Metabolic and Risk Profiles of Lean and Non-Lean Hepatic Steatosis among US Adults.
Ontology highlight
ABSTRACT:
SUBMITTER: Li M
PROVIDER: S-EPMC10343664 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
Publications
Metabolic and Risk Profiles of Lean and Non-Lean Hepatic Steatosis among US Adults.
Li Meiling M Zhang Weiping W Li Xiude X Liang Shaoxian S Zhang Yaozong Y Mo Yufeng Y Rao Songxian S Zhang Honghua H Huang Yong Y Zhu Yu Y Zhang Zhuang Z Yang Wanshui W
Nutrients 20230623 13
Hepatic steatosis can occur in lean individuals, while its metabolic and risk profiles remain unclear. We aimed to characterize the clinical and risk profiles of lean and non-lean steatosis. This cross-sectional study included 1610 patients with transient elastography-assessed steatosis. The metabolic and risk profiles were compared. Compared to their non-lean counterparts, lean subjects with steatosis had a lower degree of fibrosis (F0-F1: 91.9% vs. 80.9%), had a lower prevalence of diabetes (2 ...[more]
Similar Datasets
Project description:BackgroundThe prognostic impact of liver steatosis in obese patients is well established. Limited data on the risk factors for and impact of hepatic steatosis in lean patients are available.AimsAssess risk factors for liver steatosis in lean patients and investigate its impact on survival.MethodsPatients without viral hepatitis and with a BMI ≤ 25 kg/m2 undergoing liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by transient elastography were retrospectively identified. Clinical characteristics and laboratory test results were obtained at the time of LSM/CAP measurement. National death registry data were obtained in order to assess survival.ResultsAmong n = 218 lean patients, n = 97 (34.5%) showed significant liver steatosis (CAP ≥ 268 dB/m), while n = 184 (65.5%) had no or just mild steatosis (CAP < 268 dB/m). Patients with steatosis had higher GGT (238.0(± 450.3) vs. 112.1(± 180.0) IU/mL; p = 0.013), AST (63(± 67.4) vs. 38.5(± 32.9) IU/mL; p = 0.001), ALT (59.1(± 58.8) vs. 44.3(± 52.7) IU/mL; p = 0.048) and triglyceride levels (120.1(± 80.3) vs. 96.1(± 58.2) mg/dL; p = 0.014), and showed a trend toward more severe fibrosis (LSM 15.6(± 19.5) vs. 12.0(± 15.7) kPa; p = 0.115). In multivariate binary logistic regression analysis, only serum uric acid levels were independently associated with liver steatosis (odds ratio 1.43 per unit mg/dL; 95% CI 1.001-2.054; p = 0.049). During a mean follow-up of 38.9(± 10.6) months, n = 14 patients (5.0%) died. In the absence of advanced fibrosis, survival after 1 year was similar in patients without (98.7%) and with (98.6%) significant steatosis. Patients with advanced fibrosis had worse 1-year survival without concomitant significant steatosis (84.8%) than patients with steatosis (95.8%; log-rank p < 0.001).ConclusionsHigh serum uric acid levels increase the risk of liver steatosis in lean patients. Liver fibrosis but not hepatic steatosis is a risk factor for impaired survival in lean patients.
| S-EPMC7419366 | biostudies-literature
Project description:ObjectiveSearch for meaningful laboratory and anthropometric parameters in lean non-alcoholic fatty liver disease (lean NAFLD) in the general population. Out of 2445 subjects in a random population sample, we compared those who had a body mass index (BMI) < 25 and a fatty liver [lean NAFLD (LN), n = 5] with obese subjects who had a BMI > 30 but no fatty liver [non-NAFLD (NN), n = 27] in a follow-up examination. Ultrasonic, anthropometric and laboratory parameters were collected.ResultsThere were significant differences (p < 0.05) between the LN and the NN groups with respect to serum ferritin (199.2 ± 72.1 LN vs 106.0 ± 89.6 NN), haemoglobin (14.9 ± 0.8 LN vs 13.5 ± 1.2 NN), haematocrit (0.438 ± 0.019 LN vs 0.407 ± 0.035 NN) and Mean corpuscular haemoglobin concentration (34 ± 0.6 LN vs 33.2 ± 0.8 NN). Significantly lower values of soluble transferrin receptor were measured in the LN group (2.8 ± 0.4 LN vs 3.8 ± 1.5 NN). In both groups, the measured HOMA-IR index (homeostatic model assessment of insulin resistance index) (2.3; normal range ≤ 1) was abnormal. Mean cholesterol (6.2 ± 1.4 LN and 5.6 ± 1.1 NN) and low-density lipoprotein levels (3.8 ± 1.0 LN 3.4 ± 0.9 NN) were above the upper limit of normal in both groups, as was the mean triglycerides level in the LN group (2.6 ± 2.0). In summary, there are differences in parameters of iron and fat metabolism between subjects with LN and overweight subjects without fatty liver infiltration.
