Project description:In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including "lean NAFLD" has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.
Project description:Despite its increasing prevalence, nonalcoholic fatty liver disease (NAFLD) remains under-diagnosed in primary care. Timely diagnosis is critical, as NAFLD can progress to nonalcoholic steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and death; furthermore, NAFLD is also a risk factor linked to cardiometabolic outcomes. Identifying patients with NAFLD, and particularly those at risk of advanced fibrosis, is important so that healthcare practitioners can optimize care delivery in an effort to prevent disease progression. This review debates the practical issues that primary care physicians encounter when managing NAFLD, using a patient case study to illustrate the challenges and decisions that physicians face. It explores the pros and cons of different diagnostic strategies and tools that physicians can adopt in primary care settings, depending on how NAFLD presents and progresses. We discuss the importance of prescribing lifestyle changes to achieve weight loss and mitigate disease progression. A diagnostic and management flow chart is provided, showing the key points of assessment for primary care physicians. The advantages and disadvantages of advanced fibrosis risk assessments in primary care settings and the factors that influence patient referral to a hepatologist are also reviewed.
Project description:Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed.
Project description:Obesity is recognized as a chronic disease and one of the major healthcare challenges facing us today. Weight loss can be achieved via lifestyle, pharmacological and surgical interventions, but weight maintenance remains a lifetime challenge for individuals with obesity. Guidelines for the management of obesity have highlighted the role of primary care providers (PCPs). This review examines the long-term outcomes of clinical trials to identify effective weight maintenance strategies that can be utilized by PCPs. Because of the broad nature of the topic, a structured PubMed search was conducted to identify relevant research articles, peer-reviewed reviews, guidelines and articles published by regulatory bodies. Trials have demonstrated the benefit of sustained weight loss in managing obesity and its comorbidities. Maintaining 5-10% weight loss for ?1 year is known to ameliorate many comorbidities. Weight maintenance with lifestyle modification - although challenging - is possible but requires long-term support to reinforce diet, physical activity and behavioural changes. The addition of pharmacotherapy to lifestyle interventions promotes greater and more sustained weight loss. Clinical evidence and recently approved pharmacotherapy has given PCPs improved strategies to support their patients with maintenance of weight loss. Further studies are needed to assess the translation of these strategies into clinical practice.
Project description:Nonalcoholic fatty liver disease (NAFLD) accounts for most cases of chronic liver disease worldwide, with an estimated global prevalence of approximately 25% and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. NAFLD is strongly connected to metabolic syndrome, and for many years, fatty liver was considered to be an exclusive feature of obese patients. However, recent studies have highlighted the presence of NAFLD in non-obese subjects, with or without increased visceral fat or even in lean subjects without increased waist circumference. "Lean NAFLD" is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology, prognosis and management compared with NAFLD in overweight/obese patients. In the present editorial, we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries. Moreover, we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population. Finally, we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and non-lean cohorts.
Project description:Nonalcoholic fatty liver disease is associated with hepatic insulin resistance and may result primarily from increased hepatic de novo lipogenesis (PRIM) or secondarily from adipose tissue lipolysis (SEC). We studied mice with hepatocyte- or adipocyte-specific SREBP-1c overexpression as models of PRIM and SEC. PRIM mice featured increased lipogenic gene expression in the liver and adipose tissue. Their selective, liver-specific insulin resistance was associated with increased C18:1-diacylglycerol content and protein kinase Cε translocation. SEC mice had decreased lipogenesis mediated by hepatic cholesterol responsive element-binding protein and featured portal/lobular inflammation along with total, whole-body insulin resistance. Hepatic mitochondrial respiration transiently increased and declined with aging along with higher muscle reactive oxygen species production. In conclusion, hepatic insulin resistance originates from lipotoxicity but not from lower mitochondrial capacity, which can even transiently adapt to increased peripheral lipolysis. Peripheral insulin resistance is prevented during increased hepatic lipogenesis only if adipose tissue lipid storage capacity is preserved.
Project description:The increasing burden of nonalcoholic fatty liver disease (NAFLD) requires innovative management strategies, but an effective pharmacological agent has yet to be found. Apart from weight loss and lifestyle adjustments, one isomer of the vitamin E family-alpha-tocopherol-is currently recommended for nondiabetic steatohepatitis patients. Another member of the vitamin E family, tocotrienol (T3), has anti-inflammatory and antioxidant properties that reach beyond those of alpha-tocopherol, making it a potential agent for use in NAFLD management. This systematic review aimed to provide an overview of the effects of T3 supplementation on NAFLD from both clinical and preclinical perspectives. A literature search was performed in October 2022 using PubMed, Scopus and Web of Science. Original research articles reporting NAFLD outcomes were included in this review. The search located 12 articles (8 animal studies and 4 human studies). The literature reports state that T3 isomers or natural mixtures (derived from palm or annatto) improved NAFLD outcomes (liver histology, ultrasound or liver profile). However, the improvement depended on the severity of NAFLD, study period and type of intervention (isomers/mixture of different compositions). Mechanistically, T3 improved lipid metabolism and prevented liver steatosis, and reduced mitochondrial and endoplasmic reticulum stress, inflammation and ultimately liver fibrosis. In summary, T3 could be a potential agent for use in managing NAFLD, pending more comprehensive preclinical and human studies.
Project description:Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of insulin resistance, which is the hallmark of type 2 diabetes (T2D). NAFLD is a known risk factor for developing T2D and has a very high prevalence in those with existing T2D. The diabetes spectrum includes several conditions from prediabetes to T2D to insulin-dependent diabetes leading to macrovascular and microvascular complications. Similarly, NAFLD has a histologic spectrum that ranges from the relatively benign nonalcoholic fatty liver to the aggressive form of nonalcoholic steatohepatitis with or without liver fibrosis to nonalcoholic steatohepatitis-cirrhosis leading to end-stage liver disease. The management of T2D has witnessed significant changes over the past few decades with multiple new drug classes entering the treatment algorithm. Unfortunately, there are no U.S. Food and Drug Administration-approved medications to treat NAFLD, and guidelines for the management of NAFLD are less established. However, the field of drug development in NAFLD has witnessed a revolution over the past 5 years with the establishment of a regulatory pathway for Food and Drug Administration approval; this has generated substantial interest from pharmaceutical companies. Several diabetes medications have been studied as potential treatments for NAFLD with promising results; moreover, drugs that target specific pathways that play a role in NAFLD development and progression are being developed at a rapid pace. Given the similarities between NAFLD and T2D in terms of pathogenesis, underlying risk factors, and disease spectrum, lessons learned from optimizing treatment for T2D can be extrapolated to the management of NAFLD. The aim of this review is to use the founding principles of the comprehensive type 2 diabetes management algorithm to optimize the management of NAFLD. (Hepatology Communications 2018;2:778-785).