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Herout R, Oehlschläger S. [Gender Disparities in Urolithiasis with a Special Focus on Oxalate Metabolism in the Liver]. Aktuelle Urol 2025; 56:145-149. [PMID: 40074008 DOI: 10.1055/a-2528-0260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2025]
Abstract
The incidence and prevalence of urolithiasis are increasing in industrialized countries. In particular, an increase has been observed among young adults and women. The gender gap is closing, and gender equality (1:1) with regard to urolithiasis has already been documented for the USA. Studies have demonstrated that women have higher urine pH values than men, which promotes calcium phosphate crystallization. The tendency for men to develop calcium oxalate and uric acid stones is caused by the comparatively lower urine pH values. Malnutrition combined with a lack of exercise and the occurrence of metabolic syndrome with its underlying diseases (insulin resistance, type 2 diabetes mellitus, obesity, dyslipidaemia) are discussed as the causes of the increase in upper tract stone disease in industrialized countries. Non-alcoholic fatty liver disease (NAFLD), as the most common liver disease, is considered one of the complications of metabolic syndrome, with a prevalence of approximately 23% in Germany. Animal experiments and clinical studies have demonstrated a connection between NAFLD and increased oxalate excretion in urine. Based on the literature, NAFLD represents a possible cross-gender risk factor for kidney stone formation and is therefore considered to be a generally modifiable risk factor for recurrent urolithiasis. Simple recommendations concerning NAFLD should complement the general and metabolic workup in everyday clinical practice.
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Affiliation(s)
- Roman Herout
- Klinik und Poliklinik für Urologie, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Sven Oehlschläger
- Klinik und Poliklinik für Urologie, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany
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Taniguchi H, Ueda M, Kobayashi Y, Shima T. BMI gain and dietary characteristics are risk factors of MASLD in non-obese individuals. Sci Rep 2025; 15:2606. [PMID: 39838114 PMCID: PMC11751101 DOI: 10.1038/s41598-025-86424-x] [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: 06/26/2024] [Accepted: 01/10/2025] [Indexed: 01/23/2025] Open
Abstract
This longitudinal observational study aimed to evaluate whether cardiometabolic factors and dietary characteristics are determinants of metabolic dysfunction-associated steatotic liver disease (MASLD) in non-obese individuals (body mass index [BMI] < 25 kg/m²). The study was conducted at the Japanese Red Cross Society Kyoto Daiichi Hospital. Clinical data were longitudinally recorded at annual health checks. The diagnosis of MASLD was based on the results of abdominal ultrasonography and cardiometabolic criteria. Lifestyle behaviors and dietary characteristics were assessed using a self-administered questionnaire. A total of 4,100 non-obese middle-aged and older participants (1,636 men and 2,464 women) were followed up for an average of 6.44 ± 4.16 years. During the follow-up period, there were 410 new cases of MASLD in men (25.1%) and 484 in women (19.6%). The incidence rate was higher for men (39.7 per 1,000 person-years) than for women (30.1 per 1,000 person-years). Multivariable-adjusted logistic regression analyses using the rate of change per year with standardized values found that BMI gain was strongly associated with the onset of MASLD for both men (OR: 1.90, 95% CI: 1.64-2.19) and women (OR: 1.95, 95% CI: 1.72-2.21). Increased waist circumference and triglycerides were also associated with MASLD onset for both men and women. Lowering of high-density lipoprotein cholesterol was identified as a risk factor for MASLD in both men and women. Regarding dietary characteristics, the onset of MASLD was significantly and negatively associated with "often eating vegetables" for men (OR: 0.73, 95% CI: 0.57-0.93) and "often eating soy products" for women (OR: 0.71, 95% CI: 0.58-0.88), even after adjusting for BMI change and other covariates. These findings suggest that maintaining body weight and favorable dietary characteristics are key factors in the prevention of MASLD in non-obese individuals.
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Affiliation(s)
- Hirokazu Taniguchi
- Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, 606-8522, Japan.
| | - Miho Ueda
- Center for Health Promotion, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Yukiko Kobayashi
- Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, 606-8522, Japan
| | - Takatomo Shima
- Center for Health Promotion, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
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Han T, Li Y, Xiao J, Gong H, Deng F, Jiang W, Wang C, Chen F, Zhang C, Deng J, Zhang Y. Diagnostic Utility of Triglyceride-Glucose Index in Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study on Lean Population. Diabetes Metab Syndr Obes 2024; 17:3547-3556. [PMID: 39328264 PMCID: PMC11424687 DOI: 10.2147/dmso.s469398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 09/03/2024] [Indexed: 09/28/2024] Open
Abstract
Background Approximately 10-20% of individuals with non-alcoholic fatty liver disease (NAFLD) are lean, and the underlying pathophysiology is not yet understood. This study aims to explore the characteristics and the diagnostic value of triglyceride-glucose index (TyG) in early diagnosis of lean NAFLD. Methods 99 patients with lean NAFLD and 1891 healthy controls were included in the health examination. The characteristics were compared between groups. Restricted cubic spline was utilized to analyze the relationship between TyG index and the risk of lean NAFLD. Logistic regression and receiver operating curve (ROC) were applied to explore the diagnostic value of TyG index for lean NAFLD. Results Overall, 99 (4.97%) patients had lean NAFLD. Patients with lean NAFLD have significant abnormal glycolipid metabolism and higher TyG index. Restriction cube spline analysis showed a significant dose-response relationship between the TyG index and risk of lean NAFLD. After adjusting for confounders, the relationship remained and the risk of developing lean NAFLD increased 2.99 times for per unit increase of TyG index (95% CI: 1.94, 4.67, P<0.001). The areas under the ROC of the TyG index for lean NAFLD detection were 0.851 (0.815 to 0.886). Conclusion The TyG index is positively associated with the risk of developing lean NAFLD and could be a useful marker for early diagnosis of lean NAFLD.
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Affiliation(s)
- Tuo Han
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Ying Li
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Jing Xiao
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Hong Gong
- Department of Health Management, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Fuxue Deng
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Wei Jiang
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Congxia Wang
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Fangyao Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, People's Republic of China
| | - Chunyan Zhang
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Jie Deng
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
| | - Yan Zhang
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, People's Republic of China
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Jin Y, Wang X, Chen K, Chen Y, Zhou L, Zeng Y, Zhou Y, Pan Z, Wang D, Li Z, Liang Y, Ling W, Li D. Silymarin decreases liver stiffness associated with gut microbiota in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial. Lipids Health Dis 2024; 23:239. [PMID: 39097726 PMCID: PMC11297656 DOI: 10.1186/s12944-024-02220-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/16/2024] [Indexed: 08/05/2024] Open
Abstract
BACKGROUND Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. OBJECTIVE To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. METHOD In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. RESULTS Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. CONCLUSION These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. TRIAL REGISTRATION The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).
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Affiliation(s)
- Yufeng Jin
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China
| | - Xin Wang
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China
| | - Ke Chen
- Shunde Hospital (The First People's Hospital of Shunde), Southern Medical University, Foshan, China
| | - Yu Chen
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China
| | - Lixin Zhou
- Shunde Hospital (The First People's Hospital of Shunde), Southern Medical University, Foshan, China
| | - Yupeng Zeng
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China
| | - Yuqing Zhou
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China
| | - Zhijun Pan
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China
| | - Di Wang
- BYHEALTH Institute of Nutrition & Health, Guangzhou, 510663, China
| | - Zhongxia Li
- BYHEALTH Institute of Nutrition & Health, Guangzhou, 510663, China
| | - Yongqian Liang
- Shunde Hospital (The First People's Hospital of Shunde), Southern Medical University, Foshan, China.
| | - Wenhua Ling
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China.
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China.
- School of Public Health and Management, Ningxia Medical University, Xingqing District, Yinchuan, China.
| | - Dan Li
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, 510080, China.
- Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, 510080, China.
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Huang D, Lai H, Zhu Z, Yu H, Peng J, Chen Y, Liao X, Chen J. Inverse relationship between HBV DNA levels and liver histopathological changes in immune-tolerant CHB patients. J Viral Hepat 2024; 31:363-371. [PMID: 38581159 DOI: 10.1111/jvh.13940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/21/2024] [Accepted: 03/23/2024] [Indexed: 04/08/2024]
Abstract
Limited data exist regarding the association between hepatitis B virus (HBV) DNA levels and liver histopathological changes in patients with chronic hepatitis B (CHB) during the immune tolerant (IT) phase. In this study, we retrospectively analysed liver biopsy results from 150 adult IT-CHB patients. The liver tissue necroinflammation and fibrosis were evaluated by the Scheuer scoring system. Multivariate logistic regression, smooth curve fitting, and segmented regression models were used to examine the association between HBV DNA levels and liver histopathological changes. A total of 26%, 30.67% and 42% of IT patients had significant necroinflammation (≥G2), significant fibrosis (≥S2) and significant histopathological changes (≥G2 and/or ≥S2), respectively. HBV DNA levels were independently and non-linear inversely associated with significant necroinflammation and histopathological changes in IT-CHB patients. Patients with HBV DNA levels <107 IU/mL had a higher risk of significant histopathological changes compared to those with levels >107 IU/mL. The findings were further confirmed by smooth curve fitting analyses, subgroup and sensitivity analyses. In segmented regression model analyses, the optimal DNA value for the lowest odds ratio of significant histopathological changes was 7.26 log10 IU/mL. A non-linear inverse association between HBV DNA levels and significant histopathological changes in IT-CHB patients. DNA 7.26 log10 IU/mL may serve as a potential cut-off point to define a 'true immune tolerant phase' with minimal liver histopathological changes.
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Affiliation(s)
- Deliang Huang
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Huiyi Lai
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Zhibin Zhu
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Hong Yu
- Department of Pathology, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Jinghan Peng
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Yuanyuan Chen
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Xuejiao Liao
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Jun Chen
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
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Taniguchi H, Ueda M, Sano F, Kobayashi Y, Shima T. Dietary characteristics associated with the risk of non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease in non-obese Japanese participants: A cross-sectional study. JGH Open 2024; 8:e13082. [PMID: 38779132 PMCID: PMC11109997 DOI: 10.1002/jgh3.13082] [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: 10/16/2023] [Revised: 02/09/2024] [Accepted: 04/29/2024] [Indexed: 05/25/2024]
Abstract
Background and Aim Dietary characteristics associated with non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) in non-obese patients remain to be elucidated. This study examined the association of NAFLD and MASLD with dietary characteristics according to obesity status. Methods We performed a cross-sectional study of 15 135 participants (n = 7568 men and 7567 women) aged 35-74 years using data of annual health checks between 2008 and 2020. Obesity was defined as BMI ≥ 25 kg/m2. Diagnosis of fatty liver was based on abdominal ultrasonography. Fatty-liver-related dietary characteristics were assessed using a self-administered questionnaire. Results For non-obese participants, NAFLD was found in 31.0% of men and 19.4% of women. Non-obese MASLD was found in 27.6% of men and 18.1% of women. Multivariable-adjusted stepwise logistic regression analysis indicated that, in males, both non-obese NAFLD and non-obese MASLD were significantly and negatively associated with "often eat sesame/nuts", and positively associated with "often eat noodles/rice bowl" and "often eat evening meal" (P < 0.05). For non-obese women, both NAFLD and MASLD were significantly and positively associated with "often eat sweet buns/bread with fillings" (P < 0.05). Adjusted analyses showed that all dietary characteristics were not significantly associated with the risk of NAFLD/MASLD in obese men and women. Conclusion This cross-sectional study indicates the existence of sex and obesity differences in the association of NAFLD and MASLD with dietary characteristics. Our findings suggest that some dietary characteristics are associated with NAFLD and MASLD prevalence in non-obese Japanese participants.
