Nonalcoholic Fatty Liver Disease Risk Factors in Latin American Populations: Current Scenario and Perspectives.
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ABSTRACT:
SUBMITTER: Pinto Marques Souza de Oliveira C
PROVIDER: S-EPMC6465959 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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Nonalcoholic Fatty Liver Disease Risk Factors in Latin American Populations: Current Scenario and Perspectives.
Pinto Marques Souza de Oliveira Claudia C Pinchemel Cotrim Helma H Arrese Marco M
Clinical liver disease 20190201 2
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Project description:Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease due to an increase in the prevalence of obesity. The development of NASH leads to an increase in morbidity and mortality. While the first line of treatment is lifestyle modifications, including dietary changes and increased physical activity, there are no approved pharmacological treatment agents for NAFLD and NASH currently. Due to its complex pathophysiology, different pathways are under investigation for drug development with the focus on metabolic pathways, inflammation, and slowing or reversing fibrosis. There are several agents advancing in clinical trials, and promising results have been seen with drugs that affect hepatic steatosis, inflammation, and fibrosis. This review will provide an overview on NAFLD and some of the mechanisms of disease that are being targeted with pharmacologic agents.
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Project description:High rates of excessive calorie intake diets and sedentary lifestyles have led to a global increase in nonalcoholic fatty liver disease (NAFLD). As a result, this condition has recently become one of the leading causes of hepatocellular carcinoma (HCC). Furthermore, the incidence of NAFLD-associated HCC (NAFLD-HCC) is expected to increase in the near future. Advanced liver fibrosis is the most common risk factor for NAFLD-HCC. However, up to 50% of NAFLD-HCC cases develop without underlying liver cirrhosis. Epidemiological studies have revealed many other risk factors for this condition; including diabetes, other metabolic traits, obesity, old age, male sex, Hispanic ethnicity, mild alcohol intake, and elevated liver enzymes. Specific gene variants, such as single-nucleotide polymorphisms of patatin-like phospholipase domain 3, transmembrane 6 superfamily member 2, and membrane-bound O-acyl-transferase domain-containing 7, are also associated with an increased risk of HCC in patients with NAFLD. This clinical and genetic information should be interpreted together for accurate risk prediction. Alpha-fetoprotein (AFP) is the only biomarker currently recommended for HCC screening. However, it is not sufficiently sensitive in addressing this diagnostic challenge. The GALAD score can be calculated based on sex, age, lectin-bound AFP, AFP, and des-carboxyprothrombin and is reported to show better diagnostic performance for HCC. In addition, emerging studies on genetic and epigenetic biomarkers have also yielded promising diagnostic potential. However, further research is needed to establish an effective surveillance program for the early diagnosis of NAFLD-HCC.
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Project description:Polycystic ovary syndrome (PCOS) is one of the most common reproductive, endocrine, and metabolic disorders in premenopausal women. Clinically, PCOS is mainly caused by androgen excess and ovarian dysfunction, manifested by anovulatory menstrual cycles, infertility, and hirsutism. In addition, PCOS increases the risk of insulin resistance, obesity, cardiovascular disease, anxiety and depression, dyslipidemia, and endometrial cancer. Nonalcoholic fatty liver disease (NAFLD) is defined as ≥5% fat accumulation in the liver in the absence of remaining secondary causes and has become one of the most common chronic liver diseases worldwide. The prevalence of NAFLD is significantly higher and more severe in women with PCOS, and its pathogenesis can be associated with various risk factors such as hyperandrogenemia, insulin resistance, obesity, chronic low-grade inflammation, and genetic factors. Although there is no definitive solution for the management of NAFLD in PCOS, some progress has been made. Lifestyle modification should be the basis of management, and drugs to improve metabolism, such as insulin sensitizers and glucagon-like peptide-1 agonists, may show better efficacy. Bariatric surgery may also be a treatment of NAFLD in obese women with PCOS. This paper reviews three aspects of prevalence, risk factors, and management, in order to better understand the current state of research on NAFLD in PCOS, to explore the pathogenesis of NAFLD in PCOS, and to encourage further research on the application of drugs in this field.
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Project description:BackgroundThe prevalence and incidence of youth-onset nonalcoholic fatty liver disease (NAFLD) far exceeds other paediatric chronic liver diseases and represents a considerable public health issue globally.MethodsHere, we performed a narrative review of current knowledge regarding the epidemiology of paediatric NAFLD, selected concepts in pathogenesis, comorbidities, diagnosis, and management, and issues related to the transition to adulthood.ResultsPaediatric NAFLD has become increasingly more prevalent, especially in certain subgroups, such as children with obesity and certain races/ethnicities. The pathophysiology of paediatric NAFLD is complex and multifactorial, driven by an interaction of environmental and genetic factors. Once developed, NAFLD in childhood is associated with type 2 diabetes, hypertension, increased cardiovascular disease risk, and end-stage liver disease. This predicts an increased burden of morbidity and mortality in adolescents and young adults. Early screening and diagnosis are therefore crucial, and the development of noninvasive biomarkers remains an active area of investigation. Currently, treatment strategies are focused on lifestyle changes, but there is also research interest in pharmacological and surgical options. In the transition from paediatric to adult care, there are several potential challenges/barriers to treatment and research is needed to understand how best to support patients during this time.ConclusionsOur understanding of the epidemiology and pathophysiology of paediatric NAFLD has increased considerably over recent decades, but several critical knowledge gaps remain and must be addressed in order to better mitigate the short-term and long-term risks of youth-onset NAFLD.
