Metabolic Score for Insulin Resistance Is Inversely Related to Incident Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.
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SUBMITTER: Lee JH
PROVIDER: S-EPMC9330359 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. AIMS:To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy-proven NAFLD without pre-existing cardiovascular disease. METHODS:From 2011 to 2018, adults with biopsy-proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow-up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. RESULTS:After a median follow-up time of 5.2 years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3-4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36-6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non-invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. CONCLUSIONS:In adults with biopsy-proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.
| S-EPMC7069774 | biostudies-literature
Project description:Background and aimThe progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is believed to be the driver for future development of fibrosis and cirrhosis. Nevertheless, there remains a clear deficit in non-invasive methods for the diagnosis of NASH. The aim of the present study was to evaluate the prevalence of portal lymphadenopathy (PL) in biopsy- proven NAFLD patients and to determine whether PL correlates with NAFLD stage and severity.MethodsA retrospective study included biopsy-proven NAFLD patients with up to date (within one year) abdominal imaging by computed tomography (CT) and/or magnetic resonance imaging (MRI). Patients were clustered into three groups based on their NAFLD Activity Score (NAS): NAS1-2 (mild), NAS3-4 (moderate) and NAS≥5 (advanced). We Assessed for association between PL and other clinical and laboratory findings with NAS, NAS components and fibrosis.ResultsSeventy-five patients with NAFLD and no other competing etiologies for liver diseases or PL were included. The mean age was 50.7±14.84 years with male predominance (N = 47, 62.7%). Twenty-five (33.3%), 37 (49.3%) and 13 (17.3%) patients had mild, moderate and advanced NAS, respectively. PL significantly correlated with advanced NAS ≥ 5 (Fisher's (F) 9.5, P = 0.009). Correlation was driven mainly by a link to hepatocytes ballooning (F of 5.9, P = 0.043). In addition, PL significantly correlated with portal inflammation (F 4.29, P = 0.038). As for hepatic fibrosis, the F test wasn't significant, though spearman's coefficient (SC) was significant (0.277, P = 0.012). On multivariate analysis, PL was identified as a sole predictor of advanced NAS score (Odds ratio of 2.68, P = 0.002). Incorporation of PL into noninvasive fibrosis scores improved their diagnostic yield.ConclusionPL predicts severity of NAFLD. Its presence may serve as a novel radiological marker for NAFLD/NASH differentiation and disease progression.
| S-EPMC6267957 | biostudies-literature
Project description:PurposeNon-alcoholic fatty liver disease (NAFLD) is independently associated with the development of atrial fibrillation (AF). However, the association of AF with advanced liver fibrosis, which is related to all-cause, cardiovascular, and liver-related mortality, has not been established in NAFLD patients. We aimed to investigate the association between AF and advanced liver fibrosis in NAFLD patients.Materials and methodsOut of 53704 adults who participated in the health check-up program, 6293 subjects aged 35 years and older were diagnosed as NAFLD using ultrasound. The stage of liver fibrosis was assessed based on the newly adjusted NAFLD fibrosis score (NFS) and Fibrosis-4 (Fib-4) Index, which were used to determine the low and high cut-off values (COVs).ResultsOf 6293 patients with NAFLD, 59 (0.9%) were diagnosed with AF. Patients with AF were older (52.0 vs. 64.6 years, p<0.001), had higher body mass index (25.2 vs. 26.6 kg/m², p<0.001), and had bigger waist circumference (84.0 vs. 89.9 cm, p<0.001) than those without AF. In NAFLD patients, AF was independently associated with advanced liver fibrosis, assessed using both COVs of NFS [low-COV group: final adjusted odds ratios (aORs)=2.85, p=0.004; high-COV group: ORs=12.29, p<0.001). AF was independently associated with advanced liver fibrosis, assessed using both COVs of Fib-4 (low-COV group: aORs=2.49, p<0.001; high-COV group: aORs=3.84, p=0.016).ConclusionAF is independently associated with advanced liver fibrosis in patients with NAFLD.
