoholic fatty liver disease patients. Clin Res Hepatol Gastroenterol 2023; 47:102163. [PMID: 37331653 DOI: 10.1016/j.clinre.2023.102163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 06/04/2023] [Accepted: 06/15/2023] [Indexed: 06/20/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is related to cardiovascular disease. Cardiorespiratory fitness (CRF) is an important indicator of cardiovascular health. Therefore, we aimed to evaluate the CRF of NAFLD patients. METHODS Cross-sectional study, including 32 patients with biopsy-proved NAFLD. The patients underwent ergometric test (ET) and six-minute walk test (6MWT) to determine CRF. The test results were compared to disease parameters and with each other. RESULTS Considering the ET, 20 (62.5%) patients had very poor or poor CRF, and in 12 (37.5%), it was regular or good. In the 6MWT, 13 (40.6%) individuals had poor CRF, in 12 (37.5%), it was very poor, and in seven (21.9%), regular. NAFLD activity score (NAS) ≥5 was observed in 12 (37.5%) individuals. Twelve (37.5%) patients were sedentary, 11 (34.4%), insufficiently active, and nine (28.1%), active. Obesity and liver inflammation on biopsy were associated with very poor/poor CRF. NAS ≥5 and sedentary lifestyle were independently associated with very poor/poor CRF by ET. Although mean VO2max values determined by both tests were similar, no correlation of VO2max determined by ET and 6MWT was observed, as occurred for the distance walked in 6MWT and values of metabolic equivalent (MET) determined by ET. There was no reproducibility between CRF determined by ET and 6MWT. CONCLUSION Most NAFLD patients had very poor or poor CRF. Severe liver injury (NAS ≥5) and sedentary lifestyle were independently associated with very poor/poor fitness, according to ET. No reproducibility was observed between the CRF defined by ET and 6MWT.
Collapse
Affiliation(s)
- Luciana Carneiro Pena
- Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Aduto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Cláudia Alves Couto
- Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Aduto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | | | | | - Guilherme Grossi Lopes Cançado
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Luciana Costa Faria
- Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Aduto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Eliane Viana Mancuzo
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Serviço de Pneumologia e Cirurgia Torácica, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Teresa Cristina Abreu Ferrari
- Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Aduto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
| |
Collapse
|
33
|
Moore JA, Wheless WH, Zhang J, Marsden J, Mauldin PD, Moran WP, Schreiner AD. Gaps in Confirmatory Fibrosis Risk Assessment in Primary Care Patients with Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2023; 68:2946-2953. [PMID: 37193930 PMCID: PMC10659111 DOI: 10.1007/s10620-023-07959-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 04/25/2023] [Indexed: 05/18/2023]
Abstract
BACKGROUND As recommendations for non-invasive fibrosis risk assessment in nonalcoholic fatty liver disease (NAFLD) emerge, it is not known how often they are performed in primary care. AIMS We investigated the completion of confirmatory fibrosis risk assessment in primary care patients with NAFLD and indeterminate-risk or greater Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Scores (NFS). METHODS This retrospective cohort study of electronic health record data from a primary care clinic identified patients with diagnoses of NAFLD from 2012 through 2021. Patients with a diagnosis of a severe liver disease outcome during the study period were excluded. The most recent FIB-4 and NFS scores were calculated and categorized by advanced fibrosis risk. Charts were reviewed to identify the outcome of a confirmatory fibrosis risk assessment by liver elastography or liver biopsy for all patients with indeterminate-risk or higher FIB-4 (≥ 1.3) and NFS (≥ - 1.455) scores. RESULTS The cohort included 604 patients diagnosed with NAFLD. Two-thirds of included patients (399) had a FIB-4 or NFS score greater than low-risk, 19% (113) had a high-risk FIB-4 (≥ 2.67) or NFS (≥ 0.676) score, and 7% (44) had high-risk FIB-4 and NFS values. Of these 399 patients with an indication for a confirmatory fibrosis test, 10% (41) underwent liver elastography (24) or liver biopsy (18) or both (1). CONCLUSIONS Advanced fibrosis is a key indicator of future poor health outcomes in patients with NAFLD and a critical signal for referral to hepatology. Significant opportunities exist to improve confirmatory fibrosis risk assessment in patients with NAFLD.
