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Ntikoudi A, Spyrou A, Evangelou E, Dokoutsidou E, Mastorakos G. The Effect of Menopausal Status, Insulin Resistance and Body Mass Index on the Prevalence of Non-Alcoholic Fatty Liver Disease. Healthcare (Basel) 2024; 12:1081. [PMID: 38891156 PMCID: PMC11171981 DOI: 10.3390/healthcare12111081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/04/2024] [Accepted: 05/09/2024] [Indexed: 06/21/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is common and presents in a large proportion-up to 30%-of the global adult female population. Several factors have been linked with NAFLD in women, such as age, obesity, and metabolic syndrome. To extract appropriate details about the topic, we conducted an extensive search using various medical subject headings and entry terms including 'Menopause', 'Non-alcoholic fatty liver disease', 'Insulin resistance', and 'BMI'. This exhaustive search resulted in a total of 180 studies, among which only 19 were able to meet the inclusion criteria. While most of these studies indicated a significant rise in NAFLD prevalence among postmenopausal women, two did not find strong evidence linking menopause with NAFLD. Moreover, it was observed that women with NAFLD had higher insulin resistance levels and BMIs compared to those without the condition. In summary, it is important to consider specific factors like risk profile, hormonal status, and age along with metabolic components when treating women presenting with NAFLD. There is need for data-driven research on how gender affects the sensitivity of biomarkers towards NAFLD as well as the development of sex-specific prediction models-this would help personalize management approaches for women, who stand to benefit greatly from such tailored interventions.
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Affiliation(s)
- Anastasia Ntikoudi
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - Alketa Spyrou
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - Eleni Evangelou
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - Eleni Dokoutsidou
- Department of Nursing, University of West Attica, 12243 Athens, Greece; (A.S.); (E.E.); (E.D.)
| | - George Mastorakos
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, 11528 Athens, Greece;
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Akambase JA, Prieto JE, Mattos AZ, Mattos AA, Carrera E, Díaz-Ferrer J, Gallardo P, Curia A, Ballerga EG, Tovo CV, Balderramo D, Debes JD. Epidemiology and risk factors for histopathologic characteristics of non-alcoholic fatty liver disease in South America. Aliment Pharmacol Ther 2023; 58:526-536. [PMID: 37349900 DOI: 10.1111/apt.17615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 06/02/2023] [Accepted: 06/02/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND The burden of non-alcoholic fatty liver disease (NAFLD) in South America is among the highest in the world. However, the epidemiology and risk factors for NAFLD are insufficiently described in the region. AIM To explore the associations between clinical characteristics and histopathological features of NAFLD METHODS: This was a descriptive study of 2722 patients with NAFLD from 8 medical centres across 5 South American countries. We collected clinical, biochemical and histopathological data using a templated chart. Fibrosis was assessed by elastography or fibrosis scores and confirmed with biopsy when available. We examined associations between histopathological features and clinical characteristics with logistic regression models. Models were adjusted for country, age and sex. RESULTS The median age was 53 years (IQR: 41-62), and 63% were women. Subjects from Brazil had the highest body mass index at 42 kg/m2 . Sixty-seven percent had dyslipidemia, 46% had obesity, 30% had hypertension, 17% had type 2 diabetes mellitus (T2DM) and 34% had metabolic syndrome. Biopsy reports were available for 948 (35%), of which 58% showed fibrosis, 91% steatosis and 65% inflammation; 25% showed significant fibrosis and 27% severe steatosis. Metabolic syndrome, T2DM and hypertension were significantly associated with significant fibrosis (OR = 1.94, p < 0.001; OR = 2.93, p < 0.001 and OR = 1.60, p = 0.003, respectively), severe steatosis (OR = 2.05, p < 0.001; OR = 1.91, p = 0.001 and OR = 2.17, p < 0.001, respectively) and liver inflammation (OR = 1.66, p = 0.007; OR = 2.00, p = 0.002; OR = 1.62, p = 0.001, respectively). CONCLUSIONS In the largest NAFLD cohort study to date from South America, metabolic syndrome, hypertension and T2DM were independently associated with significant fibrosis, severe steatosis, and inflammation. The prevalence of T2DM was lower than the reported global prevalence.