| S-EPMC5801753 | biostudies-literature
Project description:BackgroundMetabolic syndrome (MetS) is a group of factors associated with increased risks of cardiovascular disease and overall mortality. Nonalcoholic fatty liver disease (NAFLD) is a common disorder that has been shown to cause hepatic steatosis and fibrosis. The relationship between NAFLD and MetS appears to be bidirectional, but very few studies have examined the role of MetS in hepatic steatosis and fibrosis. The present study investigated the relationships between MetS and its components and the severity of hepatic fibrosis and steatosis, and fibrosis independent of steatosis.MethodsThe study was a cross-sectional population-based survey of 4,678 National Health and Nutrition Examination Survey participants from 2017 to 2018 in the United States. Hepatic fibrosis and steatosis were measured using liver elastography. The MetS components were assessed using demographic, examination, laboratory, and self-reported data.ResultsUsing survey-weighted population estimates, 26% of the population had steatosis, 7.5% had fibrosis, and 3.3% had fibrosis without steatosis. The adjusted odds ratio for any level of steatosis was 4.12 times higher (95% confidence interval [CI], 3.16-5.37) and any level of fibrosis was 3.34 times higher (95% CI, 2.26-4.94) among participants with MetS than those without. The adjusted odds ratio for fibrosis without steatosis is 2.67 times higher (95% CI, 1.47-4.87) among participants with MetS than those without.ConclusionThe presence of MetS significantly increases the risk of hepatic fibrosis and steatosis, providing evidence for MetS to be considered an additional independent risk factor for hepatic fibrosis together with other known etiologies.
| S-EPMC8987451 | biostudies-literature
Project description:The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.
| S-EPMC10761858 | biostudies-literature
Project description:BackgroundANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3.MethodsWe recruited participants with ANGPTL3 deficiency related to ANGPTL3 loss-of-function (LoF) mutations, along with wild-type (WT) participants from 2 previously characterized cohorts located in Campodimele, Italy, and St. Louis, MO. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction were performed to measure hepatic fat fraction and the distribution of extrahepatic fat. To estimate the causal relationship between ANGPTL3 and hepatic fat, we generated a genetic instrument of plasma ANGPTL3 levels as a surrogate for hepatic protein synthesis and performed Mendelian randomization analyses with hepatic fat in the UK Biobank study.ResultsWe recruited participants with complete (n=6) or partial (n=32) ANGPTL3 deficiency related to ANGPTL3 LoF mutations, as well as WT participants (n=92) without LoF mutations. Participants with ANGPTL3 deficiency exhibited significantly lower total cholesterol (complete deficiency, 78.5 mg/dL; partial deficiency, 172 mg/dL; WT, 188 mg/dL; P<0.05 for both deficiency groups compared with WT), along with plasma triglycerides (complete deficiency, 26 mg/dL; partial deficiency, 79 mg/dL; WT, 88 mg/dL; P<0.05 for both deficiency groups compared with WT) without any significant difference in hepatic fat (complete deficiency, 9.8%; partial deficiency, 10.1%; WT, 9.9%; P>0.05 for both deficiency groups compared with WT) or severity of hepatic steatosis as assessed by magnetic resonance imaging. In addition, ANGPTL3 deficiency did not alter the distribution of extrahepatic fat. Results from Mendelian randomization analyses in 36 703 participants from the UK Biobank demonstrated that genetically determined ANGPTL3 plasma protein levels were causally associated with low-density lipoprotein cholesterol (P=1.7×10-17) and triglycerides (P=3.2×10-18) but not with hepatic fat (P=0.22).ConclusionsANGPTL3 deficiency related to LoF mutations in ANGPTL3, as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis. Therapeutic approaches to inhibit ANGPTL3 production in hepatocytes are not necessarily expected to result in the increased risk for hepatic steatosis that was observed with vupanorsen.