Collapse
Affiliation(s)
- Joseph A Moore
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - William H Wheless
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Jingwen Zhang
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Justin Marsden
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Patrick D Mauldin
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - William P Moran
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Andrew D Schreiner
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
| |
Collapse
|
34
|
Jiang W, Mao X, Liu Z, Zhang T, Jin L, Chen X. Global Burden of Nonalcoholic Fatty Liver Disease, 1990 to 2019: Findings From the Global Burden of Disease Study 2019. J Clin Gastroenterol 2023; 57:631-639. [PMID: 35921320 DOI: 10.1097/mcg.0000000000001739] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/06/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver diseases worldwide. We provided a comprehensive description regarding the disease burden of NAFLD in 204 countries and territories. MATERIALS AND METHODS We reported the deaths and disability-adjusted life years (DALYs) related to NAFLD in the Global Burden of Disease database by sex, age, specific causes, and regions. Estimated annual percentage change was applied to describe the changing trends. RESULTS Globally, the NAFLD-related deaths and DALYs in 2019 were 0.17 million [95% uncertainty interval (UI): 0.13 to 0.21] and 4.42 million (95% UI: 3.35 to 5.67), increased by 80.2% and 62.9% compared with 1990, respectively. The overall age-standardized rate of mortality and DALYs (ASMR and ASDR) showed a downward trend from 1990 to 2019, the estimated annual percentage change were -0.67 (95% confidence interval: -0.76, -0.57) and -0.82 (95% confidence interval: -0.93, -0.7), respectively. NAFLD-related deaths due to cirrhosis and liver cancer increased by 76.7% and 95.1% between 1990 and 2019. The ASMR and ASDR were the highest in the middle and low sociodemographical index regions in 2019, respectively. Of the 21 Global Burden of Disease regions, Eastern Europe, Central Asia, High-income North America, and Australasia experienced an increase in both ASMR and ASDR. CONCLUSIONS NAFLD imposes heavy disease burden on humankind worldwide, especially in countries with low-to-middle sociodemographical index level. More potent measures are urgently needed in regions with rising age-standardized rate to forestall the increase of NAFLD disease burden.
Collapse
Affiliation(s)
- Wei Jiang
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences
- Fudan University Taizhou Institute of Health Sciences, Taizhou
| | - Xianhua Mao
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Zhenqiu Liu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences
- Fudan University Taizhou Institute of Health Sciences, Taizhou
| | - Tiejun Zhang
- Department of Epidemiology, School of Public Health
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai
- Fudan University Taizhou Institute of Health Sciences, Taizhou
| | - Li Jin
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences
- Fudan University Taizhou Institute of Health Sciences, Taizhou
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences
- Fudan University Taizhou Institute of Health Sciences, Taizhou
| |
Collapse
|
35
|
Johira Y, Nakahara T, Kinami T, Yamasaki S, Kosaka M, Shirane Y, Miura R, Murakami S, Yano S, Amioka K, Naruto K, Ando Y, Kosaka Y, Kodama K, Uchikawa S, Fujino H, Ono A, Murakami E, Okamoto W, Yamauchi M, Kawaoka T, Hayes CN, Tsuge M, Imamura M, Aikata H, Oka S. Impact and usefulness of the transition to the new MAFLD classification for non-B, non-C HCC: a retrospective cohort study. BMC Gastroenterol 2023; 23:222. [PMID: 37380950 DOI: 10.1186/s12876-023-02851-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 06/09/2023] [Indexed: 06/30/2023] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new classification system for fatty liver disease. In this study, we investigated the clinical characteristics of patients with MAFLD-hepatocellular carcinoma (HCC) in comparison with those with nonalcoholic fatty liver disease (NAFLD) and considered the validity and challenges of the new criteria. METHODS This study included 237 untreated non-B, non-C HCC patients with hepatic steatosis. We examined the profile and laboratory findings of patients with MAFLD-HCC and NAFLD-HCC. We also classified MAFLD-HCC patients according to the factors on which the diagnosis was based and compared their clinical characteristics. RESULTS A total of 222 (94%) and 101 (43%) patients were diagnosed with MAFLD and NAFLD, respectively. MAFLD-HCC patients were more likely to be male than NAFLD-HCC, but there were no significant differences in metabolic indices, noninvasive liver fibrosis score or HCC status. In a study of MAFLD-HCC patients by diagnostic factor, those with overweight only were younger and had advanced liver fibrosis histologically, and when limited to patients younger than 70 years, the majority were overweight. Redefinition of overweight as BMI ≥ 25 reduced the number of MAFLD-HCC patients by only 5, from 222 to 217. CONCLUSIONS MAFLD accounted for the majority of non-B, non-C HCC cases with hepatic steatosis. Examination of additional cases and revision of the detailed criteria is needed so that it can be used to efficiently select patients with fatty liver who are at high risk of developing HCC.