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Affiliation(s)
- Joseph A Akambase
- Division of Epidemiology and Community Health, School of Medicine, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
- Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA
| | - Jhon E Prieto
- Centro de Enfermedades Hepáticas y Digestivas, Bogotá, Colombia
| | - Angelo Z Mattos
- Graduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Angelo A Mattos
- Graduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Enrique Carrera
- Departamento de Gastroenterología y Hepatología, Hospital Eugenio Espejo, Quito, Ecuador
| | - Javier Díaz-Ferrer
- Department of Gastroenterology, Hospital Nacional Edgardo Rebagliati Martins, HNERM, Lima, Peru
| | | | - Andrea Curia
- División Gastroenterology, Hospital de Clínicas José de San Martín - UBA, Buenos Aires, Argentina
| | - Esteban G Ballerga
- División Gastroenterology, Hospital de Clínicas José de San Martín - UBA, Buenos Aires, Argentina
| | - Cristiane V Tovo
- Graduate Program in Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Domingo Balderramo
- Departamento de Gastroenterología, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Jose D Debes
- Division of Epidemiology and Community Health, School of Medicine, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
- Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA
- Department of Medicine, University of MInnesota, Minneapolis, United States
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Tang Z, Ding Y, Zhang R, Zhang M, Guan Q, Zhang L, Wang H, Chen Y, Jiang R, Zhang W, Wang J. Genetic polymorphisms of Ca 2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease. Front Endocrinol (Lausanne) 2023; 13:1056283. [PMID: 36686460 PMCID: PMC9846251 DOI: 10.3389/fendo.2022.1056283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/13/2022] [Indexed: 01/05/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is recognized to be closely associated with endoplasmic reticulum stress and mitochondrial dysfunction, while previous studies have emphasized the important role of calcium homeostasis from the mitochondria-associated endoplasmic reticulum membrane (MAM) in the endoplasmic reticulum and mitochondria. This article will assess the association between genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in MAM and NAFLD risk. Methods A case-control study was conducted in a community of Nanjing, China during April to December 2020. 2701 subjects were enrolled and genotyped for 6 genetic variants in HSPA5 and ITPR2 genes. Logistic regression analysis was used to assess impact of these variants on NAFLD risk. Results After adjusting for age, gender, total cholesterol and glucose, we identified that HSPA5 rs12009 variant genotypes (recessive model: OR= 0.801, 95% CI= 0.652-0.986, P= 0.036), rs430397 variant genotypes (recessive model: OR= 0.546, 95% CI= 0.314-0.950, P= 0.032), and ITPR2 rs11048570 variant genotypes (recessive model: OR= 0.673, 95% CI= 0.453-0.999, P= 0.049) were associated with a reduced risk of NAFLD. Multivariate stepwise regression analysis indicated that gender, glucose, body mass index, triglycerides and favorable alleles were independent influencers of NAFLD (all P< 0.05). The area under the receiver operating characteristic curve was 0.764 (95% CI= 0.745-0.783, P< 0.001). Conclusion The variant genotypes of Ca2+ transport-associated genes HSPA5 (rs12009 and rs430397) and ITPR2 (rs11048570) might contribute to the reduction of the NAFLD risk in Chinese Han population, which can provide new insight into NAFLD pathogenesis.
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Affiliation(s)
- Zongzhe Tang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Yajie Ding
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Ru Zhang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Mengting Zhang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Qing Guan
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Liuxin Zhang
- Department of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Hongliang Wang
- Department of General Practice, Ninghai Road Community Health Service Center, Nanjing, China
| | - Yue Chen
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Rong Jiang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Wei Zhang
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Jie Wang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
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Rojas YAO, Cuellar CLV, Barrón KMA, Arab JP, Miranda AL. Non-alcoholic fatty liver disease prevalence in Latin America: A systematic review and meta-analysis. Ann Hepatol 2022; 27:100706. [PMID: 35427804 DOI: 10.1016/j.aohep.2022.100706] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/29/2022] [Accepted: 03/30/2022] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) produces high morbidity and mortality rates. Its worldwide prevalence is 25%, but evidence from Latin America (LA) is lacking. We aimed to estimate the prevalence of NAFLD in the adult population of LA. We conducted a systematic review and meta-analysis. Data were collected from OVID, Cochrane Library and LILACS search engines. We used terms related to NAFLD and LA countries. Observational studies in adults who were born and live in LA were included. Two reviewers evaluated the articles, extracted data and assessed the risk of bias. Discrepancies were resolved by consensus or by a third reviewer. A validated tool was used to assess risk of bias. We found and analyzed 19 articles (n=5625). The prevalence in the general and captive population found was 24%. Populations with type 2 diabetes mellitus or obesity had a higher mean prevalence that reached 68%. We concluded that the average prevalence of NAFLD in LA is around 24%. Among high-risk groups, this value increases to 68%. Further studies in the general population using appropriate designs are required for an accurate estimate of the prevalence of NAFLD in LA.
