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Elzein SM, Brombosz EW, Kodali S. Cardiac abnormalities pre- and post-liver transplantation for metabolic dysfunction-associated steatohepatitis – Evidence and special considerations. JOURNAL OF LIVER TRANSPLANTATION 2024; 15:100228. [DOI: 10.1016/j.liver.2024.100228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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Yang Y, Yu L, Sheng Z, Lin H, Weng Z, Song W, Cao B, Zhao Y, Gao Y, Ni S, Wang H, Ma T, Huang L, Sun C, Li J. The first selective VAP-1 inhibitor in China, TT-01025-CL: safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multiple-ascending doses. Front Pharmacol 2024; 15:1327008. [PMID: 38741586 PMCID: PMC11089243 DOI: 10.3389/fphar.2024.1327008] [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: 10/24/2023] [Accepted: 04/09/2024] [Indexed: 05/16/2024] Open
Abstract
Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers. Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10-300 mg [single dose]; 20-100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers. Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100-300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25-0.5 h post-dose and was maintained 48-168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20-100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups. Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development.
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Affiliation(s)
- Yuanxun Yang
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Lei Yu
- TransThera Sciences (Nanjing), Inc., Nanjing, China
| | - Zejuan Sheng
- TransThera Sciences (Nanjing), Inc., Nanjing, China
| | - Hui Lin
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zuyi Weng
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Wei Song
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Bei Cao
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yu Zhao
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | | | - Shumao Ni
- TransThera Sciences (Nanjing), Inc., Nanjing, China
| | - Huimin Wang
- TransThera Sciences (Nanjing), Inc., Nanjing, China
| | - Tingting Ma
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Lei Huang
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Caixia Sun
- TransThera Sciences (Nanjing), Inc., Nanjing, China
| | - Juan Li
- Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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Beer S, Babel J, Martin N, Blank V, Wiegand J, Karlas T. Non-invasive assessment of steatohepatitis indicates increased risk of coronary artery disease. PLoS One 2023; 18:e0286882. [PMID: 37768969 PMCID: PMC10538770 DOI: 10.1371/journal.pone.0286882] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 05/25/2023] [Indexed: 09/30/2023] Open
Abstract
INTRODUCTION Fatty liver diseases (FLD), especially defined as metabolic dysfunction-associated FLD (MAFLD), is of growing importance for patients and health-care providers. Extrahepatic comorbidities, predominantly coronary artery disease (CAD), contribute to excess morbidity and mortality in FLD. Although the association of FLD and CAD is well known, underlying pathophysiological links are not fully understood. Non-invasive means of liver diagnostic enable a fast and thorough characterization of FLD. We therefore assessed the severity of FLD in a cohort of patients at risk of CAD. METHODS Patients scheduled for coronary angiography were characterized by anthropometry, serum-based indices of liver fibrosis (NFS, FIB4), abdominal ultrasound and vibration controlled transient elastography (VCTE) including controlled attenuation parameter (CAP) and the Fibroscan-AST (FAST) score. Patients were stratified according to indication of therapeutic coronary intervention. RESULTS 120 patients were recruited, MAFLD was found in 41%, while advanced fibrosis or cirrhosis were present in only 5%. Coronary vascular intervention was indicated in 42% (n = 50). Severity of steatosis assessed by CAP and risk of fibrosis defined by elevated liver stiffness (VCTE>8 kPa) and fibrosis indices were associated with the need for coronary intervention. FAST score, a marker of fibrotic steatohepatitis, was elevated in the intervention group (0.22 vs. 0.12, p<0.001). Multivariate regression analysis revealed FAST score as strongest predictor of CAD (OR 2.3 95%, CI 1.40-2.96). DISCUSSION MAFLD is a frequent comorbidity in patients at CAD risk, but advanced liver disease has a low prevalence in patients undergoing elective coronary angiography. Therefore, a routine VCTE-based screening for FLD cannot be recommended in cardiac patients. The association of indicators of steatohepatitis with advanced CAD points to inflammatory processes as a conjoint mechanism of both diseases.
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Affiliation(s)
- Sebastian Beer
- Department of Medicine II, Division of Gastroenterology, Leipzig University Medical Center, Leipzig, Germany
- Integrated Research and Treatment Center Adiposity Diseases, Faculty of Medicine, University of Leipzig, Leipzig, Germany
| | - Jonas Babel
- Department of Medicine II, Division of Gastroenterology, Leipzig University Medical Center, Leipzig, Germany
- Department of Operative Medicine II, Division of Visceral-, Transplant-, Thoracic- and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany
| | - Neef Martin
- Department of Cardiology, Leipzig University Medical Center, Leipzig, Germany
| | - Valentin Blank
- Department of Medicine II, Division of Gastroenterology, Leipzig University Medical Center, Leipzig, Germany
- Department of Internal Medicine I (Gastroenterology, Pneumology) and Division of Interdisciplinary Ultrasound, University Hospital Halle (Saale), Halle (Saale), Germany
| | - Johannes Wiegand
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Thomas Karlas
- Department of Medicine II, Division of Gastroenterology, Leipzig University Medical Center, Leipzig, Germany
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Effects of anti-inflammatory dietary patterns on non-alcoholic fatty liver disease: a systematic literature review. Eur J Nutr 2023; 62:1563-1578. [PMID: 36690886 DOI: 10.1007/s00394-023-03085-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 01/03/2023] [Indexed: 01/25/2023]
Abstract
PURPOSE Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition. Low-grade chronic inflammation contributes to disease progression. Diet has protective effects on hepatic health and inflammatory pathways. The purpose of this review is to systematically review and describe the effects of anti-inflammatory dietary patterns on NAFLD. METHODS The Cochrane CENTRAL Library, Cumulative Index of Nursing and Allied Health Literature, Embase, MEDLINE and Web of Science databases were searched. A total of 252 records were identified, 7 of which were included in this review. The revised Cochrane risk-of-bias tool was used to conduct a quality assessment for randomised trials. Certainty of evidence was assessed using the grading of recommendations, assessment, development, and evaluation tool. RESULTS Of the 7 included studies, 6 were classified as low risk of bias and studies ranged from high to very low certainty of evidence. In the randomised-controlled studies systematically reviewed, either adherence to the Mediterranean, DASH, or FLiO diet was studied, against usual care or energy matched controls, with a total of 255 participants. Anti-inflammatory dietary pattern adherence significantly reduced the severity of most hepatic and inflammatory markers, and secondary outcomes. A minority of outcomes were improved significantly more than controls. CONCLUSION Anti-inflammatory dietary patterns showed benefits to NAFLD risk factors, severity markers and inflammatory markers compared to the control diet. It is unclear whether reductions in the evaluated parameters are related solely to the anti-inflammatory diet or weight loss resulting from caloric restriction, as improvements in control groups were also evidenced. Current limited body of evidence indicates need for further research including isocaloric dietary patterns, longer interventions, measures of inflammatory markers, and studies including normal-weight subjects to confirm findings at higher certainty. PROSPERO REGISTRATION CRD42021269382.
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Chew NW, Muthiah MD, Sanyal AJ. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: pathophysiology and implications for cardiovascular disease. CARDIOVASCULAR ENDOCRINOLOGY AND METABOLISM 2023:137-173. [DOI: 10.1016/b978-0-323-99991-5.00003-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Li Q, Wang L, Wu J, Wang J, Wang Y, Zeng X. Role of age, gender and ethnicity in the association between visceral adiposity index and non-alcoholic fatty liver disease among US adults (NHANES 2003-2018): cross-sectional study. BMJ Open 2022; 12:e058517. [PMID: 35314476 PMCID: PMC8938699 DOI: 10.1136/bmjopen-2021-058517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVES The association between visceral adiposity index (VAI) and the prevalence of non-alcoholic fatty liver disease (NAFLD) has not been fully determined. Here, we aimed to explore the association between VAI and NAFLD in the general US population, and further investigate whether the association involves population differences. DESIGN Cross-sectional population-based study. SETTING The National Health and Nutrition Examination Survey (2003-2018). PARTICIPANTS A total of 7522 participants aged 20 years or older who have complete information for NAFLD assessment test were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES NAFLD was assessed by the modified fatty liver index for the US population (USFLI) using a cut-off point of 30. Correlation between VAI and NAFLD prediction scores was calculated using the partial correlation analysis. Logistic regression models were further used to estimate ORs and 95% CIs. RESULTS Insulin resistance (IR), inflammation and waist circumference-adjusted partial correlation analysis indicated that VAI scores were positively correlated with USFLI (r=0.404 for men, and r=0.395 for women; p<0.001). In a comparison of the highest versus the lowest quartiles of VAI, multivariable logistic regression analysis demonstrated a positive association between VAI and NAFLD (OR (95% CI)=1.97 (1.12 to 3.47) for men, OR (95% CI)=4.03 (1.98 to 8.20) for women). The stratified analyses revealed that the positive association involves age/gender-specific and ethnic differences. As for the impact of metabolic disorders, our results revealed that the association was independent of IR and diabetes, but it would be confounded by other metabolic disorders. However, no significant association was found between VAI and hepatic fibrosis. CONCLUSION VAI is positively associated with the prevalence of NAFLD, but not hepatic fibrosis among US adults, and the association involves age/gender-specific and ethnic differences. The results reported here have important public health implications in NAFLD screening in the future.
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Affiliation(s)
- Qianwen Li
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Ling Wang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- Faculty of Medicine, Macau University of Science and Technology, Macau SAR, People's Republic of China
| | - Jian Wu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Jing Wang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Yanjie Wang
- School of Management, Xinxiang Medical University, Xinxiang, China
| | - Xin Zeng
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
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Kim Y, Han E, Lee JS, Lee HW, Kim BK, Kim MK, Kim HS, Park JY, Kim DY, Ahn SH, Lee BW, Kang ES, Cha BS, Lee YH, Kim SU. Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease. Gut Liver 2021; 16:290-299. [PMID: 34238770 PMCID: PMC8924809 DOI: 10.5009/gnl210084] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/28/2021] [Accepted: 05/12/2021] [Indexed: 11/05/2022] Open
Abstract
Background/Aims Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. Methods Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥–0.640. ASCVD risk was evaluated using the American College of Cardiology/American Heart Association guidelines. Results The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023). Conclusions Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.
