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Association between metabolic syndrome and liver histology among NAFLD patients without diabetes.

ABSTRACT: BACKGROUND:Metabolic syndrome (MetS) and obesity are associated with non-alcoholic fatty liver disease (NAFLD). The aim of this observational study was to examine the relationship of MetS and a diagnosis of non-alcoholic steatohepatitis (NASH) in patients without diabetes in the NASH Clinical Research Network (CRN). METHODS:Clinical, demographic, histological, laboratory and anthropometric data were collected on 356 adult patients without diabetes with NAFLD. Obesity was defined as body mass index ?30.0. MetS was determined using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATPIII) 2001 criteria to include 3 or more of the following: increased waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, hypertension and elevated fasting blood glucose. RESULTS:Most patients were obese (71%) and had MetS (67%). Obesity was more prevalent among patients with MetS (80% vs 52%; p?0.001). Markers of insulin resistance such as homoeostasis model assessment of insulin resistance (6.5 vs 4.9, p?0.001) were higher among those with MetS compared with those without MetS. Histologically, patients without MetS had higher hepatocellular (p=0.04) and reticuloendothelial system iron (p=0.04). Patients with MetS were more likely to have severe hepatic steatosis (p=0.04) and chronic portal inflammation (p=0.01). On multiple logistic regression analysis, patients with definite NASH were almost 2.5 times more likely to have MetS than those without definite NASH (OR=2.41, p=0.01). CONCLUSIONS:MetS is common in patients without diabetes with NAFLD and is associated with greater insulin resistance, hepatic steatosis and portal inflammation. While patients without MetS have greater iron overload, patients with MetS may have an increased propensity to have NASH. Therefore, presence of MetS in patients without diabetes with NAFLD may serve as a potential criterion for liver biopsy. TRIAL REGISTRATION NUMBER:NCT00063622; Pre-results.

SUBMITTER: Kanwar P

PROVIDER: S-EPMC5128831 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association between metabolic syndrome and liver histology among NAFLD patients without diabetes.

Kanwar Pushpjeet P Nelson James E JE Yates Katherine K Kleiner David E DE Unalp-Arida Aynur A Kowdley Kris V KV

BMJ open gastroenterology 20161109 1

<h4>Background</h4>Metabolic syndrome (MetS) and obesity are associated with non-alcoholic fatty liver disease (NAFLD). The aim of this observational study was to examine the relationship of MetS and a diagnosis of non-alcoholic steatohepatitis (NASH) in patients without diabetes in the NASH Clinical Research Network (CRN).<h4>Methods</h4>Clinical, demographic, histological, laboratory and anthropometric data were collected on 356 adult patients without diabetes with NAFLD. Obesity was defined a ...[more]

PMID: 27933201

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Project description:Nonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of metabolic syndrome (MetS) among adults. Emerging data suggest that MetS may be associated with nonalcoholic fatty liver disease (NAFLD) in children as well. We sought to determine whether MetS or its component features are associated with specific histological features or severity of NAFLD.Children and adolescents aged 6-17 years enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with clinical data obtained within 6 months of liver biopsy were included. MetS was defined as the presence of three or more of the following features as determined by application of age-adjusted normative values: central obesity, dyslipidemia, impaired fasting glucose, and elevated blood pressure. Liver biopsies were evaluated by the Pathology Committee of the NASH CRN.Two hundred fifty four children were included in the analysis, of whom 65 (26%) met specified criteria for MetS. Among children with MetS, there is a higher proportion of females who were on average older in age and pubertal. The risk of MetS was greatest among those with severe steatosis (odds ratio (OR)=2.58 for grade 3 vs. grade 1 steatosis, P=0.001). The presence of hepatocellular ballooning was also significantly associated with MetS (OR=2.10, P=0.03). Those with advanced fibrosis (stage 3/4) had an OR for MetS of 3.21 (P=0.04) vs. those without fibrosis (stage 0). Borderline zone 1 or definite NASH patterns compared with "not NASH" were strongly associated with MetS (OR=4.44, P=0.005 and OR=4.07, P=0.002, respectively). The mean NAFLD Activity Score (NAS) was greater among children with MetS vs. those without (4.8 +/- 1.4 vs. 4.3 +/- 1.4, P=0.01). Central obesity was significantly associated with steatosis, fibrosis, hepatocellular ballooning, and NAFLD pattern. Insulin resistance was significantly associated with steatosis, fibrosis, hepatocellular ballooning, NAS, and NAFLD pattern.MetS is common among children with NAFLD and is associated with severity of steatosis, hepatocellular ballooning, NAS, NAFLD pattern, and the presence of advanced fibrosis. Individual MetS features, particularly central obesity and insulin resistance, were also associated with severity of NAFLD. MetS features should be considered in children with NAFLD as individually and collectively they help identify children with more advanced disease.

Project description:BackgroundType 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investigate (a) whether GDF-15 concentrations were associated with liver fibrosis and involved in the relationship between T2DM and liver fibrosis and (b) what factors linked with T2DM are associated with increased GDF-15 concentrations.MethodsNinety-nine patients with NAFLD (61% men, 42.4% T2DM) were studied. Serum GDF-15 concentrations were measured by electro-chemiluminescence immunoassay. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. Regression modelling, receiver operator characteristic curve analysis and Sobel test statistics were used to test associations, risk predictors and the involvement of GDF-15 in the relationship between T2DM and liver fibrosis, respectively.ResultsPatients with NAFLD and T2DM (n = 42) had higher serum GDF-15 concentrations [mean (SD): 1271.0 (902.1) vs. 640.3 (332.5) pg/ml, p < 0.0001], and a higher proportion had VCTE assessed ≥F2 fibrosis (48.8 vs. 23.2%, p = 0.01) than those without T2DM. GDF-15 was independently associated with liver fibrosis (p = 0.001), and GDF-15 was the most important single factor predicting ≥F2 or ≥F3 fibrosis (≥F2 fibrosis AUROC 0.75, (95% CI 0.63-0.86), p < 0.001, with sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values of 56.3%, 86.9%, 69.2% and 79.1%, respectively). GDF-15 was involved in the association between T2DM and ≥F2 fibrosis (Sobel test statistic 2.90, p = 0.004). Other factors associated with T2DM explained 60% of the variance in GDF-15 concentrations (p < 0.0001). HbA1c concentrations alone explained 30% of the variance (p < 0.0001).ConclusionsGDF-15 concentrations are a predictor of liver fibrosis and potentially involved in the association between T2DM and liver fibrosis in NAFLD. HbA1c concentrations explain a large proportion of the variance in GDF-15 concentrations.

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Association between metabolic syndrome and liver histology among NAFLD patients without diabetes.

Publications

Association between metabolic syndrome and liver histology among NAFLD patients without diabetes.

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