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Project description:Latin American populations may present patterns of sociodemographic, ethnic and cultural diversity that can defy current universal models of healthy aging. The potential combination of risk factors that influence aging across populations in Latin American and Caribbean (LAC) countries is unknown. Compared to other regions where classical factors such as age and sex drive healthy aging, higher disparity-related factors and between-country variability could influence healthy aging in LAC countries. We investigated the combined impact of social determinants of health (SDH), lifestyle factors, cardiometabolic factors, mental health symptoms and demographics (age, sex) on healthy aging (cognition and functional ability) across LAC countries with different levels of socioeconomic development using cross-sectional and longitudinal machine learning models (n = 44,394 participants). Risk factors associated with social and health disparities, including SDH (β > 0.3), mental health (β > 0.6) and cardiometabolic risks (β > 0.22), significantly influenced healthy aging more than age and sex (with null or smaller effects: β < 0.2). These heterogeneous patterns were more pronounced in low-income to middle-income LAC countries compared to high-income LAC countries (cross-sectional comparisons), and in an upper-income to middle-income LAC country, Costa Rica, compared to China, a non-upper-income to middle-income LAC country (longitudinal comparisons). These inequity-associated and region-specific patterns inform national risk assessments of healthy aging in LAC countries and regionally tailored public health interventions.
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Project description:Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.
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Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, with a global prevalence estimated at approximately 25%. NAFLD is also the leading cause of liver cirrhosis, hepatocellular carcinoma, and death. Additionally, the risk of cardiovascular disease increases with greater NAFLD severity. The liver- and cardiovascular disease-related mortality incident rate ratios among the NAFLD population were 0.77 and 4.79 per 1,000 person-years, respectively. We intend to discuss the risk factors associated with NAFLD in terms of development and progression. Obesity or higher body mass index is closely associated with NAFLD in a dose-dependent manner, but growing evidence suggests that central obesity plays a more important role in the development of NAFLD. Saturated fat and fructose have been reported to be closely related to NAFLD. Fructose intake promotes lipogenesis and impairs mitochondria fat oxidation. The presence of type 2 diabetes is the most powerful predictive risk factor for hepatic fibrosis in patients with NAFLD. Single nucleotide polymorphism is not only associated with the prevalence of NAFLD but also associated with increased liver disease mortality. Obstructive sleep apnea, intestinal dysbiosis, and sarcopenia are associated with the development of NAFLD.
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Project description:Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long-term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long-term outcomes, and patient-reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. CONCLUSION:Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361-371).
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Project description:Nonalcoholic fatty liver disease (NAFLD) is a continuum of liver abnormalities often starting as simple steatosis and to potentially progress into nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Because of its increasing prevalence, NAFLD is becoming a major public health concern, in parallel with a worldwide increase in the recurrence rate of diabetes and metabolic syndrome. It has been estimated that NASH cirrhosis may surpass viral hepatitis C and become the leading indication for liver transplantation in the next decades. The broadening of the knowledge about NASH pathogenesis and progression is of pivotal importance for the discovery of new targeted and more effective therapies; aim of this review is to offer a comprehensive and updated overview on NAFLD and NASH pathogenesis, the most recommended treatments, drugs under development and new drug targets. The most relevant in vitro and in vivo models of NAFLD and NASH will be also reviewed, as well as the main molecular pathways involved in NAFLD and NASH development.
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Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries with almost 25% affected adults worldwide. The growing public health burden is getting evident when considering that NAFLD-related liver transplantations are predicted to almost double within the next 20 years. Typically, hepatic alterations start with simple steatosis, which easily progresses to more advanced stages such as nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. This course of disease finally leads to end-stage liver disease such as hepatocellular carcinoma, which is associated with increased morbidity and mortality. Although clinical trials show promising results, there is actually no pharmacological agent approved to treat NASH. Another important problem associated with NASH is that presently the liver biopsy is still the gold standard in diagnosis and for disease staging and grading. Because of its invasiveness, this technique is not well accepted by patients and the method is prone to sampling error. Therefore, an urgent need exists to find reliable, accurate and noninvasive biomarkers discriminating between different disease stages or to develop innovative imaging techniques to quantify steatosis.
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