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Affiliation(s)
- Yuna Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Mi Kyung Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hye Soon Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung-Wan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Bong-Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Yong-Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Taharboucht S, Guermaz R, Brouri M, Chibane A. Subclinical atherosclerosis and arterial stiffness in nonalcoholic fatty liver disease: A case-control study in Algerian population. JOURNAL DE MEDECINE VASCULAIRE 2021; 46:129-138. [PMID: 33990287 DOI: 10.1016/j.jdmv.2021.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 03/20/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) was described for the first time in 1980, and became within a few years one of the most frequent causes of chronic liver disease. However, during the last decade, many studies suggested a strong relationship between NAFLD and cardiovascular diseases including carotid atherosclerosis evoking the hypothesis that NAFLD is a factor or a marker of cardiovascular risk. In Algeria, data on this subject are rare or inexistent. The objective of our work was to study the relationship between NAFLD and atherosclerosis in an Algerian population without diabetes. PATIENTS AND METHODS It is a case-control study with a strict matching by age and sex. Non-diabetic participants between 30 and 70 years of age were consecutively included in the department of internal medicine of the public hospital of El Biar. The diagnosis of NAFLD was made by ultrasound and hepatic elasticity was assessed by FibroScan®. We collected the data of the carotid ultrasound, the carotid-femoral pulse wave velocity (cfPWV), ankle-brachial pressure index and arterial pressure (consultation and ambulatory monitoring). Non parametric statistical methods (chi 2 McNemar for the percentages, t Friedman test for medium) were used and the association between variables was estimated by odds ratio (OR). These analyses were performed using SPSS 21.0 software (IBM). RESULTS 213 patients with NAFLD, with a mean age of 48.5 years±10.14 (100 men/113 women) were matched to 213 controls. The presence of carotid atherosclerotic plaque (CAP) was higher in NAFLD than in controls (31.92% (n=68) vs. 7.05% (n=15), P<0.001). In multivariate analysis, the CAP (OR 8.6, 95% CI [3.6-20.5], P<0.001), high Intima media thickness (OR 2.8, 95% CI [1.4-5.4], P=0.002), CRP≥6mg/l (OR 14.7, 95% CI [5.9-36.9], P=0.001), abdominal obesity (OR 3.8, 95% CI [1.4-9.7], P=0.05), high cfPWV (OR 4.4, 95% CI [2.4-8.1], P<0.001), elevated alanine aminotransferase(OR 4.0, 95% CI [1.6-9.8], P=0.002), overall obesity (OR 2.0, 95% CI [1.0-3.8], P=0.03), dyslipidemia (OR 2.0, 95% CI [1.0-3.8], P=0.02), and elevated GGT (OR 2.8, 95% [1.1-7.1] were independently associated to NAFLD. CONCLUSION Our study suggests that NAFLD is significantly associated with carotid atherosclerosis and arterial stiffness. These results may have implications in the management of patients with NAFLD in terms of cardiovascular prevention.
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Affiliation(s)
- S Taharboucht
- Internal medecine department, CHU de Douera, University of Blida 1, Algiers, Algeria.
| | - R Guermaz
- Internal medecine department, EPH EL BIAR, University of Algiers, Algiers, Algeria
| | - M Brouri
- Internal medecine department, EPH EL BIAR, University of Algiers, Algiers, Algeria
| | - A Chibane
- Internal medecine department, CHU de Douera, University of Blida 1, Algiers, Algeria
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Chen W, Wang M, Jing X, Wu C, Zeng Y, Peng J, Cai X. High risk of colorectal polyps in men with non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2020; 35:2051-2065. [PMID: 32579269 DOI: 10.1111/jgh.15158] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 06/05/2020] [Accepted: 06/14/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM This meta-analysis aims to explore the risk of colorectal polyps among non-alcoholic fatty liver disease (NAFLD) patients. METHODS We searched PubMed, EMBASE, and Cochrane library databases using predefined search term to identify eligible studies (published up to 7 November 2019). Data from selected studies were extracted by using a standardized information collection form, and meta-analyses were performed using random-effects model. The statistical heterogeneity among studies (I2 ), subgroup analyses, meta-regression analyses, and the possibility of publication bias were assessed. RESULTS Twenty observational (12 cross-sectional, two case-control, and six cohort) studies met the eligibility criteria, involving 142 387 asymptomatic adults. In cross-sectional/case-control studies, NAFLD was found to be associated with an increased risk of colorectal polyps (odds ratio [OR] = 1.34; 95% confidence interval [CI] = 1.23-1.47) (including unclassified colorectal polyps, hyperplastic polyps, adenomas, and cancers) with statistically significant heterogeneity (I2 = 67.8%; P < 0.001). NAFLD was also associated with a higher risk of incident colorectal polyps (hazard ratio = 1.60; 95% CI = 1.36-1.87) with low heterogeneity (I2 = 21.8%; P = 0.263) in longitudinal studies. The severity of NAFLD was associated with a higher risk of colorectal adenomas (OR = 1.57; 95% CI = 1.30-1.88), but not colorectal cancer (OR = 1.37; 95% CI = 0.92-2.03). The subgroup analysis according to gender showed that NAFLD was significantly associated with a higher risk of colorectal polyps in the male population without significant heterogeneity (OR = 1.47; 95% CI = 1.29-1.67, I2 = 0%), but not in the female population (OR = 0.88; 95% CI = 0.60-1.29, I2 = 34.2%). CONCLUSIONS NAFLD was associated with an increased risk of colorectal polyps. There was a significant difference of the relationship between genders, which suggested more precise screening colonoscopy recommendation in NAFLD patients according to gender.
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Affiliation(s)
- Wenxia Chen
- Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Muqing Wang
- Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Xubin Jing
- Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Chaofen Wu
- Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Yicheng Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Jianwei Peng
- Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Xianbin Cai
- Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
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Ren G, Kim T, Kim HS, Young ME, Muccio DD, Atigadda VR, Blum SI, Tse HM, Habegger KM, Bhatnagar S, Coric T, Bjornsti MA, Shalev A, Frank SJ, Kim JA. A Small Molecule, UAB126, Reverses Diet-Induced Obesity and its Associated Metabolic Disorders. Diabetes 2020; 69:2003-2016. [PMID: 32611548 PMCID: PMC7458036 DOI: 10.2337/db19-1001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 06/18/2020] [Indexed: 12/13/2022]
Abstract
Targeting retinoid X receptor (RXR) has been proposed as one of the therapeutic strategies to treat individuals with metabolic syndrome, as RXR heterodimerizes with multiple nuclear receptors that regulate genes involved in metabolism. Despite numerous efforts, RXR ligands (rexinoids) have not been approved for clinical trials to treat metabolic syndrome due to the serious side effects such as hypertriglyceridemia and altered thyroid hormone axis. In this study, we demonstrate a novel rexinoid-like small molecule, UAB126, which has positive effects on metabolic syndrome without the known side effects of potent rexinoids. Oral administration of UAB126 ameliorated obesity, insulin resistance, hepatic steatosis, and hyperlipidemia without changes in food intake, physical activity, and thyroid hormone levels. RNA-sequencing analysis revealed that UAB126 regulates the expression of genes in the liver that are modulated by several nuclear receptors, including peroxisome proliferator-activated receptor α and/or liver X receptor in conjunction with RXR. Furthermore, UAB126 not only prevented but also reversed obesity-associated metabolic disorders. The results suggest that optimized modulation of RXR may be a promising strategy to treat metabolic disorders without side effects. Thus, the current study reveals that UAB126 could be an attractive therapy to treat individuals with obesity and its comorbidities.
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Affiliation(s)
- Guang Ren
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
| | - Teayoun Kim
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
| | - Hae-Suk Kim
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
| | - Martin E Young
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Donald D Muccio
- Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL
| | - Venkatram R Atigadda
- Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL
| | - Samuel I Blum
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL
| | - Hubert M Tse
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL
| | - Kirk M Habegger
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
| | - Sushant Bhatnagar
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
| | - Tatjana Coric
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL
| | - Mary-Ann Bjornsti
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL
| | - Anath Shalev
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
| | - Stuart J Frank
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
| | - Jeong-A Kim
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
- UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL
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11
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Anti-inflammatory Mechanism of Ruzu Bitters on Diet-Induced Nonalcoholic Fatty Liver Disease in Male Wistar Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:5246725. [PMID: 32774420 PMCID: PMC7395997 DOI: 10.1155/2020/5246725] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 06/13/2020] [Indexed: 01/17/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become notorious globally. Increasingly emerging evidence shows that NAFLD is strongly associated with inflammation, with proinflammatory cytokines such as interleukin-2 (IL-2), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) playing a vital role in its progression. In this work, an attempt was made to verify the anti-inflammatory activity of Ruzu herbal bitters (RHB), an antiobesity medicinal concoction, on NAFLD induced by a high-fat diet (HFD) in albino Wistar rats. Twenty-five (25) rats were divided into five groups as follows: Group 1, the normal control, was maintained on standard rat chow and received normal saline (1 ml/kg body weight (BW)/day) for twelve weeks. The other groups were maintained on HFD for twelve weeks. Thereafter, groups 2–5 were treated with pioglitazone (4 mg/kg BW/day), RHB (0.6 ml/kg BW/day), normal saline (1 ml/kg BW/day), and fenofibrate (10 mg/kg BW/day), respectively. The animals were sacrificed after the experimental period. Biochemical indicators of oxidative stress and inflammation were assayed in the liver according to standard methods. The histological features of the liver were also compared to assess liver damage. RHB significantly (p < 0.05) reduced body weight and liver index, inhibited oxidative stress, boosted antioxidant enzymes by increasing the activity and level of SOD and GSH, reduced proinflammatory markers (IL-2, IL-6, TNF-α), and reversed histological alterations induced by NAFLD in rat liver. In conclusion, the anti-inflammatory activity of RHB in the prevention of NAFLD in rats has been confirmed.
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Omar N, Koshy M, Hanafiah M, Hatta SFWM, Shah FZM, Johari B, Zamhuri I, Kasim SS, Rahman TA, Ghani RA. Relationships between severity of steatosis with glycemic control and carotid intima-media thickness among diabetic patients with ischemic heart disease. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2020; 25:64. [PMID: 33088301 PMCID: PMC7554426 DOI: 10.4103/jrms.jrms_560_17] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 07/21/2018] [Accepted: 11/20/2019] [Indexed: 12/13/2022]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) has become one of the major diseases plaguing worldwide. Several studies reported its association with ischemic heart disease (IHD). This study aims to determine the relationships between severity of steatosis with glycemic control and carotid intima-media thickness (CIMT) among a high-risk population of type 2 diabetes mellitus (T2DM) with proven IHD. Materials and Methods This was a cross-sectional study involving patients aged between 18 and 65 years diagnosed with T2DM with IHD (n = 150). Ultrasonography of the abdomen to determine NAFLD severity category and CIMT measurements was performed by two independent radiologists. NAFLD was graded according to the severity of steatosis (NAFLD-3, NAFLD-2, NAFLD-1, and NAFLD-0). Comparison between different stages of NAFLD (NAFLD-3, NAFLD-2, NAFLD-1, and NAFLD-0) was analyzed using Chi-square and analysis of variance tests for categorical and continuous variables, respectively. Results The prevalence of NAFLD was 71% (n = 107). NAFLD-1 was detected in 39% of the patients, 32% had NAFLD-2, no patients with NAFLD-3, and 29% had non-NAFLD. There were no patients with NAFLD-2 having higher systolic and diastolic blood pressure, weight, body mass index, waist circumference, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Glycated hemoglobin (HbA1c) concentration was highest within the NAFLD-2. NAFLD-2 showed higher mean CIMT. Every 1% rise in HbA1c for patients with NAFLD significantly increases the CIMT by 0.03 mm (95% CI: 0.009, 0.052, P = 0.006). Conclusion These findings suggest additional atherosclerotic risks within the NAFLD-2 group with significantly higher HbA1c and CIMT compared to the NAFLD-1 and NAFLD-0 groups. It is, therefore, vital to incorporate stricter glycemic control among patients with T2DM and IHD with moderate NAFLD as part of atherosclerotic risk management strategy.
