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Tampaki M, Cholongitas E. Key Points and Future Directions from the 2024 Chinese Guidelines for Fatty Liver Disease. J Clin Transl Hepatol 2025; 13:434-439. [PMID: 40385943 PMCID: PMC12078172 DOI: 10.14218/jcth.2025.00051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/10/2025] [Accepted: 03/14/2025] [Indexed: 05/20/2025] Open
Affiliation(s)
- Maria Tampaki
- First Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Cholongitas
- First Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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Wang Y, Wang P. Development and validation of a new diagnostic prediction model for NAFLD based on machine learning algorithms in NHANES 2017-2020.3. Hormones (Athens) 2025:10.1007/s42000-025-00634-6. [PMID: 39939537 DOI: 10.1007/s42000-025-00634-6] [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: 10/13/2024] [Accepted: 02/03/2025] [Indexed: 02/14/2025]
Abstract
AIMS Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that can trigger the metabolic syndrome. Early prevention and treatment of NAFLD is still a huge challenge for patients and clinicians. The aim of this study was to develop and validate machine learning (ML)-based predictive models. The model with optimal performance would be developed as a set of simple arithmetic tools for predicting the risk of NAFLD individually. METHODS Statistical analyses were performed in 2428 individuals extracted from the National Health and Nutrition Examination Survey (NHANES, cycle 2017-2020.3) database. Feature variables were selected by the least absolute shrinkage and selection operator (LASSO) regression. Seven ML algorithms, including logistic regression (LR), decision tree (DT), random forest (RF), extreme gradient boosting (XGB), K-nearest neighbor (KNN), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to construct models based on the feature variables and evaluate their performance. The model with the best performance was transformed into a diagnostic predictive nomogram (DPN). The DPN was developed into an online calculator and an Excel algorithm tool. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and subgroup analyses were used to compare and assess the predictive abilities of the DPN and six existing NAFLD predictive models, including the ZJU index, the hepatic steatosis index (HSI), the triglyceride-glucose index (TyG), the Framingham steatosis index (FSI), the fatty liver index (FLI), and the visceral adiposity index (VAI). RESULTS Among the 2428 participants, the prevalence of NAFLD was 47.45%. LASSO regression identified eight variables from 39 variables, including body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), triglyceride (TG), diabetes, hypertension, uric acid (UA), and race. Among the models constructed by the seven algorithms mentioned above, the LR-based model performed the best, demonstrating outstanding performance in terms of area under the curve (AUC, 0.823), accuracy (0.754), precision (0.768), specificity (0.804), and positive predictive value (0.768). It was then transformed into the DPN, which was successfully developed as an online calculator and an Excel algorithm tool. The diagnostic accuracy (AUC 0.856, 95% confidence interval (CI) 0.839-0.874, and AUC 0.823, 95% CI 0.793-0.854, respectively) and net clinical benefit of DPN in the training and validation sets were superior to those of the ZJU, HSI, TyG, FSI, FLI, and VAI. The results were maintained in subgroup analyses. CONCLUSIONS The LR model based on ML was developed, exhibiting good performance. DPN can be used as an individualized tool for rapid detection of NAFLD.
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Affiliation(s)
- Yazhi Wang
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, 730000, China
| | - Peng Wang
- The Department of Pharmacy, The 987th Hospital of Joint Logistics Support Force of People's Liberation Army, Baoji, Shaanxi, 721004, China.
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Suwała S, Junik R. Assessment of the Liver Steatosis and Fibrosis Risk in Metabolic Syndrome and Its Individual Components, Considering the Varying Definitions Used in Clinical Practice throughout Time: A Retrospective Cross-Sectional Study. Biomedicines 2024; 12:1739. [PMID: 39200204 PMCID: PMC11351204 DOI: 10.3390/biomedicines12081739] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 07/25/2024] [Accepted: 07/31/2024] [Indexed: 09/02/2024] Open
Abstract
Multiple modifications of metabolic syndrome diagnostic criteria have been made-NCEP: ATP III (from 2001, modified in 2004), IDF (2005), IDF Consortium (2009), or Polish Scientific Society Consortium standards (2022) are now frequently in use. Hepatosteatosis and hepatofibrosis are commonly mentioned aspects of metabolic syndrome that greatly increase the likelihood of developing complications. The objective of the study was to assess different diagnostic criteria for metabolic syndrome based on the prevalence of liver steatosis and fibrosis. A retrospective analysis was conducted on the medical data of 2102 patients. Out of all the single criteria, meeting the obesity criterion based on waist circumference showed the highest increase in the risk of hepatosteatosis (by 64-69%, depending on the definition used)-hypertriglyceridemia increased the risk of hepatofibrosis by 71%. Regardless of the specific criteria used, patients with metabolic syndrome had a 34-36% increased likelihood of developing hepatosteatosis-the probability of hepatofibrosis varied between 42% and 47% for the criteria established in 2004, 2005, and 2009, while the Polish 2022 criteria were not statistically significant (p = 0.818). It seems appropriate to establish consistent metabolic syndrome diagnostic criteria-the 2009 IDF guidelines are the most effective in assessing hepatosteatosis and fibrosis risk.
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Affiliation(s)
- Szymon Suwała
- Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;
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Song Z, Miao X, Xie X, Tang G, Deng J, Hu M, Liu S, Leng S. Associations between serum ferritin baselines and trajectories and the incidence of metabolic dysfunction-associated steatotic liver disease: a prospective cohort study. Lipids Health Dis 2024; 23:141. [PMID: 38760825 PMCID: PMC11100236 DOI: 10.1186/s12944-024-02129-6] [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: 03/24/2024] [Accepted: 04/30/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND AND AIMS Evidence from prospective cohort studies on the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and longitudinal changes in serum ferritin (SF) still limited. This study aimed to investigate the associations of SF baselines and trajectories with new-onset MASLD and to present a MASLD discriminant model. METHODS A total of 1895 participants who attended health examinations at least three times in a hospital in Dalian City between 2015 and 2022 were included. The main outcome was the incidence of MASLD. The associations between SF baselines and trajectories with the risk of MASLD were analyzed by Cox proportional hazards regression, restricted cubic spline (RCS) analysis and time-dependent receiver operating characteristic (ROC) curve analysis. In addition, a MASLD discrimination model was established using logistic regression analyses. RESULTS Among the 1895 participants, 492 developed MASLD during follow-up. Kaplan-Meier analysis indicated that participants in the low-stable trajectory group had a longer MASLD-free time compared with participants in other groups. Compared with those in the low-stable trajectory group, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of new-onset MASLD in the medium-high, high-stable and high-high trajectory groups were 1.54(1.18-2.00), 1.77(1.35-2.32) and 1.55(1.07-2.26), respectively (Ptrend < 0.001). The results were robust in subgroup and sensitivity analyses. Multivariate Cox proportional regression showed that SF was an independent risk factor of MASLD (HR = 1.002, 95%CI: 1.000-1.003, P = 0.003). The restricted cubic spline demonstrated a nonlinear relationship between SF and the risk of MASLD. The 8-variable model had high discriminative performance, good accuracy and clinical effectiveness. The ROC curve results showed that AUC was greater than that of the FLI, HSI and ZJU models (all P < 0.01). CONCLUSIONS Not only a higher baseline SF but also SF changing trajectory are significantly associated with risk of new-onset MASLD. SF could be a predictor of the occurrence of MASLD.
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Affiliation(s)
- Ziping Song
- Health Management Center, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Xinlei Miao
- Health Management Center, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Xiaoling Xie
- School of Public Health, Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Guimin Tang
- School of Public Health, Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Jiayi Deng
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Manling Hu
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China
| | - Shuang Liu
- School of Public Health, Dalian Medical University, Dalian, 116000, Liaoning, China
| | - Song Leng
- Health Management Center, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China.
- Department of Gastroenterology, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, China.
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Pashayee-Khamene F, Heidari Z, Fotros D, Hekmatdoost A, Karimi S, Ahmadzadeh S, Saberifiroozi M, Hatami B, Yari Z. Dietary acid load and cirrhosis-related mortality: a prospective cohort study. Sci Rep 2024; 14:3675. [PMID: 38355888 PMCID: PMC10867032 DOI: 10.1038/s41598-024-53882-8] [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: 11/25/2023] [Accepted: 02/06/2024] [Indexed: 02/16/2024] Open
Abstract
As a global health concern, cirrhosis contributes significantly to morbidity and mortality. This prospective cohort study aimed to investigate the association between dietary acid load (DAL) and cirrhosis-related mortality. Present study was conducted on 121 patients with newly diagnosed cirrhosis who were followed up for 48 months. Anthropometric measures, nutritional status and dietary intakes were assessed and DAL was estimated based on potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Crude and multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazard analyses. Participants in the high PRAL and NEAP scores had significantly higher intakes of grains and lower intakes of fruits and vegetables. Also, the intake of dairy products and legumes, nuts and seeds decreased significantly with increasing NEAP score. After adjustment of all the confounders, the risk of mortality in the second and third tertiles of PRAL was 5.9 times and 10.97 higher than those in the first tertile, respectively (P trend: 0.006). Similarly, comparing the risk of mortality in the second and third tertiles with the first tertile of NEAP showed a 4.46-fold and 12.3-fold increased risk, respectively (P trend: 0.010). Our findings suggested that DAL was significantly associated with cirrhosis-related mortality and highlight the need for further research to understand the underlying mechanisms and establish optimal DAL levels in cirrhotic patients.
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Affiliation(s)
- Fereshteh Pashayee-Khamene
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zeinab Heidari
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Danial Fotros
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Karimi
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saleheh Ahmadzadeh
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Saberifiroozi
- Liver and Pancreato-Biliary Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran.
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Kakouri NS, Thomopoulos CG, Siafi EP, Valatsou AE, Dimitriadis KS, Mani IP, Patsilinakos SP, Tousoulis DM, Tsioufis KP. Overview of the Association between Non-Alcoholic Fatty Liver Disease and Hypertension. CARDIOLOGY DISCOVERY 2023. [DOI: 10.1097/cd9.0000000000000113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its prevalence is rising. NAFLD is closely associated with metabolic syndrome, with both conditions sharing common clinical characteristics such as obesity, insulin resistance, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. Several observational studies have evaluated the relationship between NAFLD and hypertension, with the overall evidence suggesting a bidirectional relationship. It is hypothesized that activation of the sympathetic nervous and renin-angiotensin systems, observed in NAFLD with or without insulin resistance promotes the development of hypertension. In patients with hypertension, activation of these systems can lead to hepatic fibrosis and progressive inflammation through increased oxidative stress and activation of hepatic stellate cells and Kupffer cells. The present review examines the pathophysiologic and clinical evidence supporting the bidirectional association between NAFLD and hypertension.
