Liver Fat Fraction Research Articles

Fatty acid composition evaluation of abdominal adipose tissue using chemical shiftencoded MRI: Association with diabetes.

This study investigated the association between the fatty acid composition of abdominal adipose tissue in NAFLD patients using chemical shift-encoded MRI and the development of insulin resistance and T2DM. We enrolled 231 subjects with NAFLD who underwent both abdominal magnetic resonance spectroscopy and chemical shift-encoded MRI: comprising of 49 T2DM patients and 182 subjects without. MRI- and MRS-based liver fat fraction was measured from a circular region of interest on the right lobe of the liver. The abdominal fatty acid compositions were measured at the umbilical level with chemical shift-encoded MRI. Bland-Altman analysis, Student's t test, Mann-Whitney U test, and Spearman correlation analysis were performed. The logistic regression was applied to identify the independent factors for T2DM. Then, the predictive performance was assessed by Receiver operating characteristic curve analyses. An excellent agreement was found between liver fat fraction measured by MRS and MRI. (slope = 0.8; bias =-0.92%). In, patients with T2DM revealed lower fractions of mono-unsaturated fatty acid (Fmufa) (33.68 ± 10.62 vs 38.62 ± 12.21, P =.0089) and higher fractions of saturated fatty acid (Fsfa) (34.11 ± 9.746 vs 31.25 ± 8.66, P =.0351) of visceral fat tissue compared with patients without. BMI, HDL-c, Fmufa and Fsfa of visceral fat were independent factors for T2DM. Furthermore, Fsfa-S% was positively correlated with liver enzyme levels (P =.003 and 0.04). However, Fmufa-V% was negatively correlated with fasting blood glucose, HbA1c and HOMA-IR (P =.004, P =.001 and P =.03 respectively). Hence, the evaluation of fatty acid compositions of abdominal fat tissue using chemical shift-encoded MRI may have a predictive value for T2DM in patients with NAFLD.

CT assessment of liver fat fraction and abdominal fat composition can predict postoperative liver metastasis of colorectal cancer

ObjectiveThe aim of this study is to investigate the clinical value of liver fat fraction assessed by CT(CT-LFF) and abdominal fat components. We focus on predicting liver metastasis (LM) after colorectal cancer (CRC) surgery. MethodsClinical and imaging data from 79 patients who underwent radical CRC surgery between January 2019 and December 2021 were retrospectively collected. Semi-automatic software was used to quantify the area of different body tissues at the level of the third lumbar vertebra, and liver fat fraction was calculated based on the CT values. Patients were grouped according to BMI, tumor grade, T stage, N stage, vascular invasion (VI), perineural invasion (PNI), and preoperative levels of CEA and CA199. A multivariate logistic regression model was used to identify independent risk factors for early LM after surgery. The diagnostic performance was assessed using the receiver operating characteristic analysis with 5-fold cross-validation. The Kaplan-Meier method was used to draw survival curves, and Log-Rank test was used for survival analysis. ResultsThe study found that the occurrence of LM after CRC surgery was significantly associated with CA199 positivity, VI, PNI, N1-2 stage, CT-LFF, VAT index (VATI). Multivariate logistic regression analysis showed that CA199 positivity (OR = 7.659), N1-2 stage (OR = 6.394), CT-LFF (OR = 1.271), VATI (OR = 1.043) were independent risk factors for predicting LM after CRC surgery. The multivariate logistic regression model, constructed using these independent risk factors, demonstrated robust predictive performance across 5-fold cross-validations, with an average AUC of 0.898 (95 % CI: 0.828–0.969). Survival analysis showed a significant difference in liver metastasis-free survival rates between the high-risk and low-risk groups (P < 0.001). ConclusionCT-LFF and VATI assessed by CT are independent risk factors for predicting LM after CRC surgery. The multivariate prediction model combining CA199 and N stage shows high predictive performance.