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Affiliation(s)
| | | | | | - Juan Pablo Arab
- Department of Gastroenterology, School of Medicine at Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Adelina Lozano Miranda
- Liver unit, Department of Gastroenterology at Hospital Nacional Arzobispo Loayza, Lima, Peru
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Akter S. Non-alcoholic Fatty Liver Disease and Steatohepatitis: Risk Factors and Pathophysiology. Middle East J Dig Dis 2022; 14:167-181. [PMID: 36619154 PMCID: PMC9489315 DOI: 10.34172/mejdd.2022.270] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 01/20/2022] [Indexed: 01/11/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and its progressive subtype non-alcoholic steatohepatitis (NASH) are the most prevalent liver diseases, often leading to hepatocellular carcinoma (HCC). This review aims to describe the present knowledge of the risk factors responsible for the development of NAFLD and NASH. I performed a literature review identifying studies focusing on the complex pathogenic pathway and risk factors of NAFLD and steatohepatitis. The relationship between NAFLD and metabolic syndrome is well established and widely recognized. Obesity, dyslipidemia, type 2 diabetes, hypertension, and insulin resistance are the most common risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly suggests obesity and type 2 diabetes as risk factors of NASH and HCC. However, other elements, namely gender divergences, ethnicity, genetic factors, participation of innate immune system, oxidative stress, apoptotic pathways, and adipocytokines, take a leading role in the onset and promotion of NAFLD. Pathophysiological mechanisms that are responsible for NAFLD development and subsequent progression to NASH are insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell (HSC) activation, cytokine/adipokine signaling pathways, and genetic and environmental factors. Major pathophysiological findings of NAFLD are dysfunction of adipose tissue through the enhanced flow of free fatty acids (FFAs) and release of adipokines, and altered gut microbiome that generate proinflammatory signals and cause NASH progression. Understanding the pathophysiology and risk factors of NAFLD and NASH; this review could provide insight into the development of therapeutic strategies and useful diagnostic tools.
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Affiliation(s)
- Sharmin Akter
- Department of Physiology, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh,Corresponding Author: Sharmin Akter, PhD Department of Physiology, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh Tel: +0088-091-67401-6 (ext. 6320) Fax: + 880 91 61510
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El Jamaly H, Eslick GD, Weltman M. Systematic review with meta-analysis: Non-alcoholic fatty liver disease and the association with pregnancy outcomes. Clin Mol Hepatol 2022; 28:52-66. [PMID: 34530527 PMCID: PMC8755467 DOI: 10.3350/cmh.2021.0205] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND/AIMS Maternal and fetal outcomes in pregnant patients with Non-alcoholic fatty liver disease (NAFLD) have been largely unexplored. To determine the level of evidence associated with maternal and fetal outcomes in pregnant women with NAFLD. METHODS We conducted a comprehensive literature search. The studies included pregnant patients with a previous, current or subsequent diagnosis of NAFLD. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI). RESULTS Twenty-two studies, with 13,641 female NAFLD patients were reviewed. The results highlight that NAFLD patients had a statistically significant increased likelihood of baseline diabetes mellitus (OR, 6.00; 95% CI, 2.21-16.31; P<0.001; n=7), baseline Hypertension (OR, 3.75; 95% CI, 2.13-6.59; P<0.001; n=4), gestational hypertension (OR, 1.83; 95% CI, 1.03-3.26; P=0.041; n=2), and pre-eclampsia (OR, 2.43; 95% CI, 1.46-4.04; P=0.001; n=3). The odds for a past and current history of gestational diabetes mellitus were OR, 3.78; 95% CI, 2.21-6.44; P<0.001; n=5 and OR, 3.23; 95% CI, 1.97- 5.31; P<0.001; n=6, respectively. As for fetal outcomes, pregnant NAFLD patients were significantly more likely to have a premature birth (OR, 2.02; 95% CI, 1.44-2.85; P<0.001; n=4), large for gestational age birth (OR, 2.01; 95% CI, 1.72-2.37; P<0.001; n=2) or a history of prior miscarriage or abortion (OR, 1.15; 95% CI, 1.02-1.30; P=0.02; n=2). Egger's regression revealed no evidence of publication bias (P>0.05). CONCLUSION This meta-analysis provides pooled evidence that NAFLD is associated with a substantial increase in maternal diabetic and hypertensive complications and multiple adverse fetal outcomes. This data is important for clinicians managing these patients before, during and after pregnancy.