Collapse
Affiliation(s)
- Yusuke Johira
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
| | - Takahiro Kinami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shintaro Yamasaki
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masanari Kosaka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Shirane
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryoichi Miura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Serami Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shigeki Yano
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kei Amioka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kensuke Naruto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuwa Ando
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yumi Kosaka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kenichiro Kodama
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Wataru Okamoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - C Nelson Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
36
|
Armandi A, Bugianesi E. Extrahepatic Outcomes of Nonalcoholic Fatty Liver Disease: Cardiovascular Diseases. Clin Liver Dis 2023; 27:239-250. [PMID: 37024205 DOI: 10.1016/j.cld.2023.01.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Patients with nonalcoholic fatty liver disease (NAFLD) are at high risk of cardiovascular disease, including carotid atherosclerosis, coronary artery disease, heart failure, and arrhythmias. The risk is partially due to shared risk factors, but it may vary according to liver injury. A fatty liver may induce an atherogenic profile, the local necro-inflammatory changes of nonalcoholic steatohepatitis may enhance systemic metabolic inflammation, and fibrogenesis can run parallel in the liver and in the myocardium and precedes heart failure. The detrimental impact of a Western diet combines with polymorphisms in genes associated with atherogenic dyslipidemia. Shared clinical/diagnostic algorithms are needed to manage the cardiovascular risk in NAFLD.
Collapse
Affiliation(s)
- Angelo Armandi
- Department of Medical Sciences, University of Turin, Corso Dogliotti 14, Torino 10126, Italy
| | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, Corso Dogliotti 14, Torino 10126, Italy.
| |
Collapse
|
37
|
Saxena AR, Lyle SA, Khavandi K, Qiu R, Whitlock M, Esler WP, Kim AM. A phase 2a, randomized, double-blind, placebo-controlled, three-arm, parallel-group study to assess the efficacy, safety, tolerability and pharmacodynamics of PF-06835919 in patients with non-alcoholic fatty liver disease and type 2 diabetes. Diabetes Obes Metab 2023; 25:992-1001. [PMID: 36515213 DOI: 10.1111/dom.14946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/29/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022]
Abstract
AIM To assess the safety, tolerability and pharmacodynamics (PD) of the ketohexokinase inhibitor PF-06835919 in participants with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). MATERIALS AND METHODS This double-blind, placebo-controlled, parallel-group study enrolled adults with NAFLD (≥ 8% whole liver fat [WLF] using MRI proton density fat fraction [MRI-PDFF]) and T2D on stable doses of metformin (≥ 500 mg/day). Participants received once-daily placebo, PF-06835919 150 or 300 mg for 16 weeks. Randomization (1:1:1) was via an interactive response technology system. Endpoints included percentage change from baseline (CFB) in WLF using MRI-PDFF (primary endpoint) and CFB in HbA1c (co-primary endpoint) at 16 weeks, PD, safety and tolerability. RESULTS Among 164 participants randomized and treated, 145 completed the treatment (placebo, n = 50; PF-06835919 150 mg, n = 46; PF-06835919 300 mg, n = 49). At week 16, least squares mean (90% confidence interval) percentage CFB in WLF was -5.26% (-12.86%, 2.99%), -17.05% (-24.01%, -9.46%) and -19.13% (-25.51%, -12.20%) in the placebo, PF-06835919 150-mg and 300-mg groups, respectively (PF-06835919 300-mg group vs. placebo, P = .0288). Modest numerical reductions in HbA1c were observed in all groups that did not reach statistical significance. Treatment-emergent adverse event incidence was similar across groups (40.7%, 45.5% and 32.7% in the placebo, PF-06835919 150-mg and 300-mg groups, respectively), with no apparent dose-related trend. CONCLUSIONS PF-06835919 administration over 16 weeks was generally safe and well tolerated and resulted in reductions in WLF in participants with NAFLD and T2D.