Association between objectively-measured sleep duration and early cardiac and hepatic imaging changes in adolescents: insights from the EnIGMA study

Abstract Introduction Inadequate sleep duration (SD) has been associated with adverse cardiovascular (CV) events in adults and adiposity in all life stages. Furthermore, previous cross-sectional studies have shown a possible association between self-reported SD and cardiac structural alterations as detected with echocardiography and cardiovascular magnetic resonance (MR), even in young healthy people. However, there is a lack of longitudinal studies demonstrating an association between objectively-measured SD and structural cardiac alterations. Purpose To assess the association between SD and MR-derived cardiac and hepatic parameters in adolescents. Methods This study used longitudinal data collected as part of the SI! Program for Secondary Schools trial in Spain (2017-2021), which enrolled 1326 participants (mean age: 12.5±0.5 years at baseline). Measurements were taken at three different time-points: baseline, 2-year follow-up and 4-year follow-up. SD and physical activity were assessed by accelerometry for seven consecutive days at each follow-up. The participants were offered to undergo a MR scan in the final follow-up as part of the Early imaging markers of unhealthy lifestyles in adolescents (EnIGMA) study. The imaging protocol included a cine SSFP to provide images for chamber size and function, myocardial tagging acquisitions to assess myocardial strain, T1 and T2 mapping sequences to provide precise myocardial relaxation time properties, and a liver mDixonQuant sequence to obtain liver fat content, using a 3-T scanner. The cumulative effect of the independent variable (SD) and the covariates was assessed using the area under the curve (AUC) method, calculating the integral of the curve parameters during the follow-up period for each subject. To facilitate interpretation, AUC values were divided by the years of follow-up. The participants were included in the analysis if they had available data for SD in at least 2 of the 3 time-points. The association between SD and the MR parameters was assessed by linear regression models. Results 109 participants (61 girls [56.0%]; mean age=16.0±0.5 years) were included in this study. Indexed left ventricular (LV) mass, as well as indexed end-diastolic biventricular volumes were higher in boys than in girls (Figure 1). SD AUC (hours/day) was independently and inversely associated with indexed LV mass and liver fat fraction in the unadjusted and adjusted (age, gender, physical activity, body mass index percentile, and systolic and diastolic blood pressure percentiles AUCs) models (Figure 2). There were no significant associations between the SD AUC and other MR-derived parameters. Conclusion Shorter SD is independently associated with initial stages of cardiac remodeling and liver fat accumulation as assessed with state-of-the-art MR as early as in adolescence. Considering these results, health promotion programs should be implemented early in life emphasizing the importance of good sleep habits.Participant characteristicsAssociation between SD and MR

Longitudinal evaluation of pediatric and young adult metabolic dysfunction-associated steatotic liver disease defined by MR elastography.

To inform clinical monitoring of children and young adults with metabolic dysfunction-associated steatotic liver disease (MASLD) by characterizing the real-world natural history of MASLD and identifying baseline predictors of liver disease progression. This retrospective study included consecutive patients ages < 23 years with MASLD who underwent serial MR elastography (MRE) and/or MR fat fraction (FF) examinations between 09/2009 and 11/2022. Outcomes of MASLD were defined based on maximum ratio values. A relative change ≥ 19% in liver stiffness measures (LSM) and an absolute change ≥ 5% for liver FF were considered clinically meaningful. Random intercept models characterized the yearly rate of change in LSM (kilopascals per year) and FF (percentage per year). One hundred twenty-one patients (87 males, mean age at baseline: 12 ± 3 [SD] years) underwent 297 MRE examinations. The mean interval between the first and last MRE was 34 (± 24) months (range: 1-120 months). Among the 114 patients with serial LSM, 33% (38/114) showed progression, 46% (53/114) remained stable, and 21% (23/114) showed regression. Among the 88 patients with serial FF measures, 57% (50/88) showed progression, 2% (2/88) remained stable, and 41% (36/88) showed regression. LSM progression was associated with Hispanic ethnicity, baseline BMI-for-age percentile, baseline mean liver FF, and GGT changes over time. Predictors for liver FF progression included ALT, AST, GGT, and LDL. In a real-world sample of children and young adults with MASLD who underwent serial liver MRI, a minority of patients demonstrated improvements in liver stiffness or FF over time. Question In children, there is scarce data regarding the natural history of MASLD. Findings In this retrospective study, most children and young adults with MASLD had either unchanged or worsening liver stiffness (n = 91/114, 79%) and liver fat (n = 52/88, 59%). Clinical relevance Our findings emphasize the need for optimized care in pediatric MASLD. The identified risk factors for the progression of liver fat and stiffness may help to identify children who require interventions beyond changes in lifestyle.