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Affiliation(s)
- Hydar El Jamaly
- Department of Gastroenterology and Hepatology, Nepean Hospital, Penrith, Australia
- Nepean Clinical School, The University of Sydney, Penrith, Australia
| | - Guy D Eslick
- The Centre for Digestive Health and Neurogastroenterology, Hunter Medical Research Institute, The University of Newcastle, Newcastle, Australia
| | - Martin Weltman
- Department of Gastroenterology and Hepatology, Nepean Hospital, Penrith, Australia
- Nepean Clinical School, The University of Sydney, Penrith, Australia
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Norouzpour M, Marandi SM, Ghanbarzadeh M, Zare Maivan A. The effect of combined exercises on the plasma levels of retinol-binding protein 4 and its relationship with insulin resistance and hepatic fat content in postmenopausal women with nonalcoholic fatty liver disease. J Sports Med Phys Fitness 2021; 62:684-690. [PMID: 33871240 DOI: 10.23736/s0022-4707.21.12233-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Evidence suggests increased serum levels of retinol-binding protein 4 (RBP4) in postmenopausal women with nonalcoholic fatty liver disease (NAFLD). This study investigated the effect of combined exercises on the plasma levels of RBP4 and its relationship with insulin resistance and hepatic fat content in these women. METHODS This quasi-experimental study randomly assigned 24 women with fatty liver and a mean age of 56.18±4.58 years to an experimental group and a control group. The experimental group participated in ten-week incremental endurance-resistance training as combined exercises three sessions a week. Fatty liver was diagnosed with ultrasound, RBP4 levels were measured and insulin resistance was determined using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Between-group data were analyzed using ANCOVA, within-group data using the dependent t-test and Wilcoxon test and relationships between RBP4 and variables using Spearman and Pearson correlation coefficients. RESULTS Ten weeks of combined exercises significantly decreased RBP4 levels (P=0.000), HOMA-IR (P=0.011) and hepatic fat levels (P=0.000) in the experimental group compared to in the controls. The posttest showed significant correlations between RBP4 levels and hepatic fat levels (P=0.002) and no correlations between RBP4 levels and insulin resistance (P=0.116). CONCLUSIONS Combined exercises significantly reduced serum levels of RBP4 in postmenopausal women with fatty liver. RBP4 was not related to insulin resistance and effects of RBP4 on hepatic fat regulation were independent of the effects of insulin resistance.