Collapse
Affiliation(s)
- Aditi R Saxena
- Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA
| | - Stephanie-An Lyle
- Early Clinical Development, Pfizer Inc, Cambridge, Massachusetts, USA
| | - Kaivan Khavandi
- Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA
| | - Ruolun Qiu
- Early Clinical Development, Pfizer Inc, Cambridge, Massachusetts, USA
| | - Mark Whitlock
- Early Clinical Development, Pfizer Inc, Cambridge, UK
| | - William P Esler
- Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA
| | - Albert M Kim
- Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA
| |
Collapse
|
38
|
Dumond Bourie A, Potier JB, Pinget M, Bouzakri K. Myokines: Crosstalk and Consequences on Liver Physiopathology. Nutrients 2023; 15:nu15071729. [PMID: 37049569 PMCID: PMC10096786 DOI: 10.3390/nu15071729] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/29/2023] [Accepted: 03/30/2023] [Indexed: 04/03/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease mainly characterized by the hepatic accumulation of lipid inducing a deregulation of β-oxidation. Its advanced form is non-alcoholic steatohepatitis (NASH), which, in addition to lipid accumulation, induces hepatocellular damage, oxidative stress and fibrosis that can progress to cirrhosis and to its final stage: hepatocellular carcinoma (HCC). To date, no specific therapeutic treatment exists. The implications of organ crosstalk have been highlighted in many metabolic disorders, such as diabetes, metabolic-associated liver diseases and obesity. Skeletal muscle, in addition to its role as a reservoir and consumer of energy and carbohydrate metabolism, is involved in this inter-organs’ communication through different secreted products: myokines, exosomes and enzymes, for example. Interestingly, resistance exercise has been shown to have a beneficial impact on different metabolic pathways, such as lipid oxidation in different organs through their secreted products. In this review, we will mainly focus on myokines and their effects on non-alcoholic fatty liver disease, and their complication: non-alcoholic steatohepatitis and HCC.
Collapse
Affiliation(s)
- Aurore Dumond Bourie
- European Center for the Study of Diabetes (CeeD), Research Unit of Strasbourg University “Diabetes and Therapeutics”, UR7294, 67200 Strasbourg, France
| | | | - Michel Pinget
- European Center for the Study of Diabetes (CeeD), Research Unit of Strasbourg University “Diabetes and Therapeutics”, UR7294, 67200 Strasbourg, France
| | - Karim Bouzakri
- European Center for the Study of Diabetes (CeeD), Research Unit of Strasbourg University “Diabetes and Therapeutics”, UR7294, 67200 Strasbourg, France
- ILONOV, 67200 Strasbourg, France
| |
Collapse
|
39
|
Mitra S, Halder AK, Ghosh N, Mandal SC, Cordeiro MNDS. Multi-model in silico characterization of 3-benzamidobenzoic acid derivatives as partial agonists of Farnesoid X receptor in the management of NAFLD. Comput Biol Med 2023; 157:106789. [PMID: 36963353 DOI: 10.1016/j.compbiomed.2023.106789] [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: 12/02/2022] [Revised: 02/19/2023] [Accepted: 03/11/2023] [Indexed: 03/16/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a pathological condition which is strongly correlated with fat accumulation in the liver that has become a major health hazard globally. So far, limited treatment options are available for the management of NAFLD and partial agonism of Farnesoid X receptor (FXR) has proven to be one of the most promising strategies for treatment of NAFLD. In present work, a range of validated predictive cheminformatics and molecular modeling studies were performed with a series of 3-benzamidobenzoic acid derivatives in order to recognize their structural requirements for possessing higher potency towards FXR. 2D-QSAR models were able to extract the most significant structural attributes determining the higher activity towards the receptor. Ligand-based pharmacophore model was created with a novel and less-explored open access tool named QPhAR to acquire information regarding important 3D-pharmacophoric features that lead to higher agonistic potential towards the FXR. The alignment of the dataset compounds based on pharmacophore mapping led to 3D-QSAR models that pointed out the most crucial steric and electrostatic influence. Molecular dynamics (MD) simulation performed with the most potent and the least potent derivatives of the current dataset helped us to understand how to link the structural interpretations obtained from 2D-QSAR, 3D-QSAR and pharmacophore models with the involvement of specific amino acid residues in the FXR protein. The current study revealed that hydrogen bond interactions with carboxylate group of the ligands play an important role in the ligand receptor binding but higher stabilization of different helices close to the binding site of FXR (e.g., H5, H6 and H8) through aromatic scaffolds of the ligands should lead to higher activity for these ligands. The present work affords important guidelines towards designing novel FXR partial agonists for new therapeutic options in the management of NAFLD. Moreover, we relied mainly on open-access tools to develop the in-silico models in order to ensure their reproducibility as well as utilization.