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Affiliation(s)
- Niki S. Kakouri
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | | | - Eirini P. Siafi
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Angeliki E. Valatsou
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Kyriakos S. Dimitriadis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Iliana P. Mani
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | | | - Dimitrios M. Tousoulis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
| | - Konstantinos P. Tsioufis
- First Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens 11527, Greece
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Yip TCF, Wong GLH, Wong VWS, Goh GBB, Chan WK. Nonalcoholic Fatty Liver Disease: A Unique Entity or Part of the Metabolic Syndrome or Both. Med Clin North Am 2023; 107:449-463. [PMID: 37001947 DOI: 10.1016/j.mcna.2022.12.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. NAFLD is bidirectionally correlated with metabolic syndrome, which includes obesity, type 2 diabetes, hypertension, and dyslipidemia as major components. The presence of metabolic syndrome is associated with a higher prevalence of NAFLD, and vice versa. Also, the presence of metabolic syndrome in patients with NAFLD has been linked to a higher risk of cardiovascular diseases, liver-related complications, extrahepatic malignancies, and mortality, and possibly vice versa. Multidisciplinary care pathways including lifestyle modifications, control of metabolic risk, and potentially beneficial treatments are important to improve the clinical outcomes of patients with NAFLD.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, 20 College Road, Academia, Singapore 169856; Duke-NUS Medical School, Singapore.
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
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8
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Huang Q, Yu H, Zhong X, Tian Y, Cui Z, Quan Z. Association between hypertension and nonalcoholic fatty liver disease: a cross-sectional and meta-analysis study. J Hum Hypertens 2023; 37:313-320. [PMID: 35411023 DOI: 10.1038/s41371-022-00686-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 03/11/2022] [Accepted: 03/30/2022] [Indexed: 11/08/2022]
Abstract
The association between hypertension and nonalcoholic fatty liver disease (NAFLD) is not completely understood. This study aimed to investigate the association between hypertension and hepatic ultrasound examination-diagnosed positive NAFLD in healthy people; to conduct a comprehensive meta-analysis combining the results of previous studies; to explore whether hypertension was a risk factor for NAFLD. This study included 2049 adults (male: 870 and female: 1179), aged ≥20 years, whose anthropometric parameters were measured to analyze the risk of hypertension on NAFLD. We also collected data from 11 cross-sectional studies relevant to this topic using PubMed, Embase, Web of Science, CNKI, Wanfang, and CQVIP from beginning till 31 August 2020 and combined it with our data for a meta-analysis to explore whether hypertension was a risk factor for NAFLD. After adjusting for confounding factors, the odds of NAFLD in hypertensive subjects was 1.473 (95%CI: 1.119-1.938). After combining with 10 selected studies, 42711 participants were enrolled in meta-analysis. Hypertension was a risk factor for NAFLD (Z = 13.46, P < 0.001); the odds of NAFLD in hypertensive subjects was 1.43 (95%CI: 1.36-1.51). The results were consistent with the results of the meta-analysis. Further studies are required to confirm these results.
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Affiliation(s)
- Qingzhi Huang
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Hana Yu
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Xin Zhong
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Ying Tian
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Zhenhua Cui
- Department of Nephrology, Yanbian University Hospital, 119 Juzi Street, Yanji, 133000, Jilin, China
| | - Zhenyu Quan
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China.
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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: 16] [Impact Index Per Article: 8.0] [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.
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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
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10
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Mechanisms underlying the bidirectional association between nonalcoholic fatty liver disease and hypertension. Hypertens Res 2023; 46:539-541. [PMID: 36474031 DOI: 10.1038/s41440-022-01117-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 10/07/2022] [Indexed: 12/12/2022]
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Zhang S, Mak LY, Yuen MF, Seto WK. Screening strategy for non-alcoholic fatty liver disease. Clin Mol Hepatol 2023; 29:S103-S122. [PMID: 36447420 PMCID: PMC10029948 DOI: 10.3350/cmh.2022.0336] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 11/16/2022] [Indexed: 12/02/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately 25% of the general population worldwide, and is forecasted to increase global health burden in the 21st century. With the advancement of non-invasive tests for assessing and monitoring of steatosis and fibrosis, NAFLD screening is now feasible, and is increasingly highlighted in international guidelines related to hepatology, endocrinology, and pediatrics. Identifying high-risk populations (e.g., diabetes mellitus, obesity, metabolic syndrome) based on risk factors and metabolic characteristics for non-invasive screening is crucial and may aid in designing screening strategies to be more precise and effective. Many screening modalities are currently available, from serum-based methods to ultrasonography, transient elastography, and magnetic resonance imaging, although the diagnostic performance, cost, and accessibility of different methods may impact the actual implementation. A two-step assessment with serum-based fibrosis-4 index followed by imaging test vibration-controlled transient elastography can be an option to stratify the risk of liverrelated complications in NAFLD. There is a need for fibrosis surveillance, as well as investigating the cost-effectiveness of different screening algorithms and engaging primary care for first-stage triage screening.
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Affiliation(s)
- Saisai Zhang
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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Yang D, Lan J, Cen J, Han Y, Hu H. Association Between Hypertension and New-Onset Non-Alcoholic Fatty Liver Disease in Chinese Non-Obese People: A Longitudinal Cohort Study. Diabetes Metab Syndr Obes 2023; 16:345-363. [PMID: 36788988 PMCID: PMC9922508 DOI: 10.2147/dmso.s396011] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 01/18/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND Quantification of the relationship between hypertension and non-alcoholic fatty liver disease (NAFLD) risk is limited and controversial. This study aimed to investigate the relationship between hypertension and NAFLD in non-obese Chinese and to use different methods to demonstrate that hypertension is an independent risk factor for NAFLD. METHODS On 16,153 nonobese individuals, a retrospective cohort study was conducted in China to examine the impact of hypertension on incident NAFLD. We compared five methods: multivariable Cox proportional-hazards regression, propensity score-matched (PSM) analysis, propensity score adjustment method (considering the propensity score as a covariate in a multivariable Cox proportional-hazard regression), and two propensity score-based weighted methods-The first one estimated the hypertension effect in the overall study population-inverse probability of treatment weights (IPTW), the other in the hypertensive population-standardized mortality ratio (SMR) weights. We also used a genetic matching (GenMatch) algorithm to match the participants for sensitive analysis. RESULTS Between 2010 and 2014, 16,153 participants met our inclusion criteria, including 2427 (15.03%) with hypertension. A total of 2321 (14.37%) participants developed NAFLD during the median follow-up of 2.98 years. The crude hazard ratio (HR) between hypertension and incident NAFLD was 2.05 (95% confidence interval (CI): 1.87, 2.25). The adjusted HR depended on the different methods, ranging from 1.09 (95% CI: 0.77, 1.23) for the PSM method to 2.24 (95% CI: 2.05, 2.44) for the SMR weighted analysis. Hypertensive participants with high propensity scores had a higher risk of developing NAFLD in the future. Excluding participants with propensity scores <8% yielded comparable hazard ratios with a narrower range, from 1.04 to 1.80. After adjusting for the confounding variables, the relationship also existed in the GenMatch cohort as a sensitivity analysis (HR=1.06, 95% CI 1.01-1.13). CONCLUSION Hypertension is a significant cause of NAFLD in Chinese adults in non-obese Chinese adults, with the hazard ratio ranging from 1.09 to 2.24.
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Affiliation(s)
- Dezhi Yang
- Department of Cardiology Second Ward, Hechi People’s Hospital, Hechi, People’s Republic of China
| | - Jing Lan
- Department of Gastroenterology, Hechi People’s Hospital, Hechi, People’s Republic of China
| | - Ji Cen
- Department of Nephrology, Hechi People’s Hospital, Hechi, People’s Republic of China
| | - Yong Han
- Department of Emergency, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China
- Department of Emergency, The First Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China
- Correspondence: Yong Han, Department of Emergency, Shenzhen Second People’s Hospital, No. 3002 Sungang Road, Futian District, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86-755-83366388, Email
| | - Haofei Hu
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China
- Department of Nephrology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
- Haofei Hu, Department of Nephrology, Shenzhen Second People’s Hospital, No. 3002 Sungang Road, Futian District, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86-755-83366388, Email
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13
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Cattazzo F, Lombardi R, Mantovani A, Bevilacqua M, Zoncapè M, Iogna Prat L, Roccarina D, Fortuna L, Cespiati A, Sacerdoti D, Fracanzani AL, Tsochatzis E, Fava C, Dalbeni A. Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension. Nutr Metab Cardiovasc Dis 2022; 32:2839-2847. [PMID: 36404479 DOI: 10.1016/j.numecd.2022.08.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 07/31/2022] [Accepted: 08/03/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions. METHODS AND RESULTS A total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m2 and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14-20.93), while no association was found when either NAFLD or HT was considered alone. CONCLUSION Overt atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.
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Affiliation(s)
- Filippo Cattazzo
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| | - Rosa Lombardi
- Unit of Internal Medicine and Metabolic Disease, Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Anna Mantovani
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Michele Bevilacqua
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Mirko Zoncapè
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Laura Iogna Prat
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Davide Roccarina
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Leonardo Fortuna
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Annalisa Cespiati
- Unit of Internal Medicine and Metabolic Disease, Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - David Sacerdoti
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Anna L Fracanzani
- Unit of Internal Medicine and Metabolic Disease, Ca' Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Emmanouil Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Cristiano Fava
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Andrea Dalbeni
- General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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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.
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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
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Association between arterial hypertension and liver outcomes using polygenic risk scores: a population-based study. Sci Rep 2022; 12:15581. [PMID: 36114231 PMCID: PMC9481629 DOI: 10.1038/s41598-022-20084-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 09/08/2022] [Indexed: 12/03/2022] Open
Abstract
Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992–2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01–1.24, and 1.12, 95% CI 1.01–1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31–0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.
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16
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Kuraji R, Kapila Y, Numabe Y. Periodontal Disease and Nonalcoholic Fatty Liver Disease: New Microbiome-Targeted Therapy Based on the Oral–Gut–Liver Axis Concept. CURRENT ORAL HEALTH REPORTS 2022; 9:89-102. [DOI: 10.1007/s40496-022-00312-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 01/03/2025]
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Abstract
PURPOSE To investigate the potential causal link between heredity, geographical environment, diet and other lifestyle factors with long-term health consequences, we established the Xinjiang Multiethnic Cohort Study (XMC), the first large-scale prospective cohort in Xinjiang, China. PARTICIPANTS XMC commenced in 2018 and enrolled participants from three study sites (Urumqi, Hotan and Ili) in Xinjiang, China. Data collected include standard baseline questionnaire, physical measurement, biological specimen. In addition, about one-third of participants were assessed habitual diet by a more detailed semiquantitative food frequency questionnaire which included 127 foods items at baseline FINDINGS TO DATE: Finally, a total of 30 949 participants, with 32.37% from Urumqi, 41.75% from Hotan, and 25.88% from Ili were recruited in XMC. The average age of participants was 56.21 years for men, and 54.75 years for women. More than 60% of participants in all three survey sites reported an average consumption of fruit and vegetable three or more times per week. In Hotan and Ili, the staple food was wheaten food, whereas, in Urumqi, rice and wheaten food was the food staples. Consumption of white meat, such as fish and poultry, was lower in the three survey locations. Based on self-reported disease from study participants, the five most common chronic diseases among participants across all three survey locations were dyslipidaemia, hypertension, cholecystitis, diabetes, ischaemic heart disease. FUTURE PLANS First, we will collect all health-related records of the study participants in January each year for the previous year. Second, 10% of subjects were randomly selected for telephone follow-up in the final year of cohort building. Finally, as planned, we will revisit the study subjects on site every 2-3 years. Again, we will conduct face-to-face questionnaires and collect biological specimens such as blood and urine from the study subjects.