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Affiliation(s)
- Nurazam Omar
- Department of Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | - Marymol Koshy
- Department of Radiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | - Mohammad Hanafiah
- Department of Radiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | | | - Fatimah Zaherah Mohd Shah
- Department of Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | - Bushra Johari
- Department of Radiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | - Idris Zamhuri
- Department of Population Health and Preventive Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | - Sazzli Shahlan Kasim
- Department of Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | - Thuhairah Abdul Rahman
- Centre for Pathology Diagnostics and Research Laboratories, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
| | - Rohana Abdul Ghani
- Department of Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia
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13
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Prevalence of Metabolic Syndrome and Nonalcoholic Fatty Liver Disease among Premenopausal and Postmenopausal Women in Ho Municipality: A Cross-Sectional Study. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2168381. [PMID: 32420328 PMCID: PMC7210522 DOI: 10.1155/2020/2168381] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 03/23/2020] [Accepted: 04/01/2020] [Indexed: 02/07/2023]
Abstract
Methods A cross-sectional study was conducted among 185 participants: 88 premenopausal and 97 postmenopausal women obtaining healthcare service from Ho Teaching Hospital (HTH) and Ho Municipal Hospital from November 2018 to January 2020. Questionnaires were administered, and direct anthropometric measurements were taken. Blood samples were collected between 8:00 am and 10:00 am after overnight fast (12 to 18 hours; ≥8 hours) to assess fasting blood glucose, fasting lipids, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) concentrations at HTH laboratory using standard measuring procedures. This study in diagnosing metabolic syndrome and nonalcoholic fatty liver disease employed the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria and the Bedogni fatty liver index algorithm, respectively. Results The overall prevalence of MetS and NAFLD was 24.86% and 40.00% using NCEP-ATPIII and Bedogni fatty liver index algorithm, respectively. The prevalence of MetS and NAFLD among postmenopausal women was 32.99% and 49.48%, respectively, higher than 15.91% and 29.55%, respectively, observed among premenopausal women. The most prevalent MetS component among the study population was abdominal obesity (68.65%) which was significantly higher among the postmenopausal women (82.47%) than premenopausal women (53.41%) (<0.001). Hyperglycemia and hypertension were the major significant risk factors for developing MetS among premenopausal women whereas high triglyceride was the highest risk factor found among the postmenopausal women. Obesity and abdominal obesity were the most likely risk factors for developing nonalcoholic fatty liver disease among both premenopausal and postmenopausal women. Comorbidities of MetS and NAFLD were significant risk factors for developing cardiovascular diseases (CVD) (OR = 5.2, 95%CI = 2.2-12.4; p < 0.001). Conclusion This study established a significant association between coronary artery disease and comorbidities of MetS and NAFLD among the studied participants. Both conditions were found to be more prevalent among postmenopausal women compared to premenopausal women. Abdominal obesity was the most prevalent MetS component among the population. Women should be monitored for the two conditions and be educated on adopting healthy lifestyles to minimize the incidence of these conditions.
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Nonalcoholic Fatty Liver Disease and Coronary Artery Disease: Big Brothers in Patients with Acute Coronary Syndrome. ScientificWorldJournal 2020; 2020:8489238. [PMID: 32327942 PMCID: PMC7174950 DOI: 10.1155/2020/8489238] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 02/24/2020] [Accepted: 03/26/2020] [Indexed: 01/01/2023] Open
Abstract
Background The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. This study aimed to evaluate the prevalence of NAFLD, as diagnosed by ultrasound, in patients with acute coronary syndrome (ACS) and to assess whether NAFLD is associated with the severity of coronary obstruction as diagnosed by coronary angiography. Methods We performed a prospective single-center study in patients hospitalized due to acute coronary syndrome who underwent diagnostic coronary angiography. Consecutive patients who presented to the emergency room were diagnosed with acute coronary syndrome and were included. All patients underwent ultrasonography of the upper abdomen to determine the presence or absence of NAFLD; NAFLD severity was graded from 0 to 3 based on a previously validated scale. All patients underwent diagnostic coronary angiography in the same hospital, with the same team of interventional cardiologists, who were blinded to the patients' clinical and ultrasonographic data. CAD was then angiographically graded from none to severe based on well-established angiographic criteria. Results This study included 139 patients, of whom 83 (59.7%) were male, with a mean age of 59.7 years. Of the included patients, 107 (77%) patients had CAD, 63 (45%) with serious injury. Regarding the presence of NAFLD, 76 (55.2%) had NAFLD including 18 (23.6%) with grade III disease. In severe CAD, 47 (60.5%) are associated with NAFLD, and 15 (83.3%) of the patients had severe CAD and NAFLD grade III. Conclusions NAFLD is common in patients with ACS. The intensity of NAFLD detected by ultrasonography is strongly associated with the severity of coronary artery obstruction on angiography.
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Yari Z, Cheraghpour M, Aghamohammadi V, Alipour M, Ghanei N, Hekmatdoost A. Energy-dense nutrient-poor snacks and risk of non-alcoholic fattyliver disease: a case-control study in Iran. BMC Res Notes 2020; 13:221. [PMID: 32299509 PMCID: PMC7164180 DOI: 10.1186/s13104-020-05063-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 04/07/2020] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE The purpose of the present study was to determine the association between energy-dense nutrient-poor snacks intake and the risk of non-alcoholic fatty liver disease (NAFLD) in Iranian adults. For this purpose, a total of 143 cases with a newly confirmed diagnosis of NAFLD and 471 controls free of the disease were studied. Dietary intake was assessed using a food frequency questionnaire. RESULTS The percentage of calories from total energy-dense nutrient-poor snacks was 6.08% and 5.04%, in patients and controls, respectively (P = 0.036). Compared with subjects in the lowest quartile of total energy-dense nutrient-poor snacks intake, the risk of NAFLD for those in the top quartile of consumption increased by about two times, in both crude (OR: 1.94; 95% CIs 1.16-3.26; P for trend = 0.015) and adjusted (OR: 2.27; 95%CIs 1.19-4.31; P for trend = 0.001) models. The relative odds of NAFLD increased significantly in the fourth quartile of dietary cake and biscuit (OR: 1.21, P for trend = 0.037) and soft drinks (OR: 1.64, P for trend = 0.005) intake compared with the lowest corresponding quartiles, after adjustment for age, sex, body mass index, physical activity, alcohol, energy intake. Our results indicate that there might be a moderate positive association between energy-dense nutrient-poor snacks intake and risk of NAFLD.
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Affiliation(s)
- Zahra Yari
- Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | | | - Meysam Alipour
- Alimentary Tract Research Center, Imam khomeini Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nila Ghanei
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, USA
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran.
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Baars T, Sowa JP, Neumann U, Hendricks S, Jinawy M, Kälsch J, Gerken G, Rassaf T, Heider D, Canbay A. Liver parameters as part of a non-invasive model for prediction of all-cause mortality after myocardial infarction. Arch Med Sci 2020; 16:71-80. [PMID: 32051708 PMCID: PMC6963137 DOI: 10.5114/aoms.2018.75678] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 06/29/2017] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Liver parameters are associated with cardiovascular disease risk and severity of stenosis. It is unclear whether liver parameters could predict the long-term outcome of patients after acute myocardial infarction (AMI). We performed an unbiased analysis of the predictive value of serum parameters for long-term prognosis after AMI. MATERIAL AND METHODS In a retrospective, observational, single-center, cohort study, 569 patients after AMI were enrolled and followed up until 6 years for major adverse cardiovascular events, including cardiac death. Patients were classified into non-survivors (n = 156) and survivors (n = 413). Demographic and laboratory data were analyzed using ensemble feature selection (EFS) and logistic regression. Correlations were performed for serum parameters. RESULTS Age (73; 64; p < 0.01), alanine aminotransferase (ALT; 93 U/l; 40 U/l; p < 0.01), aspartate aminotransferase (AST; 162 U/l; 66 U/l; p < 0.01), C-reactive protein (CRP; 4.7 U/l; 1.6 U/l; p < 0.01), creatinine (1.6; 1.3; p < 0.01), γ-glutamyltransferase (GGT; 71 U/l; 46 U/l; p < 0.01), urea (29.5; 20.5; p < 0.01), estimated glomerular filtration rate (eGFR; 49.6; 61.4; p < 0.01), troponin (13.3; 7.6; p < 0.01), myoglobin (639; 302; p < 0.01), and cardiovascular risk factors (hypercholesterolemia p < 0.02, family history p < 0.01, and smoking p < 0.01) differed significantly between non-survivors and survivors. Age, AST, CRP, eGFR, myoglobin, sodium, urea, creatinine, and troponin correlated significantly with death (r = -0.29; 0.14; 0.31; -0.27; 0.20; -0.13; 0.33; 0.24; 0.12). A prediction model was built including age, CRP, eGFR, myoglobin, and urea, achieving an AUROC of 77.6% to predict long-term survival after AMI. CONCLUSIONS Non-invasive parameters, including liver and renal markers, can predict long-term outcome of patients after AMI.
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Affiliation(s)
- Theodor Baars
- Department for Cardiology, West German Heart and Vascular Centre Essen, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Jan-Peter Sowa
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Ursula Neumann
- Department of Bioinformatics, Straubing Center of Science, University of Applied Science Weihenstephan-Triesdorf, Straubing, Germany
| | - Stefanie Hendricks
- Department for Cardiology, West German Heart and Vascular Centre Essen, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Mona Jinawy
- Department for Cardiology, West German Heart and Vascular Centre Essen, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Julia Kälsch
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Tienush Rassaf
- Department for Cardiology, West German Heart and Vascular Centre Essen, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Dominik Heider
- Department of Bioinformatics, Straubing Center of Science, University of Applied Science Weihenstephan-Triesdorf, Straubing, Germany
- Department of Mathematics and Computer Science, University of Marburg, Marburg, Germany
| | - Ali Canbay
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
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Chung ST, Onuzuruike AU, Magge SN. Cardiometabolic risk in obese children. Ann N Y Acad Sci 2019; 1411:166-183. [PMID: 29377201 DOI: 10.1111/nyas.13602] [Citation(s) in RCA: 135] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2017] [Revised: 12/29/2017] [Accepted: 12/31/2017] [Indexed: 02/06/2023]
Abstract
Obesity in childhood remains a significant and prevalent public health concern. Excess adiposity in youth is a marker of increased cardiometabolic risk (CMR) in adolescents and adults. Several longitudinal studies confirm the strong association of pediatric obesity with the persistence of adult obesity and the future development of cardiovascular disease, diabetes, and increased risk of death. The economic and social impact of childhood obesity is further exacerbated by the early onset of the chronic disease burden in young adults during their peak productivity years. Furthermore, rising prevalence rates of severe obesity in youth from disadvantaged and/or minority backgrounds have prompted the creation of additional classification schemes for severe obesity to improve CMR stratification. Current guidelines focus on primary obesity prevention efforts, as well as screening for clustering of multiple CMR factors to target interventions. This review summarizes the scope of the pediatric obesity epidemic, the new severe obesity classification scheme, and examines the association of excess adiposity with cardiovascular and metabolic risk. We will also discuss potential questions for future investigation.