Collapse
Affiliation(s)
- Soumya Mitra
- Dr. B.C. Roy College of Pharmacy & Allied Health Sciences, Durgapur, 713206, India
| | - Amit Kumar Halder
- Dr. B.C. Roy College of Pharmacy & Allied Health Sciences, Durgapur, 713206, India; LAQV@REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007, Porto, Portugal
| | - Nilanjan Ghosh
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India
| | - Subhash C Mandal
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India
| | - M Natália D S Cordeiro
- LAQV@REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007, Porto, Portugal.
| |
Collapse
|
40
|
Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease. mBio 2023; 14:e0266322. [PMID: 36715540 PMCID: PMC9973343 DOI: 10.1128/mbio.02663-22] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Numerous studies have described specific metabolites as biomarkers of severe liver diseases, but very few have measured gut microbiota (GM)-produced metabolites in fatty liver disease. We aimed at finding GM signatures and metabolite markers in plasma and feces related to high liver fat content. Based on imaging, we divided study participants into low (<5%, LF, n = 25) and high (>5%, HF, n = 39) liver fat groups. Fecal (LF n = 14, HF n = 25) and plasma (LF n = 11, HF n = 7) metabolomes of subsets of participants were studied using liquid chromatography/high resolution mass spectrometry. The GM were analyzed using 16S rRNA gene sequencing. Additionally, blood clinical variables and diet were studied. Dyslipidemia, higher liver enzymes and insulin resistance characterized the HF group. No major differences in diet were found between the groups. In the GM, the HF group had lower abundance of Bacteroides and Prevotellaceae NK3B31 group than the LF group after adjusting for metformin use or obesity. In feces, the HF group had higher levels of lysine and histidine degradation products, while 6-hydroxybetatestosterone (metabolized by CYP3A4) was low. Higher plasma levels of caffeine and its metabolites in the HF group indicate that the activity of hepatic CYP1A2 was lower than in the LF group. Our results suggest, that low fecal Prevotellaceae NK3B31 and Bacteroides abundance, and increased lysine and histidine degradation may serve as GM biomarkers of high liver fat. Altered plasma caffeine metabolites and lowered testosterone metabolism may specify decreased CYP activities, and their potential utility, as biomarkers of fatty liver disease. IMPORTANCE Because the high prevalence of nonalcoholic fatty liver disease sets diagnostic challenges to health care, identification of new biomarkers of the disease that in the future could have potential utility as diagnostic biomarkers of high liver fat content is important. Our results show that increased amino acid degradation products in the feces may be such biomarkers. In the blood, molecules that indicate defective hepatic metabolic enzyme activities were identified in individuals with high liver fat content.
Collapse
|
41
|
Kuraji R, Shiba T, Dong TS, Numabe Y, Kapila YL. Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis. World J Gastroenterol 2023; 29:967-996. [PMID: 36844143 PMCID: PMC9950865 DOI: 10.3748/wjg.v29.i6.967] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 11/14/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.
Collapse
Affiliation(s)
- Ryutaro Kuraji
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-0071, Japan
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
| | - Takahiko Shiba
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, United States
- Department of Periodontology, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
| | - Tien S Dong
- The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-8159, Japan
| | - Yvonne L Kapila
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
- Sections of Biosystems and Function and Periodontics, Professor and Associate Dean of Research, Felix and Mildred Yip Endowed Chair in Dentistry, University of California Los Angeles, Los Angeles, CA 90095, United States
| |
Collapse
|
42
|
Tan Y, He Q, Chan KHK. Identification of shared genetic architecture between non-alcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis. Front Endocrinol (Lausanne) 2023; 14:1050049. [PMID: 37033223 PMCID: PMC10073682 DOI: 10.3389/fendo.2023.1050049] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 03/09/2023] [Indexed: 04/11/2023] Open
Abstract
BACKGROUND The incidence of complications of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) has been increasing. METHOD In order to identify the shared genetic architecture of the two disease phenotypes of NAFLD and T2D, a European population-based GWAS summary and a cross-trait meta-analysis was used to identify significant shared genes for NAFLD and T2D. The enrichment of shared genes was then determined through the use of functional enrichment analysis to investigate the relationship between genes and phenotypes. Additionally, differential gene expression analysis was performed, significant differentially expressed genes in NAFLD and T2D were identified, genes that overlapped between those that were differentially expressed and cross-trait results were reported, and enrichment analysis was performed on the core genes that had been obtained in this way. Finally, the application of a bidirectional Mendelian randomization (MR) approach determined the causal link between NAFLD and T2D. RESULT A total of 115 genes were discovered to be shared between NAFLD and T2D in the GWAS analysis. The enrichment analysis of these genes showed that some were involved in the processes such as the decomposition and metabolism of lipids, phospholipids, and glycerophospholipids. Additionally, through the use of differential gene expression analysis, 15 core genes were confirmed to be linked to both T2D and NAFLD. They were correlated with carcinoma cells and inflammation. Furthermore, the bidirectional MR identified a positive causal relationship between NAFLD and T2D. CONCLUSION Our study determined the genetic structure shared between NAFLD and T2D, offering a new reference for the genetic pathogenesis and mechanism of NAFLD and T2D comorbidities.