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Affiliation(s)
- Luo Tao
- Department of Epidemiology and Biostatistics, School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Tian Tian
- Shenzhen Campus of Sun Yat-sen University, School of Public Health (Shenzhen), Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Lirong Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Zewen Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Qi Sun
- Medical Research Design and Data Analysis Center, Academy of Traditional Chinese Medicine in Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Gaofeng Sun
- Urumqi Municipal Center for Disease Control and Prevention, Urumqi, China
| | - Jianghong Dai
- School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Hong Yan
- School of Public Health, Xi'an Jiaotong University, Xi'an, Shaanxi, China
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Li G, Peng Y, Chen Z, Li H, Liu D, Ye X. Bidirectional Association between Hypertension and NAFLD: A Systematic Review and Meta-Analysis of Observational Studies. Int J Endocrinol 2022; 2022:8463640. [PMID: 35371259 PMCID: PMC8970889 DOI: 10.1155/2022/8463640] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 01/24/2022] [Accepted: 02/22/2022] [Indexed: 12/13/2022] Open
Abstract
An increasing body of evidence connects non-alcoholic fatty liver disease (NAFLD) to hypertension. The objective of this systematic review and meta-analysis was to estimate the nature and magnitude of the association between NAFLD and hypertension. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for observational studies published up to May 1, 2021. Cohort studies that reported data on the association between NAFLD and incident hypertension or between hypertension and incident NAFLD were included. We used random-effects models to conduct meta-analysis on the measures of association from individual studies. A total of 11 studies were eligible for inclusion, among which 4 studies including 25,260 participants reported the association between hypertension and new-onset NAFLD. The presence of hypertension was significantly associated with an increased risk of incident NAFLD (HR 1.63, 95% CI: 1.41-1.88; I 2 = 37.6%). On the other hand, 9 studies with data on 46,487 participants analyzed the effects of NAFLD on incident hypertension. Pooled analysis showed that the presence of NAFLD was significantly associated with an increased incidence of hypertension (HR 1.55, 95% CI: 1.29-1.87; I 2 = 80.5%). There was significant heterogeneity among the studies in this analysis (p < 0.01). Sensitivity analyses showed that the magnitude of the association was significantly different in subgroups stratified by a mean age of participants and geographical location, which explains part of the heterogeneity. In conclusion, this meta-analysis indicates the existence of a bidirectional relationship between NAFLD and hypertension independent of traditional cardiometabolic risk factors.
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Affiliation(s)
- Gerui Li
- Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China
| | - Yuanyuan Peng
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China
| | - Ze Chen
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China
| | - Hang Li
- Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China
| | - Danli Liu
- Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China
| | - Xujun Ye
- Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China
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NFI, a clinical scoring tool for predicting non-alcoholic fatty liver in the Chinese population. Public Health 2021; 202:12-17. [PMID: 34875531 DOI: 10.1016/j.puhe.2021.10.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 09/23/2021] [Accepted: 10/26/2021] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Accurate assessment of early non-alcoholic fatty liver disease (NAFLD) is important to reduce the possible complications. The purpose of the present study was to develop a simple algorithm for the screening of NAFLD in the Chinese population based on routine anthropometric data and laboratory tests. STUDY DESIGN This is a cross-sectional design. METHODS The subjects (1145) underwent routine physical examinations. The variables in the NAFLD index (NFI) were obtained by a stepwise multiple logistic regression analysis on 1000 bootstrap samples. The area under the receiver-operating characteristic (AUROC) was used to evaluate the accuracy of the NFI. RESULTS Multivariate analysis showed that body mass index, fasting blood glucose, ratio of alanine aminotransferase to aspartate aminotransferase, and triglyceride were included in the final equation. The AUROC of the NFI was 0.919 (95% confidence interval = 0.901-0.937). An NFI of <31.0 excluded the possibility of NAFLD with a sensitivity of 96.9%, and at a value of >36.0, the NFI could detect NAFLD with a specificity of 98.9%. CONCLUSIONS NFI was a cost-effective NAFLD-screening model, which had a high accuracy for predicting NAFLD at early stages in the Chinese population.
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Kuraji R, Sekino S, Kapila Y, Numabe Y. Periodontal disease-related nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An emerging concept of oral-liver axis. Periodontol 2000 2021; 87:204-240. [PMID: 34463983 PMCID: PMC8456799 DOI: 10.1111/prd.12387] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end‐stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by‐products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta‐analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease–related nonalcoholic fatty liver disease or periodontal disease–related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life‐threatening liver disease.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan.,Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.,Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Satoshi Sekino
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne Kapila
- Department of Orofacial Sciences, University of California San Francisco School of Dentistry, San Francisco, California, USA
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
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Yoshimura Y, Hamaguchi M, Hashimoto Y, Okamura T, Nakanishi N, Obora A, Kojima T, Fukui M. Obesity and metabolic abnormalities as risks of alcoholic fatty liver in men: NAGALA study. BMC Gastroenterol 2021; 21:321. [PMID: 34372774 PMCID: PMC8353849 DOI: 10.1186/s12876-021-01893-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 07/30/2021] [Indexed: 11/30/2022] Open
Abstract
Background Hepatic steatosis has a pivotal role in the development of chronic liver diseases, even in alcohol-related liver disease. Alcoholic fatty liver disease is an important phenotype among alcohol-related liver diseases. While metabolic syndrome is a dominant risk factor of incident nonalcoholic fatty liver disease, the role of metabolic syndrome in alcoholic fatty liver disease has not been clarified yet. Methods A retrospective cohort study was performed at a health check-up center in Japan. Subjects consisted of male participants without fatty liver who consumed ethanol of 420 g/week or higher. Adjusted hazard ratios and 95% confidence intervals at the baseline examinations for incident alcoholic fatty liver disease were estimated using Cox model. Results A total of 640 participants were included in this study. During 3.91 years (IQR 1.63–7.09) of follow-up, 168 new cases of alcoholic fatty liver disease developed (49.1 cases per 1000 persons per year). After adjustment for age, smoking status, alcohol consumption, the hazard ratio for a 1 kg/m2 increase in body mass index was 1.2 (1.12–1.28). The hazard ratio of subjects with high triglyceride and low high-density lipoprotein-cholesterol levels were 1.56 (1.12–2.18) and 1.52 (1.03–2.25), respectively. Conclusions Obesity, high triglyceridemia, and low high-density lipoprotein-cholesterolemia are independent risk factors of alcoholic fatty liver disease in Japanese men who consumed alcohol habitually. In people with these risks, triglyceride lowering and high-density lipoprotein-cholesterol raising by improving insulin resistance and weight maintenance in addition to abstinence from alcohol would be effective in preventing the development of alcoholic fatty liver disease. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01893-4.
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Affiliation(s)
- Yuta Yoshimura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Takuro Okamura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Naoko Nakanishi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Akihiro Obora
- Department of Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Takao Kojima
- Department of Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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Huang G, Zhou H, Shen C, Sheng Y, Xue R, Dong C, Zhang S. Bi-directional and temporal relationship between elevated alanine aminotransferase and hypertension in a longitudinal study of Chinese adults. Clin Exp Hypertens 2021; 43:750-757. [PMID: 34355631 DOI: 10.1080/10641963.2021.1960364] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Despite the strong correlation between elevated alanine aminotransferase (ALT) and hypertension, their bi-directional and temporal relationship are currently unclear. Our study aimed to explore the bi-directional and temporal association between elevated ALT (ALT > 40 U/L) and hypertension. METHODS Measurements of alanine aminotransferase and blood pressure were obtained twice from 2013 to 2017 in 3314 Chinese adults without cardiovascular disease at baseline. Bi-directional and cross-lagged panel analyses were performed to dissect the temporal relationship between elevated ALT and hypertension. RESULTS Longitudinally, we found that baseline elevated ALT was strongly correlated with incident hypertension (odds ratios = 2.16, P = .001), and baseline hypertension was also significantly associated with incident elevated ALT (odds ratios = 1.64, P = .026). The cross-lagged path coefficients from baseline ALT to follow-up blood pressure were significantly greater than that from baseline blood pressure to follow-up ALT (β: 0.043 vs. 0.026, P < .05 for systolic blood pressure and β: 0.052 vs. 0.024, P < .05 for diastolic blood pressure). CONCLUSION Our results provide evidence for the bi-directional association of elevated ALT and hypertension among Chinese adults, and elevated ALT probably antedates the development of hypertension.
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Affiliation(s)
- Guoxin Huang
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, PR China
| | - Hui Zhou
- Departmentof Chronic Disease Management, Suzhou Industrial Park Centers for Disease Control and Prevention, Suzhou, PR China
| | - Chao Shen
- Departmentof Chronic Disease Management, Suzhou Industrial Park Centers for Disease Control and Prevention, Suzhou, PR China
| | - Yihui Sheng
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, PR China
| | - Ruyu Xue
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, PR China
| | - Chen Dong
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, PR China
| | - Shaoyan Zhang
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, PR China
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Ma C, Yan K, Wang Z, Zhang Q, Gao L, Xu T, Sai J, Cheng F, Du Y. The association between hypertension and nonalcoholic fatty liver disease (NAFLD): literature evidence and systems biology analysis. Bioengineered 2021; 12:2187-2202. [PMID: 34096467 PMCID: PMC8806441 DOI: 10.1080/21655979.2021.1933302] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue as its progression increases risks of multisystem morbidity and mortality. Recent evidence indicates a more complex relationship between hypertension and NAFLD than previously thought. In this study, a comprehensive literature search was used to gather information supporting the comorbidity phenomenon of hypertension and NAFLD. Then, systems biology approach was applied to identify the potential genes and mechanisms simultaneously associated with hypertension and NAFLD. With the help of protein-protein interaction network-based algorithm, we found that the distance between hypertension and NAFLD was much less than random ones. Sixty-four shared genes of hypertension and NAFLD modules were identified as core genes. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis indicated that some inflammatory, metabolic and endocrine signals were related to the potential biological functions of core genes. More importantly, drugs used to treat cardiovascular diseases, hypertension, hyperlipidemia, inflammatory diseases and depression could be potential therapeutics against hypertension-NAFLD co-occurrence. After analyzing public OMICs data, ALDH1A1 was identified as a potential therapeutic target, without being affected by reverse causality. These findings give a clue for the potential mechanisms of comorbidity of hypertension and NAFLD and highlight the multiple target-therapeutic strategy of NAFLD for future clinical research.