| S-EPMC7515788 | biostudies-literature
Project description:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. METHODS AND FINDINGS:We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. CONCLUSIONS:In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. TRIAL REGISTRATION:PROSPERO CRD42018115459.
| S-EPMC7192386 | biostudies-literature
Project description:Several studies have emerged indicating that sarcopenia is associated with nonalcoholic fatty liver disease, we aimed to systematically review and quantify the association between sacropenia and the histological severity of nonalcoholic fatty liver disease.Pubmed, the Cochrane Library and EMBASE were searched (until August 2017) for studies examining the relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in nonalcoholic fatty liver disease. Pooled odds ratios were estimated by fixed effects models.Three articles met our inclusion criteria, with a total of 3226 individuals. Two of the studies examined the association between sacropenia and steatohepatitis, a significant association was documented between sarcopenia and steatohepatitis (OR?=?2.35, 95%CI 1.45, 3.81). All of the three studies assessed the association between sacropenia and advanced liver fibrosis, a significant association between sarcopenia and advanced liver fibrosis (OR?=?2.41, 95%CI 1.94, 2.98). No significant heterogeneity was detected among studies in all comparisons. These results remained essentially unchanged after excluding any of the studies in the sensitivity analysis.Sarcopenia in patients with nonalcoholic fatty liver disease is associated with a higher likelihood of having steatohepatitis or advanced liver fibrosis. Demonstration of the role of sarcopenia in nonalcoholic fatty liver disease development in future studies could have important therapeutic implications.
| S-EPMC5907709 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and may progress to non-alcoholic steatohepatitis (NASH) and liver fibrosis. The deficit of pharmacological therapies for the latter mainly results from an incomplete understanding of involved pathological mechanisms. Herein, we identify apoptosis signal-regulating kinase 1 (ASK1) as a suppressor of NASH and fibrosis formation. High-fat diet-fed and aged chow-fed liver-specific ASK1-knockout mice develop a higher degree of hepatic steatosis, inflammation, and fibrosis compared to controls. In addition, pharmacological inhibition of ASK1 increased hepatic lipid accumulation in wild-type mice. In line, liver-specific ASK1 overexpression protected mice from the development of high-fat diet-induced hepatic steatosis and carbon tetrachloride-induced fibrosis. Mechanistically, ASK1 depletion blunts autophagy, thereby enhancing lipid droplet accumulation and liver fibrosis. In human livers of lean and obese subjects, ASK1 expression correlated negatively with liver fat content and NASH scores, but positively with markers for autophagy. Taken together, ASK1 may be a novel therapeutic target to tackle NAFLD and liver fibrosis.
| S-EPMC6783644 | biostudies-literature
Project description:BackgroundThe incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide parallel to the global obesity epidemic. NAFLD encompasses a range of liver pathologies and most often originates from metabolically driven accumulation of fat in the liver, or non-alcoholic fatty liver (NAFL). In a subset of NAFL patients, the disease can progress to non-alcoholic steatohepatitis (NASH), which is a more severe form of liver disease characterized by hepatocyte injury, inflammation, and fibrosis. Significant progress has been made over the past decade in our understanding of NASH pathogenesis, but gaps remain in our mechanistic knowledge of the precise metabolic triggers for disease worsening.Scope of reviewThe transition from NAFL to NASH likely involves a complex constellation of multiple factors intrinsic and extrinsic to the liver. This review focuses on early metabolic events in the establishment of NAFL and initial stages of NASH. We discuss the association of NAFL with obesity as well as the role of adipose tissue in disease progression and highlight early metabolic drivers implicated in the pathological transition from hepatic fat accumulation to steatohepatitis.Major conclusionsThe close association of NAFL with features of metabolic syndrome highlight plausible mechanistic roles for adipose tissue health and the release of lipotoxic lipids, hepatic de novo lipogenesis (DNL), and disruption of the intestinal barrier in not only the initial establishment of hepatic steatosis, but also in mediating disease progression. Human genetic variants linked to NASH risk to date are heavily biased toward genes involved in the regulation of lipid metabolism, providing compelling support for the hypothesis that NASH is fundamentally a metabolic disease.