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Affiliation(s)
- Stephanie T Chung
- Section on Ethnicity and Health, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland.,Division of Pediatric Endocrinology and Diabetes, Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC
| | - Anthony U Onuzuruike
- Section on Ethnicity and Health, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland
| | - Sheela N Magge
- Division of Pediatric Endocrinology and Diabetes, Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC
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18
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Ren XY, Shi D, Ding J, Cheng ZY, Li HY, Li JS, Pu HQ, Yang AM, He CL, Zhang JP, Ma YB, Zhang YW, Zheng TZ, Bai YN, Cheng N. Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: Jinchang cohort study. Lipids Health Dis 2019; 18:47. [PMID: 30744645 PMCID: PMC6371543 DOI: 10.1186/s12944-019-0984-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 01/23/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Some studies found out that TC/HDL-C ratio is a predictor of Cardiovascular disease (CVD) and Nonalcoholic fatty liver (NAFLD) is related to CVD. And some researches have already studied that Apolipoprotein B to Apolipoprotein A1 ratio (ApoB/ApoA1) and Triglyceride to High-density lipoprotein cholesterol ratio (TG/HDL-C) were both related with CVD and NAFLD, but few studied the association between TC/HDL-C ratio and NAFLD. So, we suspected the ratio was also related to NAFLD. The research aims to study the predictive value of TC/HDL-C to NAFLD and to help the early detection of NAFLD. METHODS Based on the Jinchang Cohort, the study contained 32,121 participants. We assessed the incidence of NAFLD by the quartiles of TC, HDL-C and TC/HDL-C. Then, the does-response relationship between these indicators and the risk of NAFLD was obtained. Finally, the receiver operator characteristic curve (ROC) was applied to decide the predictive value of TC/HDL-C. RESULTS Among the study participants, the cumulative incidence of NAFLD was 6.30% and the rate of dyslipidemia was 40.37%. The biochemical indicators of NAFLD had a difference with general population. The incidence of NAFLD raised with the quartiles of TC, TG and LDL-C raising, while decreased with the HDL-C' quartiles raising. After controlling confounding factors, TC and TC/HD-C had a positive relationship with NAFLD, while HDL-C had the opposite. Finally, the ROC analysis showed the area under the curve (AUC) of TC/HDL-C (0.645) was greater than TC (0.554), HDL-C (0.627) and Apolipoprotein B to Apolipoprotein A1 (ApoB/ApoA1) (0.613). CONCLUSIONS The TC/HDL-C ratio has significant predictive value to NAFLD.
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Affiliation(s)
- Xiao Yu Ren
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, Gansu, 730000, People's Republic of China.,Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China
| | - Dian Shi
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, Gansu, 730000, People's Republic of China.,Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China
| | - Jiao Ding
- Workers' Hospital of Jinchuan Group Co., Ltd., Jinchang, Gansu, China
| | - Zhi Yuan Cheng
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China.,Department of Surgery, School of Medicine, Yale Cancer Center, Yale University, City of New haven, CT, USA
| | - Hai Yan Li
- Workers' Hospital of Jinchuan Group Co., Ltd., Jinchang, Gansu, China
| | - Juan Sheng Li
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China
| | - Hong Quan Pu
- Workers' Hospital of Jinchuan Group Co., Ltd., Jinchang, Gansu, China
| | - Ai Min Yang
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China.,Department of Epidemiology, School of Public Health, Brown University, City of Providence, RI, USA
| | - Cai Li He
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China
| | - Jian Ping Zhang
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China
| | - Yu Bao Ma
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China
| | - Ya Wei Zhang
- Department of Surgery, School of Medicine, Yale Cancer Center, Yale University, City of New haven, CT, USA
| | - Tong Zhang Zheng
- Department of Epidemiology, School of Public Health, Brown University, City of Providence, RI, USA
| | - Ya Na Bai
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China.
| | - Ning Cheng
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, Gansu, 730000, People's Republic of China.
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Lebray P, Varnous S, Pascale A, Leger P, Luyt CE, Ratziu V, Munteanu M, Ould Amar S, Thabut D, Chastre J, Pavie A, Poynard T, Leprince P. Predictive value of liver damage for severe early complications and survival after heart transplantation: A retrospective analysis. Clin Res Hepatol Gastroenterol 2018; 42:416-426. [PMID: 29655525 DOI: 10.1016/j.clinre.2018.03.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Revised: 02/28/2018] [Accepted: 03/01/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatic dysfunction is often associated with advanced heart failure. Its impact on complications following heart transplantation is not well known. We studied the influence of preoperative hepatic dysfunction on the results of heart transplantation with a specific priority access for critical patients. METHODS Consecutive heart transplantation patients were retrospectively analyzed at listing to detect predictive factors for early complications and survival following heart transplantation. RESULTS Among heart transplant candidates (n=384), median age was 52 years, dilated and ischemic cardiopathies were present in 44% and 32%, respectively. Clinical ascites was present in 15.6% and median MELD score was 13. A temporary circulatory support and a national priority access were necessary in 14.8% and 35% respectively. Whereas 12% of the global cohort died on the waiting list, 321 patients were transplanted, 34.2% suffered from severe early complications, 26.3% needed extracorporeal membrane oxygenation in postoperative period, 27.7% died before 3 months with a 5-year survival rate of 56%. At listing, clinical ascites, and creatinine were independently associated with specific early complications i.e. primary graft dysfunction and septic shock respectively. Bilirubin level was also an independent marker of other early complications. Finally, need for postoperative circulatory support and postoperative 90-day mortality were strongly and exclusively associated with clinical ascites and creatinine at listing. In a subgroup analysis, we predicted more accurately the postoperative survival at 3 months by combining MELD score and ascites. CONCLUSION At listing, hepatic and renal dysfunctions are independent risk factors that could predict severe early complications and mortality following heart transplantation in the most severe patients.
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Affiliation(s)
- Pascal Lebray
- Hépato-gastroentérologie, Hôpital de la Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013 Paris, France.
| | | | - Alina Pascale
- Hépato-gastroentérologie, Hôpital de la Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Philippe Leger
- Hépato-gastroentérologie, Hôpital de la Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013 Paris, France; Cardiothoracic Surgical Unit, Paris, France; Anaesthesia and Intensive Care Unit Department, Pitié-Salpêtrière Hospital, Paris, France; Biopredictive Research, Paris, France
| | - Charles Edouard Luyt
- Anaesthesia and Intensive Care Unit Department, Pitié-Salpêtrière Hospital, Paris, France
| | - Vlad Ratziu
- Hépato-gastroentérologie, Hôpital de la Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | | | | | - Dominique Thabut
- Hépato-gastroentérologie, Hôpital de la Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013 Paris, France
| | - Jean Chastre
- Anaesthesia and Intensive Care Unit Department, Pitié-Salpêtrière Hospital, Paris, France
| | | | - Thierry Poynard
- Hépato-gastroentérologie, Hôpital de la Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013 Paris, France
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20
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Khammas ASA, Hassan HA, Salih SQM, Kadir H, Ibrahim RM, Nasir NNM, Mahmud R. Prevalence and risk factors of sonographically detected non alcoholic fatty liver disease in a screening centre in Klang Valley, Malaysia: an observational cross-sectional study. Porto Biomed J 2018; 4:e31. [PMID: 31595260 PMCID: PMC6726292 DOI: 10.1016/j.pbj.0000000000000031] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 08/01/2018] [Indexed: 12/19/2022] Open
Abstract
Objectives: Nonalcoholic fatty liver disease (NAFLD) is a very common liver disorder in Western countries. As of late, it has been found to be prevalent in Asia as well. It is a benign disease unless it develops into necroinflammation and fibrosis. This study was proposed to determine the prevalence and risk factors of sonography-detected NAFLD among Malaysian adults in Klang Valley, West Malaysia. Study design: An observational cross-sectional study. Methods: The participants were aged between 45 and 75 years who participated in a screening program at the Golden Horses Health Sanctuary in Klang Valley. Lipid profile and anthropometric measurements were collected from the subjects’ medical records. Ultrasound machine and a structured self-administered questionnaire were used as instruments for recruiting data from the subjects. The subjects who consumed alcohol (>140 g/wk for men and >70 g/wk for females), had hepatitis B or C viruses, liver insults, and surgery, and taken lipid-lowering medications were excluded from the study. Results: A total of 628 subjects were analyzed, and 235 (37.4%) subjects were diagnosed with definite NAFLD. They comprised 518 (82.5%) Chinese, 92 (14.6%) Malays, and 18 (2.9%) Indians. Peak prevalence of NAFLD was found in 53 to 60 years age group. The higher prevalence of NAFLD was among men (48.3%) than women (27.3%) and among Indians (61.1%) and Malays (51.1%) than among Chinese (34.2%). NAFLD has been found to be strongly correlated with male sex, high body mass index (≥23.0 kg/m2), hypertriglyceridemia, low high-density lipoprotein cholesterol, diabetes mellitus, and hypertension. Conclusion: NAFLD is quite common among adults in Malaysian urban population. The prevalence of NAFLD was inordinately high among the 53 to 60 years age group, male sex, Indians, and Malays (as compared with Chinese). Age >60 years, male sex, high body mass index (≥23.0 kg/m2), hypertriglyceridemia, and diabetes mellitus were proven to be risk predictors for NAFLD.
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Affiliation(s)
- Abdul Sattar Arif Khammas
- Department of Radiological Techniques, College of Medical and Health Technology/Baghdad, Middle Technical University, Baghdad, Iraq
| | - Hasyma Abu Hassan
- Department of Imaging, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Sarah Qahtan M Salih
- Computer Center, College of Medical and Health Technology/Baghdad, Middle Technical University, Baghdad, Iraq
| | | | - Ramlah Mohamad Ibrahim
- Department of Imaging, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.,Department of Nutrition and Dietetics
| | - Nurul Nadiah Mohamad Nasir
- Department of Imaging, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.,Department of Nutrition and Dietetics
| | - Rozi Mahmud
- Cancer Resource and Education Centre (CaRE), Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
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21
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Chinnadurai R, Ritchie J, Green D, Kalra PA. Non-alcoholic fatty liver disease and clinical outcomes in chronic kidney disease. Nephrol Dial Transplant 2018; 34:449-457. [DOI: 10.1093/ndt/gfx381] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Accepted: 12/19/2017] [Indexed: 12/11/2022] Open
Affiliation(s)
| | - James Ritchie
- Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, UK
| | - Darren Green
- Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, UK
| | - Philip A Kalra
- Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, UK
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22
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Ahmed MH, Noor SK, Bushara SO, Husain NE, Elmadhoun WM, Ginawi IA, Osman MM, Mahmoud AO, Almobarak AO. Non-Alcoholic Fatty Liver Disease in Africa and Middle East: An Attempt to Predict the Present and Future Implications on the Healthcare System. Gastroenterology Res 2017; 10:271-279. [PMID: 29118867 PMCID: PMC5667692 DOI: 10.14740/gr913w] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 10/09/2017] [Indexed: 12/24/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a group of hepatic diseases that range in severity. NAFLD is increasingly recognized as an epidemic among different populations, including those in Africa and the Middle East. The objective of this narrative review is to document the prevalence of and risk factors for NAFLD in Africa and the Middle East and the potential implications on the healthcare systems. An in-depth search on Google Scholar, Medline and PubMed was conducted using the terms "non-alcoholic fatty liver disease" and "non-alcoholic steatohepatitis", in addition to "prevalence and risk factors for NAFLD", with special emphasis on Africa and the Middle East countries. There were three types of epidemiological studies that included prevalence, risk factors and management/complications of NAFLD. There was noticeable variation in the prevalence of NAFLD among different countries, based on the variation in the prevalence of risk factors (type 2 diabetes, obesity, metabolic syndrome and dyslipidemia) and the diagnostic tool used in the study. However, the highest prevalence rate was reported in some Middle East countries. In Africa, there were few studies about NAFLD and most reported variable prevalence rates. There is an increasing prevalence of NAFLD as a result of the increasing risk factors, particularly in the Middle East, while in Africa, the situation is still unclear. Health providers in these regions are faced with many challenges that need urgent plans.