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Affiliation(s)
- Chongyang Ma
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Kai Yan
- Department of Traditional Chinese Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Zisong Wang
- Department of Traditional Chinese Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qiuyun Zhang
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Lianyin Gao
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Tian Xu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jiayang Sai
- Department of Oncology, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Fafeng Cheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yuqiong Du
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
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Lee SM, Park JS, Han YJ, Kim W, Bang SH, Kim BJ, Park CW, Kim MY. Elevated Alanine Aminotransferase in Early Pregnancy and Subsequent Development of Gestational Diabetes and Preeclampsia. J Korean Med Sci 2020; 35:e198. [PMID: 32627436 PMCID: PMC7338210 DOI: 10.3346/jkms.2020.35.e198] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/27/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is now considered as a hepatic manifestation of metabolic syndrome and elevated alanine aminotransferase (ALT) is commonly related to NAFLD in the absence of viral hepatitis or alcohol abuse. Previous studies have indicated that elevated ALT is associated with diabetes or metabolic syndrome in adults, but the clinical significance of ALT or NAFLD in pregnancy has not been well determined. The objective of this study was to determine the association between elevated ALT in early pregnancy and the development of gestational diabetes or preeclampsia in late pregnancy. METHODS In this retrospective cohort study, pregnant women who met the following inclusion criteria were included: 1) singleton pregnancy; 2) ALT levels were measured in antenatal outpatient clinic at 4-20 weeks of gestation; 3) patients were screened for gestational diabetes and delivered in Cheil General Hospital and Women's Healthcare Center. Cases with viral hepatitis or other liver diseases were excluded. The early ALT levels were divided into two groups (normal ALT [≤ 95th percentile] and elevated ALT [> 95th percentile]), and the frequency of gestational diabetes and preeclampsia was compared between the two groups of cases. Gestational diabetes was screened and diagnosed by two-step procedure (50 g oral glucose challenge test and 75 g glucose challenge test with World Health Organization [WHO] criteria). RESULTS A total of 2,322 women met the inclusion criteria. Cases with elevated early ALT levels (> 95th percentile) had a higher risk of subsequent gestational diabetes and preeclampsia (gestational diabetes by WHO criteria, 2.1% in normal ALT vs. 6.5% in elevated ALT, P < 0.01; preeclampsia, 1.0% in normal ALT vs. 4.1% in elevated ALT, P < 0.05). This relationship between elevated ALT and increased risk of gestational diabetes/preeclampsia remained significant after adjustment for maternal age and pre-pregnancy body mass index. CONCLUSION Elevated unexplained ALT in early pregnancy is associated with the risk of subsequent development of gestational diabetes and preeclampsia in late pregnancy.
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Affiliation(s)
- Seung Mi Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Joong Shin Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - You Jung Han
- Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
| | - Seung Hyun Bang
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Byoung Jae Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
| | - Chan Wook Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Moon Young Kim
- Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea.
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High-altitude chronic hypoxia ameliorates obesity-induced non-alcoholic fatty liver disease in mice by regulating mitochondrial and AMPK signaling. Life Sci 2020; 252:117633. [DOI: 10.1016/j.lfs.2020.117633] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/27/2020] [Accepted: 03/31/2020] [Indexed: 12/18/2022]
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Ma Z, Xu C, Kang X, Zhang S, Li H, Tao L, Zheng D, Guo X, Yang X. Changing trajectories of serum uric acid and risk of non-alcoholic fatty liver disease: a prospective cohort study. J Transl Med 2020; 18:133. [PMID: 32192511 PMCID: PMC7081554 DOI: 10.1186/s12967-020-02296-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 03/11/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND It is unclear the role of longitudinal trajectory of serum uric acid (SUA) on the development of non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of new-onset NAFLD. METHODS We explored the relationship between SUA trajectories and NAFLD in a cohort including 3822 participants. Individual's SUA trajectories from 2012 to 2014 were defined using group-based trajectory modeling analysis in four distinct patterns: trajectory 1 (n = 991, 25.93%), trajectory 2 (n = 1421, 37.18%), trajectory 3 (n = 1156, 30.22%), and trajectory 4 (n = 254, 6.67%). The logistic regression model was used to evaluate the association between SUA changing trajectories and subsequent NAFLD until 2016. Dose-response relationship between SUA changing trajectories and NAFLD risk was evaluated through the testing of trajectory groups as a continuous variable. RESULTS The 2-year incidence of NAFLD was 13.27%. Compared with trajectory 1, the adjusted odds risk for NAFLD development was in a dose-response relationship as follows: 1.27 (95% CI 0.91-1.78) for trajectory 2, 1.89 (95% CI 1.29-2.75) for trajectory 3, and 2.34 (95% CI 1.43-3.83) for trajectory 4. And this dose-response relationship was not affected by age, sex, and abdominal obesity. CONCLUSIONS Higher SUA changing trajectory is a risk factor for NAFLD. This finding highlights the importance of paying attention to SUA changing trajectory on the detection and prevention of NAFLD.
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Affiliation(s)
- Zhimin Ma
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
| | - Chaonan Xu
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
- Medical Engineering Department, Peking University Third Hospital, NO. 49 HuaYuan BeiLu, Haidian District, Beijing, 100191, China
| | - Xiaoping Kang
- Beijing Xiaotangshan Hospital, NO. 390 Wenquan Street, Xiaotangshan Town, Changping District, Beijing, 102211, China
| | - Shan Zhang
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
| | - Haibin Li
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
| | - Lixin Tao
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
| | - Deqiang Zheng
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
| | - Xiuhua Guo
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
- Beijing Municipal Key Laboratory of Clinical Epidemiology, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China
| | - Xinghua Yang
- School of Public Health, Capital Medical University, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China.
- Beijing Municipal Key Laboratory of Clinical Epidemiology, NO. 10 Xitoutiao, Youanmen, Fengtai District, Beijing, 100069, China.
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Zhao YC, Zhao GJ, Chen Z, She ZG, Cai J, Li H. Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension. Hypertension 2020; 75:275-284. [PMID: 31865799 DOI: 10.1161/hypertensionaha.119.13419] [Citation(s) in RCA: 151] [Impact Index Per Article: 30.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hypertension, a multifactorial disorder resulting from the interplay between genetic predisposition and environmental risk factors, affects ≈30% of adults. Emerging evidence has shown that nonalcoholic fatty liver disease (NAFLD), as an underestimated metabolic abnormality, is strongly associated with an increased risk of incident prehypertension and hypertension. However, the role of NAFLD in the development of hypertension is still obscure and is highly overlooked by the general public. Herein, we highlight the epidemiological evidence and putative mechanisms focusing on the emerging roles of NAFLD in hypertension, with the purpose of reinforcing the notion that NAFLD may serve as an independent risk factor and an important driving force in the development and progression of hypertension. Finally, we also briefly summarize the current potential treatments for NAFLD that might also be beneficial approaches against hypertension.
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Affiliation(s)
- Yan-Ci Zhao
- From the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China (Y.-C.Z., G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Institute of Model Animal of Wuhan University, P.R. China (Y.-C.Z.,G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
| | - Guo-Jun Zhao
- From the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China (Y.-C.Z., G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Institute of Model Animal of Wuhan University, P.R. China (Y.-C.Z.,G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
| | - Ze Chen
- From the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China (Y.-C.Z., G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Institute of Model Animal of Wuhan University, P.R. China (Y.-C.Z.,G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
| | - Zhi-Gang She
- From the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China (Y.-C.Z., G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Institute of Model Animal of Wuhan University, P.R. China (Y.-C.Z.,G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Basic Medical School (Z.-G.S., H.L.), Wuhan University, P.R. China
- Medical Research Institute, School of Medicine (Z.-G.S.), Wuhan University, P.R. China
| | - Jingjing Cai
- From the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China (Y.-C.Z., G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, P.R. China (J.C.)
- Institute of Model Animal of Wuhan University, P.R. China (Y.-C.Z.,G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
| | - Hongliang Li
- From the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China (Y.-C.Z., G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Institute of Model Animal of Wuhan University, P.R. China (Y.-C.Z.,G.-J.Z., Z.C., Z.-G.S., J.C., H.L.)
- Basic Medical School (Z.-G.S., H.L.), Wuhan University, P.R. China
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Unger LW, Forstner B, Muckenhuber M, Scheuba K, Eigenbauer E, Scheiner B, Pfisterer N, Paternostro R, Trauner M, Mandorfer M, Reiberger T. Hepatic Steatosis in Lean Patients: Risk Factors and Impact on Mortality. Dig Dis Sci 2020; 65:2712-2718. [PMID: 31875288 PMCID: PMC7419366 DOI: 10.1007/s10620-019-06000-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 12/05/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND The prognostic impact of liver steatosis in obese patients is well established. Limited data on the risk factors for and impact of hepatic steatosis in lean patients are available. AIMS Assess risk factors for liver steatosis in lean patients and investigate its impact on survival. METHODS Patients without viral hepatitis and with a BMI ≤ 25 kg/m2 undergoing liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by transient elastography were retrospectively identified. Clinical characteristics and laboratory test results were obtained at the time of LSM/CAP measurement. National death registry data were obtained in order to assess survival. RESULTS Among n = 218 lean patients, n = 97 (34.5%) showed significant liver steatosis (CAP ≥ 268 dB/m), while n = 184 (65.5%) had no or just mild steatosis (CAP < 268 dB/m). Patients with steatosis had higher GGT (238.0(± 450.3) vs. 112.1(± 180.0) IU/mL; p = 0.013), AST (63(± 67.4) vs. 38.5(± 32.9) IU/mL; p = 0.001), ALT (59.1(± 58.8) vs. 44.3(± 52.7) IU/mL; p = 0.048) and triglyceride levels (120.1(± 80.3) vs. 96.1(± 58.2) mg/dL; p = 0.014), and showed a trend toward more severe fibrosis (LSM 15.6(± 19.5) vs. 12.0(± 15.7) kPa; p = 0.115). In multivariate binary logistic regression analysis, only serum uric acid levels were independently associated with liver steatosis (odds ratio 1.43 per unit mg/dL; 95% CI 1.001-2.054; p = 0.049). During a mean follow-up of 38.9(± 10.6) months, n = 14 patients (5.0%) died. In the absence of advanced fibrosis, survival after 1 year was similar in patients without (98.7%) and with (98.6%) significant steatosis. Patients with advanced fibrosis had worse 1-year survival without concomitant significant steatosis (84.8%) than patients with steatosis (95.8%; log-rank p < 0.001). CONCLUSIONS High serum uric acid levels increase the risk of liver steatosis in lean patients. Liver fibrosis but not hepatic steatosis is a risk factor for impaired survival in lean patients.