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Affiliation(s)
- Masoumeh Norouzpour
- Exercise Physiology Department, Sport Sciences Faculty, University of Isfahan, Isfahan, Iran
| | - Sayed M Marandi
- Exercise Physiology Department, Sport Sciences Faculty, University of Isfahan, Isfahan, Iran -
| | - Mohsen Ghanbarzadeh
- Exercise Physiology Department, Sport Sciences Faculty, Shahid Chamran University of Ahvaz, Ahvaz, Iran
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Venetsanaki V, Polyzos SA. Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives. Curr Vasc Pharmacol 2020; 17:546-555. [PMID: 29992886 DOI: 10.2174/1570161116666180711121949] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 06/05/2018] [Accepted: 06/14/2018] [Indexed: 02/06/2023]
Abstract
There is increasing evidence that menopause is associated with the progression and severity of non-alcoholic fatty liver disease (NAFLD). Estrogen deficiency worsens non-alcoholic steatohepatitis (NASH) in mice models with fatty liver. The prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women. Although more data are needed, lower serum estradiol levels are associated with NASH in postmenopausal women. Apart from estrogen deficiency, relative androgen excess and decrease in sex hormone-binding protein are observed in postmenopausal women. These hormonal changes seem to interplay with an increase in abdominal adipose mass, also observed in postmenopausal women, and aging, which are both closely related to the severity and progressive forms of NAFLD. NAFLD adds extra morbidity to postmenopausal women, possibly increasing the risk of type 2 diabetes mellitus and cardiovascular disease. Improving parameters of the metabolic syndrome via modifications in diet and physical exercise may reduce the risk of NAFLD and its related morbidity. Limited studies have shown a beneficial effect of hormone replacement therapy (HRT) on NAFLD, although adverse hepatic effects have been attributed to progesterone in one study. Phytoestrogens may be alternatives to HRT, but their long-term efficacy and safety remain to be shown. The aim of this review was to summarize evidence linking menopause with NAFLD with a special focus on potential therapeutic perspectives.
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Affiliation(s)
- Vasiliki Venetsanaki
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Jensen T, Wieland A, Cree-Green M, Nadeau K, Sullivan S. Clinical workup of fatty liver for the primary care provider. Postgrad Med 2018; 131:19-30. [PMID: 30496690 DOI: 10.1080/00325481.2019.1546532] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is quickly emerging as a global epidemic in parallel with the rise in obesity and the Metabolic Syndrome. NAFLD, once seen simply as a passive consequence of the Metabolic Syndrome (MetS), has been found to interact with other features of MetS to exacerbate insulin resistance, diabetes, and cardiovascular disease. NAFLD is also becoming the top indication for liver transplant and an important risk factor for hepatocellular carcinoma. Treatment of this disorder is limited mainly to lifestyle modifications to promote weight loss along with consideration for off-label use of certain medications, but recent progression in clinical trials means more effective treatments are on the horizon. Therefore, the primary care provider must be prepared to recognize and determine the severity of this disorder in order to optimize management. In this review, we will discuss risk factors for NAFLD, workup and differential, and finally, offer recommendations on screening.
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Affiliation(s)
- Thomas Jensen
- a Department of Endocrinology , University of Colorado School of Medicine , Aurora , CO , USA
| | - Amanda Wieland
- b Department of Hepatology , University of Colorado School of Medicine , Aurora , CO , USA
| | - Melanie Cree-Green
- c Department of Pediatric Endocrinology , University of Colorado School of Medicine , Aurora , CO , USA
| | - Kristen Nadeau
- c Department of Pediatric Endocrinology , University of Colorado School of Medicine , Aurora , CO , USA
| | - Shelby Sullivan
- d Department of Gastroenterology , University of Colorado Denver , Aurora , CO , USA
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Arshad T, Golabi P, Paik J, Mishra A, Younossi ZM. Prevalence of Nonalcoholic Fatty Liver Disease in the Female Population. Hepatol Commun 2018; 3:74-83. [PMID: 30619996 PMCID: PMC6312650 DOI: 10.1002/hep4.1285] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 10/22/2018] [Indexed: 12/22/2022] Open
Abstract
There is a paucity of recent data about the epidemiology and long‐term outcomes of nonalcoholic fatty liver disease (NAFLD) in the female population. Our aim was to assess the prevalence, risk factors, and mortality of NAFLD in female adults of the United States. Data from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999‐2014 were used. NAFLD status was determined by the U.S. Fatty Liver Index (US‐FLI) in the absence of other liver diseases and excessive alcohol consumption. The prevalence rates, risk factors, and 5‐year all‐cause and cardiovascular mortality were determined in women with NAFLD. The most recent prevalence of NAFLD among female adults (2007‐2014) in the United States was 24.4% (95% confidence interval [CI], 22.48‐26.33). Prevalence was higher among women >44 years of age and those with body mass index ≥30 kg/m2. In addition, the average age of the female population with NAFLD has decreased over time. The fully adjusted odds ratios in women with NAFLD compared to those without NAFLD were 1.48 (95% CI, 1.20‐1.82) for cardiovascular disease (CVD), 1.89 (95% CI, 1.42‐2.52) for atherosclerotic cardiovascular disease (ASCVD) score ≥7.5%, and 1.76 (95% CI, 1.37‐2.25) for either CVD or ASCVD ≥7.5%. The 5‐year mortality for female adults with NAFLD was significantly higher than for those without NAFLD (adjusted hazard ratio, 1.48; 95% CI, 1.07‐2.05). Among women with NAFLD, those with ASCVD ≥7.5% had significantly higher 5‐year all‐cause mortality and CVD mortality. Conclusion: The prevalence of NAFLD in female NHANES participants from the United States has continued over recent years. In the female population with NAFLD, ASCVD ≥7.5% is an independent predictor of overall and cardiac‐specific mortality. NAFLD is growing in the female population in the U.S. NAFLD is associated with metabolic risk factors and increases the risk of CVD and mortality. Detection of NAFLD in females consider a serious risk threat that needs to be addressed to potentially improve their long‐term outcomes.