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Affiliation(s)
- Hirokazu Taniguchi
- Division of Applied Life Sciences, Graduate School of Life and Environmental SciencesKyoto Prefectural UniversityKyotoJapan
| | - Miho Ueda
- Center for Health Promotion, Japanese Red Cross Kyoto Daiichi HospitalKyotoJapan
| | - Fumika Sano
- Division of Applied Life Sciences, Graduate School of Life and Environmental SciencesKyoto Prefectural UniversityKyotoJapan
| | - Yukiko Kobayashi
- Division of Applied Life Sciences, Graduate School of Life and Environmental SciencesKyoto Prefectural UniversityKyotoJapan
| | - Takatomo Shima
- Center for Health Promotion, Japanese Red Cross Kyoto Daiichi HospitalKyotoJapan
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Ji W, Cheng Y, Tang S, Gu K, Liao H, Li L, Wang Y, Yang BY, Zhou Y. Exposure to ambient air pollution and metabolic dysfunction-associated fatty liver disease: Findings from over 2.7 million adults in Northwestern China. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 272:116109. [PMID: 38364762 DOI: 10.1016/j.ecoenv.2024.116109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 02/09/2024] [Accepted: 02/10/2024] [Indexed: 02/18/2024]
Abstract
Ambient air pollutants exposures may lead to aggravated Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD). However, there is still a scarcity of empirical studies that have rigorously estimated this association, especially in regions where air pollution is severe. To fill in the literature gap, we conducted a cross-sectional study involving 2711,207 adults living in five regions of southern Xinjiang Uyghur Autonomous Region in 2021. Using a Space-Time Extra-Trees model, we assessed the four-year (2017-2020) average concentrations of particulate matter with aerodynamic diameter ≤1 µm (PM1), particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), particulate matter with aerodynamic diameter ≤10 µm (PM10), ozone (O3), sulfur dioxide (SO2), and carbon monoxide (CO), and then assigned these values to the participants. Generalized linear mixed models were employed to examine the relationships between air pollutants and the prevalence of MAFLD, with adjustment for multiple confounding factors. The odds ratios and 95% confidence intervals of MAFLD were 2.002 (1.826-2.195), 1.133 (1.108-1.157), 1.034 (1.027-1.040), 1.077 (1.023-1.134), 2.703 (2.322-3.146) and 1.033 (1.029-1.036) per 10 µg/m3 increase in the 4-year average PM1, PM2.5, PM10, O3, SO2 and CO exposures, respectively. The robustness of the findings was confirmed by a series of sensitivities. In summary, long-term exposure to ambient air pollutants was associated with increased odds of MAFLD, particularly in males and individuals with unhealthy lifestyles.
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Affiliation(s)
- Weidong Ji
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou , Guangdong 510080, China
| | - Yinlin Cheng
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou , Guangdong 510080, China
| | - Shengsheng Tang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou , Guangdong 510080, China
| | - Kuiying Gu
- Vanke School of Public Health, Tsinghua University, Beijing 100084, China
| | - Huipeng Liao
- Vanke School of Public Health, Tsinghua University, Beijing 100084, China
| | - Lin Li
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou , Guangdong 510080, China
| | - Yushan Wang
- Center of Health Management, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
| | - Bo-Yi Yang
- Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Guangdong Provincial Engineering Technology Research Center of Environmental and Health risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.
| | - Yi Zhou
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou , Guangdong 510080, China.
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Prasad M, Gupta S, Sarin SK. The Independent Association of Non-alcoholic Fatty Liver Disease With Incident Cardiovascular Disease: A GRADE Evaluation of the Evidence Through a Systematic Review and Meta-analysis. J Clin Exp Hepatol 2024; 14:101277. [PMID: 38076375 PMCID: PMC10709169 DOI: 10.1016/j.jceh.2023.08.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 08/25/2023] [Indexed: 09/13/2024] Open
Abstract
Background We conducted a systematic review and meta-analysis to study the association between non-alcoholic fatty liver disease (NAFLD) and incident cardiovascular disease (CVD). Methods We searched Medline, Embase, Cochrane database and TRIP database. Random-effects model meta-analyses were used to obtain pooled effect sizes and 95% confidence intervals. The certainty in evidence was rated using the GRADE tool. Results Altogether 36 studies including a total of 7,068,007 participants were included in the systematic review and meta-analysis. Pooled data from 19 cohort studies demonstrated a significant increase in the risk of non-fatal CVD events in patients with NAFLD (HR 1.57, 95% CI 1.33-1.85, I2 = 95%). Pooled data from eight studies showed a significant increase in fatal CVD (HR 1.40, 95% CI 1.24-1.57, I2 =27%), and eight cohort studies suggested a significant increase in combined non-fatal and fatal CVD (HR 1.41, 95% CI 1.13-1.76, I2 =80%). Meta-analysis of studies reporting adjusted estimates in NAFLD patients with fibrosis revealed a significant increase in CVD events with acceptable level of heterogeneity (HR 1.64, 95% CI 1.25-2.16, I2 = 31%). The anticipated absolute increase in the risk of combined fatal and non-fatal CVD was estimated to be 29 more per thousand with NAFLD; that of fatal CVD events 16 more per thousand and that of non-fatal CVD events 19 more per thousand with NAFLD. The GRADE rating ranged from very low to low for overall and subgroup analyses. Conclusion The present systematic review suggests that NAFLD increases the risk of incident CVD. Cohort studies with the ability to analyze subgroup effects based on severity, along with randomized controlled trials that provide experimental evidence demonstrating a decrease in cardiovascular disease events through the treatment of non-alcoholic fatty liver disease, are necessary to validate and reinforce these findings.
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Affiliation(s)
- Manya Prasad
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sunanda Gupta
- Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, New Delhi, India
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Guan H, Liu K, Fan X, Yu H, Qin Y, Yang J, Zhu Z, Shen C, Pan E, Lu Y, Zhou J, Su J, Wu M. Association of gamma-glutamyl transferase concentrations with all-cause and cause-specific mortality in Chinese adults with type 2 diabetes. J Diabetes 2023; 15:674-684. [PMID: 37161588 PMCID: PMC10415869 DOI: 10.1111/1753-0407.13399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 03/06/2023] [Accepted: 04/15/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. METHODS We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. RESULTS During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m2 group and those without dyslipidemia. CONCLUSIONS Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.
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Affiliation(s)
- Haoyu Guan
- Department of Epidemiology, School of Public HealthNanjing Medical UniversityNanjingChina
| | - Ke Liu
- Department of Epidemiology and Health Statistics, School of Public HealthSoutheast UniversityNanjingChina
| | - Xikang Fan
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Hao Yu
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Yu Qin
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Jie Yang
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Zheng Zhu
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Chong Shen
- Department of Epidemiology, School of Public HealthNanjing Medical UniversityNanjingChina
| | - Enchun Pan
- Department of Chronic Disease Prevention and ControlHuai'an City Center for Disease Control and PreventionHuai'anChina
| | - Yan Lu
- Department of Chronic Disease Prevention and ControlSuzhou City Center for Disease Control and PreventionSuzhouChina
| | - Jinyi Zhou
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Jian Su
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Ming Wu
- Department of Epidemiology, School of Public HealthNanjing Medical UniversityNanjingChina
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
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10
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Grob SR, Suter F, Katzke V, Rohrmann S. The Association between Liver Enzymes and Mortality Stratified by Non-Alcoholic Fatty Liver Disease: An Analysis of NHANES III. Nutrients 2023; 15:3063. [PMID: 37447388 DOI: 10.3390/nu15133063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/30/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
Associations between liver enzymes or De Ritis ratio (DRR; aspartate aminotransferase (AST)/alanine aminotransferase (ALT)) and mortality stratified by non-alcoholic fatty liver disease (NAFLD), which have rarely been analyzed in previous studies, were investigated using the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Participants without risk factors for liver diseases other than NAFLD were linked with National Death Index records through 2019 (n = 11,385) and divided into two cohorts with or without NAFLD, based on ultrasound examination. Liver enzyme concentrations were categorized into sex-specific deciles and subsequently grouped (AST and ALT: 1-3, 4-9, 10; gamma glutamyltransferase (GGT): 1-8, 9-10). DRR was categorized into tertiles. Cox proportional hazards regression models adjusted for confounders were fitted to estimate associations with mortality. Compared with low levels, high GGT and DRR in participants with and without NAFLD had significantly higher hazard ratios for all-cause mortality. Compared with intermediate concentrations, low ALT showed higher all-cause mortality in participants with and without NAFLD, whereas low AST had higher HR in participants without NAFLD and high AST in those with NAFLD. Mortality was associated with liver enzymes or DRR in participants both with and without NAFLD, indicating that the relationship is not mediated solely by hepatocellular damage.
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Affiliation(s)
- Saskia Rita Grob
- Medical Faculty, University of Zurich, Pestalozzistrasse 3, CH-8032 Zurich, Switzerland
| | - Flurina Suter
- Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Hirschengraben 84, CH-8001 Zurich, Switzerland
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, DE-69120 Heidelberg, Germany
| | - Sabine Rohrmann
- Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Hirschengraben 84, CH-8001 Zurich, Switzerland
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11
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Niemelä O, Bloigu A, Bloigu R, Aalto M, Laatikainen T. Associations between Liver Enzymes, Lifestyle Risk Factors and Pre-Existing Medical Conditions in a Population-Based Cross-Sectional Sample. J Clin Med 2023; 12:4276. [PMID: 37445311 DOI: 10.3390/jcm12134276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/20/2023] [Accepted: 06/24/2023] [Indexed: 07/15/2023] Open
Abstract
While alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) enzymes are commonly used indicators of liver dysfunction recent studies have suggested that these may also serve as predictive biomarkers in the assessment of extrahepatic morbidity. In order to shed further light on the interactions between serum liver enzyme abnormalities, factors of lifestyle and health status we examined ALT and GGT activities in a population-based sample of 8743 adult individuals (4048 men, 4695 women from the National FINRISK 2002 Study, mean age 48.1 ± 13.1 years) with different levels of alcohol drinking, smoking, physical activity, body weight and the presence or absence of various pre-existing medical conditions. The assessments also included laboratory tests for inflammation, lipid status and fatty liver index (FLI), a proxy for fatty liver. The prevalence of ALT and GGT abnormalities were significantly influenced by alcohol use (ALT: p < 0.0005 for men; GGT: p <0.0005 for both genders), smoking (GGT: p <0.0005 for men, p =0.002 for women), adiposity (p < 0.0005 for all comparisons), physical inactivity (GGT: p <0.0005; ALT: p <0.0005 for men, p <0.05 for women) and coffee consumption (p <0.0005 for GGT in both genders; p <0.001 for ALT in men). The total sum of lifestyle risk factor scores (LRFS) influenced the occurrence of liver enzyme abnormalities in a rather linear manner. Significantly higher LRFS were observed in the subgroups of individuals with pre-existing medical conditions when compared with those having no morbidities (p <0.0005). In logistic regression analyses adjusted for the lifestyle factors, both ALT and GGT associated significantly with fatty liver, diabetes and hypertension. GGT levels also associated with coronary heart disease, angina pectoris, cardiac insufficiency, cerebrovascular disease, asthma and depression. Combinations of abnormal ALT and GGT activities significantly increased the odds for hypertension coinciding with abnormalities in biomarkers of inflammation, lipid status and FLI. The data indicates that ALT and GGT activities readily respond to unfavorable factors of lifestyle associating also with a wide array of pre-existing medical conditions. The data supports close links between both hepatic and extrahepatic morbidities and lifestyle risk factors and may open new insights on a more comprehensive use of liver enzymes in predictive algorithms for assessing mechanistically anchored disease conditions.