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Affiliation(s)
- Lukas W Unger
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
| | - Bernadette Forstner
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
| | - Moritz Muckenhuber
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
| | - Katharina Scheuba
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
| | - Ernst Eigenbauer
- IT-Systems and Communications, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
| | - Bernhard Scheiner
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Nikolaus Pfisterer
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
- Krankenanstalt Rudolfstiftung, Krankenanstaltenverbund Wien (KAV), Vienna, Austria
| | - Rafael Paternostro
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
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Wang Y, Xu H, Sun G, Xue M, Sun S, Huang T, Zhou J, Loor JJ, Li M. Transcriptome Analysis of the Effects of Fasting Caecotrophy on Hepatic Lipid Metabolism in New Zealand Rabbits. Animals (Basel) 2019; 9:ani9090648. [PMID: 31484452 PMCID: PMC6769842 DOI: 10.3390/ani9090648] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 08/21/2019] [Accepted: 08/30/2019] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Caecotrophy in small herbivores, including rabbits, is the instinctive behavior of eating soft feces. Little is known about the impact of caecotrophy on growth and metabolism. In the present study, we used an Elizabeth circle to prevent rabbits from eating soft feces and measured changes in feed intake, body weight, internal organ weight, serum biochemical indices and liver lipid droplet accumulation. Liver tissue was also used for transcriptome sequencing. Results indicated that fasting caecotrophy decreased rabbit growth and lipid synthesis in the liver. Abstract In order to investigate the effects of fasting caecotrophy on hepatic lipid metabolism in rabbits, 12 weaned female New Zealand white rabbits were randomly divided into (n = 6/group) a control and fasting caecotrophy group. Rabbits in the experimental group were treated with an Elizabeth circle to prevent them from eating their own soft feces for a 60-day period. Growth and blood biochemical indices, transcriptome sequencing and histology analysis of the liver were performed. Compared with the control group, final weight, weight gain, liver weight, growth rate and feed conversion ratio, all decreased in the experimental group (p < 0.05). RNA sequencing (RNA-seq) analysis revealed a total of 301.2 million raw reads (approximately 45.06 Gb of high-quality clean data) that were mapped to the rabbit genome. After a five-step filtering process, 14,964 genes were identified, including 444 differentially expressed genes (p < 0.05, foldchange ≥ 1). A number of differently expressed genes linked to lipid metabolism were further analyzed including CYP7A1, SREBP, ABCA1, GPAM, CYP3A1, RBP4 and RDH5. The KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation of the differentially expressed genes indicated that main pathways affected were pentose and glucuronide interactions, starch and sucrose metabolism, retinol metabolism and PPAR signaling. Overall, the present study revealed that preventing caecotrophy reduced growth and altered lipid metabolism, both of which will help guide the development of new approaches for rabbits’ feeding and production. These data also provide a reference for studying the effects of soft feces in other small herbivores.
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Affiliation(s)
- Yadong Wang
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
| | - Huifen Xu
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
| | - Guirong Sun
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
| | - Mingming Xue
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
| | - Shuaijie Sun
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
| | - Tao Huang
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
| | - Jianshe Zhou
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
| | - Juan J Loor
- Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Champaign, IL 61801, USA.
| | - Ming Li
- College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.
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El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2019; 20:ijms20092215. [PMID: 31064058 PMCID: PMC6539803 DOI: 10.3390/ijms20092215] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 04/19/2019] [Accepted: 04/28/2019] [Indexed: 12/16/2022] Open
Abstract
With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.
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Affiliation(s)
- Hamza El Hadi
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
- Department of Medicine, Klinikum Rheine, 48431 Rheine, Germany.
| | - Angelo Di Vincenzo
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
| | - Roberto Vettor
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
| | - Marco Rossato
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
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Liu H, Yao Y, Wang Y, Ma L, Liu X, Guo S, Feng X, Chen Y, Chen X, Liu Z, Ji L, Li D, Zhou Y. Ideal cardiovascular health metrics and the risk of non-alcoholic fatty liver disease: A cross-sectional study in northern China. Liver Int 2019; 39:950-955. [PMID: 30712318 DOI: 10.1111/liv.14060] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 01/10/2019] [Accepted: 01/21/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND PURPOSE The components of ideal cardiovascular health (CVH) metrics have been shown to be associated with non-alcoholic fatty liver disease (NAFLD). The present study aimed to determine the association between ideal CVH metrics and NAFLD. METHODS A total of 10,511 participants (47.26% men) aged 18 to 92 years were selected from the Jidong and Kailuan communities. Ideal CVH was based on 7 ideal CVH metrics: smoking, body mass index (BMI), physical activity, diet, total cholesterol, blood pressure and fasting blood glucose. NAFLD was determined by abdominal ultrasonography. All participants underwent questionnaire assessments and clinical and laboratory examinations. Logistic regression models were used to analyse the relationship of CVH metrics and the number of ideal CVH metrics with NAFLD. RESULTS The prevalence rates of NAFLD by CVH summary score quartiles were 64.38% (2,015/3,130), 50.16% (786/1,567), 33.28% (1,194/3,588) and 20.89% (465/2,226). Participants in the highest quartile showed a lower odds ratio (OR) than those in the lowest quartile (fully adjusted OR: 0.17, 95% CI: 0.17-0.20, P < 0.001). Similar results were observed in subjects stratified by sex and age (45 years). The ORs were progressively decreased with an increased number of ideal CVH metrics (all P < 0.001). CONCLUSIONS NAFLD was significantly associated with both the summary score of CVH metrics and the number of ideal CVH metrics. The combined evaluation of ideal CVH may contribute to the prevention of NAFLD.
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Affiliation(s)
- Huamin Liu
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Yan Yao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Youxin Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Likun Ma
- Department of Cardiology, Anhui Provincial Hospital, Hefei, China
| | - Xuezhen Liu
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Shasha Guo
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Xia Feng
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Yanru Chen
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Xueyu Chen
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Zhongni Liu
- Department of Pathophysiology, Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Harbin, China
| | - Long Ji
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Dong Li
- School of Public Health, Taishan Medical University, Tai'an, China
| | - Yong Zhou
- Sanbo Brain Institute, Sanbo Brain Hospital, Capital Medical University, Beijing, China
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Abstract
Nonalcoholic fatty liver disease and hypertension are closely related but there has been little genetic evidence to link them. In this issue, Musso et al. provide evidence that a common variant in AGTR1 (A1166C) is associated with both incident hypertension and nonalcoholic fatty liver disease, as well as nonalcoholic steatohepatitis, fibrosis, dyslipidemia, and insulin resistance. AGTR1 is strongly expressed in adipose, liver, and arteries. The mechanism of this gain-of-function variant is unclear but may include adipose or endothelial dysfunction and immune activation. Despite previous unsuccessful clinical trials of angiotensin receptor blockers in nonalcoholic steatohepatitis, individuals with the rs5186A>C variant may have greater benefit from this therapy.
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Pang Y, Kartsonaki C, Turnbull I, Guo Y, Chen Y, Clarke R, Bian Z, Bragg F, Millwood IY, Yang L, Huang Y, Yang Y, Zhang X, Chen J, Li L, Holmes MV, Chen Z. Adiposity in relation to risks of fatty liver, cirrhosis and liver cancer: a prospective study of 0.5 million Chinese adults. Sci Rep 2019; 9:785. [PMID: 30692555 PMCID: PMC6349919 DOI: 10.1038/s41598-018-36460-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 11/23/2018] [Indexed: 12/25/2022] Open
Abstract
Adiposity is an increasing public health problem in China. We aimed to examine the associations of adiposity with non-alcoholic fatty liver disease (NAFLD) and other chronic liver diseases in Chinese adults. The prospective China Kadoorie Biobank recruited 512,891 adults aged 30-79 years from 10 areas. During 10 years of follow-up, 7,386 incident liver disease cases were recorded among 503,991 participants without prior cancer or chronic liver disease at baseline. The mean body mass index (BMI) (SD) was 23.7 (3.3) kg/m2 and mean waist circumference (WC) 80.3 (9.8) cm, with 33% having BMI ≥25 kg/m2. Throughout the range examined (BMI 15-50) BMI showed a log-linear positive association with NAFLD (n = 1,298), with adjusted HR per 5 kg/m2 of 2.81 (95% CI 2.63-3.01), adjusting for regression dilution. There were also positive associations of percent body fat, WC, and waist-to-hip ratio with NAFLD, with HRs per 1-SD of 2.27 (2.14-2.41), 2.60 (2.44-2.76), and 1.84 (1.76-1.92). BMI was unrelated to viral hepatitis (n = 1,477), and had a U-shaped association with cirrhosis (n = 2,082) and an inverse association with liver cancer (n = 2,568), which disappeared after excluding the first 5 years of follow-up. Among Chinese adults, adiposity was a major risk factor for NAFLD but not other chronic liver diseases.
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Affiliation(s)
- Yuanjie Pang
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Christiana Kartsonaki
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
| | - Iain Turnbull
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Yu Guo
- Chinese Academy of Medical Sciences, 9 Dongdan San Tiao, Beijing, 100730, China
| | - Yiping Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Robert Clarke
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Zheng Bian
- Chinese Academy of Medical Sciences, 9 Dongdan San Tiao, Beijing, 100730, China
| | - Fiona Bragg
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Iona Y Millwood
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Ling Yang
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Ying Huang
- Guangxi Zhuang Autonomous Region Center for Disease Control, Guangxi Province, Nanning, 530028, China
| | - Yan Yang
- Huixian People's Hospital, Henan Province, Xinxiang, 453600, China
| | - Xukui Zhang
- Huixian Center for Disease Control, Henan Province, Xinxiang, 453600, China
| | - Junshi Chen
- National Center for Food Safety Risk Assessment, 37 Guangqu Road, Beijing, 100021, China
| | - Liming Li
- Chinese Academy of Medical Sciences, 9 Dongdan San Tiao, Beijing, 100730, China
- School of Public Health, Peking University, Beijing, 100191, China
| | - Michael V Holmes
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Old Road, Oxford, OX3 7LE, UK
| | - Zhengming Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
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Pang Y, Kartsonaki C, Turnbull I, Guo Y, Clarke R, Chen Y, Bragg F, Yang L, Bian Z, Millwood IY, Hao J, Han X, Zang Y, Chen J, Li L, Holmes MV, Chen Z. Diabetes, Plasma Glucose, and Incidence of Fatty Liver, Cirrhosis, and Liver Cancer: A Prospective Study of 0.5 Million People. Hepatology 2018; 68:1308-1318. [PMID: 29734463 PMCID: PMC6220764 DOI: 10.1002/hep.30083] [Citation(s) in RCA: 129] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 05/03/2018] [Indexed: 12/18/2022]
Abstract
The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We examined the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults and the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalized nonalcoholic fatty liver disease (NAFLD), and 244 hospitalized alcoholic liver disease (ALD) cases were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared to those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% confidence interval 1.30-1.70) for liver cancer, 1.81 (1.57-2.09) for cirrhosis, 1.76 (1.47-2.16) for NAFLD, and 2.24 (1.42-3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03-1.06) for liver cancer, 1.07 (1.05-1.09) for cirrhosis, 1.07 (1.05-1.10) for NAFLD, and 1.10 (1.05-1.15) for ALD. These associations did not differ by HBV infection. CONCLUSION In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with higher risks of liver cancer and major chronic liver diseases.