Collapse
Affiliation(s)
- Yajing Tan
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Qian He
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Kei Hang Katie Chan
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Electrical Engineering, City University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Epidemiology, Center for Global Cardiometabolic Health, Brown University, Providence, RI, United States
- *Correspondence: Kei Hang Katie Chan,
| |
Collapse
|
43
|
Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease. Obes Surg 2023; 33:247-255. [PMID: 36464738 DOI: 10.1007/s11695-022-06380-7] [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: 08/12/2022] [Revised: 11/17/2022] [Accepted: 11/27/2022] [Indexed: 12/07/2022]
Abstract
PURPOSE Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. MATERIALS AND METHODS This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. RESULTS One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8 years, and BMI was 48.6 ± 7.5 kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. CONCLUSION Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.
Collapse
|
44
|
Pipitone RM, Ciccioli C, Infantino G, La Mantia C, Parisi S, Tulone A, Pennisi G, Grimaudo S, Petta S. MAFLD: a multisystem disease. Ther Adv Endocrinol Metab 2023; 14:20420188221145549. [PMID: 36726391 PMCID: PMC9885036 DOI: 10.1177/20420188221145549] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 11/26/2022] [Indexed: 01/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), affecting about 25% of general population and more than 50% of dysmetabolic patients, is an emerging cause of chronic liver disease and its complications. Recently, an international consensus of experts proposed to rename this disease as 'Metabolic dysfunction-Associated Fatty Liver Disease' (MAFLD) to focus on the bidirectional interplay between fatty liver and metabolic alterations and to stress the need of assessing fatty liver independently from alcohol consumption and other coexisting causes of liver disease. The peculiarity of NAFLD/MAFLD lies in the presence of a higher risk of not only - as expected - liver-related events but also of extrahepatic events, mostly cardiovascular and cancers. Available evidence suggests that these associations are not only the expression of sharing the same risk factors but shed light about the ability of NAFLD/MAFLD and particularly of its progressive form - nonalcoholic/metabolic dysfunction-associated steatohepatitis - to act as an independent risk factor via promotion of atherogenic dyslipidemia and a proinflammatory, profibrogenic, and procoagulant systemic environment. The present review summarizes available epidemiological and clinical evidence supporting the concept of NAFLD/MAFLD as a multisystemic disease, and highlights potential explanatory mechanisms underlying the association between NAFLD/MAFLD and extrahepatic disorders.
Collapse
Affiliation(s)
- Rosaria Maria Pipitone
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Carlo Ciccioli
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Giuseppe Infantino
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Claudia La Mantia
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Stefanie Parisi
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Adele Tulone
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Grazia Pennisi
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Stefania Grimaudo
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | | |
Collapse
|
45
|
Prognostic value of De Ritis ratio with aspartate aminotransferase and alanine aminotransferase within the reference range. Clin Chim Acta 2023; 538:46-52. [PMID: 36370837 DOI: 10.1016/j.cca.2022.11.005] [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: 11/04/2022] [Accepted: 11/04/2022] [Indexed: 11/10/2022]
Abstract
BACKGROUND Whether aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (De Ritis ratio) with AST and ALT activities within the reference range has prognostic value is unknown. METHODS This study included 3392 patients with stable coronary artery disease and AST and ALT activities within the reference range. Patients are categorized in groups according to tertiles of the De Ritis ratio: a group with De Ritis ratio in the 1st tertile (De Ritis ratio: 0.22 to 0.81; n = 1131), a group with De Ritis ratio in the 2nd tertile (De Ritis ratio: >0.81 to 1.09; n = 1130) and a group with De Ritis ratio in the 3rd tertile (De Ritis ratio: >1.09 to 3.40; n = 1131). The primary endpoint was 3-year mortality. RESULTS The mean value of De Ritis ratio was 1.00 ± 0.39 (range: 0.22-3.40). Overall, there were 234 deaths at 3 years: 43 deaths in patients of 1st tertile, 75 deaths in patients of 2nd tertile and 116 deaths in patients of 3rd tertile of De Ritis ratio (Kaplan-Meier estimates of 3-year mortality, 4.4 %, 7.8 % and 12.5 %, respectively; (adjusted hazard ratio = 1.24, 95 % confidence interval 1.12 to 1.38; P < 0.001 for 1 unit higher De Ritis ratio). The C-statistic of the risk prediction model for mortality with baseline demographical and clinical variables without De Ritis ratio was 0.803 [0.774-0.832] and it increased to 0.810 [0.782-0.839] after inclusion of De Ritis ratio into the model (P = 0.038). CONCLUSIONS An elevated De Ritis ratio with aminotransferase levels within the reference range was associated with the increased risk of mortality.
