Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that have been associated with an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Insulin resistance and ...central obesity are the key components of MetS, ultimately leading to liver fat accumulation and the subsequent development of necroinflammatory liver injury. However, the origin and nature of the metabolic stressors responsible for stimulating the progression of simple steatosis to nonalcoholic steatohepatitis (NASH) remain to be clearly identified. In addition, epidemiologic research on the association between MetS and NAFLD has provided only limited information to guide the development of targeted interventions, in particular, nutrition and pharmacologic prevention programs. This review summarizes the evidence supporting the proposal that NAFLD is not invariably associated with the presence of MetS, and mechanisms other than insulin resistance may contribute to the chronic inflammatory processes that underpin the development of liver fat accumulation and the subsequent architectural distortion of the liver. A special focus is given to increased hemoglobin as a risk factor for the development of NAFLD in the absence of MetS.
The study variables, comprising demographic and laboratory data along with liver biopsy examinations, were sourced from the Turkish NAFLD Biobank electronic database maintained by the Marmara ...University Institute of Gastroenterology. Additionally, 541 (80.3%) had elevated high density lipoprotein (HDL) levels or were on lipid-lowering treatment, while 655 (96.6%) had a BMI greater than or equal to 25 kg/m2 or had an increased sex-specific waist circumference of more than 94/80 cm, with 651 (96%) for greater than or equal to 95/91 cm. ...421 (62.1%) patients exhibited increased blood pressure levels or were undergoing antihypertensive treatment, and 513 (75.7%) had elevated triglyceride levels or were on lipid-lowering therapy. ...we found that the MAFLD and MASLD criteria identify a similar population to NAFLD, but MASLD appears to accommodate a larger number of patients with biopsy-proven NAFLD. Ethics approval The study protocol adhered to the ethical guidelines set forth in the Declaration of Helsinki and received approval from the Medical Ethics Committee of Marmara University School of Medicine (protocol No. 09.2018.086).
Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the ...clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
Non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of fat within the cytoplasm of hepatocytes (exceeding 5% of liver weight) in individuals without significant ...alcohol consumption, has rapidly evolved into a pressing global health issue, affecting approximately 25% of the world population. This condition, closely associated with obesity, type 2 diabetes, and the metabolic syndrome, encompasses a spectrum of liver disorders ranging from simple steatosis without inflammation to non-alcoholic steatohepatitis (NASH) and cirrhotic liver disease. Recent research has illuminated the complex interplay between metabolic and immune responses in the pathogenesis of NASH, underscoring the critical role played by T and B lymphocytes. These immune cells not only contribute to necroinflammatory changes in hepatic lobules but may also drive the onset and progression of liver fibrosis. This narrative review aims to provide a comprehensive exploration of the effector mechanisms employed by T cells, B cells, and their respective subpopulations in the pathogenesis of NASH. Understanding the immunological complexity of NASH holds profound implications for the development of targeted immunotherapeutic strategies to combat this increasingly prevalent and burdensome metabolic liver disease.
The exclusion of other chronic liver diseases including “excess” alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). ...However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, “positive criteria” to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward.
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide – with an estimated global prevalence of 37%. Different from nonalcoholic fatty liver ...disease (NAFLD), which is an exclusion diagnosis, MAFLD is defined by a set of positive criteria. This recent change in terminology is challenging because MAFLD and NAFLD denote two similar, albeit not identical, clinical populations. When the diagnostic criteria for MAFLD are applied, liver histology appears more severe and clinical outcomes are less favorable. However, the clinical management of MAFLD and NAFLD remains similar. While liver biopsy is still the reference standard for achieving a final diagnosis, noninvasive imaging- or biomarker-based diagnostic modalities are currently gaining momentum. However, liver biopsy should be recommended when diagnostic challenges exist. In this review, we compared the epidemiology, natural history, and diagnosis of MAFLD with respect to the traditional NAFLD definition.
The term non-alcoholic fatty liver disease (NAFLD) comprises at least four pathological entities (definite nonalcoholic steatohepatitis NASH, borderline "zone 3" pattern, borderline "zone 1" pattern, ...not steatohepatitis with steatosis) with distinct patterns of lipid storage, fibrosis, and hepatocyte injury. Recent pathophysiological advances hold promise to provide much needed surrogate non-invasive biomarkers to detect steatohepatitis, fibrosis, and monitor NASH progression (or resolution, in the setting of clinical trials) without the cumbersome use of liver biopsy. Herein, we reviewed the current status of multimodal biomarker candidates derived from biochemical and genetic studies of NASH, as well as potential markers derived from imaging studies. A literature search was conducted in March 2013 on PubMed, Ovid Embase, Ovid Medline and Scopus using the following search terms: steatosis, non-alcoholic steatohepatitis, biomarker, genetics, imaging, clinical trials. Rather than to biopsy, the identification of steatohepatitis and fibrosis may originate primarily from prespecified multimodal biomarker data, including positive findings on serum or genetic biomarkers, and imaging tests like MR elastography or Fibroscan. In the setting of clinical trials, it seems recommendable to widen and expand the therapeutic vision beyond insulin resistance and focus on trials in very early NASH stages. The paradigm shift towards an earlier noninvasive characterization and diagnosis of NASH and fibrosis will be crucial to redefine and establish successful interventional trials.
Proteomic platforms have gained increasing attention in the clinical spectrum of nonalcoholic fatty liver disease (NAFLD). This approach allows for the unbiased discovery of circulating biochemical ...markers, i.e., it is not limited to known molecules of presumed importance. This manuscript provides an overview of proteomic serum biomarker discovery in NAFLD. Hemoglobin is currently the most widely replicated proteomic circulating biomarker of NAFLD; it was identified as a biomarker of fatty liver in two distinct proteomic studies and subsequently validated using distinct analytical methods by independent research groups in large replication cohorts. Given the increasing availability of numerous serum samples and the refinement of the technological platforms available to scrutinize the blood proteome, large collaborative studies between academia and industry are warmly encouraged to identify novel, unbiased circulating biomarkers of NAFLD.
► Proteomics enables an unbiased discovery approach to identify circulating biochemical markers. ► Proteomic data should always be validated using distinct analytical methods. ► Hemoglobin is the most reliable proteomic marker of nonalcoholic fatty liver disease.
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