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Affiliation(s)
- Onni Niemelä
- Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and Tampere University, 60220 Seinäjoki, Finland
| | - Aini Bloigu
- Research Unit of Population Health, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
| | - Risto Bloigu
- Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
| | - Mauri Aalto
- Department of Psychiatry, Seinäjoki Central Hospital and Tampere University, 33100 Tampere, Finland
| | - Tiina Laatikainen
- Department of Public Health and Social Welfare, Finnish Institute for Health and Welfare (THL), 00271 Helsinki, Finland
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland
- Joint Municipal Authority for North Karelia Social and Health Services, 80210 Joensuu, Finland
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12
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Abstract
The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.
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Affiliation(s)
- Onni Niemelä
- Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and Tampere University, Seinäjoki, Finland.
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13
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Bischoff SC, Ockenga J, Eshraghian A, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. Practical guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2023; 42:987-1024. [PMID: 37146466 DOI: 10.1016/j.clnu.2023.03.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 05/07/2023]
Abstract
BACKGROUND Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases. METHODS The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text. RESULTS In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; and Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim gGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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14
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Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of Liver Disease: 2023 Update. J Hepatol 2023:S0168-8278(23)00194-0. [PMID: 36990226 DOI: 10.1016/j.jhep.2023.03.017] [Citation(s) in RCA: 708] [Impact Index Per Article: 354.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/06/2023] [Accepted: 03/09/2023] [Indexed: 03/31/2023]
Abstract
Liver disease accounts for 2 million deaths and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately 2/3 of all liver related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and nonalcoholic fatty liver disease (NAFLD). Hepatotropic viruses are the etiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, NAFLD, viral hepatitis, and HCC. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.
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Affiliation(s)
- Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, India
| | - Sumeet K Asrani
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX, United States.
| | - Juan Pablo Arab
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Yvonne Ayerki Nartey
- Department of Internal Medicine, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Elisa Pose
- Liver Unit, Hospital Clinic of Barcelona. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, MN, United States
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15
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Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study. Sci Rep 2023; 13:1751. [PMID: 36720971 PMCID: PMC9888340 DOI: 10.1038/s41598-022-25970-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 12/07/2022] [Indexed: 02/01/2023] Open
Abstract
Population-based data regarding the prognostic implication of gamma-glutamyl transferase (GGT) have been inconsistent. We examined the association of GGT with all-cause and disease-specific mortality. Using the Korean nationwide database, we included 9,687,066 subjects without viral hepatitis or cirrhosis who underwent a health examination in 2009. Subjects were classified into three groups by sex-specific tertile of serum GGT levels. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases codes. During the median follow-up period of 8.3 years, 460,699 deaths were identified. All-cause mortality increased as serum GGT levels became higher (hazard ratio [HR], 95% confidence interval [CI] 1.05, 1.04-1.05 in the middle tertile, and 1.33, 1.32-1.34 in the high tertile) compared to the low tertile of serum GGT levels. Similar trends were observed for cardiovascular disease (CVD) (HR, 95% CI 1.07, 1.05-1.09 in the middle tertile, 1.29, 1.26-1.31 in the high tertile), cancer (HR, 95% CI 1.08, 1.07-1.10 in the middle tertile, 1.38, 1.36-1.39 in the high tertile), respiratory disease (HR, 95% CI 1.10, 1.08-1.13 in the middle tertile, 1.39, 1.35-1.43 in the high tertile), and liver disease mortality (HR, 95% CI 1.74, 1.66-1.83 in the middle tertile, 6.73, 6.46-7.01 in the high tertile). Regardless of smoking, alcohol consumption and history of previous CVD and cancer, a higher serum GGT levels were associated with a higher risk of mortality. Serum GGT levels may be useful for risk assessment of all-cause and disease-specific mortality in general population.
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16
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Exploring the Validity of Available Markers and Indices in the Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD) in People with Type 2 Diabetes in Saudi Arabia. Diseases 2023; 11:diseases11010010. [PMID: 36648875 PMCID: PMC9887592 DOI: 10.3390/diseases11010010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 01/12/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is common among Saudi patients with type 2 diabetes (T2DM). However, recommended clinical procedures to detect it are unavailable in many locations. Therefore, better and more available diagnostic biomarkers for NAFLD are needed. Various serum parameters were suggested, and algorithms that employ routine measurements in clinical practice have been developed for the prediction of fat stores in the liver in different populations. However, no such studies have been conducted on Saudis. We aimed to compare selected biochemical markers and calculated indices in T2DM patients diagnosed with NAFLD and patients without NAFLD to find the best markers associated with NAFLD. A cross-sectional study was employed to recruit 67 people with T2DM from endocrine outpatient clinics at King Abdul-Aziz University Hospital. NAFLD was detected by ultrasonography in 28 patients. Demographic information, anthropometric, and blood pressure (BP) measurements were taken. Fasting blood samples were obtained to measure glucose, glycated haemoglobin, lipid profile, liver function tests, and highly sensitive C-reactive protein. Fatty liver index, hepatic steatosis index, NAFLD-liver fat score, and triglyceride and glucose index were calculated. Following stepwise forward likelihood ratio regression with independent variables included in one model using binary logistic regression with age and waist circumference (WC) entered as covariates, elevated diastolic BP and low high-density lipoprotein- cholesterol remained significantly associated with NAFLD (p = 0.002 and 0.03, respectively). However, none of the investigated indices could be used to diagnose the disease adequately due to low specificity, even after calculating new cut-off values. Investigating novel markers and adjusting existing equations used to calculate indices to improve sensitivity and specificity in our population is needed.
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17
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Meloni A, Cadeddu C, Cugusi L, Donataccio MP, Deidda M, Sciomer S, Gallina S, Vassalle C, Moscucci F, Mercuro G, Maffei S. Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors. Int J Mol Sci 2023; 24:ijms24021588. [PMID: 36675097 PMCID: PMC9864423 DOI: 10.3390/ijms24021588] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/29/2022] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk.
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Affiliation(s)
- Antonella Meloni
- Department of Radiology, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy
| | - Christian Cadeddu
- Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy
| | - Lucia Cugusi
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
| | | | - Martino Deidda
- Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy
| | - Susanna Sciomer
- Department of Clinical and Internal Medicine, Anesthesiology and Cardiovascular Sciences, University of Rome “Sapienza”, Policlinico Umberto I, 00185 Roma, Italy
| | - Sabina Gallina
- Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Cristina Vassalle
- Medicina di Laboratorio, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy
| | - Federica Moscucci
- Department of Clinical and Internal Medicine, Anesthesiology and Cardiovascular Sciences, University of Rome “Sapienza”, Policlinico Umberto I, 00185 Roma, Italy
| | - Giuseppe Mercuro
- Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy
| | - Silvia Maffei
- Endocrinologia Cardiovascolare Ginecologica ed Osteoporosi, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy
- Correspondence: ; Tel.: +39-050-315-2216
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18
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Bischoff SC, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2022; 41:2364-2405. [PMID: 35970666 DOI: 10.1016/j.clnu.2022.07.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France; Department of Clinical Nutrition, Paul-Brousse-Hospital, Villejuif, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim GGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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19
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Olteanu VA, Balan GG, Timofte O, Dascalu CG, Gologan E, Gilca-Blanariu GE, Diac MM, Sandu I, Stefanescu G. Risk Predictors of Advanced Fibrosis in Non-Alcoholic Fatty Liver Disease. Diagnostics (Basel) 2022; 12:2136. [PMID: 36140537 PMCID: PMC9498120 DOI: 10.3390/diagnostics12092136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/22/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
The assessment of fibrosis in chronic liver diseases using non-invasive methods is an important topic in hepatology. The aim of this study is to identify patients with non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis by establishing correlations between biological/ultrasound markers and non-invasively measured liver stiffness. This study enrolled 116 patients with non-alcoholic fatty liver disease, which were evaluated clinically, biologically, and by ultrasound. Liver fibrosis was quantified by measuring liver stiffness by shear wave elastography (SWE). Multiple correlation analysis of predictors of liver fibrosis identified a number of clinical, biological, and ultrasound parameters (BMI, blood glucose, albumin, platelet count, portal vein diameter, bipolar spleen diameter) that are associated with advanced liver fibrosis in patients with non-alcoholic fatty liver disease. The correlations between the degree of liver fibrosis and the risk values of some serological and ultrasound markers obtained in our study could be useful in clinical practice for the identification of advanced fibrosis in patients with NAFLD.
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Affiliation(s)
- Vasile-Andrei Olteanu
- Gastroenterology Department, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, St. 1 Spiridon Emergency County Hospital, 1, Independentei Boulevard, 700111 Iasi, Romania
| | - Gheorghe G. Balan
- Gastroenterology Department, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, St. 1 Spiridon Emergency County Hospital, 1, Independentei Boulevard, 700111 Iasi, Romania
| | - Oana Timofte
- Gastroenterology Department, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, St. 1 Spiridon Emergency County Hospital, 1, Independentei Boulevard, 700111 Iasi, Romania
| | - Cristina Gena Dascalu
- Department of Medical Informatics, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
| | - Elena Gologan
- Gastroenterology Department, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
| | - Georgiana-Emanuela Gilca-Blanariu
- Gastroenterology Department, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, St. 1 Spiridon Emergency County Hospital, 1, Independentei Boulevard, 700111 Iasi, Romania
| | - Madalina-Maria Diac
- Forensic Sciences Department, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
- Institute of Legal Medicine Iasi, 700455 Iasi, Romania
| | - Ion Sandu
- Science Department, Interdisciplinary Research Institute, Alexandru Ioan Cuza University of Iasi, 11 Carol I Boulevard, 700506 Iasi, Romania
- Academy of Romanian Scientists (AORS), 54 Splaiul Independenței St., Sector 5, 050094 Bucharest, Romania
| | - Gabriela Stefanescu
- Gastroenterology Department, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, St. 1 Spiridon Emergency County Hospital, 1, Independentei Boulevard, 700111 Iasi, Romania
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20
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Bischoff SC, Barazzoni R, Busetto L, Campmans‐Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon‐Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline. United European Gastroenterol J 2022; 10:663-720. [PMID: 35959597 PMCID: PMC9486502 DOI: 10.1002/ueg2.12280] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational SciencesUniversity of TriesteTriesteItaly
| | - Luca Busetto
- Department of MedicineUniversity of PadovaPadovaItaly
| | - Marjo Campmans‐Kuijpers
- Department of Gastroenterology and HepatologyUniversity Medical Centre GroningenGroningenThe Netherlands
| | - Vincenzo Cardinale
- Department of Medico‐Surgical Sciences and BiotechnologiesSapienza University of RomeRomeItaly
| | - Irit Chermesh
- Department of GastroenterologyRambam Health Care CampusAffiliated with Technion‐Israel Institute of TechnologyHaifaIsrael
| | - Ahad Eshraghian
- Department of Gastroenterology and HepatologyAvicenna HospitalShirazIran
| | - Haluk Tarik Kani
- Department of GastroenterologyMarmara UniversitySchool of MedicineIstanbulTurkey
| | - Wafaa Khannoussi
- Hepato‐Gastroenterology DepartmentMohammed VI University HospitalOujdaMorocco
- Laboratoire de Recherche des Maladies Digestives (LARMAD)Mohammed the First UniversityOujdaMorocco
| | - Laurence Lacaze
- Department of NutritionRennes HospitalRennesFrance
- Department of general surgeryMantes‐la‐Jolie HospitalFrance
- Department of clinical nutritionPaul Brousse‐Hospital, VillejuifFrance
| | - Miguel Léon‐Sanz
- Department of Endocrinology and NutritionUniversity Hospital Doce de OctubreMedical SchoolUniversity ComplutenseMadridSpain
| | - Juan M. Mendive
- La Mina Primary Care Academic Health Centre. Catalan Institute of Health (ICS)University of BarcelonaBarcelonaSpain
| | - Michael W. Müller
- Department of General and Visceral SurgeryRegionale Kliniken HoldingKliniken Ludwigsburg‐Bietigheim gGmbHBietigheim‐BissingenGermany
| | - Johann Ockenga
- Medizinische Klinik IIKlinikum Bremen‐MitteBremenGermany
| | - Frank Tacke
- Department of Hepatology & GastroenterologyCharité Universitätsmedizin BerlinCampus Virchow‐Klinikum and Campus Charité MitteBerlinGermany
| | - Anders Thorell
- Department of Clinical ScienceDanderyds HospitalKarolinska InstitutetStockholmSweden
- Department of SurgeryErsta HospitalStockholmSweden
| | - Darija Vranesic Bender
- Department of Internal MedicineUnit of Clinical NutritionUniversity Hospital Centre ZagrebZagrebCroatia
| | - Arved Weimann
- Department of General, Visceral and Oncological SurgerySt. George HospitalLeipzigGermany
| | - Cristina Cuerda
- Departamento de MedicinaUniversidad Complutense de MadridNutrition UnitHospital General Universitario Gregorio MarañónMadridSpain
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21
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Dietrich CF, Shi L, Löwe A, Dong Y, Potthoff A, Sparchez Z, Teufel A, Guth S, Koch J, Barr RG, Cui XW. Conventional ultrasound for diagnosis of hepatic steatosis is better than believed. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1235-1248. [PMID: 34171931 DOI: 10.1055/a-1491-1771] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. Detection and staging of hepatic steatosis are of most importance in nonalcoholic fatty liver disease (NAFLD), a disease with a high prevalence of more than 1 billion individuals affected. Ultrasound (US) is one of the most used noninvasive imaging techniques used in the diagnosis of hepatic steatosis. Detection of hepatic steatosis with US relies on several conventional US parameters, which will be described. US is the first-choice imaging in adults at risk for hepatic steatosis. The use of some scoring systems may add additional accuracy especially in assessing the severity of hepatic steatosis. SUMMARY In the presented paper, we discuss screening and risk stratification, ultrasound features for diagnosing hepatic steatosis, B-mode criteria, focal fatty patterns and Doppler features of the hepatic vessels, and the value of the different US signs for the diagnosis of liver steatosis including classifying the severity of steatosis using different US scores. Limitations of conventional B-mode and Doppler features in the evaluation of hepatic steatosis are also discussed, including those in grading and assessing the complications of steatosis, namely fibrosis and nonalcoholic steatohepatitis. KEY MESSAGES Ultrasound is the first-line imaging examination for the screening and follow-up of patients with liver steatosis. The use of some scoring systems may add additional accuracy in assessing the severity of steatosis. Conventional B-mode and Doppler ultrasound have limitations in grading and assessing the complications of steatosis.