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Affiliation(s)
- Yuanjie Pang
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Christiana Kartsonaki
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Iain Turnbull
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Yu Guo
- Chinese Academy of Medical SciencesBeijingChina
| | - Robert Clarke
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Yiping Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Fiona Bragg
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Ling Yang
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Zheng Bian
- Chinese Academy of Medical SciencesBeijingChina
| | - Iona Y. Millwood
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | | | - Xianyong Han
- Yongqinglu Community Health Service CenterQingdaoChina
| | - Yajing Zang
- Qingdao Center for Disease Prevention and ControlQingdaoChina
| | - Junshi Chen
- National Center for Food Safety Risk AssessmentBeijingChina
| | - Liming Li
- Chinese Academy of Medical SciencesBeijingChina
- School of Public HealthPeking University
| | - Michael V. Holmes
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- National Institute for Health Research Oxford Biomedical Research CentreOxford University HospitalOxfordUK
| | - Zhengming Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population HealthUniversity of OxfordOxfordUK
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Oikonomou D, Georgiopoulos G, Katsi V, Kourek C, Tsioufis C, Alexopoulou A, Koutli E, Tousoulis D. Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated? Eur J Gastroenterol Hepatol 2018; 30:979-985. [PMID: 30048367 DOI: 10.1097/meg.0000000000001191] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To provide a comprehensive review summarizing the existing evidence on the association between nonalcoholic fatty liver disease (NAFLD) and hypertension (HT) independent of other components of metabolic syndrome. METHODS We searched the literature through Medline and the Cochrane Library for studies evaluating the relationship between hypertension and fatty liver disease. RESULTS Studies testing this association are limited, but agree that HT and fatty liver disease are inter-related independent of other components of the metabolic syndrome such as obesity and diabetes mellitus. Clinical evidence shows that NAFLD is associated with new-onset HT, whereas increased blood pressure is related to the development of fatty liver disease and the possible subsequent progression to liver fibrosis. Insulin resistance and activation of the renin-angiotensin-aldosterone system (RAAS) might provide potential pathophysiologic links between these clinical entities. Until further evidence is available, patients with HT should be meticulously evaluated and treated for fatty liver disease and vice versa. RAAS inhibitors have been tested in NAFLD, presenting a favorable profile by decreasing insulin resistance and fibrosis progression. CONCLUSION NAFLD and HT are associated independent of traditional cardiovascular risk factors. Insulin resistance appears to be the main linking mechanism. Although RAAS inhibitors are the most beneficial treatment option for HT in patients with NAFLD, randomized studies on the administration of these agents in HT patients with NAFDL are warranted to provide optimal treatment options in these high cardiovascular risk individuals.
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Affiliation(s)
| | | | | | | | | | | | - Evaggelia Koutli
- Department of Internal Medicine, 'Hippokration' Hospital, University of Athens, Medical School, Athens, Greece
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Long MT, Pedley A, Massaro JM, Hoffmann U, Ma J, Loomba R, Chung RT, Benjamin EJ. A simple clinical model predicts incident hepatic steatosis in a community-based cohort: The Framingham Heart Study. Liver Int 2018; 38:1495-1503. [PMID: 29377504 PMCID: PMC6206437 DOI: 10.1111/liv.13709] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 01/18/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The factors associated with incident hepatic steatosis are not definitively known. We sought to determine factors associated with incident hepatic steatosis, as measured on computed tomography, in the community. METHODS We studied Framingham Heart Study participants without heavy alcohol use or baseline hepatic steatosis who underwent computed tomography scans between 2002-2005 (baseline) and 2008-2011 (follow-up). We performed a stepwise logistic regression procedure to determine the predictors associated with incident hepatic steatosis. RESULTS We included 685 participants (mean age: 45.0 ± 6.2 years, 46.8% women). The incidence of hepatic steatosis in our sample was 17.1% over a mean 6.3 years of follow-up. Participants who developed hepatic steatosis had more adverse cardiometabolic profiles at baseline compared to those free of hepatic steatosis at follow-up. Multivariable stepwise regression analysis showed that a simple clinical model including age, sex, body mass index, alcohol consumption and triglycerides was predictive of incident hepatic steatosis (C statistic = 0.791, 95% CI: 0.748-0.834). A complex clinical model, which included visceral adipose tissue volume and liver phantom ratio added to the simple clinical model, and had improved discrimination for predicting incident hepatic steatosis (C statistic = 0.826, 95% CI: 0.786-0.866, P < .0001). CONCLUSIONS The combination of demographic, clinical and imaging characteristics at baseline was predictive of incident hepatic steatosis. The use of our predictive model may help identify those at increased risk for developing hepatic steatosis who may benefit from risk factor modification although further investigation is warranted.
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Affiliation(s)
- Michelle T. Long
- Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- Framingham Heart Study, Framingham, MA, USA
| | - Alison Pedley
- Framingham Heart Study, Framingham, MA, USA
- Merck Research Labs, Kenilworth, NJ, USA
| | - Joseph M. Massaro
- Framingham Heart Study, Framingham, MA, USA
- Department of Mathematics and Statistics, Boston University, Boston, MA, USA
| | - Udo Hoffmann
- Radiology Department, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jiantao Ma
- Framingham Heart Study, Framingham, MA, USA
- Population Sciences Branch, National Heart, Lung, and Blood Institute, Framingham, MA, USA
| | - Rohit Loomba
- NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA, USA
- Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA
- Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, USA
| | - Raymond T. Chung
- Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Emelia J. Benjamin
- Framingham Heart Study, Framingham, MA, USA
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
- Cardiology and Preventive Medicine Sections, Evans Department of Medicine, Boston University School of Medicine, Boston, MA, USA
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Cai H, Lu S, Chen Y, Das MBBS MRCOG S, Niu Z, Zhuo G, Lai L, Zhang Z. Serum retinol binding protein 4 and galectin-3 binding protein as novel markers for postmenopausal nonalcoholic fatty liver disease. Clin Biochem 2018; 56:95-101. [DOI: 10.1016/j.clinbiochem.2018.04.017] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Revised: 04/17/2018] [Accepted: 04/17/2018] [Indexed: 02/06/2023]
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Cai J, Zhang XJ, Li H. Progress and challenges in the prevention and control of nonalcoholic fatty liver disease. Med Res Rev 2018; 39:328-348. [PMID: 29846945 DOI: 10.1002/med.21515] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 05/02/2018] [Accepted: 05/12/2018] [Indexed: 12/17/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets.
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Affiliation(s)
- Jingjing Cai
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China.,Institute of Model Animal of Wuhan University, Wuhan, China
| | - Xiao-Jing Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Institute of Model Animal of Wuhan University, Wuhan, China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Institute of Model Animal of Wuhan University, Wuhan, China.,Basic Medical School, Wuhan University, Wuhan, China
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Lonardo A, Nascimbeni F, Mantovani A, Targher G. Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence? J Hepatol 2018; 68:335-352. [PMID: 29122390 DOI: 10.1016/j.jhep.2017.09.021] [Citation(s) in RCA: 532] [Impact Index Per Article: 76.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/13/2017] [Accepted: 09/23/2017] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become one of the most common forms of chronic liver disease worldwide and its prevalence is expected to continue rising. NAFLD has traditionally been considered a consequence of metabolic syndrome (MetS). However, the link between NAFLD and MetS components, especially type 2 diabetes mellitus (T2DM), hypertension (HTN), and cardiovascular disease (CVD) is more complex than previously thought. Indeed, the adverse effects of NAFLD extend far beyond the liver, with a large body of clinical evidence now suggesting that NAFLD may precede and/or promote the development of T2DM, HTN and atherosclerosis/CVD. The risk of developing these cardiometabolic diseases parallels the underlying severity of NAFLD. Accumulating evidence suggests that the presence and severity of NAFLD is associated with an increased risk of incident T2DM and HTN. Moreover, long-term prospective studies indicate that the presence and severity of NAFLD independently predicts fatal and nonfatal CVD events. In this review, we critically discuss the rapidly expanding body of clinical evidence that supports the existence of a bi-directional relationship between NAFLD and various components of MetS, particularly T2DM and HTN, as well as the current knowledge regarding a strong association between NAFLD and CVD morbidity and mortality. Finally, we discuss the most updated putative biological mechanisms through which NAFLD may contribute to the development of HTN, T2DM and CVD.
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Affiliation(s)
- Amedeo Lonardo
- Division of Internal Medicine, Department of Biomedical, Metabolic and Neural Sciences, Azienda Ospedaliero-Universitaria, Ospedale Civile di Baggiovara, Modena, Italy
| | - Fabio Nascimbeni
- Division of Internal Medicine, Department of Biomedical, Metabolic and Neural Sciences, Azienda Ospedaliero-Universitaria, Ospedale Civile di Baggiovara, Modena, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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Lorbeer R, Bayerl C, Auweter S, Rospleszcz S, Lieb W, Meisinger C, Heier M, Peters A, Bamberg F, Hetterich H. Association between MRI-derived hepatic fat fraction and blood pressure in participants without history of cardiovascular disease. J Hypertens 2017; 35:737-744. [PMID: 28253218 DOI: 10.1097/hjh.0000000000001245] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVES We assessed whether liver fat content, as determined by MRI, correlates with blood pressure (BP), a major vascular risk factor, in individuals from the general population without history of stroke and coronary or peripheral artery disease. METHODS Cross-sectional data from 384 participants (161 women; aged 39-73 years) of a MRI substudy of the KORA FF4 survey were used. Hepatic fat fraction (HFF) was measured in the left and right lobe of the liver using single voxel multiecho H-spectroscopy and at the level of the portal vein using a multiecho Dixon-sequence. Associations of HFF with SBP and DBP as well as hypertension were assessed by right censored normal regression (accounting for antihypertensive treatment) and by logistic regression, respectively. RESULTS High levels of HFF measured on the level of the portal vein (90th percentile, 21.8%), compared with low HFF levels (10th percentile, 1.7%), were associated with higher SBP (131 vs. 122 mmHg; overall P = 0.001), higher DBP (82 vs. 76 mmHg, P < 0.001) and with higher odds of hypertension [odds ratio (OR) = 2.16, P = 0.025]. A level of 5.13% (54th percentile) was identified as optimal HFF cut-off for the prediction of hypertension (OR = 2.00, P = 0.015). Alcohol consumption emerged as an effect modifier for the association between HFF and hypertension (nonalcohol drinker: OR = 3.76, P = 0.025; alcohol drinker: OR = 1.59, P = 0.165). CONCLUSION MRI-derived subclinical HFF is associated with SBP and DBP as well as with hypertension in participants from the general population without history of cardiovascular disease.
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Affiliation(s)
- Roberto Lorbeer
- aInstitute of Clinical Radiology, Ludwig Maximilian University Hospital, MunichbInstitute of Epidemiology II, Helmholtz Zentrum München, NeuherbergcInstitute of Epidemiology, Christian Albrecht University, KieldKORA Myocardial Infarction Registry, Central Hospital of Augsburg, AugsburgeGerman Center for Diabetes Research (DZD e.V.), NeuherbergfGerman Center for Cardiovascular Disease Research (DZHK e.V.), MunichgDepartment of Diagnostic and Interventional Radiology, Eberhard Karl University Tübingen, Tübingen, Germany
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Zhou YJ, Zheng JN, Liu WY, Miele L, Vitale A, Van Poucke S, Zou TT, Fang DH, Shen S, Zhang DC, Zheng MH. The NAFL Risk Score: A simple scoring model to predict 4-y risk for non-alcoholic fatty liver. Clin Chim Acta 2017; 468:17-24. [PMID: 28111272 DOI: 10.1016/j.cca.2017.01.021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Revised: 01/14/2017] [Accepted: 01/18/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND Although several risk factors for non-alcoholic fatty liver (NAFL) have been reported, there are few clinical scores that predict its incidence in the long term. We developed and validate a scoring model for individual prediction of 4-y risk for NAFL. METHODS Four-year follow-up data of 8226 initially NAFL-free subjects enrolled for an annual physical examination from Wenzhou Medical Center were analyzed. These subjects are randomly split into the training and the validation cohort. Univariate and multivariable logistic regression models were employed for model development. The selected variables were assigned an integer or half-integer risk score proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. We also compared the predictive performance of with that of the NAFLD Index by computing the area under the receiver operating characteristic curve (AUROC). RESULTS The NAFL Risk Score was developed as 0 to 18 points comprising of BMI, TG×GGT, ALT/AST, LDL-C/HDL-C and UA in both sexes. Comparison of the observed with the estimated incidence of NAFL at both cohorts showed satisfactory precision. In addition, the NAFL Risk Score showed relatively good discriminative power (AUROC=0.739 for males, 0.823 for females) compared with the NAFLD Index (AUROC=0.661 for males, 0.729 for females) in these Chinese subjects. CONCLUSIONS We developed and validated the NAFL Risk Score, a new scoring model to predict 4-y risk for NAFL. The NAFL Risk Score may be clinically simple and useful for assessing individual risk for NAFL.