Ex Vivo Demonstration of a Novel Dual-Frequency Ultrasound Method for Quantitative Measurements of Liver Fat Content

ObjectiveThe rise in metabolic dysfunction–associated steatotic liver disease prevalence, closely linked with metabolic syndromes and obesity, demands accurate, cost-effective diagnostic methods for early-stage fat quantification in the liver. Here we demonstrate a novel dual-frequency ultrasound method that enables the quantitative measurement of liver fat fraction ex vivo and its correlation with actual fat content. MethodsA total of 24 Wistar rats were divided into four different groups, where three groups were given a high-fat diet for 2, 4, and 6 wk, and the last group was given a control diet for 6 wk. Livers were imaged with ultrasound ex vivo in a water bath with a dual-frequency ultrasound transducer and experimental imaging protocol implemented on the Verasonics Vantage research ultrasound scanner. Ultrasound data were post-processed to estimate the non-linear bulk elasticity parameter and the liver samples were analyzed with respect to fat fraction and triglycerides. ResultsRats given a high-fat diet had increased mean levels of liver fat compared with the control group. More importantly, correlation between the ultrasound-based estimation of the non-linear bulk elasticity parameter and fat fraction and triglycerides on an individual level was found to be strong (R2 = 0.81, p = 5.8 × 10-9 and R2 = 0.72, p = 3.6 × 10-7, respectively). ConclusionThis study demonstrates the potential of the novel dual-frequency ultrasound method for the quantitative measurement of liver fat fraction in excised rat livers, showing great promise for this method to become clinically relevant in the diagnosis and follow-up of patients with fatty liver disease.

Oxidative Gaseous Air Pollutant Exposure Interacts with PNPLA3 Genotype to Influence Liver Fat Fraction and Multi-Omics Profiles in Young Adults

Oxidative Gaseous Air Pollutant Exposure Interacts with PNPLA3 Genotype to Influence Liver Fat Fraction and Multi-Omics Profiles in Young Adults

Automated Comprehensive CT Assessment of the Risk of Diabetes and Associated Cardiometabolic Conditions.

Background CT performed for various clinical indications has the potential to predict cardiometabolic diseases. However, the predictive ability of individual CT parameters remains underexplored. Purpose To evaluate the ability of automated CT-derived markers to predict diabetes and associated cardiometabolic comorbidities. Materials and Methods This retrospective study included Korean adults (age ≥ 25 years) who underwent health screening with fluorine 18 fluorodeoxyglucose PET/CT between January 2012 and December 2015. Fully automated CT markers included visceral and subcutaneous fat, muscle, bone density, liver fat, all normalized to height (in meters squared), and aortic calcification. Predictive performance was assessed with area under the receiver operating characteristic curve (AUC) and Harrell C-index in the cross-sectional and survival analyses, respectively. Results The cross-sectional and cohort analyses included 32166 (mean age, 45 years ± 6 [SD], 28833 men) and 27 298 adults (mean age, 44 years ± 5 [SD], 24 820 men), respectively. Diabetes prevalence and incidence was 6% at baseline and 9% during the 7.3-year median follow-up, respectively. Visceral fat index showed the highest predictive performance for prevalent and incident diabetes, yielding AUC of 0.70 (95% CI: 0.68, 0.71) for men and 0.82 (95% CI: 0.78, 0.85) for women and C-index of 0.68 (95% CI: 0.67, 0.69) for men and 0.82 (95% CI: 0.77, 0.86) for women, respectively. Combining visceral fat, muscle area, liver fat fraction, and aortic calcification improved predictive performance, yielding C-indexes of 0.69 (95% CI: 0.68, 0.71) for men and 0.83 (95% CI: 0.78, 0.87) for women. The AUC for visceral fat index in identifying metabolic syndrome was 0.81 (95% CI: 0.80, 0.81) for men and 0.90 (95% CI: 0.88, 0.91) for women. CT-derived markers also identified US-diagnosed fatty liver, coronary artery calcium scores greater than 100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95. Conclusion Automated multiorgan CT analysis identified individuals at high risk of diabetes and other cardiometabolic comorbidities. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Pickhardt in this issue.