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Affiliation(s)
- Christoph F Dietrich
- Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
| | - Long Shi
- Department of Ultrasound, Jingmen No. 2 People's Hospital, Jingmen, Hubei, China
| | - Axel Löwe
- Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
| | - Yi Dong
- Ultrasound Department, Zhongshan Hospital Fudan University, Shanghai, China
| | - Andrej Potthoff
- Gastroenterology and Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Zeno Sparchez
- Department of Internal Medicine-Gastroenterology, University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Andreas Teufel
- Division of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Sabine Guth
- Conradia Medical Prevention Hamburg, Hamburg, Deutschland
| | - Jonas Koch
- Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
| | - Richard G Barr
- Northeastern Ohio Medical University, Southwoods Imaging, Youngstown, OH, USA
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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22
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Calapod OP, Marin AM, Pantea Stoian A, Fierbinteanu-Braticevici C. Clinical Model for the Prediction of Severe Liver Fibrosis in Adult Patients with Type II Diabetes Mellitus. Diagnostics (Basel) 2022; 12:diagnostics12081829. [PMID: 36010180 PMCID: PMC9406388 DOI: 10.3390/diagnostics12081829] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/26/2022] [Accepted: 07/27/2022] [Indexed: 02/07/2023] Open
Abstract
Background and Objectives: Non-alcoholic fatty liver disease (NAFLD)-related severe liver fibrosis is associated with a higher risk of progressing to decompensated cirrhosis and hepatic failure and developing NAFLD-related hepatocellular carcinoma (HCC), particularly in populations with diabetes. Our pilot study aims to evaluate the performances of various noninvasive methods in predicting liver fibrosis in a population of patients with diabetes and to establish a new scoring system for the prediction of severe fibrosis (>F3). Materials and Methods: A total of 175 patients with diabetes were enrolled for liver fibrosis evaluation. Using the degree of agreement (concordance) between a noninvasive score based on serum biomarkers (NAFLD fibrosis score) and point shear-wave elastography (pSWE) as the reference method, we generated receiver operating characteristic (ROC) curves and performed a multivariate analysis to predict severe liver fibrosis. Results: In our population of patients with diabetes, gamma-glutamyltransferase (GGT), age, body mass index (BMI), the homeostatic model assessment of insulin resistance (HOMA-IR), and glycosylated hemoglobin (HbA1C) were significant predictors for the diagnosis of the F3/F4 group (area under the ROC: 0.767, 0.743, 0.757, 0.772, and 0.7, respectively; p < 0.005 for all). Moreover, the combined composite score (the sum of GGT, age, BMI, HOMA index, and HbA1C) had the highest diagnostic performance at a cut-off value of 3 (AUROC—0.899; p < 0001). The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 91.20%, 79%, 79%, and 89%, respectively, and 89% of patients were correctly classified as having severe liver fibrosis. In contrast with the Fibrosis 4 (FIB-4) score and the AST-to-platelet ratio index (APRI), the composite score had the best accuracy in discriminating advanced fibrosis. Conclusions: The proposed composite score had a reliable and acceptable diagnostic accuracy in identifying patients with diabetes at risk of having severe fibrosis using readily available laboratory and clinical data.
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Affiliation(s)
- Ovidiu Paul Calapod
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Correspondence: (O.P.C.); (A.P.S.)
| | - Andreea Maria Marin
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, ”Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Prof. Dr. N. C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
- Correspondence: (O.P.C.); (A.P.S.)
| | - Carmen Fierbinteanu-Braticevici
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Emergency University Hospital of Bucharest, 050098 Bucharest, Romania
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23
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Huber Y, Schulz A, Schmidtmann I, Beutel M, Pfeiffer N, Münzel T, Galle PR, Wild PS, Lackner KJ, Schattenberg JM. Prevalence and Risk Factors of Advanced Liver Fibrosis in a Population-Based Study in Germany. Hepatol Commun 2022; 6:1457-1466. [PMID: 35122404 PMCID: PMC9134815 DOI: 10.1002/hep4.1899] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 12/15/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022] Open
Abstract
The prevalence of liver disease, and especially of advanced liver fibrosis, in the German population is poorly defined. The aim of the study was to explore liver enzymes and surrogate scores of hepatic steatosis and advanced hepatic fibrosis in a population-based cohort study in Germany. In the cross-sectional population-based Gutenberg Health study, data of 14,950 participants enrolled between 2007 and 2012 were captured and analyzed. The distribution of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), fatty liver index (FLI), and Fibrosis-4 (FIB-4) score, as well as the underlying risk factors, were assessed by regression models. Elevated liver enzymes in this population-based sample were seen in 19.9% for ALT, 12.8% for AST, and 14% for GGT. Risk factors for liver disease included alcohol use and the presence of the metabolic syndrome, which were both risk factors associated with increased liver enzymes. The FLI suggested that 37.5% of the population exhibited hepatic steatosis and 1.1% of patients exhibited a FIB-4 above the upper cutoff, while 19.2% were in the intermediate range. Interestingly, advanced fibrosis was significantly more frequent in men compared with women (FIB-4: 1.5% vs. 0.6% [P < 0.0001]; NFS: 3.6% vs. 1.9% [P < 0.0001]). In addition, age was a relevant risk factor for exhibiting a noninvasive surrogate score suggestive of advanced fibrosis in the current study population. Conclusion: Elevated liver enzymes were seen in almost a fifth of the German population. At the population-based level, the prevalence of advanced fibrosis was estimated at 1% in Germany.
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Affiliation(s)
- Yvonne Huber
- Department of Medicine IUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Andreas Schulz
- Preventive Cardiology and Preventive MedicineDepartment of CardiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Irene Schmidtmann
- Institute of Medical Biostatistics, Epidemiology and InformaticsUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Manfred Beutel
- Department of Psychosomatic Medicine and PsychotherapyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Norbert Pfeiffer
- Department of OphthalmologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Thomas Münzel
- Center for Cardiology - Cardiology IUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany.,German Center for Cardiovascular ResearchPartner Site Rhine-MainMainzGermany
| | - Peter R Galle
- Department of Medicine IUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Philipp S Wild
- Preventive Cardiology and Preventive MedicineDepartment of CardiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany.,German Center for Cardiovascular ResearchPartner Site Rhine-MainMainzGermany.,Center for Thrombosis and HemostasisUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Karl J Lackner
- Institute for Clinical Chemistry and Laboratory MedicineUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
| | - Jörn M Schattenberg
- Department of Medicine IUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany.,Metabolic Liver Research ProgramDepartment of Medicine IUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
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24
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Duell PB, Welty FK, Miller M, Chait A, Hammond G, Ahmad Z, Cohen DE, Horton JD, Pressman GS, Toth PP. Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol 2022; 42:e168-e185. [PMID: 35418240 DOI: 10.1161/atv.0000000000000153] [Citation(s) in RCA: 317] [Impact Index Per Article: 105.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.
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25
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Ding C, Tang Y, Zhu W, Huang P, Lian P, Ran J, Huang X. Sodium-glucose cotransporter protein-2 inhibitors and glucagon-like peptide-1 receptor agonists versus thiazolidinediones for non-alcoholic fatty liver disease: A network meta-analysis. Acta Diabetol 2022; 59:519-533. [PMID: 34988690 DOI: 10.1007/s00592-021-01830-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 11/22/2021] [Indexed: 02/07/2023]
Abstract
AIMS Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disorders worldwide. Some hypoglycemic drugs can improve NAFLD. However, it is unclear which of these types of hypoglycemic drugs are more effective for NAFLD. Therefore, we conducted a network meta-analysis to determine the effect of thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on NAFLD patients. METHODS A literature search of PubMed, EMBASE, the Cochrane Library, and Medline was conducted, and the literature from database inception up to April 30, 2021 was obtained. Liver function tests, lipid profiles, body mass index (BMI) and glycemic parameters were obtained from randomized controlled trials. Weighted mean differences (WMDs), relative risks and 95% confidence intervals (CIs) were calculated for continuous outcomes, and the I2 statistic was used to evaluate the heterogeneity of the studies. RESULTS In total, 22 trials, including 1361 patients, were selected. In direct meta-analysis, GLP-1 receptor agonists were superior to TZDs in decreasing alanine aminotransferase (WMD, -0.40, 95% CI: -0.60 to -0.20), γ-glutamyl transferase (WMD, -5.00, 95% CI: -6.47 to -3.53), BMI (WMD, -4.10, 95%CI: -6.55 to -1.65) and triglycerides (WMD, - 0.50, 95% CI: -0.68 to -0.32). Based on Bayesian network meta-analysis, the effect of SGLT-2 inhibitors on weight loss was superior to that of TZDs (WMD, -1.80, 95%CI: -3.30 to -0.41). CONCLUSIONS GLP-1 receptor agonists and SGLT-2 inhibitors improved liver enzymes, BMI, blood lipid, blood glucose and insulin resistance in NAFLD patients.