| S-EPMC10805521 | biostudies-literature
Project description:The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight loss is the only available treatment, but administration of fibroblast growth factor 21 (FGF21) analogues have, in addition to weight loss, shown improvements on liver metabolic health but the mechanisms behind are not entirely clear. The aim of this study was to investigate the hepatic metabolic profile in response to FGF21 treatment. Diet-induced obese (DIO) mice were treated with s.c. administration of FGF21 or subjected to caloric restriction by switching from high fat diet (HFD) to chow to induce 20% weight loss and changes were compared to vehicle dosed DIO mice. Cumulative caloric intake was reduced by chow, while no differences were observed between FGF21 and vehicle dosed mice. The body weight loss in both treatment groups was associated with reduced body fat mass and hepatic triglycerides (TG), while hepatic cholesterol was slightly decreased by chow. Liver glycogen was decreased by FGF21 and increased by chow. The hepatic gene expression profiles suggest that FGF21 increased uptake of fatty acids and lipoproteins, channeled TGs toward the production of cholesterol and bile acid, reduced lipogenesis and increased hepatic glucose output. Furthermore, FGF21 appeared to reduce inflammation and regulate hepatic leptin receptor-a expression. In conclusion, FGF21 affected several metabolic pathways to reduce hepatic steatosis and improve hepatic health and markedly more genes than diet restriction (61 vs 16 out of 89 investigated genes).
| S-EPMC7424338 | biostudies-literature
Project description:BackgroundIt is not clear if chronic hepatitis B (CHB) infection potentiates the severity of hepatic steatosis (HS) in patients with metabolic risk factors. We tested for the effect modification of hepatitis B viral load on the association between metabolic risk factors and HS.MethodsIn this retrospective cross-sectional study, we included adult subjects, who had non-cirrhotic nonalcoholic fatty liver disease and CHB infection with positive hepatitis B envelope antibody. We reported descriptive statistics, stratified by detectable and undetectable hepatitis B viral load, by Kruskal-Wallis Rank Sum Test and chi-square. We reported coefficients of two multivariate regression predicting odds of HS > stage 2, testing for interaction between metabolic risk factors and hepatitis B viral load.ResultsWhen controlled for age, sex, and hepatitis B treatment, the odds of HS > stage 2 increased significantly by 77% for each additional metabolic risk factor [odds ratio (OR) 1.77, 95% confidence interval (CI): 1.20-2.69, P=0.005]. The odds of HS > stage 2 was not associated with detectable hepatitis B viral load (OR 1.00, 95% CI: 0.83-1.19, P=0.986). The association between the odds of HS > stage 2 and metabolic risk factors did not significantly change as hepatitis B viral load increased [ratio of odds ratio (ROR) 1.01, 95% CI: 0.94-1.08, P=0.839].ConclusionsOur study does not find evidence of effect modification of hepatitis B viral load on the association between metabolic risk factors and HS in non-cirrhotic and hepatitis B envelope antibody positive patients with CHB viral infection. It suggests that the odds of HS in CHB infected patients is affected by metabolic risk factors and not by hepatitis B viremia.