Correlation analysis of dynamic changes of abdominal fat during rapid weight loss after bariatric surgery: A prospective magnetic resonance imaging study

ObjectiveThe factors related to the changes in the liver and abdominal adipose tissue during the rapid weight loss after bariatric surgery remain uncertain. MethodsThis study included 44 participants who had undergone sleeve gastrectomy. The study aimed to analyze changes and correlations of body weight (BW), laboratory tests, and magnetic resonance imaging (MRI) indicators of the liver and abdominal adipose tissue conducted before and after bariatric surgery at 1, 3, and 6 months. ResultsFollowing a rapid weight loss within 6 months of surgery, there was a concurrent decrease in blood glucose, blood lipids, and fat content of the liver and abdomen and the changes showed a correlation. The change of BW (ΔBW) was positively correlated with the change of hepatic proton density fat fraction (ΔPDFF) in one and three months after surgery and was positively correlated with the change of abdominal visceral fat area (ΔAVFA) in six months after surgery, (P<0.05). In one month after surgery, ΔPDFF was positively correlated with the change of aspartate aminotransferase (ΔAST), change of alanine aminotransferase (ΔALT), and change of triglyceride glucose (ΔTYG) index (P<0.05). ΔPDFF was positively correlated with the change of hepatic native T1 values (P<0.001) and was moderately negatively correlated with the change of hepatic apparent diffusion coefficient (ΔADC) values in three months after surgery (P<0.05). ConclusionΔBW can serve as an indirect indicator for evaluating changes in liver fat fraction at 1 and 3 months after bariatric surgery and indicative of changes in visceral fat 6 months after surgery. ΔPDFF was positively correlated with ΔAST, ΔALT and ΔTYG index in 1 months after surgery.

Liver fibrosis and liver stiffness in patients with obesity and type 1 diabetes.

To compare hepatic stiffness and fat fraction in patients with obesity and type 1 diabetes (T1D) with type 2 diabetes (T2D) with a similar body mass index (BMI). In this prospective cross-sectional study, 90 participants with T1D (BMI 30.5 ± 4.5 kg/m2; diabetes duration 20.5 ± 9.8 years; HbA1c 8.2% ± 1.4%) and 69 with T2D (BMI: 30.8 ± 4.6 kg/m2; diabetes duration: 11.7 ± 7.8 years; HbA1c: 7.3% ± 1.4%) were included. Liver fat fraction and stiffness were examined by magnetic resonance imaging and elastography, respectively. Logistic regressions were used to evaluate associations with biomedical variables. The mean liver stiffness score in patients with obesity and T1D was 2.2 ± 0.5 kPa, while in T2D it was 2.6 ± 0.8 kPa (P < .001). The liver fat fraction in patients with obesity and T1D was 3.7% ± 6.3%, and in T2D it was 10.6% ± 7.9% (P < .001). Metabolic dysfunction-associated steatotic liver disease (MASLD) was present in 13.3% of patients with T1D and in 69.6% of patients with T2D, whereas fibrosis was suggested in 7.8% of patients with T1D and in 27.5% of patients with T2D. Liver stiffness was four times higher in patients with T2D compared with those with T1D (odds ratio = 5.4, 95% confidence interval: 2.1-13.6, P < .001). Aspartate transaminase (AST), alanine transaminase, gamma-glutamyl transferase (GGT), triglycerides and the android-to-gynoid ratio were associated with elevated fat fraction in both cohorts. AST and GGT were associated with elevated liver stiffness in both cohorts. Patients with obesity and T1D had lower liver fat and liver stiffness compared with those patients with T2D, despite similar levels of BMI, a longer duration of diabetes and worse glycaemic control.

Effect of N-acetyl cysteine in children with metabolic dysfunction-associated steatotic liver disease-A pilot study.

Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction-associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N-acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy-confirmed MASLD. Thirteen children (n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double-blind, placebo-controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high-sensitivity c-reactive protein (hs-CRP), and interleukin-6 (IL-6) were also measured. homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. Sixteen-week NAC treatment improved (baseline adjusted between-group p < .05 for all) markers of inflammation (IL-6 and hs-CRP), oxidative stress (GSH), and IR (HOMA-IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes. Sixteen-week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.