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Affiliation(s)
- Chen Ding
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Yaxin Tang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Wenqiang Zhu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Piaopiao Huang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Pingan Lian
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Juanli Ran
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Xiansheng Huang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
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26
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Naeem M, Markus MRP, Mousa M, Schipf S, Dörr M, Steveling A, Aghdassi A, Kühn JP, Kromrey ML, Nauck M, Targher G, Völzke H, Ittermann T. Associations of liver volume and other markers of hepatic steatosis with all-cause mortality in the general population. Liver Int 2022; 42:575-584. [PMID: 34894052 DOI: 10.1111/liv.15133] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 12/15/2022]
Abstract
AIMS We examined the associations between liver volume and other quantitative and qualitative markers of hepatic steatosis with all-cause mortality in the general population. METHODS We included 2769 German middle-aged individuals with a median follow-up of 8.9 years (23,898 person-years). Quantitative markers used were serum liver enzymes and FIB-4 score, while qualitative markers of hepatic steatosis included magnetic resonance imaging (MRI) measurements of liver fat content and total liver volume. Cox proportional hazards models, adjusted for confounding factors, were undertaken to investigate the associations of liver volume and other markers of hepatic steatosis with all-cause mortality. RESULTS A larger MRI-assessed liver volume was associated with a nearly three-fold increased risk of all-cause mortality (Hazard Ratio = 3.16; 95% confidence interval 1.88; 5.30), independent of age, sex, body mass index, food frequency score, alcohol consumption and education level. This association was consistent in all subgroups considered (men vs. women; presence or absence of overweight/obesity, metabolic syndrome or diabetes). Higher serum liver enzyme levels and FIB-4 score were also significantly associated with higher all-cause mortality in the total population and in all subgroups. No independent associations were found between other quantitative and qualitative markers of hepatic steatosis and the risk of all-cause mortality. CONCLUSIONS We showed for the first time that larger liver volume was associated with a three-fold increase in long-term risk of all-cause mortality. This association remained significant after adjustment for age, sex, alcohol consumption, obesity and other coexisting metabolic disorders.
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Affiliation(s)
- Muhammad Naeem
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.,Department of Zoology, University of Malakand, Chakdara, Pakistan
| | - Marcello R P Markus
- Department of Internal Medicine B - Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany.,DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
| | - Mohammed Mousa
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Sabine Schipf
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Marcus Dörr
- Department of Internal Medicine B - Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Greifswald, Germany.,DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
| | - Antje Steveling
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Ali Aghdassi
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Jens-Peter Kühn
- Institute and Policlinic for Diagnostic and Interventional Radiology, University Hospital, Carl Gustav Carus University, Dresden, Germany
| | - Marie-Luise Kromrey
- Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
| | - Matthias Nauck
- Institute for Laboratory Medicine and Clinical Chemistry, University Medicine Greifswald, Greifswald, Germany
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - Henry Völzke
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.,DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.,DZD (German Center for Diabetes Research), Site Greifswald, Greifswald, Germany
| | - Till Ittermann
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.,DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
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27
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Lin H, Zhang X, Li G, Wong GLH, Wong VWS. Epidemiology and Clinical Outcomes of Metabolic (Dysfunction)-associated Fatty Liver Disease. J Clin Transl Hepatol 2021; 9:972-982. [PMID: 34966660 PMCID: PMC8666360 DOI: 10.14218/jcth.2021.00201] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/24/2021] [Accepted: 08/13/2021] [Indexed: 12/13/2022] Open
Abstract
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease and affects at least a quarter of the global adult population. It has rapidly become one of the leading causes of hepatocellular carcinoma and cirrhosis in Western countries. In this review, we discuss the nomenclature and definition of MAFLD as well as its prevalence and incidence in different geographical regions. Although cardiovascular disease remains the leading cause of death in MAFLD patients, the proportion of patients dying from hepatic complications increases sharply as the disease progresses to advanced liver fibrosis and cirrhosis. In addition, patients with MAFLD are at increased risk of various extrahepatic cancers. Although a causal relationship between MAFLD and extrahepatic cancers has not been established, clinicians should recognize the association and consider cancer screening (e.g., for colorectal cancer) as appropriate.
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Affiliation(s)
| | | | | | | | - Vincent Wai-Sun Wong
- Correspondence to: Vincent Wai-Sun Wong, Department of Medicine and Therapeutics, 9/F, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China. ORCID: https://orcid.org/0000-0003-2215-9410. Tel: 852-3505-1205, Fax: 852-2637-3852, E-mail:
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Gutiérrez-Cuevas J, Santos A, Armendariz-Borunda J. Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases. Int J Mol Sci 2021; 22:11629. [PMID: 34769060 PMCID: PMC8583943 DOI: 10.3390/ijms222111629] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Obesity is now a worldwide epidemic ensuing an increase in comorbidities' prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes of death in the world. Several studies provide evidence for an association between MAFLD and atherosclerosis and cardio-metabolic disorders, including CVDs such as coronary heart disease and stroke. Therefore, the combination of MAFLD/NASH is associated with vascular risk and CVD progression, but the underlying mechanisms linking MAFLD/NASH and CVD are still under investigation. Several underlying mechanisms may probably be involved, including hepatic/systemic insulin resistance, atherogenic dyslipidemia, hypertension, as well as pro-atherogenic, pro-coagulant, and pro-inflammatory mediators released from the steatotic/inflamed liver. MAFLD is strongly associated with insulin resistance, which is involved in its pathogenesis and progression to NASH. Insulin resistance is a major cardiovascular risk factor in subjects without diabetes. However, T2D has been considered the most common link between MAFLD/NASH and CVD. This review summarizes the evidence linking obesity with MAFLD, NASH, and CVD, considering the pathophysiological molecular mechanisms involved in these diseases. We also discuss the association of MAFLD and NASH with the development and progression of CVD, including structural and functional cardiac alterations, and pharmacological strategies to treat MAFLD/NASH and cardiovascular prevention.
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Affiliation(s)
- Jorge Gutiérrez-Cuevas
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
| | - Arturo Santos
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico;
| | - Juan Armendariz-Borunda
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico;
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Mantovani A, Csermely A, Petracca G, Beatrice G, Corey KE, Simon TG, Byrne CD, Targher G. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2021; 6:903-913. [PMID: 34555346 DOI: 10.1016/s2468-1253(21)00308-3] [Citation(s) in RCA: 331] [Impact Index Per Article: 82.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/17/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Studies have reported a significant association between non-alcoholic fatty liver disease (NAFLD) and increased incidence of cardiovascular disease (CVD). However, the magnitude of the risk and whether this risk changes with the severity of NAFLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of incident CVD events. METHODS We systematically searched PubMed, Scopus, and Web of Science from database inception to July 1, 2021, to identify eligible observational studies examining the risk of incident CVD events amongst adult (age ≥18 years) individuals with and without NAFLD and in which NAFLD was diagnosed by imaging, International Classification of Diseases codes, or liver biopsy. The primary outcomes were CVD death, non-fatal CVD events, or both. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on Open Science Framework, number osf.io/5z7gf. FINDINGS We identified 36 longitudinal studies with aggregate data on 5 802 226 middle-aged individuals (mean age 53 years [SD 7]) and 99 668 incident cases of fatal and non-fatal CVD events over a median follow-up of 6·5 years (IQR 5·0-10·2). NAFLD was associated with a moderately increased risk of fatal or non-fatal CVD events (pooled random-effects HR 1·45, 95% CI 1·31-1·61; I2=86·18%). This risk markedly increased across the severity of NAFLD, especially the stage of fibrosis (pooled random-effects HR 2·50, 95% CI 1·68-3·72; I2=73·84%). All risks were independent of age, sex, adiposity measures, diabetes, and other common cardiometabolic risk factors. Sensitivity analyses did not modify these results. INTERPRETATION NAFLD is associated with an increased long-term risk of fatal or non-fatal CVD events. CVD risk is further increased with more advanced liver disease, especially with higher fibrosis stage. These results provide evidence that NAFLD might be an independent risk factor for CVD morbidity and mortality. FUNDING None.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Alessandro Csermely
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Graziana Petracca
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giorgia Beatrice
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Kathleen E Corey
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Tracey G Simon
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - 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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Sivasubramaniyam T, Yang J, Pollock E, Chon J, Schroer SA, Li YZ, Metherel AH, Dodington DW, Bazinet RP, Woo M. Hepatic Igf1-Deficiency Protects Against Atherosclerosis in Female Mice. Endocrinology 2021; 162:6153998. [PMID: 33647942 DOI: 10.1210/endocr/bqab040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Indexed: 12/20/2022]
Abstract
Atherosclerosis is the leading cause of cardiovascular disease (CVD), with distinct sex-specific pathogenic mechanisms that are poorly understood. Aging, a major independent risk factor for atherosclerosis, correlates with a decline in circulating insulin-like growth factor-1 (IGF-1). However, the precise effects of Igf1 on atherosclerosis remain unclear. In the present study, we assessed the essential role of hepatic Igf1, the major source of circulating IGF-1, in atherogenesis. We generated hepatic Igf1-deficient atherosclerosis-prone apolipoprotein E (ApoE)-null mice (L-Igf1-/-ApoE-/-) using the Cre-loxP system driven by the Albumin promoter. Starting at 6 weeks of age, these mice and their littermate controls, separated into male and female groups, were placed on an atherogenic diet for 18 to 19 weeks. We show that hepatic Igf1-deficiency led to atheroprotection with reduced plaque macrophages in females, without significant effects in males. This protection from atherosclerosis in females was associated with increased subcutaneous adiposity and with impaired lipolysis. Moreover, this impaired lipid homeostasis was associated with disrupted adipokine secretion with reduced circulating interleukin-6 (IL-6) levels. Together, our data show that endogenous hepatic Igf1 plays a sex-specific regulatory role in atherogenesis, potentially through athero-promoting effects of adipose tissue-derived IL-6 secretion. These data provide potential novel sex-specific mechanisms in the pathogenesis of atherosclerosis.
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Affiliation(s)
- Tharini Sivasubramaniyam
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
| | - Jiaqi Yang
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
| | - Evan Pollock
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
| | - Joseph Chon
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
| | - Stephanie A Schroer
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
| | - Yu Zhe Li
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
- Institute of Medical Science, University of Toronto, Toronto, Ontario, M5G 2M9, Canada
| | - Adam H Metherel
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, M5S 3E2, Canada
| | - David W Dodington
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
| | - Richard P Bazinet
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, M5S 3E2, Canada
| | - Minna Woo
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada
- Institute of Medical Science, University of Toronto, Toronto, Ontario, M5G 2M9, Canada
- Department of Immunology, University of Toronto, Toronto, Ontario, M5G 2M9, Canada
- Division of Endocrinology and Metabolism, Department of Medicine, University Health Network/ Sinai Health System, University of Toronto, Toronto, Ontario, M5G 2C4, Canada
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Canbay A, Kachru N, Haas JS, Meise D, Ozbay AB, Sowa JP. Healthcare resource utilization and costs among nonalcoholic fatty liver disease patients in Germany. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:615. [PMID: 33987313 PMCID: PMC8106103 DOI: 10.21037/atm-20-7179] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are associated with progression to advanced liver diseases that include compensated cirrhosis, decompensated cirrhosis, liver transplantation, and hepatocellular carcinoma (HCC). This study characterized comorbidities, healthcare resource utilization (HRU), and associated costs among NAFLD patients in Germany. Methods German healthcare claims data between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorized as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant, or HCC. Within each stage, annual all-cause HRU and costs were measured during the pre- and post-index periods. Results Among 4,580,434 patients in the database, proportion of NAFLD was 4.7% (n=215,655). Of them, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant, and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis, and HCC compared with non-progressors (52.07%, 56.46%, 57.58% vs. 27.49% for cardiovascular disease; 77.13%, 76.61%, 83.47% vs. 54.89% for hypertension; 47.20%, 53.81%, 52.89% vs. 35.21% for hyperlipidemia; 49.88%, 36.67%, 48.21% vs. 20.38% for type 2 diabetes mellitus). The mean annual numbers of post-index outpatient visits and inpatient hospitalizations were significantly higher in patients with advanced liver diseases versus non-progressors. Mean annual costs were significantly higher among patients with advanced liver diseases (compensated cirrhosis, €10,291; decompensated cirrhosis, €22,561; liver transplant, €34,089; HCC, €35,910) than non-progressors (€3,818, P<0.001, except liver transplant cohort). This trend remained consistent after adjusting for baseline demographics and comorbidities. Conclusions NAFLD patients in Germany are grossly underdiagnosed and exert substantial healthcare resource use and economic burden, particularly those with advanced liver diseases. Optimal strategies for early identification and management are needed to prevent disease progression and limit the rising costs.