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Affiliation(s)
- Tamoore Arshad
- Center for Liver Disease, Department of Medicine Inova Fairfax Hospital Falls Church VA
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
| | - James Paik
- Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
| | - Alita Mishra
- Center for Liver Disease, Department of Medicine Inova Fairfax Hospital Falls Church VA
| | - Zobair M Younossi
- Center for Liver Disease, Department of Medicine Inova Fairfax Hospital Falls Church VA.,Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
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Al-Dayyat HM, Rayyan YM, Tayyem RF. Non-alcoholic fatty liver disease and associated dietary and lifestyle risk factors. Diabetes Metab Syndr 2018; 12:569-575. [PMID: 29571977 DOI: 10.1016/j.dsx.2018.03.016] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 03/16/2018] [Indexed: 12/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide with a reported prevalence ranging 20-30% depending on the studied populations. The high prevalence of NAFLD is probably due to the contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle. NAFLD patients are at increased risk of cardiovascular and liver related mortality. The cornerstone of any treatment regimen for patients with NAFLD is lifestyle modification focused on weight loss, exercise, and improving insulin sensitivity. The purpose of this review is to outline the effect of diet and lifestyle factors on developing NAFLD.
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Affiliation(s)
- Hana'a Mahmoud Al-Dayyat
- Department of Nutrition and Food Technology, Faculty of Agriculture, The University of Jordan, Amman, Jordan
| | - Yaser Mohammed Rayyan
- Department of Gastroenterology & Hepatology, School of Medicine, The University of Jordan, Amman, Jordan
| | - Reema Fayez Tayyem
- Department of Nutrition and Food Technology, Faculty of Agriculture, The University of Jordan, Amman, Jordan.
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Cai H, Lu S, Chen Y, Das MBBS MRCOG S, Niu Z, Zhuo G, Lai L, Zhang Z. Serum retinol binding protein 4 and galectin-3 binding protein as novel markers for postmenopausal nonalcoholic fatty liver disease. Clin Biochem 2018; 56:95-101. [DOI: 10.1016/j.clinbiochem.2018.04.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Revised: 04/17/2018] [Accepted: 04/17/2018] [Indexed: 02/06/2023]
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13
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Xu M, Zheng XM, Jiang F, Qiu WQ. MicroRNA-190b regulates lipid metabolism and insulin sensitivity by targeting IGF-1 and ADAMTS9 in non-alcoholic fatty liver disease. J Cell Biochem 2018; 119:5864-5874. [PMID: 29575055 DOI: 10.1002/jcb.26776] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 02/02/2018] [Indexed: 01/09/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid accumulation and insulin resistance, yet the underlying molecular mechanisms are poorly understood. MiR-190b is thought to play a role in hepatocellular carcinoma by modulating insulin resistance; however, its role in NAFLD remains unknown. Here, we found that miR-190b expression was significantly increased in the liver tissues of patients with NAFLD, compared to normal tissues. Moreover, miR-190b was upregulated in a high-fat diet NAFLD mouse model and a free fatty acid-induced NAFLD cellular model. Knockdown of miR-190b decreased aspartate transaminase (AST), alanine transaminase (ALT), triglyceride (TG), and total cholesterol (TC). It also reduced expression of the lipogenic genes fatty acid synthase (FAS) and 3-hydroxy-3-methylglutarylCoA reductase (HMGCR), alleviated hepatic steatosis, improved glucose tolerance, elevated insulin sensitivity, and activated insulin receptor substrate (IRS)2/Akt signaling in vivo and/or in vitro. Furthermore, we confirmed that miR-190b directly targeted IGF-1 and ADAMTS9. MiR-190b overexpression suppressed expression of IGF-1 and ADAMTS9, which were increased by miR-190b inhibition. Expression of IGF-1 and ADAMTS9 was inversely correlated with miR-190b in liver tissues of patients with NAFLD, respectively. We also found that IGF-1 or ADAMTS9 inhibition partially reversed the effects of miR-190b on lipid metabolism and insulin signaling in vitro. Taken together, the data reveal that miR-190b inhibition suppressed lipid accumulation and improved insulin sensitivity by targeting IGF-1 and ADAMTS9, suggesting that miR-190b inhibition may be a therapeutic strategy against NAFLD.