Liver stiffness measurement by magnetic resonance elastography predicts cirrhosis and decompensation in alcohol-related liver disease

PurposeTo evaluate magnetic resonance elastography (MRE)—based liver stiffness measurement as a biomarker to predict the onset of cirrhosis in early-stage alcohol-related liver disease (ALD) patients, and the transition from compensated to decompensated cirrhosis in ALD.MethodsPatients with ALD and at least one MRE examination between 2007 and 2020 were included in this study. Patient demographics, liver chemistries, MELD score (within 30 days of the first MRE), and alcohol abstinence history were collected from the electronic medical records. Liver stiffness and fat fraction were measured. Disease progression was assessed in the records by noting cirrhosis onset in early-stage ALD patients and decompensation in those initially presenting with compensated cirrhosis. Nomograms and cut-off values of liver stiffness, derived from Cox proportional hazards models were created to predict the likelihood of advancing to cirrhosis or decompensation.ResultsA total of 182 patients (132 men, median age 57 years) were included in this study. Among 110 patients with early-stage ALD, 23 (20.9%) developed cirrhosis after a median follow-up of 6.2 years. Among 72 patients with compensated cirrhosis, 33 (45.8%) developed decompensation after a median follow-up of 4.2 years. MRE-based liver stiffness, whether considered independently or adjusted for age, alcohol abstinence, fat fraction, and sex, was a significant and independent predictor for both future cirrhosis (Hazard ratio [HR] = 2.0–2.2, p = 0.002–0.003) and hepatic decompensation (HR = 1.2–1.3, p = 0.0001–0.006). Simplified Cox models, thresholds, and corresponding nomograms were devised for practical use, excluding non-significant or biased variables.ConclusionsMRE-based liver stiffness assessment is a useful predictor for the development of cirrhosis or decompensation in patients with ALD.Graphical

Magnetic resonance imaging T1 mapping of the liver, pancreas and spleen in children

PurposeTo characterize T1 relaxation times of the pancreas, liver, and spleen in children with and without abdominal pathology.MethodsThis retrospective study included pediatric patients (< 18-years-old). T1 mapping was performed with a Modified Look-Locker Inversion Recovery sequence. Patients were grouped based on review of imaging reports and electronic medical records. The Kruskal–Wallis test with Dunn’s multiple comparison was used to compare groups.Results220 participants were included (mean age: 11.4 ± 4.2 years (1.5 T); 10.9 ± 4.5 years (3 T)). Pancreas T1 (msec) was significantly different between subgroups at 1.5 T (p < 0.0001). Significant pairwise differences included: normal (median: 583; IQR: 561–654) vs. acute pancreatitis (731; 632–945; p = 0.0024), normal vs. chronic pancreatitis (700; 643–863; p = 0.0013), and normal vs. acute + chronic pancreatitis (1020; 897–1099; p < 0.0001). Pancreas T1 was also significantly different between subgroups at 3 T (p < 0.0001). Significant pairwise differences included: normal (779; 753–851) vs. acute pancreatitis (1087; 910–1259; p = 0.0012), and normal vs. acute + chronic pancreatitis (1226; 1025–1367; p < 0.0001).Liver T1 was significantly different between subgroups only at 3 T (p = 0.0011) with pairwise differences between normal (818, 788–819) vs. steatotic (959; 848–997; p = 0.0017) and normal vs. other liver disease (882; 831–904; p = 0.0455). Liver T1 was weakly correlated with liver fat fraction at 1.5 T (r = 0.39; 0.24–0.52; p < 0.0001) and moderately correlated at 3 T (r = 0.64; 0.49–0.76; p < 0.0001).There were no significant differences in splenic T1 relaxation times between subgroups.ConclusionPancreas T1 relaxation times are higher at 1.5 T and 3 T in children with pancreatitis and liver T1 relaxation times are higher in children with steatotic and non-steatotic chronic liver disease at 3 T.

MAVMET trial: maraviroc and/or metformin for metabolic dysfunction associated fatty liver disease in adults with suppressed HIV.

Metabolic dysfunction associated fatty liver disease (MAFLD) is over-represented in people with HIV (PWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism. Open-label, 48-week randomized trial with a 2 x 2 factorial design. Multicenter HIV clinics. Nondiabetic, virologically suppressed PLWH, aged at least 35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features). Adjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone. Change in liver fat fraction (LFF) between baseline and week-48 using magnetic resonance proton density fat fraction (MR PDFF). Six sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between March 19, 2018, and November 11, 2019. Seventy percent had imaging/biopsy and at least one 1 MAFLD criteria. The analysis included 82/90 with week-0 and week-48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40, 38, 8, and 14% had grade zero, one, two, and three steatosis, respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% confidence interval, 95% CI 2.97-5.48], P < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53 to 0.68, P = 0.45]), MET (-0.62 [-1.81 to 0.56, P = 0.30]), and MVC+MET (-1.04 [-2.74 to 0.65, P = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%. Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced liver fat as measured by MRPDFF compared to ART alone.