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Affiliation(s)
- Ali Canbay
- Department of Internal Medicine, Ruhr-University Bochum, Bochum, Germany
| | - Nandita Kachru
- Gilead Sciences, Inc., Health Economics Outcomes Research, Foster City, CA, USA
| | | | | | - A Burak Ozbay
- Gilead Sciences, Inc., Health Economics Outcomes Research, Foster City, CA, USA
| | - Jan-Peter Sowa
- Department of Internal Medicine, Ruhr-University Bochum, Bochum, Germany
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Ting YW, Kong ASY, Zain SM, Chan WK, Tan HL, Mohamed Z, Pung YF, Mohamed R. Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort. Clin Mol Hepatol 2021; 27:486-498. [PMID: 33618508 PMCID: PMC8273635 DOI: 10.3350/cmh.2020.0162] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 02/18/2021] [Indexed: 12/13/2022] Open
Abstract
Background/Aims 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients. Methods Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded. Results HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00–0.64; P=0.033 and HR, 0.01; 95% CI, 0.00–0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese. Conclusion HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.
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Affiliation(s)
- Yi-Wen Ting
- Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | | | - Shamsul Mohd Zain
- The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Hwa-Li Tan
- The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Zahurin Mohamed
- The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yuh-Fen Pung
- Department of Biomedical Sciences, University of Nottingham (Malaysia Campus), Selangor, Malaysia
| | - Rosmawati Mohamed
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Hsu PF, Wang YW, Lin CC, Wang YJ, Ding YZ, Liou TL, Huang SS, Lu TM, Chan WL, Lin SJ, Leu HB. The association of the steatosis severity in fatty liver disease with coronary plaque pattern in general population. Liver Int 2021; 41:81-90. [PMID: 33373113 DOI: 10.1111/liv.14637] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 07/09/2020] [Accepted: 07/25/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with cardiovascular disease (CVD). However, whether the steatosis severity of NAFLD is independently associated with coronary artery atherosclerosis is still controversial. METHODS Consecutive Taiwanese individuals (1502) who received coronary computed tomography angiography (CCTA) and abdominal sonography as part of a general routine health evaluation were enrolled. The association between steatosis severity, coronary atherosclerosis involvement and various plaque patterns were analysed. RESULTS Compared with non-steatosis, NAFLD subjects had more cardiovascular risk factors that correlated with the severity of steatosis (P for the trend <.05). The presence of atherosclerotic plaques correlated with the severity of steatosis (none: 53%, mild: 64.1%, and moderate to severe: 66.9%; P for the trend <.001). Parameters of coronary atherosclerosis, including atheroma burden obstructive score (ABOS), segment involvement score (SIS) and segment stenosis score (SSS), were higher in the moderate to severe steatosis group. After adjusting for major confounding factors, the severity of steatosis still correlated with the mixed plaque pattern (P = .043). Subgroup analysis of the risk of the presence of overall coronary and mixed plaques showed a significant association with increasing severity of steatosis, especially among these who were <65 years old, male, without metabolic syndrome, and with lower low-density lipoprotein choleseterol values. CONCLUSION In this general population, steatosis severity of NAFLD is associated with coronary artery atherosclerosis burden. Furthermore, steatosis severity correlated with the risk of the presence of coronary plaques, especially high-risk plaques, and was independent of traditional risk factors.
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Affiliation(s)
- Pai-Feng Hsu
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Public Health, National Yang-Ming University, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ying-Wen Wang
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chung-Chi Lin
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yuan-Jen Wang
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yaw-Zon Ding
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Teh-Ling Liou
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shao-Sung Huang
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tse-Min Lu
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wan-Leong Chan
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shing-Jong Lin
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.,Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hsin-Bang Leu
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.,Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
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Forlano R, Mullish BH, Nathwani R, Dhar A, Thursz MR, Manousou P. Non-Alcoholic Fatty Liver Disease and Vascular Disease. Curr Vasc Pharmacol 2020; 19:269-279. [DOI: 10.2174/1570161118666200318103001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 02/24/2020] [Accepted: 03/01/2020] [Indexed: 02/07/2023]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease
worldwide. However, notably, the primary cause of morbidity and mortality in patients with NAFLD is
cardiovascular disease (CVD), with fibrosis stage being the strongest disease-specific predictor. It is
globally projected that NAFLD will become increasingly prevalent, especially among children and
younger adults. As such, even within the next few years, NAFLD will contribute considerably to the
overall CVD burden.
In this review, we discuss the role of NAFLD as an emerging risk factor for CVD. In particular, this
article aims to provide an overview of pathological drivers of vascular damage in patients with NAFLD.
Moreover, the impact of NAFLD on the development, severity and the progression of subclinical and
clinical CVD will be discussed. Finally, the review illustrates current and potential future perspectives
to screen for CVD in this high-risk population.
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Affiliation(s)
- Roberta Forlano
- Liver Unit, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Benjamin H. Mullish
- Liver Unit, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Rooshi Nathwani
- Liver Unit, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Ameet Dhar
- Liver Unit, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Mark R. Thursz
- Liver Unit, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Pinelopi Manousou
- Liver Unit, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
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35
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Su Y, Liu Z, Yang L, Li Y, Jiang S, Yao H, Du G. PPARγ gene Pro12Ala variants reduce the risk of obese individuals to non-alcoholic fatty liver: A study in Uygur Chinese population residing in Northwestern China. Clin Res Hepatol Gastroenterol 2020; 44:894-904. [PMID: 32505733 DOI: 10.1016/j.clinre.2020.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 02/02/2020] [Accepted: 02/12/2020] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To investigate the association of polymorphisms of Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) gene with clinical and biochemical parameters in Uygur Chinese population with non-alcoholic fatty liver (NAFLD) METHODS: In this case-control study, we recruited 467 NAFLD cases and 524 controls. Examination of abdominal ultrasound, clinical and biochemical profiles, as well as polymerase chain reaction-restriction fragment length polymorphisms of Pro12Ala of PPARγ gene were performed. The association of PPARγ gene Pro12Ala variants with clinical and biochemical parameters was analyzed. RESULTS There was no statistically significant difference between NAFLD and control groups in the frequencies of genotypic and allele distribution (P>0.05), while significantly difference of genotypic (P=0.032) and allele (P=0.015) distribution was found between NAFLD and control groups in the obese. Using logistics multivariate regression analysis by adjusting age, sex, body mass index, diabetes, hyperuricemia and dyslipidemia, both Pro12Ala and Ala12Ala polymorphisms were not associated with the presence of NAFLD. However, above two polymorphisms were found to be related to NAFLD in obesity group (odds ratio=0.442, P=0.031 and odds ratio=0.039, P=0.010, respectively) CONCLUSION: In Uygur Chinese population, PPARr gene Ala variants reduce the risk of NAFLD in obese individuals.
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Affiliation(s)
- Yinxia Su
- Health Management Institute, Xinjiang Medical University, China; Public Health School of Xinjiang Medical University, China
| | - Zhenhui Liu
- Department of Microrepair and Reconstruction, the First Affiliated Hospital of Xinjiang Medical University, China
| | - Lei Yang
- Department of abdominal ultrasound, the First Affiliated Hospital of Xinjiang Medical University, China
| | - Yuanyuan Li
- Public Health School of Xinjiang Medical University, China
| | - Sheng Jiang
- Department of Endocrinology, the First Affiliated Hospital of Xinjiang Medical University, China
| | - Hua Yao
- Health Management Institute, Xinjiang Medical University, China.
| | - Guoli Du
- Department of Endocrinology, the First Affiliated Hospital of Xinjiang Medical University, China.
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Lu GH, Gong SG, Li C, Zhao QH, Jiang R, Luo CJ, Wang L, Zhang R. Prognostic Value of Gamma-Glutamyltransferase in Male Patients With Idiopathic Pulmonary Arterial Hypertension. Front Cardiovasc Med 2020; 7:580908. [PMID: 33195467 PMCID: PMC7644547 DOI: 10.3389/fcvm.2020.580908] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 09/29/2020] [Indexed: 12/04/2022] Open
Abstract
Background: The elevated gamma-glutamyltransferase (GGT) activity is regarded as an indicator of cardiovascular disease, with males having higher values than females. The greater incidence of idiopathic pulmonary arterial hypertension (IPAH) is observed in women, whereas prognosis is poor in men. The present study aims to investigate the potential association of GGT on male patients. Methods: Serum GGT levels were measured in 338 consecutive adult IPAH patients, who underwent bone morphogenetic protein receptor type 2 (BMPR2) genetic counseling, and matched with healthy subjects by sex and age. The followed interval was 48 ± 34 months. Results: Increased serum GGT levels were more common in patients with IPAH than controls (p < 0.001). GGT values were significantly higher in male patients than those of females (p < 0.001). Compared with female patients with BMPR2 mutation, GGT level in male patients with BMPR2 mutation was further increased (p = 0.002). Higher GGT levels were associated with worse hemodynamics and Nterminal pro B-type natriuretic peptide in all patients. However, males with a GGT concentration ≥ 53 U/L had a worse survival than those of females. Contrarily, if GGT concentration <53 U/L, there was no survival difference between male and female patients. After adjustment for relevant variables of clinical features and hemodynamics, baseline higher GGT levels remained increased risks of all-cause mortality in males rather than females. During rehospitalization follow-up, male patients still had significantly higher values of GGT than females. Conclusions: Increased GGT levels were correlated with BMPR2 mutation, hemodynamic dysfunction, and poor outcomes in male patients with IPAH. Further studies are needed to explain the origin of abnormal GGT and its potential pathogenesis in men.
