Editorial: The broader aspects of non-alcoholic fatty liver disease in children.
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ABSTRACT:
SUBMITTER: Mandato C
PROVIDER: S-EPMC9583345 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Editorial: The broader aspects of non-alcoholic fatty liver disease in children.
Mandato Claudia C Miele Luca L Socha Piotr P Vajro Pietro P
Frontiers in pediatrics 20221006
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Project description:Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of about 25%. Incidence is increasing with rising levels of obesity, type 2 diabetes and the metabolic syndrome, and NAFLD is predicted to become the leading cause of cirrhosis requiring liver transplantation in the next decade. However, the cardiovascular disease is the most common cause of death and only a minority will develop fibrosis and liver-related complications. Therefore, it is imperative to identify patients with advanced disease using non-invasive markers of fibrosis, which include serology-based tests (eg NAFLD Fibrosis Score and ELF test) and imaging (eg transient elastography). This targets appropriate patients for referral to secondary care for additional investigations such as liver biopsy and specialist care. Lifestyle modification and weight loss remains the cornerstone of management, but we are about to enter a new era of promising pharmacotherapies for NASH and fibrosis.
| S-EPMC6334080 | biostudies-literature
Project description:In 2020, international consensus guidelines recommended the renaming of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD), supported by diagnostic criteria. MAFLD affects up to 25% of the global population. However, the rates of MAFLD are likely to be underestimated due to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. Within the next decade, MAFLD has been projected to become a major cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide, as well as the most common indication for liver transplantation in the US. This transition in terminology and clinical criteria may increase momentum and clinical evidence at multiple levels, including patient diagnosis, management, and care, and provide the basis for new research areas and clinical development for therapeutics. The diagnostic criteria for MAFLD are practical, simple, and superior to the existing NAFLD criteria for identifying patients at increased risk of developing progressive liver disease. This Editorial aims to present the historical evolution of the terminology for fatty liver disease and the advantages of diagnosis, patient management, and future research on MAFLD.
| S-EPMC8284081 | biostudies-literature
Project description:Background & aimsLittle is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography.MethodsWe performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ≥30 kg/m2 ). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included.ResultsApproximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78).ConclusionsIndividuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.
| S-EPMC6758911 | biostudies-literature
Project description:Glutathione is a tripeptide synthesized at cytosolic level, that exists in cells in a reduced form (thiol-reduced-GSH-) and in an oxidized form (disulfide-oxidized). The antioxidant function of GSH has led to speculation about its therapeutic role in numerous chronic diseases characterized by altered redox balance and reduced GSH levels, including, for instance, neurodegenerative disorders, cancer, and chronic liver diseases. Among these latter, non-alcoholic fatty liver disease (NAFLD), characterized by lipid accumulation in hepatocytes, in the absence of alcohol abuse or other steatogenic factors, is one of the most prevalent. The umbrella term NAFLD includes the pure liver fat accumulation, the so-called hepatic steatosis or non-alcoholic fatty liver, and the progressive form with inflammation, also known as non-alcoholic steatohepatitis, which is related to the increase in oxidative stress and reactive oxygen species, eventually leading to liver fibrosis. Although the pathogenetic role of oxidative stress in these diseases is well established, there is still limited evidence on the therapeutic role of GSH in such conditions. Hence, the aim of this review is to depict the current molecular and pharmacological knowledge on glutathione, focusing on the available studies related to its therapeutic activity in NAFLD.
| S-EPMC10075255 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and is related to fatal and non-fatal liver, metabolic, and cardiovascular complications. Its non-invasive diagnosis and effective treatment remain an unmet clinical need. NAFLD is a heterogeneous disease that is most commonly present in the context of metabolic syndrome and obesity, but not uncommonly, may also be present without metabolic abnormalities and in subjects with normal body mass index. Therefore, a more specific pathophysiology-based subcategorization of fatty liver disease (FLD) is needed to better understand, diagnose, and treat patients with FLD. A precision medicine approach for FLD is expected to improve patient care, decrease long-term disease outcomes, and develop better-targeted, more effective treatments. We present herein a precision medicine approach for FLD based on our recently proposed subcategorization, which includes the metabolic-associated FLD (MAFLD) (i.e., obesity-associated FLD (OAFLD), sarcopenia-associated FLD (SAFLD, and lipodystrophy-associated FLD (LAFLD)), genetics-associated FLD (GAFLD), FLD of multiple/unknown causes (XAFLD), and combined causes of FLD (CAFLD) as well as advanced stage fibrotic FLD (FAFLD) and end-stage FLD (ESFLD) subcategories. These and other related advances, as a whole, are expected to enable not only improved patient care, quality of life, and long-term disease outcomes, but also a considerable reduction in healthcare system costs associated with FLD, along with more options for better-targeted, more effective treatments in the near future.