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Affiliation(s)
- Mohamed H. Ahmed
- Department of Medicine and HIV Metabolic Clinic, Milton Keynes University Hospital NHS Foundation Trust, Eaglestone, Milton Keynes, Buckinghamshire, UK
| | - Sufian K. Noor
- Department of Medicine, Faculty of Medicine and Health Sciences, Nile Valley University, Atbara, Sudan
| | - Sarra O. Bushara
- Department of Medicine, Faculty of Medicine and Health Sciences, Nile Valley University, Atbara, Sudan
| | - Nazik Elmalaika Husain
- Department of Pathology, Faculty of Medicine and Health Sciences, Omdurman Islamic University, Khartoum, Sudan
| | - Wadie M. Elmadhoun
- Department of Pathology, Faculty of Medicine and Health Sciences, Nile Valley University, Atbara, Sudan
| | | | - Meissa M. Osman
- Department of Pediatric, University Hospitals of Leicester NHS Trust, Leicester, UK
| | | | - Ahmed O. Almobarak
- Department of Pathology, Faculty of Medicine, University of Medical Sciences and Technology, Khartoum, Sudan
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23
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Shao D, Han J, Hou X, Fry J, Behring JB, Seta F, Long MT, Roy HK, Cohen RA, Matsui R, Bachschmid MM. Glutaredoxin-1 Deficiency Causes Fatty Liver and Dyslipidemia by Inhibiting Sirtuin-1. Antioxid Redox Signal 2017; 27:313-327. [PMID: 27958883 PMCID: PMC5563925 DOI: 10.1089/ars.2016.6716] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AIMS Nonalcoholic fatty liver (NAFL) is a common liver disease associated with metabolic syndrome, obesity, and diabetes that is rising in prevalence worldwide. Various molecular perturbations of key regulators and enzymes in hepatic lipid metabolism cause NAFL. However, redox regulation through glutathione (GSH) adducts in NAFL remains largely elusive. Glutaredoxin-1 (Glrx) is a small thioltransferase that removes protein GSH adducts without having direct antioxidant properties. The liver contains abundant Glrx but its metabolic function is unknown. RESULTS Here we report that normal diet-fed Glrx-deficient mice (Glrx-/-) spontaneously develop obesity, hyperlipidemia, and hepatic steatosis by 8 months of age. Adenoviral Glrx repletion in the liver of Glrx-/- mice corrected lipid metabolism. Glrx-/- mice exhibited decreased sirtuin-1 (SirT1) activity that leads to hyperacetylation and activation of SREBP-1 and upregulation of key hepatic enzymes involved in lipid synthesis. We found that GSH adducts inhibited SirT1 activity in Glrx-/- mice. Hepatic expression of nonoxidizable cysteine mutant SirT1 corrected hepatic lipids in Glrx-/- mice. Wild-type mice fed high-fat diet develop metabolic syndrome, diabetes, and NAFL within several months. Glrx deficiency accelerated high-fat-induced NAFL and progression to steatohepatitis, manifested by hepatic damage and inflammation. INNOVATION These data suggest an essential role of hepatic Glrx in regulating SirT1, which controls protein glutathione adducts in the pathogenesis of hepatic steatosis. CONCLUSION We provide a novel redox-dependent mechanism for regulation of hepatic lipid metabolism, and propose that upregulation of hepatic Glrx may be a beneficial strategy for NAFL. Antioxid. Redox Signal. 27, 313-327.
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Affiliation(s)
- Di Shao
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts
| | - Jingyan Han
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts
| | - Xiuyun Hou
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts
| | - Jessica Fry
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts
| | - Jessica B Behring
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts
| | - Francesca Seta
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts
| | - Michelle T Long
- 3 Division of Gastroenterology, Boston Medical Center , Boston, Massachusetts
| | - Hemant K Roy
- 3 Division of Gastroenterology, Boston Medical Center , Boston, Massachusetts
| | - Richard A Cohen
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts.,2 Cardiovascular Proteomics Center, Boston University School of Medicine , Boston, Massachusetts
| | - Reiko Matsui
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts
| | - Markus M Bachschmid
- 1 Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts.,2 Cardiovascular Proteomics Center, Boston University School of Medicine , Boston, Massachusetts
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24
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Metabolic clinic for individuals with HIV/AIDS: a commitment and vision to the future of HIV services. Cardiovasc Endocrinol 2017; 6:109-112. [PMID: 31646127 DOI: 10.1097/xce.0000000000000128] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 05/30/2017] [Indexed: 12/17/2022] Open
Abstract
One of the biggest current challenges in managing an ageing cohort living with the HIV is handling dyslipidaemia, diabetes, metabolic syndrome and nonalcoholic fatty liver disease. Combination antiretroviral therapy decrease mortality and morbidity in HIV patients, but lead to increase in insulin resistance, dyslipidaemia, abnormalities of fat distribution and high risk of cardiovascular disease. Therefore, a metabolic clinic was established for individuals living with HIV in the Milton Keynes University Hospital NHS Foundation Trust. The clinic meets considerable demands by service users and hence has the potential to be popular. This review focuses on the importance of the development of a metabolic clinic for the purpose of audit, research, teaching and exchange of knowledge between HIV specialists and the metabolic team in the management of complex cases. Therefore, the metabolic clinic should be an integral part of HIV services especially as the cohort of the 'older' HIV population increases.
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25
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Magge SN, Goodman E, Armstrong SC, Daniels S, Corkins M, de Ferranti S, Golden NH, Kim JH, Magge SN, Schwarzenberg SJ, Sills IN, Casella SJ, DeMeglio LA, Gonzalez JL, Kaplowitz PB, Lynch JL, Wintergerst KA, Bolling CF, Armstrong SC, Muth ND, Rausch JC, Rogers VW, Schwartz RP. The Metabolic Syndrome in Children and Adolescents: Shifting the Focus to Cardiometabolic Risk Factor Clustering. Pediatrics 2017; 140:peds.2017-1603. [PMID: 28739653 DOI: 10.1542/peds.2017-1603] [Citation(s) in RCA: 241] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Metabolic syndrome (MetS) was developed by the National Cholesterol Education Program Adult Treatment Panel III, identifying adults with at least 3 of 5 cardiometabolic risk factors (hyperglycemia, increased central adiposity, elevated triglycerides, decreased high-density lipoprotein cholesterol, and elevated blood pressure) who are at increased risk of diabetes and cardiovascular disease. The constellation of MetS component risk factors has a shared pathophysiology and many common treatment approaches grounded in lifestyle modification. Several attempts have been made to define MetS in the pediatric population. However, in children, the construct is difficult to define and has unclear implications for clinical care. In this Clinical Report, we focus on the importance of screening for and treating the individual risk factor components of MetS. Focusing attention on children with cardiometabolic risk factor clustering is emphasized over the need to define a pediatric MetS.
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Affiliation(s)
- Sheela N. Magge
- Division of Endocrinology and Diabetes, and Center for Translational Science, Children's National Health System, Washington, District of Columbia
| | - Elizabeth Goodman
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; and
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26
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and leading cause of cirrhosis in the United States and developed countries. NAFLD is closely associated with obesity, insulin resistance and metabolic syndrome, significantly contributing to the exacerbation of the latter. Although NAFLD represents the hepatic component of metabolic syndrome, it can also be found in patients prior to their presentation with other manifestations of the syndrome. The pathogenesis of NAFLD is complex and closely intertwined with insulin resistance and obesity. Several mechanisms are undoubtedly involved in its pathogenesis and progression. In this review, we bring together the current understanding of the pathogenesis that makes NAFLD a systemic disease.
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Affiliation(s)
- Isabella Reccia
- Department of Surgery and Cancer Faculty of Medicine, Hammersmith Hospital, Imperial College London, UK.
| | - Jayant Kumar
- Department of Surgery and Cancer Faculty of Medicine, Hammersmith Hospital, Imperial College London, UK.
| | - Cherif Akladios
- Department of Surgery and Cancer Faculty of Medicine, Hammersmith Hospital, Imperial College London, UK.
| | - Francesco Virdis
- Department of Surgery and Cancer Faculty of Medicine, Hammersmith Hospital, Imperial College London, UK.
| | - Madhava Pai
- Department of Surgery and Cancer Faculty of Medicine, Hammersmith Hospital, Imperial College London, UK.
| | - Nagy Habib
- Department of Surgery and Cancer Faculty of Medicine, Hammersmith Hospital, Imperial College London, UK.
| | - Duncan Spalding
- Department of Surgery and Cancer Faculty of Medicine, Hammersmith Hospital, Imperial College London, UK.
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27
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Dinani A, Sanyal A. Nonalcoholic fatty liver disease: implications for cardiovascular risk. Cardiovasc Endocrinol 2017; 6:62-72. [PMID: 31646122 PMCID: PMC6768515 DOI: 10.1097/xce.0000000000000126] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 03/23/2017] [Indexed: 12/20/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic in the USA affecting ∼30% of the population. It has been closely linked to metabolic syndrome and type 2 diabetes, with strong implications for cardiovascular disease (CVD). This review focuses on the relationship between NAFLD and CVD and the proposed interactions interlinking these two diseases. This appraisal also discusses treatments targeting NAFLD in the context of CVD. NAFLD is a multisystem disease and ultimately the goals of therapy are to ameliorate CVD and prevent coronary artery disease morbidity and mortality.
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Affiliation(s)
- Amreen Dinani
- Department of Gastroenterology and Hepatology, NewYork-Presbyterian Brooklyn Methodist, NewYork-Presbyterian Healthcare System, Brooklyn, New York
| | - Arun Sanyal
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
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28
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Ahmed IA, Mikail MA, Ibrahim M. Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits. Nutr Res 2017. [PMID: 28633869 DOI: 10.1016/j.nutres.2017.04.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (P<.05) ameliorated by the administration of BA juice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit.
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Affiliation(s)
- Idris Adewale Ahmed
- Department of Nutrition Sciences, International Islamic University Malaysia (IIUM); Department of Biotechnology, Lincoln University College, Malaysia.
| | | | - Muhammad Ibrahim
- Department of Nutrition Sciences, International Islamic University Malaysia (IIUM).
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29
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Effects of Turmeric on Homocysteine and Fetuin-A in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Double-Blind Placebo-Controlled Study. IRANIAN RED CRESCENT MEDICAL JOURNAL 2017. [DOI: 10.5812/ircmj.43193] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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30
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Silva AKSE, Gomes FODS, Santos Silva BD, Ribeiro EL, Oliveira AC, Araújo SMDR, de Lima IT, Oliveira AGV, Rudnicki M, Abdalla DS, Lima MDCAD, Pitta IDR, Peixoto CA. Chronic LPSF/GQ-02 treatment attenuates inflammation and atherosclerosis development in LDLr−/− mice. Eur J Pharmacol 2016; 791:622-631. [DOI: 10.1016/j.ejphar.2016.09.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/25/2016] [Accepted: 09/28/2016] [Indexed: 12/12/2022]
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31
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Alvarado A, Arce I. Metabolic Functions of the Lung, Disorders and Associated Pathologies. J Clin Med Res 2016; 8:689-700. [PMID: 27635172 PMCID: PMC5012236 DOI: 10.14740/jocmr2668w] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/08/2016] [Indexed: 01/04/2023] Open
Abstract
The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth's atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration.