Intranasal Oxytocin for Obesity

BackgroundAccumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity.MethodsIn this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm2], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6.ResultsSixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [−1036 to 1428]; visceral fat: 3.1 cm2 [−11.0 to 17.2]; liver fat: −0.01 [−0.03 to 0.01]; resting energy expenditure: −64.0 kcal/day [−129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (−31.4 vs. 120.6 kcal; difference [95% confidence interval], −152.0 kcal [−302.3 to −1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups.ConclusionsIn this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.)

Multiparametric magnetic resonance imaging of the liver and spleen in Gaucher disease.

To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3.0T MRI and MRE between January 2019 and February 2020. Clinical, laboratory, and imaging data was collected. Mann-Whitney, Kruskal-Wallis, and Spearman's correlation were applied to evaluate liver and spleen MRI and MRE, clinical and laboratory variables, and GD-DS3. ERT and SRT treatment groups were compared. Hepatomegaly was seen in 15% and splenomegaly in 42% of the population. Moderate and strong and correlations were found between liver and spleen iron overload (rho = 0.537; p = 0.002); between liver and spleen volume (rho = 0.692, p < 0.001) and between liver and spleen stiffness (rho = 0.453, p = 0.006). Moderate correlations were found between liver stiffness and GD-DS3 (rho = 0.559; p < 0.001) and between splenic volume and GD-DS3 (rho = 0.524; p = 0.001). The prevalence of hepatosplenomegaly, liver fibrosis, and liver iron overload in treated patients with GD is low, which may be related to the beneficial effect of treatment. Liver MRE and splenic volume correlate with severity score and may be biomarkers of disease severity.

478 Magnetic Resonance Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease

OBJECTIVES/GOALS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern due to its increasing prevalence and association with type 2 diabetes mellitus. Non-invasive magnetic resonance-based biomarkers can aid in the monitoring of disease progression and identification of patients at risk for chronic liver disease. METHODS/STUDY POPULATION: Over 600 subjects will be recruited from the San Antonio Mexican American Family Study and from a second study, which consists of (i) T2DM patients diagnosed with either MASLD or metabolic dysfunction-associated steatohepatitis (MASH) or (ii) metabolically healthy controls. Hydrogen-1 MRS and diffusion-weighted MRI (DW-MRI) will be used to measure liver fat fraction and liver stiffness biomarkers, respectively. Several potential biomarkers of liver stiffness will be evaluated in vivo using the intravoxel incoherent motion (IVIM) model for DW-MRI. To further improve the diagnostic accuracy of patients with liver fibrosis, we will integrate MRI/MRS data with relevant clinical indicators of hepatic metabolism. Results will be compared to biopsy samples to evaluate the model’s diagnostic accuracy. RESULTS/ANTICIPATED RESULTS: Based on preliminary data, we predict that IVIM will be able to accurately diagnose hepatic fibrosis in patients with MASLD, allowing it to be implemented in clinics with high-field MRI units easily. Previous studies have shown correlations between IVIM estimates and fibrosis stages, however, none included additional clinical indicators of liver disease in their models. We have already found significant differences in metabolic measurements such as fasting plasma glucose and HbA1c levels. Additionally, the use of machine learning in developing these models has shown improvements in the ability to extract features from the data. The aim is to achieve high accuracy and robustness in the staging of liver fibrosis. DISCUSSION/SIGNIFICANCE: Over 100 million people in the US are affected by MASLD. Without treatment, it progresses from hepatic steatosis to MASH, fibrosis (liver stiffening), and ultimately to hepatic cirrhosis and hepatocellular carcinoma (HCC). Continued research efforts and clinical implementation of MRI and MRS are vital in combating the growing burden of MASLD.