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Affiliation(s)
- Gang-Hua Lu
- Tongji University School of Medicine, Shanghai, China
| | - Su-Gang Gong
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chao Li
- Tongji University School of Medicine, Shanghai, China
| | - Qin-Hua Zhao
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Rong Jiang
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ci-Jun Luo
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lan Wang
- Tongji University School of Medicine, Shanghai, China
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
- Lan Wang
| | - Rui Zhang
- Tongji University School of Medicine, Shanghai, China
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
- *Correspondence: Rui Zhang
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Mantovani A, Scorletti E, Mosca A, Alisi A, Byrne CD, Targher G. Complications, morbidity and mortality of nonalcoholic fatty liver disease. Metabolism 2020; 111S:154170. [PMID: 32006558 DOI: 10.1016/j.metabol.2020.154170] [Citation(s) in RCA: 329] [Impact Index Per Article: 65.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 01/23/2020] [Accepted: 01/27/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized public health problem, affecting up to a quarter of the world's adult population. The burden of NAFLD is influenced by the epidemics of obesity and type 2 diabetes mellitus (T2DM) and the prevalence of these conditions is not expected to decrease in the forthcoming decades. Consequently, the burden of NAFLD-related liver complications (non-alcoholic steatohepatitis [NASH], cirrhosis and hepatocellular carcinoma) and the need for life-saving liver transplantation are also expected to increase further in the near future. A large body of clinical evidence indicates that NAFLD is associated not only with increased liver-related morbidity and mortality, but also with an increased risk of developing other important extra-hepatic diseases, such as cardiovascular disease (that is the predominant cause of death in patients with NAFLD), extra-hepatic cancers (mainly colorectal cancers), T2DM and chronic kidney disease. Thus, NAFLD creates a considerable health and economic burden worldwide and often results in poor quality of life. This narrative review provides an overview of the current literature on main complications, morbidity and mortality of this common and burdensome liver disease.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Eleonora Scorletti
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton, UK; Department of Gastroenterology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Antonella Mosca
- Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital, Rome, Italy
| | - Anna Alisi
- Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton, UK
| | - 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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Canbay A, Kachru N, Haas JS, Sowa JP, Meise D, Ozbay AB. Patterns and predictors of mortality and disease progression among patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2020; 52:1185-1194. [PMID: 33016540 DOI: 10.1111/apt.16016] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 05/05/2020] [Accepted: 07/15/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Factors associated with mortality and disease progression in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are poorly understood. AIMS To assess the impact of liver disease severity, demographics and comorbidities on all-cause mortality and liver disease progression in a large, real-world cohort of NAFLD patients. METHODS Claims data from the German Institut für angewandte Gesundheitsforschung database between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorised as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma (HCC). The longitudinal probability of mortality and incidence of progression were calculated for disease severity cohorts and multivariable analyses performed for adjusted mortality. RESULTS Among 4 580 434 patients in the database, prevalence of NAFLD was 4.7% (n = 215 655). Of those, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis and HCC compared with non-progressors. The longitudinal probability of mortality for non-progressors, compensated cirrhosis, decompensated cirrhosis and HCC was 3.6%, 18.7%, 28.8% and 68%, respectively. Independent predictors of mortality included cardiovascular disease, type 2 diabetes mellitus, hypertension, obesity and renal impairment. The cumulative incidence of progression in NAFLD and compensated cirrhosis patients was 10.7% and 16.7%, respectively, over 5 years of follow-up. CONCLUSION NAFLD patients were severely under-diagnosed and had a high probability of mortality that increased with disease progression. Early identification and effective management to halt or reverse fibrosis are essential to prevent progression.
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Affiliation(s)
- Ali Canbay
- Department of Internal Medicine, Ruhr-University, Bochum, Germany
| | - Nandita Kachru
- Health Economics Outcomes Research, Gilead Sciences Inc., Foster City, CA, USA
| | | | - Jan-Peter Sowa
- Department of Internal Medicine, Ruhr-University, Bochum, Germany
| | | | - Ahmet Burak Ozbay
- Health Economics Outcomes Research, Gilead Sciences Inc., Foster City, CA, USA
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Mohammed MA, Omar NM, Mohammed SA, Amin AM, Gad DF. FICK-3 Score Combining Fibrosis-4, Insulin Resistance and Cytokeratin-18 in Predicting Non-alcoholic Steatohepatitis in NAFLD Egyptian Patients. Pak J Biol Sci 2020; 22:457-466. [PMID: 31930835 DOI: 10.3923/pjbs.2019.457.466] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE As liver biopsy had multiple procedure-related complications, the introduction of reliable noninvasive tests for accurate discrimination of NASH and liver fibrosis in patients with NAFLD are mandatory. The aim was to elucidate the diagnostic value of fibrosis-4 index (FIB-4), Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and Cytokeratin-18 fragments (CK18-Fs) in the prediction of NASH and liver fibrosis. MATERIALS AND METHODS One hundred Egyptian patients with NAFLD selected from outpatient's clinics of Mansoura University Hospitals underwent histological examination through liver biopsy after approval and consent. The FIB-4, HOMA-IR, CK18-Fs (measured using a human ELISA Kit) and their combination in FICK-3 score were investigated for predicting NASH and liver fibrosis. Receiver operating characteristic (ROC) curves and multivariate logistic regression were analyzed. RESULTS In patients with NAFLD, the areas under the ROC were significantly high (AUC: 0.765, 0.700, 0.803, 0.835 for FIB-4, HOMA-IR, CK18-Fs, FICK-3 score, respectively, p = 0.05) displaying a highly statistically significant predictive ability for NASH. Significantly higher AUCs for these parameters were demonstrated predicting early-or advanced-stage liver fibrosis (AUC >0.7, p<0.01). Also, the combined FICK-3 score (the sum of FIB-4 >1.46, HOMA-IR >2.11 and CK18-Fs >307U L-1) had highly significant predictive values for NASH and liver fibrosis and had the best diagnostic accuracy at a cutoff value of 1(AUC >0.8, p<0.001). Contrasted with other diagnostic scores, FICK-3 had the best diagnostic accuracy for detection of fibrotic NASH (AUC = 0.954, p<0.001) and positively correlated with the histological features of NAFLD. CONCLUSION The new combination FICK-3 score was a reliable and significant predictor for NASH and liver fibrosis in NAFLD Egyptian patients.
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Fujii H, Doi H, Ko T, Fukuma T, Kadono T, Asaeda K, Kobayashi R, Nakano T, Doi T, Nakatsugawa Y, Yamada S, Nishimura T, Tomatsuri N, Sato H, Okuyama Y, Kimura H, Kishimoto E, Nakabe N, Shima T. Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study. BMC Gastroenterol 2020; 20:217. [PMID: 32650722 PMCID: PMC7350574 DOI: 10.1186/s12876-020-01369-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 07/06/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels. METHODS We designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models. RESULTS The change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group. CONCLUSIONS The incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.
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Affiliation(s)
- Hideki Fujii
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan.
| | - Haruna Doi
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Tetsuhisa Ko
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Taito Fukuma
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Toru Kadono
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Kohei Asaeda
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Reo Kobayashi
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Takahiro Nakano
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Toshifumi Doi
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Yoshikazu Nakatsugawa
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Shinya Yamada
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Takeshi Nishimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Naoya Tomatsuri
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Hideki Sato
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Yusuke Okuyama
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Etsuko Kishimoto
- Department of Center for Health promotion, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Nami Nakabe
- Department of Center for Health promotion, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
| | - Takatomo Shima
- Department of Center for Health promotion, Japanese Red Cross Kyoto Daiichi Hospital, Hon-machi15-749, Higashiyama-ku, Kyoto, 605-0981, Japan
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Goyal A, Arora H, Arora S. Prevalence of fatty liver in metabolic syndrome. J Family Med Prim Care 2020; 9:3246-3250. [PMID: 33102278 PMCID: PMC7567270 DOI: 10.4103/jfmpc.jfmpc_1108_19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 12/16/2019] [Accepted: 01/07/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND In Western world, non-alcohlic fatty liver disease (NAFLD) is considered to be the commonest liver problem, and it is being recognised as a major cause of liver-related morbidity and mortality. As the prevalence of overweight/obesity and metabolic syndrome increases, NASH may become one of the more common causes of end stage liver disease and hepatocellular carcinoma. But much information is not available in this association. So an attempt has been made to correlate both. AIMS The aims of this study are: 1. to study the prevalence of non-alcoholic fatty liver in metabolic syndrome; and 2. to study the correlation between the non-alcoholic fatty liver and metabolic syndrome along with its individual components. MATERIALS AND METHODS The study was an observational and analytical study of patients attending OPD and indoor patients of the Department of Medicine, G.G.S. Medical College and Hospital Faridkot. In total, 100 patients diagnosed as metabolic syndrome according to the NCEP ATP III criteria were subjected to ultrasonography; age and sex matched 100 controls were also taken; and the relationship between metabolic syndrome and NAFLD was studied. RESULTS In total, 73% cases of metabolic syndrome according to NCEP ATPIII were having fatty liver, while in controls 38% persons were having fatty liver which is statistically significant. CONCLUSIONS Fatty liver was found to be highly prevalent in metabolic syndrome, and the early detection of fatty liver can help in modifying the disease course and delaying more serious complications like cirrhosis of liver and hepatocellular carcinoma.
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Affiliation(s)
- Anita Goyal
- Department of Family Medicine, GGS Medical College and Hospital Faridkot, Affliated to Baba Farid University of Health Sciences, Faridkot, Punjab, India
| | - Hobinder Arora
- Department of Social and Preventive Medicine, GGS Medical College and Hospital Faridkot, Affliated to Baba Farid University of Health Sciences, Faridkot, Punjab, India
| | - Sumit Arora
- Department of Medicine, GGS Medical College and Hospital Faridkot, Affliated to Baba Farid University of Health Sciences, Faridkot, Punjab, India
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Saki S, Saki N, Poustchi H, Malekzadeh R. Assessment of Genetic Aspects of Non-alcoholic Fatty Liver and Premature Cardiovascular Events. Middle East J Dig Dis 2020; 12:65-88. [PMID: 32626560 PMCID: PMC7320986 DOI: 10.34172/mejdd.2020.166] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 03/19/2019] [Indexed: 12/12/2022] Open
Abstract
Recent evidence has demonstrated a strong interplay and multifaceted relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). CVD is the major cause of death in patients with NAFLD. NAFLD also has strong associations with diabetes and metabolic syndrome. In this comprehensive review, we aimed to overview the primary environmental and genetic risk factors of NAFLD, and CVD and also focus on the genetic aspects of these two disorders. NAFLD and CVD are both heterogeneous diseases with common genetic and molecular pathways. We have searched for the latest published articles regarding this matter and tried to provide an overview of recent insights into the genetic aspects of NAFLD and CVD. The common genetic and molecular pathways involved in NAFLD and CVD are insulin resistance (IR), subclinical inflammation, oxidative stress, and atherogenic dyslipidemia. According to an investigation, the exact associations between genomic characteristics of NAFLD and CVD and casual relationships are not fully determined. Different gene polymorphisms have been identified as the genetic components of the NAFLDCVD association. Some of the most documented ones of these gene polymorphisms are patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), adiponectin-encoding gene (ADIPOQ), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), leptin receptor (LEPR), sterol regulatory element-binding proteins (SREBP), tumor necrosis factor-alpha (TNF-α), microsomal triglyceride transfer protein (MTTP), manganese superoxide dismutase (MnSOD), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), and mutation in DYRK1B that substitutes cysteine for arginine at position 102 in kinase-like domain. Further cohort studies with a significant sample size using advanced genomic assessments and next-generation sequencing techniques are needed to shed more light on genetic associations between NAFLD and CVD.