| S-EPMC10224312 | biostudies-literature
Project description:The rapidly increasing prevalence of childhood obesity and its associated co-morbidities such as hypertriglyceridemia, hyper-insulinemia, hypertension, early atherosclerosis, metabolic syndrome, and non-alcoholic fatty liver disease are major public health concerns in many countries. Therefore the trends in child and adolescent obesity should be closely monitored over time, as in the near future, we may anticipate a major increase of young adults with the stigmata of the metabolic syndrome, and of the related non-alcoholic fatty liver disease (NAFLD), that may lead to non-alcoholic steatohepatitis.
| S-EPMC4922334 | biostudies-literature
Project description:The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment.
| S-EPMC4958712 | biostudies-literature
Project description:PurposeNon-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver injury that has gained concern in clinical hepatology. The principal aim of this study was to find differences in protein expression between patients with NAFLD and healthy controls.Experimental designChanges in protein expression of liver samples from each of the three groups of subjects, controls, non-alcoholic steatosis, and non-alcoholic steatohepatitis (NASH), were analyzed by DIGE combined with MALDI TOF/TOF analysis, a proteomic approach that allows to compare hundreds of proteins simultaneously.ResultsForty-three proteins exhibiting significant changes (ratio ≥1.5, p<0.05) were characterized, 22 comparing steatosis samples versus control samples and 21 comparing NASH versus control samples. Ten of these proteins were further analyzed by Western blot in tissue samples to confirm the observed changes of protein expression using DIGE. The proteins validated were further tested in serum samples of different cohorts of patients.Conclusions and clinical relevanceFollowing this approach we identified two candidate markers, carbamoyl phosphate synthase 1 and 78 kDa glucose-regulated protein, differentially expressed between control and NASH. This proteomics approach demonstrates that DIGE combined with MALDI TOF/TOF and Western blot analysis of tissue and serum samples is a useful approach to identify candidate markers associated with NAFLD, resulting in proteins whose level of expression can be correlated to a disease state.
| S-EPMC3040121 | biostudies-literature
Project description:BackgroundThe spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from isolated hepatic steatosis to non-alcoholic steatohepatitis to fibrosis. We aimed to introduce useful biomarkers released during liver inflammation and fibrogenesis that are easy to use in outpatient clinic and adjust to children to evaluate each NAFLD stage without biopsy.MethodsThis prospective study included 60 patients aged under 19 years whose alanine aminotransferase (ALT) levels were elevated from March 2021. All patients were proven to have NAFLD by ultrasonography and laboratory work-up to exclude other causes of hepatitis. Fibroscan and additional laboratory tests for biomarkers [procollagen type1 amino-terminal propeptide (P1NP), osteocalcin, interleukin-6 (IL-6), and Mac-2 binding protein glycosylated isomer (M2BPGi)] were performed. Fibroscan-AST (FAST) score was used for the comparison of steatohepatitis and liver stiffness measurement (kPa) was used for the comparison of advanced fibrosis.ResultsThe biomarker that showed a significant difference between the FAST-positive and negative groups was the P1NP/osteocalcin ratio with a p-value of 0.008. The area under receiver operating characteristic (AUROC) of P1NP/osteocalcin ratio*ALT values (values obtained through multivariate analysis) was 0.939 with the cut-off value of 305.38. The biomarkers that showed a significant difference between the LSM-positive and negative groups were IL-6 and M2BPGi with a p-values of 0.005 and <0.001. AUROC of IL-6 *AST values (values obtained through multivariate analysis) was 0.821 with the cut-off value of 228.15. M2BPGi showed a significant linear relationship with LSM in Pearson correlation analysis (Pearson correlation coefficient = 0.382; p = 0.003). The diagnostic capability of M2BPGi to evaluate advanced fibrosis showed an acceptable result (AUROC = 0.742; p = 0.022).ConclusionsNon-invasive biomarkers can be used to predict each stage of NAFLD in children. The measurements of P1NP, IL-6 or M2BPGi along with the basic chemistry tests would help determine the stage of NAFLD they correspond to at the time of initial diagnosis and predict responsiveness after the treatment.
| S-EPMC9013938 | biostudies-literature
Project description:Metabolism of carbohydrates and lipids and protein degradation occurs in the liver and contributes to the body's homeostasis by secreting a variety of mediators. Any imbalance in this homeostasis due to excess fat consumption and the pathologic events accompanying lipotoxicity, autophagy dysregulation, endoplasmic reticulum stress, and insulin resistance may cause disturbances in the secretion of the proteins from the liver and their physiologic modifications and interactions with others. Since the liver secretome plays a role in the regulation of fuel metabolism and inflammation not only in the liver per se but also in other organs, the proteins belong to the utmost targets for treating metabolic and inflammatory diseases (e.g., COVID-19), depending on the available and feasible approaches to controlling their biological effects. However, in this era, we still come across new liver-derived proteins but are yet unable to entirely understand the pathologic basis underlying disease progression. This review aims to provide an updated overview of liver secretome biology with explanatory mechanisms with regard to the progression of metabolic and inflammatory liver diseases.
| S-EPMC9703441 | biostudies-literature