Collapse
|
46
|
He W, Huang C, Wang L, Su W, Wang S, Huang P, Zhang X, Huang Y, Zhao Y, Lin M, Shi X, Li X. The correlation between triiodothyronine and the severity of liver fibrosis. BMC Endocr Disord 2022; 22:313. [PMID: 36503486 PMCID: PMC9743744 DOI: 10.1186/s12902-022-01228-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis. METHODS We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms. RESULTS Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2+CD9+ macrophage, which had been identified an important player in the progression of liver fibrosis. CONCLUSION The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.
Collapse
Affiliation(s)
- Weiwei He
- School of Medicine, Xiamen University, Xiamen, China
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Caoxin Huang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Liying Wang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Weijuan Su
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Shunhua Wang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Peiying Huang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Xiaofang Zhang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Yinxiang Huang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Yan Zhao
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Mingzhu Lin
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China
| | - Xiulin Shi
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China.
- Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, No.55 Zhenhai Road, 361003, Xaimen, China.
| | - Xuejun Li
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
- Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, Fujian, China.
- Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, No.55 Zhenhai Road, 361003, Xaimen, China.
| |
Collapse
|
47
|
Kaur S, Garg N, Rubal R, Dhiman M. Correlative study on heavy metal-induced oxidative stress and hypertension among the rural population of Malwa Region of Punjab, India. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:90948-90963. [PMID: 35881282 DOI: 10.1007/s11356-022-20850-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/11/2022] [Indexed: 06/15/2023]
Abstract
Heavy metal-induced toxicity contributes to the progression of various metabolic disorders and possible mechanisms involved in disease progression are not well established. In this study, the correlation of heavy metal exposure and hypertension have been demonstrated. The results showed that in hypertensive subjects, the lipid profiles (triglycerides, LDL-C, HDL-C, and total cholesterol) and cardiac markers (CK-MB and LDH) were altered abruptly. As a consequence of heavy- induced oxidative stress, the oxidants (TBARS and protein carbonyls) and antioxidants (SOD, GSH, and TAC) were significantly increased and decreased, respectively in hypertension subjects. The concentrations of heavy metals (Pb, Cd, and As) exceeded the permissible limits in hypertensive subjects. The Nrf-2 genotyping indicated that heavy metals may induce mutations at molecular level. The results of correlation analysis revealed that the heavy metals interact with cellular components and interfere with metabolic processes which then results in disturbed lipid profile, enhanced oxidative stress, and reduced antioxidant status. The current study systematically estimated the association of hair and nail heavy metal concentrations with hypertension among the population residing in the Malwa region of Punjab. The proposed study highlighted that heavy metals act as a silent risk factor in the hypertension progression in the population of Malwa region. Future studies are required to confirm current findings and further scrutinize the effect of heavy metals exposure in early adulthood, early, and late mid-life to develop metabolic complications such as hypertension.
Collapse
Affiliation(s)
- Sukhchain Kaur
- Department of Microbiology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, India
| | - Neha Garg
- Department of Microbiology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, India
| | - Rubal Rubal
- Department of Microbiology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, India
| | - Monisha Dhiman
- Department of Microbiology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, India.
| |
Collapse
|
48
|
Josloff K, Beiriger J, Khan A, Gawel RJ, Kirby RS, Kendrick AD, Rao AK, Wang RX, Schafer MM, Pearce ME, Chauhan K, Shah YB, Marhefka GD, Halegoua-DeMarzio D. Comprehensive Review of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease. J Cardiovasc Dev Dis 2022; 9:419. [PMID: 36547416 PMCID: PMC9786069 DOI: 10.3390/jcdd9120419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/16/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022] Open
Abstract
Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk. We also discuss the emerging and complex biochemical relationship between NAFLD and its common comorbid conditions, and how they coalesce to increase CVD risk. With NAFLD's rising prevalence and deleterious effects on the cardiovascular system, a complete understanding of the disease must be undertaken, as well as effective strategies to prevent and treat its common comorbid conditions.