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Affiliation(s)
- Sara Saki
- Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Saki
- Hoveizeh Cohort Study, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Poustchi
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Kumar R, Priyadarshi RN, Anand U. Non-alcoholic Fatty Liver Disease: Growing Burden, Adverse Outcomes and Associations. J Clin Transl Hepatol 2020; 8:76-86. [PMID: 32274348 PMCID: PMC7132013 DOI: 10.14218/jcth.2019.00051] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 12/03/2019] [Accepted: 12/09/2019] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a systemic disorder with a complex multifactorial pathogenesis and heterogenous clinical manifestations. NAFLD, once believed to be an innocuous condition, has now become the most common cause of chronic liver disease in many countries worldwide. NAFLD is already highly prevalent in the general population, and owing to a rising incidence of obesity and diabetes mellitus, the incidence of NAFLD and its impact on global healthcare are expected to increase in the future. A subset of patients with NAFLD develops progressive liver disease leading to cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD has emerged as one of the leading causes of cirrhosis and hepatocellular carcinoma in recent years. Moreover, HCC can occur in NAFLD even in absence of cirrhosis. Compared with the general population, NAFLD increases the risk of liver-related, cardiovascular and all-cause mortality. NAFLD is bidirectionally associated with metabolic syndrome. NAFLD increases the risk and contributes to aggravation of the pathophysiology of atherosclerosis, cardiovascular diseases, diabetes mellitus, and chronic kidney disease. In addition, NAFLD is linked to colorectal polyps, polycystic ovarian syndrome, osteoporosis, obstructive sleep apnea, stroke, and various extrahepatic malignancies. Extended resection of steatotic liver is associated with increased risk of liver failure and mortality. There is an increasing trend of NAFLD-related cirrhosis requiring liver transplantation, and the recurrence of NAFLD in such patients is almost universal. This review discusses the growing burden of NAFLD, its outcomes, and adverse associations with various diseases.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | | | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna, India
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Gimadiev PP, Niiazov AR, Mukhin VE, Ogurtsov PP. [The Diagnostic Importance of Circulating MicroRNA for Non-Alcoholic Fatty Liver Disease (review of literature).]. Klin Lab Diagn 2020; 64:723-729. [PMID: 32040895 DOI: 10.18821/0869-2084-2019-64-12-723-729] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 10/18/2019] [Indexed: 12/15/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases in the world. The biopsy is required to confirm the diagnosis but due to its invasiveness, this procedure is not suitable for the massive screening. There are laboratory criteria of primary medical examination of the patients who are suspected to have NAFLD that allow diagnosing the pathological process, but these criteria do not comply with clinicians' requirements. At the same time, it is crucial to identify the patients in the initial stages of NAFLD. Recently, the attention of the scientists was concentrated on the research of the mechanism of NAFLD development and new diagnostic approaches. Accumulating results of this research show that NAFLD development is regulated with epigenetic factors, including microRNAs family (microRNA, miR), that may have high diagnostic and prognostic value. In this review, data extracted from PubMed are used to discuss the potential role of microRNA in the liver lipid metabolism and fatty liver disease. The possibilities of micro RNA (miR-16, miR-21, miR-34a, miR-103, miR-122, miR-145, miR-192, and others) use as prospective biomarkers for low-invasive NAFLD diagnostic, evaluation of steatosis activity and fibrosis score and stages, and prognostic markers of the disease are reviewed. This research discusses the analytical characteristics, benefits and possible limitations of their use in the clinical practice. The preliminary data allow claiming that some microRNAs are extremely perspective low-invasive diagnostic instrument and further research is required to investigate the impact of certain microRNAs in the pathogenetic mechanism of NAFLD development.
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Affiliation(s)
- P P Gimadiev
- Рeoples' Friendship University of Russia (RUDN University), 117198, Moscow, Russia.,LTD «Eurotest», 129110, Moscow, Russia
| | - A R Niiazov
- Institute of Biomedical Problems of Russian Academy of Sciences, 123007, Moscow, Russia
| | - V E Mukhin
- Рeoples' Friendship University of Russia (RUDN University), 117198, Moscow, Russia
| | - P P Ogurtsov
- Рeoples' Friendship University of Russia (RUDN University), 117198, Moscow, Russia
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Stahl EP, Dhindsa DS, Lee SK, Sandesara PB, Chalasani NP, Sperling LS. Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review. J Am Coll Cardiol 2020; 73:948-963. [PMID: 30819364 DOI: 10.1016/j.jacc.2018.11.050] [Citation(s) in RCA: 266] [Impact Index Per Article: 53.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Revised: 11/14/2018] [Accepted: 11/26/2018] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are both manifestations of end-organ damage of the metabolic syndrome. Through multiple pathophysiological mechanisms, CVD and NAFLD are associated with each other. Systemic inflammation, endothelial dysfunction, hepatic insulin resistance, oxidative stress, and altered lipid metabolism are some of the mechanisms by which NAFLD increases the risk of CVD. Patients with NAFLD develop increased atherosclerosis, cardiomyopathy, and arrhythmia, which clinically result in cardiovascular morbidity and mortality. Defining the mechanisms linking these 2 diseases offers the opportunity to further develop targeted therapies. The aim of this comprehensive review is to examine the association between CVD and NAFLD and discuss the overlapping management approaches.
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Affiliation(s)
- Eric P Stahl
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Devinder S Dhindsa
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
| | - Suegene K Lee
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Pratik B Sandesara
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia
| | - Naga P Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Laurence S Sperling
- Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.
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Huang JF, Tsai PC, Yeh ML, Huang CF, Huang CI, Hsieh MH, Dai CY, Yang JF, Chen SC, Yu ML, Chuang WL, Chang WY. Risk stratification of non-alcoholic fatty liver disease across body mass index in a community basis. J Formos Med Assoc 2020; 119:89-96. [PMID: 30952479 DOI: 10.1016/j.jfma.2019.03.014] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/25/2019] [Accepted: 03/18/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The features and risk analysis of non-alcoholic fatty liver disease (NAFLD) in a community-based setting remain elusive. The predictors between obese and lean subjects need further clarification. We aimed to assess the characteristics of NAFLD during a community screening. The associated metabolic abnormalities and cardiovascular risk assessment were also analyzed. METHODS A total of 2483 subjects receiving multi-purpose health screening at 10 primary care centers were recruited. They received clinical assessment, including demographic data, laboratory examination, and abdominal sonography. RESULTS The prevalence of NAFLD and metabolic syndrome were 44.5%, and 15.8%, respectively. Among those NAFLD subjects, 1212 (48.8%) subjects were obese (BMI≥ 24 kg/m2). There was an increasing trend of NAFLD according to age, ranging from 25.8% of those aged <30 years to 54.4% of those aged 50-70 years (P for trend< 0.0001). High insulin resistance (IR) was the significant predictive factor for NAFLD in both obese (odds ratio [OR] = 3.85, 95% confidence interval [CI] = 1.87-8.36, P = 0.0002) and lean subjects (OR = 2.52, 95% CI = 1.13-5.54, p = 0.02). The prevalence of high Framingham Risk Score (≥7.5%) was 56.7% (211/372) among the male subjects, which was significantly higher than that (26%, 191/734) of the females (P < 0.001). There was a significant increase of high Framingham Risk Score according to BMI, ranging from 23.1% of BMI<24 kg/m2 to 45% of BMI>27 kg/m2 (P for trend< 0.0001). CONCLUSION IR is predictive of NAFLD irrespective of BMI. The cardiovascular risk may exist in lean NAFLD subjects.
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Affiliation(s)
- Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Ching-I Huang
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Jeng-Fu Yang
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Shinn-Chern Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Wen-Yu Chang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
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Wang L, Ahn YJ, Asmis R. Sexual dimorphism in glutathione metabolism and glutathione-dependent responses. Redox Biol 2019; 31:101410. [PMID: 31883838 PMCID: PMC7212491 DOI: 10.1016/j.redox.2019.101410] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 12/12/2019] [Accepted: 12/13/2019] [Indexed: 01/07/2023] Open
Abstract
Glutathione is the most abundant intracellular low molecular weight thiol in cells and tissues, and plays an essential role in numerous cellular processes, including antioxidant defenses, the regulation of protein function, protein localization and stability, DNA synthesis, gene expression, cell proliferation, and cell signaling. Sexual dimorphisms in glutathione biology, metabolism and glutathione-dependent signaling have been reported for a broad range of biological processes, spanning the human lifespan from early development to aging. Sex-depended differences with regard to glutathione and its biology have also been reported for a number of human pathologies and diseases such as neurodegeneration, cardiovascular diseases and metabolic disorders. Here we review the latest literature in this field and discuss the potential impact of these sexual dimorphisms in glutathione biology on human health and diseases.
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Affiliation(s)
- Luxi Wang
- Department of Internal Medicine, Wake Forest School of Medicine, USA
| | - Yong Joo Ahn
- Department of Internal Medicine, Wake Forest School of Medicine, USA
| | - Reto Asmis
- Department of Internal Medicine, Wake Forest School of Medicine, USA.
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Velarde-Ruiz Velasco J, García-Jiménez E, García-Zermeño K, Morel-Cerda E, Aldana-Ledesma J, Castro-Narro G, Cerpa-Cruz S, Tapia-Calderón D, Mercado-Jauregui L, Contreras-Omaña R. Extrahepatic complications of non-alcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2019. [DOI: 10.1016/j.rgmxen.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Velarde-Ruiz Velasco JA, García-Jiménez ES, García-Zermeño KR, Morel-Cerda EC, Aldana-Ledesma JM, Castro-Narro GE, Cerpa-Cruz S, Tapia-Calderón DK, Mercado-Jauregui LA, Contreras-Omaña R. Extrahepatic complications of non-alcoholic fatty liver disease: Its impact beyond the liver. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2019; 84:472-481. [PMID: 31488310 DOI: 10.1016/j.rgmx.2019.05.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 04/20/2019] [Accepted: 05/02/2019] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently one of the main causes of chronic liver disease in Western countries, with a 25% prevalence reported in the general population worldwide. Visceral adiposity and liver fat promote a state of systemic inflammation, predisposing individuals with NAFLD to the extrahepatic pathologies of cardiovascular disease (the most common cause of death in patients with NAFLD), diabetes mellitus, chronic kidney disease, hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea, and an increased risk for presenting with gastrointestinal and extraintestinal neoplasias. Different mechanisms between NAFLD and its association with extrahepatic diseases have been reported, and lipotoxicity is the main cause of inflammatory pathway activation that results in extrahepatic tissue damage.
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Affiliation(s)
- J A Velarde-Ruiz Velasco
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México.
| | - E S García-Jiménez
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - K R García-Zermeño
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - E C Morel-Cerda
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - J M Aldana-Ledesma
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - G E Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - S Cerpa-Cruz
- Servicio de Reumatología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - D K Tapia-Calderón
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - L A Mercado-Jauregui
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - R Contreras-Omaña
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología (CIEHG), Pachuca, Hidalgo, México
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Gepner Y, Shelef I, Komy O, Cohen N, Schwarzfuchs D, Bril N, Rein M, Serfaty D, Kenigsbuch S, Zelicha H, Yaskolka Meir A, Tene L, Bilitzky A, Tsaban G, Chassidim Y, Sarusy B, Ceglarek U, Thiery J, Stumvoll M, Blüher M, Stampfer MJ, Rudich A, Shai I. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol 2019; 71:379-388. [PMID: 31075323 DOI: 10.1016/j.jhep.2019.04.013] [Citation(s) in RCA: 154] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 03/26/2019] [Accepted: 04/17/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIM It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. METHODS In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. RESULTS Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. CONCLUSIONS %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. LAY SUMMARY High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.
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Affiliation(s)
- Yftach Gepner
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute, Tel Aviv University, Israel
| | - Ilan Shelef
- Soroka University Medical Center, Beer-Sheva, Israel
| | - Oded Komy
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Noa Cohen
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Dan Schwarzfuchs
- Soroka University Medical Center, Beer-Sheva, Israel; Nuclear Research Center-Negev, Dimona, Israel
| | - Nitzan Bril
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Michal Rein
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Dana Serfaty
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Shira Kenigsbuch
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Hila Zelicha
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Anat Yaskolka Meir
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Lilac Tene
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Avital Bilitzky
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Gal Tsaban
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | | | | | - Uta Ceglarek
- Department of Medicine, University of Leipzig, Germany
| | | | | | | | - Meir J Stampfer
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard School of Public Health, Boston, MA, USA
| | - Assaf Rudich
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Iris Shai
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
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