| S-EPMC8324696 | biostudies-literature
Project description:BackgroundWe investigated the association between muscle strength and the prevalence of advanced fibrosis among individuals with non-alcoholic fatty liver disease (NAFLD) using a nationwide cross-sectional survey.MethodsIndividuals, 20 to 79 years of age, from the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2016 were selected (N = 14 861), with sample weights applied. Muscle strength was quantified as the handgrip strength divided by the body mass index (BMI); low muscle strength (LMS) was defined as the lowest quartile (Q1 ) of the handgrip strength/BMI for our sample population. NAFLD was defined as hepatic steatosis index >36. Advanced fibrosis was defined as a fibrosis-4 index score ≥1.30 (FibrosisFIB4 ).ResultsThe mean age of the study population was 45.6 ± 0.2 years, and 42.4% were male. As muscle strength increased, the mean BMI and age decreased accordingly, and the proportions of diabetes, dyslipidaemia, hypertension, and obesity decreased significantly (P < 0.001 for all). In a crude analysis, the LMS was associated with an increased prevalence of NAFLD (odds ratio [OR] 3.62, 95% confidence interval [CI] 3.25-4.03, P < 0.001), which remained significant even after adjustment for age, sex, obesity, insulin resistance, diabetes, hypertension, dyslipidaemia, and high-sensitivity C-reactive protein (OR 1.66, 95% CI 1.28-2.16, P < 0.001). In this logistic regression model, the prevalence of NAFLD decreased by 24% with each quartile increment in muscle strength (OR 0.76, 95% CI 0.68-0.85, P < 0.001). Among individuals with NAFLD (n = 2092), LMS was significantly associated with the presence of advanced fibrosis (FibrosisFIB4 ) independently of age, sex, obesity, diabetes, hypertension, dyslipidaemia, and high-sensitivity C-reactive protein (OR 1.66, 95% CI 1.01-2.49, P = 0.015), which lost its statistical significance after additional adjustment for insulin resistance.ConclusionsLow muscle strength is independently associated with NAFLD. The significant association between LMS and advanced fibrosis in NAFLD may be mediated through insulin resistance.
| S-EPMC7567158 | biostudies-literature
Project description:BackgroundDespite clinical trials with antioxidant supplementation, few studies have been conducted to evaluate the nutritional status of antioxidant vitamins and minerals, and none have reported on the status of these serum antioxidants associated with the dietary intake of antioxidants by non-alcoholic fatty liver disease (NAFLD) patients.ObjectiveTo evaluate association between serum and dietetics antioxidants with liver fibrosis in patients with NAFLD.MethodsAcross-section analysis with out with 72 patients diagnosed with NAFLD. Hepatic fibrosis was measured by FibroScan®, and liver stiffness ≥7.9 kPa was considered to indicate advanced fibrosis. Retinol, alpha-tocopherol, ascorbic acid, beta-carotene, serum zinc, and selenium were evaluated, as was the dietary intake of these micronutrients in the previous 24 h (using 24-h dietary recall). The Mann-Whitney test was used to compare the fibrosis groups and, a linear regression analysis was performed to determine associated risk factors between age, sex, BMI, hepatic fibrosis, and serum antioxidants.ResultsA high proportion of inadequate serum retinol (20.8%), vitamin C (27%), and selenium (73.6%) was observed in the patients with NAFLD, in addition to a significant inadequacy of vitamin A (98.3%) and vitamin E (100%) intake. Patients with advanced liver fibrosis had reduced levels of serum retinol (P = 0.002), with liver fibrosis being the independent risk factor associated with serum retinol lower.ConclusionHepatic fibrosis was associated with a reduction in serum retinol and was reduced in advanced fibrosis. NAFLD patients showed an important serum deficiency and insufficient dietary intake of the evaluated micronutrients.
| S-EPMC7502233 | biostudies-literature
Project description:Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.
| S-EPMC6338132 | biostudies-literature