| S-EPMC9813647 | biostudies-literature
Project description:BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is a key risk factor for cardiovascular disease (CVD), potentially driven by shared metabolic mechanisms. Metabolic perturbations associated with MASLD and CVD remain underexplored in people with HIV (PWH).MethodsWe used data from the longitudinal multicenter 2000HIV study comprising 1895 virally suppressed PWH, out of which 970 had available liver and carotid artery measurements. Transient elastography with controlled attenuation parameter (CAP) was performed for the assessment of liver steatosis (CAP > 263 dB/m) and fibrosis (LSM ≥ 7.0). Historic and future incident CVD within 2-year follow-up, defined as myocardial infarction, stroke, peripheral arterial disease, and angina pectoris, were extracted from the medical files, while atherosclerotic plaque(s) in the carotid arteries were assessed using ultrasonography. Metabolic perturbations were analyzed using mass spectrometry-based untargeted metabolomics (n = 500 metabolites) and nuclear magnetic resonance spectroscopy for targeted lipids and other metabolites (n = 246 metabolites).ResultsPWH with liver steatosis were more likely to have arterial plaques (47% vs. 36%; P value = 0.003) and CVD history (11% vs. 6.8%; P value = 0.021) than PWH without liver steatosis. These associations were only significant in lean PWH, in contrast to those with BMI ≥ 25 kg/m2. Metabolic pathways associated with liver steatosis and fibrosis primarily involved lipid and amino acid metabolism, and they were validated by targeted lipoproteomic measurements. Interestingly, metabolomic pathways and lipoproteomic signatures associated with MASLD were mostly distinct from those associated with CVD parameters. However, several metabolic pathways were shared, especially in lean PWH. These include arachidonic acid metabolism and formation of prostaglandin, purine metabolism, cholecalciferol metabolism, and glycine, serine, alanine, and threonine metabolism.ConclusionMetabolic disturbances linked to liver steatosis and CVD diverge across BMI categories in PWH. Lean PWH, unlike their overweight/obese counterparts, show common metabolic perturbations between MASLD and CVD, particularly involving arachidonic acid metabolism. This suggests that lean PWH with liver steatosis may face a heightened risk of CVD due to shared metabolic pathways, potentially opening avenues for targeted interventions, such as aspirin therapy, to mitigate this risk.
| S-EPMC11817758 | biostudies-literature
Project description:Introduction and objectivesVarious studies have identified single-nucleotide polymorphisms (SNPs) associated with nonalcoholic fatty liver disease (NAFLD) and related traits, including ones located in or near the LYPLAL1, GCKR, PPP1R3B, TM6SF2, MBOAT7, and PNPLA3 genes. However, these SNPs were identified primarily in populations of European ancestry. This study examined the associations of these previously identified SNPs with hepatic steatosis in a sample of Mexican-origin adults living in Southern Arizona.Materials and methodsA total of 307 Mexican-origin adults between the ages of 18 and 64 with a body mass index (BMI) of 25 kg/m2 or higher were genotyped at the following SNPs: rs12137855 (LYPLAL1), rs1260326 (GCKR), rs4240624 (PPP1R3B), rs58542926 (TM6SF2), rs641738 (MBOAT7), and rs738409 (PNPLA3). Hepatic steatosis was assessed by transient elastography (FibroScan®) with controlled attenuation parameter. Regression models examined the association between each of the six SNPs and hepatic steatosis. BMI was examined as a potential modifier of the genetic associations.ResultsParticipants were, on average, 45 years old and mostly female (63%) with an overall mean hepatic steatosis of 288.1 dB/m. Models showed no associations between LYPLAL1, GCKR, PPP1R3B, TM6SF2, or MBOAT7 and hepatic steatosis. Only PNPLA3 was statistically significantly associated with hepatic steatosis in both unadjusted and adjusted models (p<0.01). There was no effect modification observed with BMI.ConclusionsSNPs associated with NAFLD in populations of European descent did not strongly contribute to hepatic steatosis in individuals of Mexican-origin, except for rs738409 (PNPLA3). Further efforts are necessary to explore additional SNPs that may be associated with NAFLD in this high-risk population.
| S-EPMC10486257 | biostudies-literature
Project description:Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non-Hodgkin lymphoma (NHL). In this retrospective case-control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R-CHOP) or R-CHOP + etoposide (EPOCH-R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3- to 6-month intervals and reviewed for steatosis. Patients with de novo steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow-up 53 months), 25 (10%) developed de novo steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m2; P = 0.014) and hyperlipidemia (12% versus 2%; P = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m2 (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls (P = 0.003). Etoposide-containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; P < 0.001) despite similar baseline risk factors. Conclusion: The recovery period from NHL chemotherapy appears to be a "hot spot" for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.
| S-EPMC6357828 | biostudies-literature