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Affiliation(s)
- Alcibey Alvarado
- Internal Medicine and Neumology, Clinica de Diagnostico Medico, San Jose, Costa Rica
| | - Isabel Arce
- Medicine and General Surgery, Medicine School, University of Costa Rica, San Jose, Costa Rica
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32
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Canbay A, Gerken G, Bechmann LP. [Hepatic steatosis : Differential diagnostics and current aspects]. Internist (Berl) 2016; 57:879-92. [PMID: 27510334 DOI: 10.1007/s00108-016-0112-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The frequency of non-alcoholic fatty liver disease (NAFLD) has continously increased over the last few decades in parallel with the increasing prevalence of metabolic syndrome. With the increasing frequency of obesity and type 2 diabetes an increase in non-alcoholic steatohepatitis (NASH) is also to be expected. The NASH-associated liver cirrhosis and primary hepatocellular carcinoma (HCC) are indications for liver transplantation (LTX), which is gaining importance in Germany. In contrast, liver cirrhosis as a result of alcoholic steatohepatitis (ASH) is already the leading cause for LTX in Germany. A significant number of patients with ASH cirrhosis develop HCC. Less common causes of hepatic steatosis are secondary and include chemotherapy-associated steatohepatitis (CASH). In this article the causes, diagnostics and novel therapeutic approaches for the various forms of steatosis are discussed.
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Affiliation(s)
- A Canbay
- Klinik für Gastroenterologie und Hepatologie, Hufelandstr. 55, 45122, Essen, Deutschland
| | - G Gerken
- Klinik für Gastroenterologie und Hepatologie, Hufelandstr. 55, 45122, Essen, Deutschland
| | - L P Bechmann
- Klinik für Gastroenterologie und Hepatologie, Hufelandstr. 55, 45122, Essen, Deutschland.
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33
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Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic fatty liver disease and dyslipidemia: An update. Metabolism 2016; 65:1109-23. [PMID: 27237577 DOI: 10.1016/j.metabol.2016.05.003] [Citation(s) in RCA: 430] [Impact Index Per Article: 47.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/02/2016] [Accepted: 05/05/2016] [Indexed: 11/21/2022]
Abstract
Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma. Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression. NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking. NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction. Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality. In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed. NAFLD treatment is also reviewed with a focus on lipid-lowering drugs. Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered.
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Affiliation(s)
- Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK.
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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34
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Canbay A, Sowa JP, Syn WK, Treckmann J. NASH Cirrhosis - the New Burden in Liver Transplantation: How Should It Be Managed? Visc Med 2016; 32:234-238. [PMID: 27722159 DOI: 10.1159/000446379] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a continuously increasing cause of chronic liver disease and a health burden in all populations affected by the obesity and metabolic syndrome pandemic. Cirrhotic alterations or hepatocellular carcinoma developing from NAFLD may require liver transplantation (LTx). METHODS Current literature was screened for data on LTx in the setting of NAFLD. RESULTS NAFLD-associated LTx is expected to increase in number and relevance during the next decade. NAFLD is part of the metabolic syndrome and thus connected to various metabolic alterations and comorbidities such as diabetes or hyperlipidemia. Moreover, NAFLD comprises an independent risk factor for cardiovascular and chronic kidney disease, which again are important risk factors for outcome of surgical interventions. Postoperative immunosuppression, possible steatosis of the liver graft, and a continued presence of metabolic alterations may lead to early recurrence of steatosis or even non-alcoholic steatohepatitis. Currently, no data are available on combined approaches of weight loss and LTx for NAFLD. CONCLUSION Specific guidelines on how to manage NAFLD-associated LTx are lacking. This particular situation requires close monitoring of metabolic syndrome-associated comorbidities. NAFLD represents a novel challenge to established LTx procedures.
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Affiliation(s)
- Ali Canbay
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Jan-Peter Sowa
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Wing-Kin Syn
- Division of Gastroenterology and Hepatology, The Medical University of South Carolina, Charleston, SC, USA; Section of Gastroenterology, Ralph H. Johnson Veteran Affairs Medical Center, Charleston, SC, USA
| | - Jürgen Treckmann
- Department of General, Visceral, and Transplantation Surgery, University Hospital, University Duisburg-Essen, Essen, Germany
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Yun KE, Nam GE, Lim J, Park HS, Chang Y, Jung HS, Kim CW, Ko BJ, Chung EC, Shin H, Ryu S. Waist Gain Is Associated with a Higher Incidence of Nonalcoholic Fatty Liver Disease in Korean Adults: A Cohort Study. PLoS One 2016; 11:e0158710. [PMID: 27420035 PMCID: PMC4946777 DOI: 10.1371/journal.pone.0158710] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 06/21/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We examined the relationship between changes in waist circumference (WC) and the incidence of nonalcoholic fatty liver disease (NAFLD). METHODS A cohort study of 37,130 men and women were followed-up annually or biennially. Differences in WC between baseline and subsequent measurements were categorized in quartiles: first (WC loss), second (no change in WC as the reference), third and highest quartiles (WC gain). The presence of fatty liver was determined using ultrasound. Parametric Cox modeling was used to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) of the incidence of NAFLD. RESULTS During 127,324.4 person-years of follow-up, 6249 participants developed NAFLD. Despite adjusting for possible confounders, the risk of development of NAFLD increased with increasing quartiles of WC change in a dose-response manner (p for trend < 0.001). Compared with the reference, WC loss was associated with a lower risk of NAFLD (men: aHR 0.79 [95% CI: 0.73-0.87]; women: 0.72 [0.63-0.81]), and the highest quartile (WC gain) was associated with a higher risk of NAFLD (men: 1.30 [1.19-1.42]; women: 1.48 [1.31-1.67]). CONCLUSION Waist gain appears to increase the risk of developing NAFLD, independently of the baseline body mass index and WC.
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Affiliation(s)
- Kyung Eun Yun
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Ga Eun Nam
- Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan-si, South Korea
| | - Jisun Lim
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hye Soon Park
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Hyun-Suk Jung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Chan-Won Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Byung-Joon Ko
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Eun Chul Chung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea
| | - Hocheol Shin
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
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Rief P, Pichler M, Raggam R, Hafner F, Gerger A, Eller P, Brodmann M, Gary T. The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. Medicine (Baltimore) 2016; 95:e3843. [PMID: 27310963 PMCID: PMC4998449 DOI: 10.1097/md.0000000000003843] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The aspartat aminotransferase (AST)/alanin aminotransferase (ALT) (De-Ritis) ratio (AAR) is an easily applicable blood test. An elevated AAR on the one hand has been associated with an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD on the other hand is associated with an increase in cardiovascular disease, all-cause mortality, and diabetes. As the AAR is also elevated in case of muscular damage, we investigated AAR and its association with critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients.In our cross-sectional study, we included 1782 PAOD patients treated at our institution from 2005 to 2010. Patients with chronic alcohol consumption (>20 g/day) were excluded. AAR was calculated and the cohort was categorized into tertiles according to the AAR. An optimal cut-off value for the continuous AAR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI.In our cohort, occurrence of CLI significantly increased with an elevation in AAR. As an optimal cut-off value, an AAR of 1.67 (sensitivity 34.1%, specificity 81.0%) was identified. Two groups were categorized, 1st group containing 1385 patients (AAR < 1.67) and a 2nd group with 397 patients (AAR > 1.67). CLI was more frequent in AAR > 1.67 patients (166 [41.9%]) compared to AAR < 1.67 patients (329 [23.8%]) (P < 0.001), as was prior myocardial infarction (28 [7.1%] vs 54 [3.9%], P = 0.01). Regarding inflammatory parameters, C-reactive protein (median 8.1 mg/L [2.9-28.23] vs median 4.3 mg/L [2.0-11.5]) and fibrinogen (median 427.5 mg/dL [344.25-530.0] vs 388.0 mg/dL [327.0-493.0]) also significantly differed in the 2 patient groups (both P < 0.001). Finally, an AAR > 1.67 was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] 1.7-2.3) for CLI even after adjustment for other well-established vascular risk factors.An increased AAR is significantly associated with patients at high risk for CLI and other cardiovascular endpoints. The AAR is a broadly available and cheap marker, which might be useful to highlight patients at high risk for vascular endpoints.
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Affiliation(s)
| | | | | | | | | | - Philipp Eller
- Intensive Care Unit, Department of Internal Medicine, Medical University Graz, Graz, Austria
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Wang S, Zhang C, Zhang G, Yuan Z, Liu Y, Ding L, Sun X, Jia H, Xue F. Association between white blood cell count and non-alcoholic fatty liver disease in urban Han Chinese: a prospective cohort study. BMJ Open 2016; 6:e010342. [PMID: 27251683 PMCID: PMC4893843 DOI: 10.1136/bmjopen-2015-010342] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES The white blood cell (WBC) count is a simple and convenient marker of inflammation for use in medical practice; however, its association with non-alcoholic fatty liver disease (NAFLD) has not been determined. We examined the relationship between WBC and NAFLD to provide a convenient and useful marker for the prediction of NAFLD. SETTING A longitudinal cohort participating in a large health check-up programme for the Chinese population was selected and followed up from 2005 to 2011. PARTICIPANTS A total of 21 307 male and female participants without NAFLD who underwent health check-ups at least twice between 2005 and 2011 were included in this study. 15 201 participants (7286 men and 7915 women) were eligible for inclusion. RESULTS The baseline distribution of age, WBC, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum total protein (TP), albumin (ALB) and globin (GLO) and the prevalence of males, hypertension, hyperglycaemia, smoking and regular exercise were significantly different between the incident NAFLD and non-NAFLD groups (p<0.05). Cox proportional hazards regression analysis was performed to estimate the HRs and 95% CIs of WBC, which predicted the occurrence of NAFLD. Compared with the lowest WBC quartile (Q1), the HRs and 95% CIs of the other WBC quartiles (Q2, Q3 and Q4) for incident NAFLD were 1.090 (0.978 to 1.215), 1.174 (1.055 to 1.305) and 1.152 (1.035 to 1.281), respectively, after adjusting for age, gender, smoking, regular exercise, BMI, hypertension, hyperglycaemia, TC, TG, HDL-C, LDL-C, ALB and GLO. CONCLUSIONS Our study clearly showed that WBC count was a significant factor associated with incident NAFLD in Han Chinese.