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Affiliation(s)
- Yu-Jie Zhou
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Ji-Na Zheng
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Wen-Yue Liu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Luca Miele
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Institute of Internal Medicine, Catholic University of Rome, Rome, Italy
| | | | - Sven Van Poucke
- Department of Anesthesiology, Critical Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Tian-Tian Zou
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; School of the Second Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Dan-Hong Fang
- Department of Cardiovascular Medicine, The Heart Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Shengrong Shen
- Department of Food Science & Nutrition, Zhejiang University, Hangzhou, China
| | - Dong-Chu Zhang
- Wenzhou Medical Center, Wenzhou People's Hospital, Wenzhou, China
| | - Ming-Hua Zheng
- Department of Hepatology, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
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Li Y, Wang J, Tang Y, Han X, Liu B, Hu H, Li X, Yang K, Yuan J, Miao X, Yao P, Wei S, Wang Y, Liang Y, Zhang X, Guo H, Pan A, Yang H, Hu FB, Wu T, He M. Bidirectional association between nonalcoholic fatty liver disease and type 2 diabetes in Chinese population: Evidence from the Dongfeng-Tongji cohort study. PLoS One 2017; 12:e0174291. [PMID: 28350839 PMCID: PMC5369778 DOI: 10.1371/journal.pone.0174291] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 03/07/2017] [Indexed: 02/06/2023] Open
Abstract
Objectives The aim of this study is to examine the bidirectional association between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. NAFLD was classified as none, mild, moderate/severe based on ultrasound examination. The analysis to examine the association between NAFLD and incident T2DM risk included 18,111 participants free of diabetes at baseline and the duration of follow-up was 4.60 ± 0.60 years. Cox proportional regression model was used to calculate the hazard ratio (HR) for the association. The analysis to investigate the association between T2DM and incident NAFLD risk included 12,435 participants free of NAFLD at baseline. Logistic regression model was used to calculate the odd ratio (OR) of NAFLD. Results Compared with those without NAFLD, individuals with mild or moderate/severe NAFLD had a monotonic elevated risk of developing T2DM (HR: 1.88 [95% CI: 1.63–2.18] and 2.34 [1.85–2.96], respectively) after adjustment for potential confounders. In a parallel analysis, compared to participants with fasting plasma glucose < 6.1 mmol/L, the ORs of developing NAFLD in subjects with impaired fasting glucose and T2DM were 1.35 (95% CI: 1.16–1.57) and 1.40 (95% CI: 1.22–1.62), respectively. Conclusions Our results provide compelling evidence that the NAFLD-T2DM association is bidirectional in Chinese population.
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Affiliation(s)
- Yaru Li
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jing Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuhan Tang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xu Han
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Bing Liu
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hua Hu
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiulou Li
- Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
| | - Kun Yang
- Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
| | - Jing Yuan
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoping Miao
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ping Yao
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Sheng Wei
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Youjie Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuan Liang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaomin Zhang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huan Guo
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - An Pan
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Handong Yang
- Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
| | - Frank B. Hu
- Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
| | - Tangchun Wu
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Meian He
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- * E-mail:
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Ma J, Hwang SJ, Pedley A, Massaro JM, Hoffmann U, Chung RT, Benjamin EJ, Levy D, Fox CS, Long MT. Bi-directional analysis between fatty liver and cardiovascular disease risk factors. J Hepatol 2017; 66:390-397. [PMID: 27729222 PMCID: PMC5250546 DOI: 10.1016/j.jhep.2016.09.022] [Citation(s) in RCA: 161] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 09/25/2016] [Accepted: 09/29/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The relations of non-alcoholic fatty liver disease to cardiovascular disease (CVD) risk factors are not fully understood. The objective of our study is to explore the bi-directional relationships of fatty liver to CVD risk factors. METHODS We prospectively evaluated whether liver fat predicted the development of CVD risk factors and whether CVD risk factors predicted new onset fatty liver during 6years of follow-up in middle- to older-aged Framingham Heart Study participants. We estimated liver fat using multi-detector computed tomography. RESULTS We included 1051 participants (mean age 45±6years, 46% women). The prevalence of fatty liver was 18% at baseline. In participants without fatty liver at baseline, 101 participants developed incident fatty liver over approximately 6years. Baseline liver fat (per standard deviation increase) was associated with increased odds of incident hypertension (OR 1.42; 95% CI 1.15-1.76; p=0.001) and incident type 2 diabetes (OR 1.43; 95% CI 1.09-1.88, p<0.001). In a parallel analysis, individuals with hypertension (OR 3.34; 95% CI 2.04-5.49), hypertriglyceridemia (OR 3.04; 95% CI: 1.84-5.02), impaired fasting glucose (OR 2.92; 95% CI 1.76-4.82), or type 2 diabetes (OR 4.15; 95% CI 1.19-14.46) at baseline had higher odds of incident fatty liver compared to individuals without those conditions (all p<0.03). In both analyses, the observed associations remained similar after additional adjustments for measures of adiposity. CONCLUSIONS The present study demonstrated bi-directional relationships between fatty liver and CVD risk factors among middle- to older-aged Framingham Heart Study participants. LAY SUMMARY It is not fully understood whether non-alcoholic fatty liver (NAFLD) disease precedes or develops after increased cardiovascular disease (CVD) risk factors. The findings of our study suggest a bi-directional relationship between NAFLD and CVD risk factors.
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Affiliation(s)
- Jiantao Ma
- The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts
| | - Shih-Jen Hwang
- The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts
| | - Alison Pedley
- The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts
| | - Joseph M. Massaro
- The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Department of Mathematics and Statistics, Boston University, Boston, Massachusetts
| | - Udo Hoffmann
- Radiology Department, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Raymond T. Chung
- Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Emelia J. Benjamin
- The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section, Boston University School of Medicine, Boston, Massachusetts
| | - Daniel Levy
- The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts
| | - Caroline S. Fox
- The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, Division of Endocrinology and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Michelle T. Long
- Division of Gastroenterology, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
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Du T, Sun X, Yuan G, Zhou X, Lu H, Lin X, Yu X. Sex differences in the impact of nonalcoholic fatty liver disease on cardiovascular risk factors. Nutr Metab Cardiovasc Dis 2017; 27:63-69. [PMID: 27956025 DOI: 10.1016/j.numecd.2016.10.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 10/08/2016] [Accepted: 10/12/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Information on sex differences in the association of nonalcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) risk factors is scarce. We examined whether men exhibit greater differences in established CVD risk factors between NAFLD and non-NAFLD than women. METHODS AND RESULTS We conducted a cross-sectional analysis using a cohort of 10761 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography. In the setting of NAFLD and non-NAFLD, although men had significantly higher levels of atherogenic lipids as indicated by higher levels of triglyceride, triglyceride/HDL-cholesterol, and lower levels of HDL-cholesterol and worsen renal function as indicated by higher levels of creatinine and lower levels of estimated glomerular filtration rate (eGFR) than female counterparts, men with NAFLD showed greater relative differences in atherogenic lipids and deteriorated renal function than women with NAFLD when compared with their non-NAFLD counterparts. The interactions between sex and NAFLD on triglyceride, HDL-cholesterol, triglyceride/HDL-cholesterol, creatinine, and eGFR were statistically significant (P < 0.05). In the multivariate Logistic regression analyses, we observed a stronger association of TG with NAFLD and comparable associations of eGFR or HDL-C with NAFLD in men compared with women. CONCLUSION There was greater adverse influence of NAFLD per se on triglyceride, and triglyceride/HDL-cholesterol in men compared with women. The greater adverse influence of NAFLD per se on HDL-C and eGFR in men compared with women probably related to the gender differences in TG levels.
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Affiliation(s)
- T Du
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - X Sun
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - G Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - X Zhou
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - H Lu
- Department of Health Examination, Wuhan Iron and Steel Company (WISCO) General Hospital, Wuhan 430080, China
| | - X Lin
- Department of Endocrinology, Wuhan Iron and Steel Company (WISCO) General Hospital, Wuhan 430080, China
| | - X Yu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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Wang Y, Zeng Y, Lin C, Chen Z. Hypertension and non-alcoholic fatty liver disease proven by transient elastography. Hepatol Res 2016; 46:1304-1310. [PMID: 26932594 DOI: 10.1111/hepr.12688] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Revised: 01/20/2016] [Accepted: 02/26/2016] [Indexed: 12/12/2022]
Abstract
AIM The relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension is poorly understood. In the present study, we aimed to assess the relationship between essential hypertension and NAFLD, by using a new diagnostic tool, transient elastography (TE). METHODS We enrolled 836 subjects in this study. All subjects underwent a comprehensive questionnaire survey and blood test. Each patient had undergone TE to detect the controlled attenuation parameter, which was used to and quantify liver steatosis with the help of TE. RESULTS Participants with hypertension showed a higher prevalence of NAFLD defined by TE (P < 0.05). After adjusting for body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, triglycerides, total cholesterol, and high-density lipoprotein cholesterol, the odds ratio for NAFLD, comparing the grade 3 group (systolic blood pressure level ≥ 180 mmHg and/or diastolic blood pressure level ≥ 110 mmHg) with the normal group, was 1.476 (95% confidence interval, 1.166-2.551). A stepwise multivariate linear regression analysis (R2 = 0.084, P = 0.043) retained NAFLD, BMI, and AST as significant predictors of the systolic blood pressure levels. Additionally, stepwise multivariate linear regression analysis (R2 = 0.199, P = 0.037) retained NAFLD, controlled attenuation parameter, BMI, triglycerides, and high-density lipoprotein cholesterol as significant predictors of diastolic blood pressure levels. In addition, BMI, AST, and alanine aminotransferase were associated with systolic blood pressure levels among individuals with NAFLD; BMI, AST, and total cholesterol were associated with diastolic blood pressure levels among individuals with NAFLD. CONCLUSION The main finding of our study is that hypertensive patients have a higher prevalence of NAFLD defined by TE, and NAFLD is independently associated with hypertension and blood pressure category.