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Affiliation(s)
- Min Xu
- Department of Medical laboratory, Zhumadian Central Hospital, Zhumadian, China
| | - Xi-Ming Zheng
- Department of Medical laboratory, Zhumadian Central Hospital, Zhumadian, China
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Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk. Adv Ther 2017; 34:1291-1326. [PMID: 28526997 PMCID: PMC5487879 DOI: 10.1007/s12325-017-0556-1] [Citation(s) in RCA: 394] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) spans steatosis through nonalcoholic steatohepatis, cirrhosis, and hepatocellular carcinoma (HCC) associated with striking systemic features and excess cardiovascular and liver-related mortality. The pathogenesis of NAFLD is complex and multifactorial. Endocrine derangements are closely linked with dysmetabolic traits. For example, in animal and human studies, female sex is protected from dysmetabolism thanks to young individuals' ability to partition fatty acids towards ketone body production rather than very low density lipoprotein (VLDL)-triacylglycerol, and to sex-specific browning of white adipose tissue. Ovarian senescence facilitates both the development of massive hepatic steatosis and the fibrotic progression of liver disease in an experimental overfed zebrafish model. Consistently, estrogen deficiency, by potentiating hepatic inflammatory changes, hastens the progression of disease in a dietary model of nonalcoholic steatohepatitis (NASH) developing in ovariectomized mice fed a high-fat diet. In humans, NAFLD more often affects men; and premenopausal women are equally protected from developing NAFLD as they are from cardiovascular disease. It would be expected that early menarche, definitely associated with estrogen activation, would produce protection against the risk of NAFLD. Nevertheless, it has been suggested that early menarche may confer an increased risk of NAFLD in adulthood, excess adiposity being the primary culprit of this association. Fertile age may be associated with more severe hepatocyte injury and inflammation, but also with a decreased risk of liver fibrosis compared to men and postmenopausal status. Later in life, ovarian senescence is strongly associated with severe steatosis and fibrosing NASH, which may occur in postmenopausal women. Estrogen deficiency is deemed to be responsible for these findings via the development of postmenopausal metabolic syndrome. Estrogen supplementation may at least theoretically protect from NAFLD development and progression, as suggested by some studies exploring the effect of hormonal replacement therapy on postmenopausal women, but the variable impact of different sex hormones in NAFLD (i.e., the pro-inflammatory effect of progesterone) should be carefully considered.