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Affiliation(s)
- Shukang Wang
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
| | - Chengqi Zhang
- Health Management Center, Shandong Provincial QianFoShan Hospital, Jinan, China
| | - Guang Zhang
- Health Management Center, Shandong Provincial QianFoShan Hospital, Jinan, China
| | - Zhongshang Yuan
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
| | - Yanxun Liu
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
| | - Lijie Ding
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
| | - Xiubin Sun
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
| | - Hongying Jia
- The Second Hospital of Shandong University, Jinan, China
| | - Fuzhong Xue
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
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Sowa JP, Fingas CD, Canbay A. Mixed lineage kinase 3 connects hepatocellular lipotoxicity with macrophage chemotaxis. Hepatology 2016; 63:685-7. [PMID: 26547377 DOI: 10.1002/hep.28333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 11/04/2015] [Indexed: 12/07/2022]
Affiliation(s)
- Jan-Peter Sowa
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Christian Dominik Fingas
- Department of General, Visceral and Transplantation Surgery, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Ali Canbay
- Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany
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Yang MH, Sung J, Gwak GY. The associations between apolipoprotein B, A1, and the B/A1 ratio and nonalcoholic fatty liver disease in both normal-weight and overweight Korean population. J Clin Lipidol 2016; 10:289-98. [DOI: 10.1016/j.jacl.2015.11.017] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Revised: 11/20/2015] [Accepted: 11/26/2015] [Indexed: 12/27/2022]
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Prevalence of and predictive factors for nonalcoholic fatty liver disease in Sudanese individuals with type 2 diabetes: Is metabolic syndrome the culprit? Arab J Gastroenterol 2015; 16:54-8. [PMID: 26174761 DOI: 10.1016/j.ajg.2015.06.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Revised: 04/04/2015] [Accepted: 06/07/2015] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND STUDY AIM Non-alcoholic fatty liver disease (NAFLD) is a common global chronic liver condition. The prevalence of NAFLD among individuals with type 2 diabetes is estimated to be as high as 75%. The aim of this study was to determine the prevalence of NAFLD among individuals with type 2 diabetes in Sudan. PATIENTS AND METHODS This was a cross-sectional hospital-based study, which was carried out at the Jabir Abu-Elizz diabetic centre in Khartoum; 167 outpatients with type 2 diabetes were enrolled. NAFLD was diagnosed based on ultrasound, following exclusion of significant alcohol intake and secondary causes of liver diseases. NAFLD was defined as hepatic steatosis in the absence of alcohol intake, medication, previous liver disease and negative results for the serological test for hepatitis B and C. Logistic regression analysis was used to determine independent risk factors for the development of NAFLD in individuals with type 2 diabetes. RESULTS The number of female subjects was 89 (53.3%), and most subjects (145, 86.8%) were between the ages of 40 and 70 years. The overall prevalence of fatty liver among individuals with type 2 diabetes was found to be 50.3%. Age, duration of diabetes, hypertension and HbA1c levels appeared to have no impact on the prevalence of NAFLD. The possible predictors of NAFLD were overweight, obesity, central obesity, high triglyceride level and low high-density lipoprotein cholesterol (HDL-c) level. A higher prevalence of NAFLD was observed in individuals with three components of the metabolic syndrome. CONCLUSION NAFLD was observed in half of the diabetic population, and its occurrence correlates positively with metabolic syndrome risk factors.
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Seif el-Din SH, El-Lakkany NM, El-Naggar AA, Hammam OA, Abd El-Latif HA, Ain-Shoka AA, Ebeid FA. Effects of rosuvastatin and/or β-carotene on non-alcoholic fatty liver in rats. Res Pharm Sci 2015; 10:275-87. [PMID: 26600855 PMCID: PMC4623617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in patients exhibit one or more features of the metabolic syndrome. This study investigates the effect of rosuvastatin (RSV) and/or β-carotene (βC) in NAFLD-induced rats. Rats were classified into nine groups; normal (I), NAFLD-induced with high-fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with RSV (IV, V), βC (VI, VII) or both RSV+βC (VIII, IX), respectively. After four weeks, rats were sacrificed to obtain serum samples and liver tissues. Liver histology, lipid profile, liver oxidative stress markers, and adipocytokines were measured. Liver sections of rats with NAFLD-HFD revealed steatosis, lose of hepatic architecture, inflammation and hepatocyte vacuolation with high percentage of cell fibrosis. Serum levels of ALT, AST, ALP, gamma glutamyl transferase (GGT) and lipid profile (triglycerides, cholesterol, LDL and VLDL) were significantly increased (P<0.05) compared with normal. Also, hepatic malondialdehyde level and serum leptin, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-β1 (TGF-β1) were increased. Meanwhile, superoxide dismutase (SOD) activity, GSH content in liver, serum HDL and adiponectin were decreased (P<0.05) vs normal. These changes were observed to a lesser extent in NAFLD-RD group. Administration of RSV or/and βC almost improved all previously mentioned parameters. Moreover, hepatic steatosis was decreased and inflammation was markedly ameliorated with reduction of TNF-α and TGF-β. These results were more pronounced in the groups VIII and IX vs each drug alone. In conclusion RSV and βC could be beneficial for the treatment and prevention of NAFLD. Combined RSV with βC is more effective than RSV alone.
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Affiliation(s)
- Sayed H. Seif el-Din
- Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt
| | - Naglaa M. El-Lakkany
- Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt
| | - Abeer A. El-Naggar
- Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt
| | - Olfat A. Hammam
- Department of Pathology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt
| | - Hekma A. Abd El-Latif
- Department of Pharmacology, Faculty of Pharmacy, Umm Al-Qura University, Saudi Arabia
| | - Afaf A. Ain-Shoka
- Department of Pharmacology, Faculty of Pharmacy, Cairo University, Giza, Egypt
| | - Fatma A. Ebeid
- Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt
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Yang M, Xu D, Liu Y, Guo X, Li W, Guo C, Zhang H, Gao Y, Mao Y, Zhao J. Combined Serum Biomarkers in Non-Invasive Diagnosis of Non-Alcoholic Steatohepatitis. PLoS One 2015; 10:e0131664. [PMID: 26121037 PMCID: PMC4486729 DOI: 10.1371/journal.pone.0131664] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 06/05/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Non-alcoholic steatoheaptitis (NASH), the critical stage of non-alcoholic fatty liver disease (NAFLD), is of chronic progression and can develop cirrhosis even hepatocellular carcinoma (HCC). However, non-invasive biomarkers for NASH diagnosis remain poorly applied in clinical practice. Our study aims at testing the accuracy of the combination of cytokeratin-18 M30 fragment (CK-18-M30), fibroblast growth factor 21 (FGF-21), interleukin 1 receptor antagonist (IL-1Ra), pigment epithelium-derived factor (PEDF) and osteoprotegerin (OPG) in diagnosing NAFLD and NASH. METHODS 179 patients with biopsy-proven NAFLD were enrolled as training group, 91 age- and gender-matched healthy subjects were recruited at the same time as controls. 63 other NAFLD patients were separately collected as validation group. 45 alcoholic fatty liver disease (AFLD) patients, 50 hepatitis B virus (HBV) patients, 52 hepatitis C virus (HCV) patients were also included. Serum biomarker levels were measured by enzyme-linked immunosorbent assay. RESULTS Serum levels of CK-18-M30, FGF-21, IL-1Ra and PEDF increased, while OPG decreased in a stepwise fashion in controls, non-NASH NAFLD patients and NASH patients (P < 0.01). The area under receiver-operating characteristics curve to diagnose NASH was 0.86 for CK-18-M30, 0.89 for FGF-21, 0.89 for IL-1Ra, 0.89 for PEDF and 0.89 for OPG. CK-18-M30 had 70% negative predictive value (NPV) and 79% positive predictive value (PPV) to diagnose NASH. A 5-step approach measuring CK-18-M30 followed by FGF21, IL-1Ra, PEDF and OPG gradually improved the NPV to 76% and PPV to 85%, which reached 80% and 76% respectively in the validation cohort. CONCLUSION Compared to single biomarker, stepwise combination of CK-18-M30, FGF-21, IL-1Ra, PEDF and OPG can further improve the accuracy in diagnosing NASH.
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Affiliation(s)
- Mei Yang
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Dongping Xu
- Institute of Infectious Diseases/Liver Failure Medical Center, Beijing 302 Hospital, Beijing, China
| | - Yuan Liu
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Xiaodong Guo
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Wenshu Li
- Center for Clinical Trial, Beijing 302 Hospital, Beijing, China
| | - Chaonan Guo
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Hongping Zhang
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Yinjie Gao
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
| | - Yuanli Mao
- Center for Clinical Laboratory, Beijing 302 Hospital, Beijing, China
| | - Jingmin Zhao
- Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China
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Lückhoff HK, Kruger FC, Kotze MJ. Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries. World J Hepatol 2015; 7:1192-1208. [PMID: 26019735 PMCID: PMC4438494 DOI: 10.4254/wjh.v7.i9.1192] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/18/2014] [Accepted: 04/02/2015] [Indexed: 02/06/2023] Open
Abstract
Heterogeneity in clinical presentation, histological severity, prognosis and therapeutic outcomes characteristic of non-alcoholic fatty liver disease (NAFLD) necessitates the development of scientifically sound classification schemes to assist clinicians in stratifying patients into meaningful prognostic subgroups. The need for replacement of invasive liver biopsies as the standard method whereby NAFLD is diagnosed, graded and staged with biomarkers of histological severity injury led to the development of composite prognostic models as potentially viable surrogate alternatives. In the present article, we review existing scoring systems used to (1) confirm the presence of undiagnosed hepatosteatosis; (2) distinguish between simple steatosis and NASH; and (3) predict advanced hepatic fibrosis, with particular emphasis on the role of NAFLD as an independent cardio-metabolic risk factor. In addition, the incorporation of functional genomic markers and application of emerging imaging technologies are discussed as a means to improve the diagnostic accuracy and predictive performance of promising composite models found to be most appropriate for widespread clinical adoption.
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Long MT, Wang N, Larson MG, Mitchell GF, Palmisano J, Vasan RS, Hoffmann U, Speliotes EK, Vita JA, Benjamin EJ, Fox CS, Hamburg NM. Nonalcoholic fatty liver disease and vascular function: cross-sectional analysis in the Framingham heart study. Arterioscler Thromb Vasc Biol 2015; 35:1284-91. [PMID: 25745056 DOI: 10.1161/atvbaha.114.305200] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 02/23/2015] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk of cardiovascular disease; however, it is not known whether NAFLD contributes to cardiovascular disease independent of established risk factors. We examined the association between NAFLD and vascular function. APPROACH AND RESULTS We conducted a cross-sectional study of 2284 Framingham Heart Study participants without overt cardiovascular disease who had liver fat attenuation measured on computed tomography and who had measurements of vascular function and covariates. We evaluated the association between NAFLD and vascular function using multivariable partial correlations adjusting for age, sex, cohort, smoking, diabetes mellitus, hyperlipidemia, hypertension, body mass index, and visceral adipose tissue. The prevalence of NAFLD in our sample (mean age, 52±12 years; 51.4% women) was 15.3%. In age-, sex-, and cohort-adjusted analyses, greater liver fat was modestly associated with lower flow-mediated dilation (r=-0.05; P=0.02), lower peripheral arterial tonometry ratio (r=-0.20; P<0.0001), higher carotid-femoral pulse wave velocity (r=0.13; P<0.0001), and higher mean arterial pressure (r=0.11; P<0.0001). In multivariable-adjusted models, NAFLD remained associated with higher mean arterial pressure (r=0.06; P=0.005) and lower peripheral arterial tonometry ratio (r=-0.12; P<0.0001). The association between NAFLD and peripheral arterial tonometry ratio persisted after further adjustment for body mass index and visceral adipose tissue. CONCLUSIONS For multiple measures of vascular function, the relationship with NAFLD appeared largely determined by shared cardiometabolic risk factors. The persistent relationship with reduced peripheral arterial tonometry response beyond established risk factors suggests that NAFLD may contribute to microvascular dysfunction.