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Affiliation(s)
- Yaohui Wang
- Department of Health Management Center, The Third XiangYa Hospital of Central South University, Changsha, Hunan, 410013, China
| | - Yuhua Zeng
- Department of Health Management Center, The Third XiangYa Hospital of Central South University, Changsha, Hunan, 410013, China
| | - Changwei Lin
- Department of General Surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan, 410013, China
| | - Zhiheng Chen
- Department of Health Management Center, The Third XiangYa Hospital of Central South University, Changsha, Hunan, 410013, China
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Xiao J, Wu CL, Gao YX, Wang SL, Wang L, Lu QY, Wang XJ, Hua TQ, Shen H, Cai H. Prevalence of metabolic syndrome and its risk factors among rural adults in Nantong, China. Sci Rep 2016; 6:38089. [PMID: 27901076 PMCID: PMC5128865 DOI: 10.1038/srep38089] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 11/03/2016] [Indexed: 02/06/2023] Open
Abstract
The prevalence of metabolic syndrome (MS) varies worldwide due to genetic and environmental factors. A population-based cross-sectional study, with 37,582 participants recruited in Nantong, China in 2007-2008 (stage I) and 2013 (stage II). Socio-demographic, lifestyle factors, disease history and fasting blood sample were collected. The prevalence of MS was much higher in 2013 (42.6%) than that in 2007-2008 (21.6%), which was significantly higher in older people in both stages. Participants with two or more familial history of diseases were associated with a higher MS prevalence compared to those who didn’t have familial history of diseases. Total physical activity (PA) was associated with 24 and 19% decreased risk of MS in men and women. Occupational PA in moderate and vigorous intensity was associated with a 25%-45% decreased risk of MS. Female smokers who smoked more than 10 cigarettes per day or over 25 years were associated with 96 and 74% increased MS risk, respectively. The highest quartile of rice wine consumption was associated with a lower risk of MS with OR of 0.63 in women, compared with female non-drinkers. These findings indicated that PA and rice wine are two protective factors in MS prevention in rural areas of East China.
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Affiliation(s)
- Jing Xiao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, P.R. China
| | - Chuan-Li Wu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, P.R. China
| | - Yue-Xia Gao
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, P.R. China
| | - Shu-Lan Wang
- Rugao Center for Diseases Prevention and Control, Nantong, Jiangsu, P.R. China
| | - Lei Wang
- Rugao Center for Diseases Prevention and Control, Nantong, Jiangsu, P.R. China
| | - Qing-Yun Lu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, P.R. China
| | - Xiao-Jian Wang
- Department of Chronic Disease and Prevention, Center for Disease Control and Prevention of Haian, Nantong, Jiangsu, P.R. China
| | - Tian-Qi Hua
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, P.R. China
| | - Huan Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, P.R. China
| | - Hui Cai
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, P.R. China.,Division of Epidemiology, Vanderbilt University Medical Center, 2525 West End Avenue, 6th floor, Nashville, TN, 37203-1738, USA
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Cai S, Sun W, Fan Y, Guo X, Xu G, Xu T, Hou Y, Zhao B, Feng X, Liu T. Effect of mulberry leaf (Folium Mori) on insulin resistance via IRS-1/PI3K/Glut-4 signalling pathway in type 2 diabetes mellitus rats. PHARMACEUTICAL BIOLOGY 2016; 54:2685-2691. [PMID: 27158744 DOI: 10.1080/13880209.2016.1178779] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
CONTEXT Folium Mori, the leaf of Morus alba L. (Moraceae), has been used in traditional Chinese medicine (TCM) for treating diabetes. However, it is unclear which components in the mulberry leaf are effective for the treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE To investigate the flavonoids and polyphenols in mulberry leaves and their antihyperglycemic and antihyperlipidemic effects in T2DM rats. MATERIALS AND METHODS Male Sprague-Dawley rats were divided into five groups: normal control (NC), diabetic control (DBC), diabetic group with 0.3 mg/kg b.w./day rosiglitazone (RSG), diabetic group with 7 g/kg b.w./day TCM formula and diabetic group with 2 g/kg b.w./day Folium Mori extract (FME). After 4 weeks, the rats were sacrificed; biochemical parameters, gene and protein expression were measured. RESULTS The FBG level was significantly lower in the FME group than in the DBC group (p < 0.05). In oral glucose tolerance test, the AUC was significantly lower in the FME group (p < 0.05). The HOMA-IR level was significantly decreased in the FME group (p < 0.05). FME decreased the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) levels (p < 0.05). FME increased the mRNA and protein expression of IRS-1, PI3K p85α and Glut-4 increased significantly (p < 0.05). Histological analysis revealed amelioration of lipid accumulation following FME treatment. Additionally, immunohistochemical analysis displayed stronger staining of Glut-4 in the FME group compared to the DBC group. DISCUSSION AND CONCLUSION FME could decrease the body weight, blood glucose, TG, TC and LDL levels, and improve insulin resistance. FME possessed significant antihyperglycemic and antihyperlipidemic activities via the IRS-1/PI3K/Glut-4 signalling pathway.
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Affiliation(s)
- Shengyu Cai
- a Beijing University of Chinese Medicine , Beijing , P.R. China
| | - Wen Sun
- b Key Laboratory of the Health-Cultivation of the Ministry of Education , Beijing University of Chinese Medicine , Beijing , P.R. China
- c Beijing Key Laboratory of the Health-Cultivation , Beijing , P.R. China
- d Beijing International Technology Cooperation Base for Prevention and Treatment of Diabetes Mellitus with Chinese Medicine , Beijing , P.R. China
| | - Yixin Fan
- e Department of Science and Technology , Beijing University of Chinese Medicine , Beijing , P.R. China
| | - Xuan Guo
- f Dongfang Hospital Affiliated to Beijing University of Chinese Medicine , Beijing , P.R. China
| | - Guangyuan Xu
- f Dongfang Hospital Affiliated to Beijing University of Chinese Medicine , Beijing , P.R. China
| | - Tunhai Xu
- g School of Chinese Pharmacy , Beijing University of Chinese Medicine , Beijing , P.R. China
| | - Yi Hou
- f Dongfang Hospital Affiliated to Beijing University of Chinese Medicine , Beijing , P.R. China
| | - Baosheng Zhao
- h Scientific Research Experiment Center, Beijing University of Chinese Medicine , Beijing , P.R. China
| | - Xingzhong Feng
- i Beijing Shijitan Hospital, Capital Medical University , Beijing , P.R. China
| | - Tonghua Liu
- b Key Laboratory of the Health-Cultivation of the Ministry of Education , Beijing University of Chinese Medicine , Beijing , P.R. China
- c Beijing Key Laboratory of the Health-Cultivation , Beijing , P.R. China
- d Beijing International Technology Cooperation Base for Prevention and Treatment of Diabetes Mellitus with Chinese Medicine , Beijing , P.R. China
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Du T, Sun X, Yuan G, Zhou X, Lu H, Lin X, Yu X. Lipid phenotypes in patients with nonalcoholic fatty liver disease. Metabolism 2016; 65:1391-8. [PMID: 27506745 DOI: 10.1016/j.metabol.2016.06.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 06/13/2016] [Accepted: 06/21/2016] [Indexed: 11/23/2022]
Abstract
OBJECTIVE There has been conflicting evidence regarding the role of single lipid species in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to explore the associations between dyslipidemia phenotypes (combinations of lipid parameters) and the risk of NAFLD. METHODS We conducted a cross-sectional analysis using a cohort of 9560 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography. RESULTS Of 3709 participants with NAFLD, 41.8% were classified as normolipemia (NL), 3.8% as combined hyperlipidemia, 3.2% as hypercholesterolemia, 17.7% as dyslipidemia of metabolic syndrome (MetS), 10.2% as isolated low high-density lipoprotein cholesterol (HDL-C), and 23.3% as isolated hypertriglyceridemia. The multivariable-adjusted odds ratios (ORs) (with 95% confidence intervals) for NAFLD in those with combined hyperlipidemia, those with hypercholesterolemia, those with MetS dyslipidemia, those with low HDL-C, and those with hypertriglyceridemia compared with those with NL were 4.79 (3.19-7.20), 1.26 (0.94-1.69), 3.31 (2.74-3.99), 1.13 (0.95-1.34), and 2.63 (2.26-3.08), respectively. The associations between combined hyperlipidemia, MetS dyslipidemia, or hypertriglyceridemia and risk of NAFLD were consistently seen in various evaluated subgroups. The interactions between lipid phenotypes and sex, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), or uric acid (UA) were not significant for NAFLD (all P>0.05). CONCLUSIONS There were diverse dyslipidemia phenotypes in patients with NAFLD. Combined hyperlipidemia, MetS dyslipidemia, and hypertriglyceridemia were strongly and independently associated with increased risk of NAFLD. Gender, BMI, BP, FPG, and UA status did not modify the associations between dyslipidemia phenotypes and NAFLD.
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Affiliation(s)
- Tingting Du
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xingxing Sun
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xinrong Zhou
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Huimin Lu
- Department of Health Examination, Wuhan Iron and Steel Company (WISCO) General Hospital, Wuhan, 430080, China
| | - Xuan Lin
- Department of Endocrinology, Wuhan, Iron and Steel Company (WISCO) General Hospital, Wuhan, 430080, China
| | - Xuefeng Yu
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J Gastroenterol 2016; 22:7236-7251. [PMID: 27621571 PMCID: PMC4997649 DOI: 10.3748/wjg.v22.i32.7236] [Citation(s) in RCA: 197] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 06/28/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis (laboratory tests and ultrasonography) or cannot be applied as a screening procedure (liver biopsy). Among the non-invasive tests, transient elastography (FibroScan(®), TE) with controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.
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Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev 2016; 17:510-9. [PMID: 27020692 DOI: 10.1111/obr.12407] [Citation(s) in RCA: 289] [Impact Index Per Article: 32.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 02/07/2016] [Accepted: 02/15/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The association between obesity and nonalcoholic fatty liver disease (NAFLD) has not been fully quantified, and the magnitude of NAFLD risk associated with obesity is still unclear. A meta-analysis of cohort studies was performed to elucidate the NAFLD risk associated with obesity. METHODS Pubmed, Web of Science and Embase were searched for cohort studies assessing NAFLD risk associated with obesity or increased body mass index (BMI). Relative risks (RRs) with 95% confidence intervals (95%CIs) were pooled using random-effects model of meta-analysis. RESULTS Twenty-one cohort studies including 13 prospective studies and 8 retrospective studies were finally included. There were a total of 381,655 participants in the meta-analysis. Compared with normal weight, obesity independently led to a 3.5-fold increased risk of developing NAFLD (RR = 3.53, 95%CI 2.48 to 5.03, P < 0.001). Meta-analysis also suggested an obvious dose-dependent relationship between BMI and NAFLD risk (per 1-unit increment in BMI: RR = 1.20, 95%CI 1.14 to 1.26, P < 0.001). Subgroup analyses further identified the robustness of the association above. No obvious risk of publication bias was observed. CONCLUSION Obese individuals have a 3.5-fold increased risk of developing NAFLD, and there is an obvious dose-dependent relationship between BMI and NAFLD risk. © 2016 World Obesity.
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Affiliation(s)
- L Li
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - D-W Liu
- Department of Urinary Surgery, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
| | - H-Y Yan
- Department of Gastroenterology, 210 Hospital of PLA, Dalian, China
| | - Z-Y Wang
- Surgical Center, Zhucheng People's Hospital, Zhucheng, China
| | - S-H Zhao
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - B Wang
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China
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