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Affiliation(s)
- Stefano Ballestri
- Azienda USL di Modena, Pavullo Hospital, Pavullo nel Frignano, Italy
| | - Fabio Nascimbeni
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandra Marrazzo
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Dante Romagnoli
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Amedeo Lonardo
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
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15
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Gonzales CA, Bacchetti P, Khalili M. Impact of gender and menopausal status on metabolic parameters in chronic hepatitis C infection. J Viral Hepat 2016; 23:232-9. [PMID: 26554398 PMCID: PMC4809676 DOI: 10.1111/jvh.12487] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 09/17/2015] [Indexed: 12/12/2022]
Abstract
Hepatitis C infection (HCV) and menopause are associated with insulin resistance (IR), and IR accelerates HCV-induced liver disease. The relationship between menopause and IR has not been studied in this population. This study aimed to assess the impact of menopause on IR and metabolic syndrome in HCV. One hundred and three (69 men, 16 premenopausal, 18 postmenopausal women) noncirrhotic, nondiabetic HCV-infected adults underwent IR measurement via steady-state plasma glucose during a 240-min insulin suppression test. Metabolic syndrome was defined by at least three of five standard laboratory/clinical criteria. The patient characteristics were as follows: mean age 48 years, waist circumference 94.4 ± 12.4 cm and 37.9% Caucasian. SSPG was higher in postmenopausal than premenopausal women or men (mean difference 18, 95% CI -41 to 76 and 35, 95% CI -3 to 72 mg/dL; respectively). After adjusting for waist circumference, female gender, nonwhite race and triglycerides were positively associated and high-density lipoprotein negatively associated with steady-state plasma glucose. Compared to men, both pre- (Coef 48, 95% CI 12-84) and postmenopausal women (Coef 49, 95% CI 17-82) had higher steady-state plasma glucose. Compared to premenopausal women, men (OR 2.0, 95% CI 0.38-10.2) and postmenopausal women (OR 2.9, 95% CI 0.46-18.8) had higher odds of metabolic syndrome, but this was statistically nonsignificant. Both liver inflammation (OR 7.9) and nonwhite race (OR 6.9) were associated with metabolic syndrome. We conclude that women are at inc-reased risk for IR in HCV. There may also be an increased risk of metabolic syndrome postmenopause. Along with lifestyle modification and weight loss, women with metabolic abnormalities represent an especially at-risk group warranting HCV treatment to prevent adverse metabolic outcomes.
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Affiliation(s)
- C A Gonzales
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - P Bacchetti
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
| | - M Khalili
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
- Liver Center, University of California San Francisco, San Francisco, CA, USA
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16
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Chung GE, Yim JY, Kim D, Lim SH, Yang JI, Kim YS, Yang SY, Kwak MS, Kim JS, Cho SH. The influence of metabolic factors for nonalcoholic Fatty liver disease in women. BIOMED RESEARCH INTERNATIONAL 2015; 2015:131528. [PMID: 25973422 PMCID: PMC4417996 DOI: 10.1155/2015/131528] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Revised: 03/27/2015] [Accepted: 03/29/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS Women after menopause have increased insulin resistance and visceral fat, which may increase the prevalence of nonalcoholic fatty liver disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly defined. In this study, we aimed to determine the risk factors for NAFLD in women. METHODS A retrospective cohort study was conducted. Women who underwent abdominal ultrasonography and blood sampling for routine health check-ups were recruited. RESULTS Among 1,423 subjects, 695 women (48.9%) were in a menopausal state. The prevalence of NAFLD was higher in postmenopausal women than in premenopausal women (27.2% versus 14.4%, P < 0.001). In premenopausal women, low HDL-cholesterol, central obesity, and homeostasis model assessment-estimated insulin resistance showed a significant association with the increased risk of NAFLD in multivariate analysis. In postmenopausal women, the presence of diabetes, triglyceridemia, and central obesity showed a significant association with the risk of NAFLD. The presence of menopause and hormone replacement therapy in postmenopausal women were not risk factors for NAFLD. CONCLUSIONS Our findings showed different metabolic factors for NAFLD in pre- and postmenopausal women. However, the key issues are the same: central obesity and insulin resistance. These results reemphasize the importance of metabolic factors irrespective of menopausal status in the pathogenesis of NAFLD in women.
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Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jeong Yoon Yim
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Donghee Kim
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seon Hee Lim
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jong In Yang
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Young Sun Kim
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sun Young Yang
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Min-Sun Kwak
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sang-Heon Cho
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul, Republic of Korea
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Tapan S, Sertoglu E, Kayadibi H, Uyanik M. Selection criteria for patients with non-alcoholic fatty liver disease and diabetes mellitus to achieve reliable results. Climacteric 2015; 18:329. [PMID: 25765619 DOI: 10.3109/13697137.2014.974533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Serkan Tapan
- Gulhane School of Medicine, Department of Medical Biochemistry , Ankara ;
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Wang XC, Gusdon AM, Liu H, Qu S. Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation. World J Gastroenterol 2014; 20:14821-14830. [PMID: 25356042 PMCID: PMC4209545 DOI: 10.3748/wjg.v20.i40.14821] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 05/14/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials.
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