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Affiliation(s)
- Michelle T Long
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Na Wang
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Martin G Larson
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Gary F Mitchell
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Joseph Palmisano
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Ramachandran S Vasan
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Udo Hoffmann
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Elizabeth K Speliotes
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Joseph A Vita
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Emelia J Benjamin
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Caroline S Fox
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.)
| | - Naomi M Hamburg
- From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
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Kwak MS, Yim JY, Kim D, Park MJ, Lim SH, Yang JI, Chung GE, Kim YS, Yang SY, Kim MN, Lee CH, Yoon JH, Lee HS. Nonalcoholic fatty liver disease is associated with coronary artery calcium score in diabetes patients with higher HbA1c. Diabetol Metab Syndr 2015; 7:28. [PMID: 25844093 PMCID: PMC4384364 DOI: 10.1186/s13098-015-0025-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 03/18/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND In patients with diabetes, studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and coronary artery calcium score (CACS) have shown conflicting results. The aim of this study was to evaluate the association between NAFLD and CACS in diabetic patients. METHODS This is the cohort study performed in Seoul National University Hospital Gangnam Healthcare Center. NAFLD was defined as cases with the typical ultrasonographic findings without excessive alcohol consumption, medications causing hepatic steatosis or other chronic liver diseases. CACS was evaluated using the Agatston method. Diabetes was defined as cases with fasting serum glucose ≥ 126 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or those taking anti-diabetic medications. Multivariate linear regression analyses were performed with use of the interaction term of NAFLD × glycemic level and other confounders of CACS such as age, sex, hypertension, body mass index, waist circumference, HDL cholesterol and triglyceride. RESULTS A total of 213 participants with diabetes were included in the study. As 77 subjects (36.2%) had CACS 0, causing left sided skewness, CACS was analyzed after log transformation to Ln (CACS + 1). A statistically significant interaction was observed between NAFLD and HbA1c ≥ 7% (P for interaction = 0.014). While NAFLD was not associated with CACS in the group with HbA1c < 7% (P = 0.229), it was significantly associated in the group with HbA1c ≥ 7% (P = 0.010) after adjusting for covariates in multivariate analyses. CONCLUSIONS This study demonstrated an effect modification of glycemic level on the association between NAFLD and CACS. NAFLD was independently associated with CACS only in diabetes patients with higher HbA1c, after adjustment for confounders.
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Affiliation(s)
- Min-Sun Kwak
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Jeong Yoon Yim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Donghee Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Min Jung Park
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Seon Hee Lim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Jong In Yang
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Goh Eun Chung
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Young Sun Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Sun Young Yang
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Mi Na Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Chang-Hoon Lee
- />Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- />Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Suk Lee
- />Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Stachowicz A, Olszanecki R, Suski M, Wiśniewska A, Totoń-Żurańska J, Madej J, Jawień J, Białas M, Okoń K, Gajda M, Głombik K, Basta-Kaim A, Korbut R. Mitochondrial aldehyde dehydrogenase activation by Alda-1 inhibits atherosclerosis and attenuates hepatic steatosis in apolipoprotein E-knockout mice. J Am Heart Assoc 2014; 3:e001329. [PMID: 25392542 PMCID: PMC4338726 DOI: 10.1161/jaha.114.001329] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background Mitochondrial dysfunction has been shown to play an important role in the development of atherosclerosis and nonalcoholic fatty liver disease (NAFLD). Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the detoxification of reactive aldehydes, is considered to exert protective function in mitochondria. We investigated the influence of Alda‐1, an activator of ALDH2, on atherogenesis and on the liver steatosis in apolipoprotein E knockout (apoE−/−) mice. Methods and Results Alda‐1 caused decrease of atherosclerotic lesions approximately 25% as estimated by “en face” and “cross‐section” methods without influence on plasma lipid profile, atherosclerosis‐related markers of inflammation, and macrophage and smooth muscle content in the plaques. Plaque nitrotyrosine was not changed upon Alda‐1 treatment, and there were no changes in aortic mRNA levels of factors involved in antioxidative defense, regulation of apoptosis, mitogenesis, and autophagy. Hematoxylin/eosin staining showed decrease of steatotic changes in liver of Alda‐1‐treated apoE−/− mice. Alda‐1 attenuated formation of 4‐hydroxy‐2‐nonenal (4‐HNE) protein adducts and decreased triglyceride content in liver tissue. Two‐dimensional electrophoresis coupled with mass spectrometry identified 20 differentially expressed mitochondrial proteins upon Alda‐1 treatment in liver of apoE−/− mice, mostly proteins related to metabolism and oxidative stress. The most up‐regulated were the proteins that participated in beta oxidation of fatty acids. Conclusions Collectively, Alda‐1 inhibited atherosclerosis and attenuated NAFLD in apoE−/− mice. The pattern of changes suggests a beneficial effect of Alda‐1 in NAFLD; however, the exact liver functional consequences of the revealed alterations as well as the mechanism(s) of antiatherosclerotic Alda‐1 action require further investigation.
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Affiliation(s)
- Aneta Stachowicz
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
| | - Rafał Olszanecki
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
| | - Maciej Suski
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
| | - Anna Wiśniewska
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
| | - Justyna Totoń-Żurańska
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
| | - Józef Madej
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
| | - Jacek Jawień
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
| | - Magdalena Białas
- Department of Pathomorphology, Jagiellonian University Medical College, Krakow, Poland (M.B., K.O.)
| | - Krzysztof Okoń
- Department of Pathomorphology, Jagiellonian University Medical College, Krakow, Poland (M.B., K.O.)
| | - Mariusz Gajda
- Department of Histology, Jagiellonian University Medical College, Krakow, Poland (M.G.)
| | - Katarzyna Głombik
- Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland (K., A.B.K.)
| | - Agnieszka Basta-Kaim
- Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland (K., A.B.K.)
| | - Ryszard Korbut
- Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland (A.S., R.O., M.S., A.W., J.T., M., J.J., R.K.)
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Al-Rasadi K, Rizzo M, Montalto G, Berg G. Nonalcoholic Fatty Liver Disease, Cardiovascular Risk, and Carotid Inflammation. Angiology 2014; 66:601-3. [DOI: 10.1177/0003319714557353] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Khalid Al-Rasadi
- Department of Clinical Biochemistry, Sultan Qaboos University Hospital, Muscat, Oman
| | - Manfredi Rizzo
- Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Giuseppe Montalto
- Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Gabriela Berg
- Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
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Kampschulte M, Stöckl C, Langheinrich AC, Althöhn U, Bohle RM, Krombach GA, Stieger P, Churin Y, Kremer S, Dierkes C, Rath T, Roeb E, Roderfeld M. Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis. J Transl Med 2014; 94:1273-82. [PMID: 25199052 DOI: 10.1038/labinvest.2014.112] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Revised: 07/17/2014] [Accepted: 08/07/2014] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease has been linked to cardiovascular diseases and atherosclerosis. The aim of the current study was to characterize the hepatic pathology leading to fibrosis and tumors in a murine model of atherosclerosis. Male apolipoprotein E/low-density lipoprotein receptor double-knockout mice (AL) mice were fed with a high fat and high cholesterol western diet for 35 weeks (AL mice on WD). Protein and mRNA analysis as well as micro-computed tomography (micro-CT) were performed to assess oxidative stress, liver damage, inflammation, fibrosis, signaling pathways, vascularization, and tumorigenesis. Controls were chosen to distinguish between genetically and dietary effects in steatohepatitis and associated tumorigenesis. Hepatic inflammation and dyslipidemia were increased in AL mice on WD compared with wild-type mice on WD. Uniquely, AL mice on WD showed a spontaneous development of tumors (30% of cases) and thickening of intrahepatic vessel walls. Functionally relevant underlying signaling pathways such as NF-κB, Stat3, JNK, and AKT were differentially regulated between AL and wild-type mice on WD. Micro-CT was capable of visualizing and quantitatively distinguishing tumor neovascularization from vascularization in non-neoplastic liver tissue. AL mice on WD diet represent a novel model combining atherosclerosis and nonalcoholic fatty liver disease. Signaling pathways of liver cell damage and compensatory liver regeneration in combination with enhanced inflammation appear to be crucial for the spontaneous development of tumors in AL mice on WD. Micro-CT represents a new and powerful technique for the ultrastructural and three-dimensional assessment of the vascular architecture of liver tumors.
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Affiliation(s)
- Marian Kampschulte
- Department of Radiology, Justus-Liebig University Giessen, Giessen, Germany
| | - Christiane Stöckl
- Department of Radiology, Justus-Liebig University Giessen, Giessen, Germany
| | - Alexander C Langheinrich
- Department of Diagnostic and Interventional Radiology, BG Trauma Hospital, Frankfurt/Main, Germany
| | - Ulrike Althöhn
- Department of Radiology, Justus-Liebig University Giessen, Giessen, Germany
| | - Rainer M Bohle
- Department of Pathology, Saarland University, Homburg, Germany
| | | | - Philipp Stieger
- Department of Cardiology, Angiology and Pneumology, Otto von Guericke University Magdeburg, Magdeburg, Germany
| | - Yuri Churin
- Department of Gastroenterology, Justus-Liebig University Giessen, Giessen, Germany
| | - Sandra Kremer
- Department of Gastroenterology, Justus-Liebig University Giessen, Giessen, Germany
| | | | - Timo Rath
- 1] Department of Gastroenterology, Justus-Liebig University Giessen, Giessen, Germany [2] Department of Medicine 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Elke Roeb
- Department of Gastroenterology, Justus-Liebig University Giessen, Giessen, Germany
| | - Martin Roderfeld
- Department of Gastroenterology, Justus-Liebig University Giessen, Giessen, Germany
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Vuković R, Blažetić S, Oršolić I, Heffer M, Vari SG, Gajdoš M, Krivošíková Z, Kramárová P, Kebis A, Has-Schön E. Impact of ovariectomy, high fat diet, and lifestyle modifications on oxidative/antioxidative status in the rat liver. Croat Med J 2014; 55:218-27. [PMID: 24891280 PMCID: PMC4049208 DOI: 10.3325/cmj.2014.55.218] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Aim To estimate the impact of high fat diet and estrogen deficiency on the oxidative and antioxidative status in the liver of the ovariectomized rats, as well as the ameliorating effect of physical activity or consumption of functional food containing bioactive compounds with antioxidative properties on oxidative damage in the rat liver. Methods The study was conducted from November 2012 to April 2013. Liver oxidative damage was determined by lipid peroxidation levels expressed in terms of thiobarbituric acid reactive substances (TBARS), while liver antioxidative status was determined by catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) activities, and glutathione (GSH) content. Sixty-four female Wistar rats were divided into eight groups: sham operated and ovariectomized rats that received either standard diet, high fat diet, or high fat diet supplemented with cereal selenized onion biscuits or high fat diet together with introduction of physical exercise of animals. Results High fat diet significantly increased TBARS content in the liver compared to standard diet (P = 0.032, P = 0.030). Furthermore, high fat diet decreased the activities of CAT, GR, and GST, as well as the content of GSH (P < 0.050). GPx activity remained unchanged in all groups. Physical activity and consumption of cereal selenized onion biscuits showed protective effect through increased GR activity in sham operated rats (P = 0.026, P = 0.009), while in ovariectomized group CAT activity was increased (P = 0.018) in rats that received cereal selenized onion biscuits. Conclusion Feeding rats with high fat diet was accompanied by decreased antioxidative enzyme activities and increased lipid peroxidation. Bioactive compounds of cereal selenized onion biscuits showed potential to attenuate the adverse impact of high fat diet on antioxidative status.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Elizabeta Has-Schön
- Elizabeta Has-Schön, Department of Biology, Cara Hadrijana 8/A, 31000 Osijek, Croatia,
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Cruz-Garcia L, Schlegel A. Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids. J Lipid Res 2014; 55:1944-58. [PMID: 25030662 DOI: 10.1194/jlr.m052845] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot.
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Affiliation(s)
- Lourdes Cruz-Garcia
- University of Utah Molecular Medicine (U2M2) Program,University of Utah, Salt Lake City, UT 84112 Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes,University of Utah, Salt Lake City, UT 84112
| | - Amnon Schlegel
- University of Utah Molecular Medicine (U2M2) Program,University of Utah, Salt Lake City, UT 84112 Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes,University of Utah, Salt Lake City, UT 84112 Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, UT 84112
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