Spleen volume is independently associated with non-alcoholic fatty liver disease, liver volume and liver fibrosis

Non-alcoholic fatty liver disease (NAFLD) can lead to irreversible liver damage manifesting in systemic effects (e.g., elevated portal vein pressure and splenomegaly) with increased risk of deadly outcomes. However, the association of spleen volume with NAFLD and related type 2-diabetes (T2D) is not fully understood. The UK Biobank contains comprehensive health-data of 500,000 participants, including clinical data and MR images of >40,000 individuals. The present study estimated the spleen volume of 37,066 participants through automated deep learning-based image segmentation of neck-to-knee MR images. The aim was to investigate the associations of spleen volume with NAFLD, T2D and liver fibrosis, while adjusting for natural confounders. The recent redefinition and new designation of NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD), promoted by major organisations of studies on liver disease, was not employed as introduced after the conduct of this study. The results showed that spleen volume decreased with age, correlated positively with body size and was smaller in females compared to males. Larger spleens were observed in subjects with NAFLD and T2D compared to controls. Spleen volume was also positively and independently associated with liver fat fraction, liver volume and the fibrosis-4 score, with notable volumetric increases already at low liver fat fractions and volumes, but not independently associated with T2D. These results suggest a link between spleen volume and NAFLD already at an early stage of the disease, potentially due to initial rise in portal vein pressure.

Erratum: Head-to-head comparison of magnetic resonance elastography-based liver stiffness, fat fraction, and T1 relaxation time in identifying at-risk NASH.

Erratum: Head-to-head comparison of magnetic resonance elastography-based liver stiffness, fat fraction, and T1 relaxation time in identifying at-risk NASH.

Addition of Dulaglutide or Empagliflozin to Standard-of-Care Treatment: Effect on Liver Steatosis in Patients With Type 2 Diabetes Mellitus.

Background Patients with liver steatosis and diabetes mellitus can benefit from medications like glucagon-like peptide 1 receptor agonists or sodium-glucose co-transporter 2 inhibitors, as far as both hyperglycemia and fatty liver are concerned. Studies comparing members of both these families have not yet been published. We aimed to compare the effects of Empagliflozin and Dulaglutide, focusing primarily on liver steatosis. Methodology This prospective, observational, controlled study enrolled 78 patients from two centers in Athens, Greece. Adults with type 2 diabetes mellitus (DM2) and nonalcoholic fatty liver disease were assigned to one of three groups and received either Empagliflozin or Dulaglutide or any other medical treatment deemed appropriate by their physician. The primary endpoint was the reduction in liver fat fraction, assessed using magnetic resonance imaging-proton density fat fraction. Additionally, we evaluated the proportion of patients achieving a relative reduction above 30% of their initial liver fat concentration. Results The Empagliflozin group exhibited a reduction in liver fat fraction. Furthermore, the percentage of patients with a relative reduction of liver steatosis, >30%, was significantly larger in this group, compared to the Dulaglutide and Control groups. Significant body weight reduction was observed in all three groups, but no improvement in fibrosis assessing scores was noted. Conclusions Empagliflozin is effective in improving liver steatosis, while Dulaglutide does not exhibit a similar effect. Larger studies, comparing these or related agents, are necessary,to further assess benefits in patients with DM2 and nonalcoholic fatty liver.

Implication of Bone Mineral Density and Body Composition Parameters for Length of Hospital Stay in Patients with COVID-19.

Multisystem information, including musculoskeletal information, can be captured from chest CT scans of patients with COVID-19 without further examination. This study aims to assess the relationship between chest CT-extracted baseline bone mineral density (BMD) and body composition parameters and the length of hospital stay in these patients. A retrospective analysis was performed in a cohort of 88 patients with COVID-19. Correlation analysis and a generalized linear model (GLM) were used to assess the associations between the length of hospital stay and covariates, including age, sex, body mass index (BMI), BMD and body composition variables. The mean length of hospital stay was 27.4±8.7 days. The length of hospital stay was significantly positively associated with age (r=0.202, p=0.046) and the paraspinal muscle fat ratio (r=0.246, p=0.021). The GLM involving age, sex, BMD, paraspinal muscle fat ratio, subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area, and liver fat fraction (LFF) showed that the length of hospital stay was positively correlated with VAT area (β coefficients, 95% CI: 9.304, 1.141-17.478, p=0.025). The musculoskeletal features extracted from chest CT correlated with the prognosis of COVID-19 patients. Factors including old age, a higher paraspinal muscle fat ratio and a larger VAT area in patients with COVID-19 were associated with longer hospital stays.