Collapse
Affiliation(s)
- Kevan Josloff
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Jacob Beiriger
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Adnan Khan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Richard J. Gawel
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Richard S. Kirby
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Aaron D. Kendrick
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Abhinav K. Rao
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Roy X. Wang
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Michelle M. Schafer
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Margaret E. Pearce
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Kashyap Chauhan
- Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Yash B. Shah
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Gregary D. Marhefka
- Department of Internal Medicine, Division of Cardiology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| |
Collapse
|
49
|
Yepmo M, Potier JB, Pinget M, Grabarz A, Bouzakri K, Dumond Bourie A. Discussing the role of circular RNA in the pathogenesis of non-alcoholic fatty liver disease and its complications. Front Endocrinol (Lausanne) 2022; 13:1035159. [PMID: 36407314 PMCID: PMC9667057 DOI: 10.3389/fendo.2022.1035159] [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: 09/02/2022] [Accepted: 10/17/2022] [Indexed: 01/24/2023] Open
Abstract
Circular RNAs (circRNAs) are class of non-coding RNA, which are characterized by a covalently closed loop structure. Functionally they can act on cellular physiology, notably by sponging microRNAs (miR), regulating gene expression or interacting with binding protein. To date, circRNAs might represent an interesting, underexploited avenue for new target discovery for therapeutic applications, especially in the liver. The first characteristic of non-alcoholic fatty liver disease (NAFLD) is hepatic cholesterol accumulation, followed by its advanced form of the affection, nonalcoholic steatohepatitis (NASH), due to the occurrence of lobular inflammation, irreversible fibrosis, and in some cases hepatocellular carcinoma (HCC). Therefore, studies have investigated the importance of the dysregulation of circRNAs in the onset of metabolic disorders. In this review, we summarize the potential role of circRNAs in the development of metabolic diseases associated with the liver such as NAFLD or NASH, and their potential to become therapeutic strategies for these pathologies.
Collapse
Affiliation(s)
- Melissa Yepmo
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
| | - Jean-Baptiste Potier
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
- ILONOV, Strasbourg, France
| | - Michel Pinget
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
| | | | - Karim Bouzakri
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
- ILONOV, Strasbourg, France
| | - Aurore Dumond Bourie
- Centre européen d’étude du Diabète, Unité Mixte de Recherche de l’Université de Strasbourg « Diabète et Thérapeutique », Strasbourg, France
| |
Collapse
|
50
|
Lee SM, Jung YM, Choi ES, Kwak SH, Koo JN, Oh IH, Kim BJ, Kim SM, Kim SY, Kim GM, Joo SK, Koo BK, Shin S, Norwitz ER, Park CW, Jun JK, Kim W, Park JS. Metabolic Dysfunction-Associated Fatty Liver Disease and Subsequent Development of Adverse Pregnancy Outcomes. Clin Gastroenterol Hepatol 2022; 20:2542-2550.e8. [PMID: 34798335 DOI: 10.1016/j.cgh.2021.11.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/28/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), rather than nonalcoholic fatty liver disease (NAFLD), was proposed to better describe liver disease associated with metabolic dysfunction (MD). In this study, we attempted to investigate the impact of MAFLD on pregnancy complications. METHODS The current study is a secondary analysis of a multicenter prospective cohort designed to examine the risk of NAFLD during pregnancy. In the first trimester, enrolled pregnant women were evaluated for hepatic steatosis by liver ultrasonography, and blood samples were collected for biochemical measurements. The study population was divided into 3 groups: no NAFLD, hepatic steatosis but without metabolic dysfunction (non-MD NAFLD), and MAFLD. The primary outcome was the subsequent development of adverse pregnancy outcomes, including gestational diabetes mellitus, pregnancy-associated hypertension, preterm birth, and fetal growth abnormalities. RESULTS The study population consisted of 1744 pregnant women, including 1523 with no NAFLD, 43 with non-MD NAFLD, and 178 with MAFLD. The risk of subsequent development of adverse pregnancy outcomes was higher in MAFLD than in non-MD NAFLD (adjusted odds ratio, 4.03; 95% CI, 1.68-9.67), whereas the risk was not significantly different between no NAFLD and non-MD NAFLD. Among women with no NAFLD, the presence of MD increased the risk of adverse pregnancy outcomes. However, women with MAFLD were at higher risk for adverse pregnancy outcomes than women with no NAFLD without MD or those with no NAFLD with MD. CONCLUSIONS In pregnant women, MAFLD may be associated with an increased risk of subsequent adverse pregnancy outcomes.
Collapse
Affiliation(s)
- Seung Mi Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Young Mi Jung
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Saem Choi
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Soo Heon Kwak
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | | | | | - Byoung Jae Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea
| | - Sun Min Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea
| | - Sang Youn Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Gyoung Min Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
| | - Sae Kyung Joo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea
| | - Bo Kyung Koo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea
| | - Sue Shin
- Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea
| | - Errol R Norwitz
- Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, Massachusetts
| | - Chan-Wook Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Kwan Jun
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.
| | - Joong Shin Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
| |
Collapse
|