Proton Density Fat Fraction Research Articles

Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis.

Bariatric intervention has been reported to be an effective way to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in obese individuals. The current systemic review aimed to assess the changes in MRI-determined hepatic proton density fat fraction (MRI-PDFF) and nonalcoholic fatty liver disease activity score (NAS) after bariatric surgery or intragastric balloon/gastric banding in MASLD patients with obesity. We searched various databases including PubMed, OVID Medline, EMBASE, and Cochrane Library. Primary outcomes were the changes in intrahepatic fat on MRI-PDFF and histologic features of metabolic dysfunction-associated steatohepatitis (MASH). Thirty studies with a total of 3,134 patients were selected for meta-analysis. Bariatric intervention significantly reduced BMI (ratio of means, 0.79) and showed 72% reduction of intrahepatic fat on MRI-PDFF at 6 months after bariatric intervention (ratio of means, 0.28). Eight studies revealed that NAS was reduced by 60% at 3-6 months compared to baseline, 40% at 12-24 months, and 50% at 36-60 months. Nineteen studies revealed that the proportion of patients with steatosis decreased by 44% at 3-6 months, 37% at 12-24 months, and 29% at 36-60 months; lobular inflammation by 36% at 12-24 months and 51% at 36-60 months; ballooning degeneration by 38% at 12-24 months; significant fibrosis (≥F2) by 18% at 12-24 months and by 17% at 36-60 months after intervention. Bariatric intervention significantly improved MRI-PDFF and histologic features of MASH in patients with obesity. Bariatric intervention might be the effective alternative treatment option for patients with MASLD who do not respond to lifestyle modification or medical treatment.

Ultrasound-Derived Fat Fraction for Hepatic Steatosis Assessment: Prospective Study of Agreement With MRI PDFF and Sources of Variability in a Heterogeneous Population.

BACKGROUND. Metabolic dysfunction-associated steatotic liver disease is a growing global public health concern. Quantitative ultrasound measurements, such as ultrasound-derived fat fraction (UDFF), could provide noninvasive, cost-effective, and portable steatosis evaluation. OBJECTIVE. The purpose of this article was to evaluate utility of UDFF for steatosis assessment using proton density fat fraction (PDFF) as reference in patients undergoing liver MRI for heterogeneous indications and to assess UDFF variability. METHODS. This prospective study included a primary analysis of 187 patients (mean age, 53.8 years; 112 men, 75 women) who underwent 3-T liver MRI for any clinical indication from December 2020 to July 2021. Patients underwent investigational PDFF measurement, including determination of PDFFwhole-liver (mean PDFF of entire liver), and PDFFvoxel (PDFF in single voxel within right lobe, measured by MR spectroscopy), as well as investigational ultrasound with UDFF calculation (mean of five inter-costal measurements) within 1 hour after MRI. In a subanalysis, 21 of these patients underwent additional UDFF measurements 1, 3, and 5 hours after meal consumption. The study also included repeatability and reproducibility analysis of 30 patients (mean age, 26.3 years; 10 men, 20 women) who underwent clinical abdominal ultrasound between November 2022 and January 2023; in these patients, three operators sequentially performed UDFF measurements. RESULTS. In primary analysis, UDFF and PDFFwhole-liver measurements showed intra-class correlation coefficient (ICC) of 0.79. In Bland-Altman analysis, UDFF and PDFFvoxel measurements showed mean difference of 1.5% (95% CI, 0.6-2.4%), with 95% limits of agreement from -11.0% to 14.0%. UDFF measurements exhibited AUC for detecting PDFFvoxel at historic thresholds of 6.5% and greater, 17.4% and greater, and 22.1% and greater of 0.90, 0.95, and 0.95, respectively. In subanalysis, mean UDFF was not significantly different across time points with respect to meal consumption (p = .21). In repeatability and reproducibility analysis, ICC for intraoperator repeatability ranged from 0.98 to 0.99 and for interoperator reproducibility from 0.90 to 0.96. Visual assessment of patient-level data plots indicated increasing variability of mean UDFF measurements across operators and of intercostal measurements within individual patients with increasing steatosis. CONCLUSION. UDFF showed robust agreement with PDFF, diagnostic performance for steatosis grades, and intraoperator repeatability and interoperator reproducibility. Nonetheless, UDFF exhibited bias toward slightly larger values versus PDFF; intraoperator and interoperator variation increased with increasing steatosis. CLINICAL IMPACT. UDFF shows promise for steatosis assessment across diverse populations, although continued optimization remains warranted.

Associations between dietary fatty acids and liver fat accumulation in the UK Biobank

Steatotic liver disease, defined as >5% of hepatic fat content, is a major contributor to global morbidity and mortality, in particular due to its category metabolic associated steatotic liver disease (MASLD)(1). While its prevention focuses on promoting physical activity and maintaining a healthy weight and balanced diet, the associations between dietary fatty acids and liver fat remain unclear(2,3). The aim of this study was to examine the associations between dietary fatty acids and liver fat in the absence of excessive alcohol intake, independently of energy intake.Analyses were conducted on 9,268 non-diabetic participants from the UK Biobank with no pre- existing liver chronic illness or cardiovascular disease at baseline, and without excessive alcohol consumption. Dietary intake of total fat, saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) was measured using the mean of ≥2 Oxford WebQ 24-hr dietary assessments, responded to between 2009 and 2012. Liver proton density fat fraction (LPDFF) was measured by magnetic resonance imaging between 2016 and 2020. Multivariable linear regression models were calculated to assess the associations between fatty acid intakes and LPDFF, adjusting for key demographic and lifestyle confounders. In addition, associations between LPDFF and 10 individual SFAs, 7 PUFAs, and 4 MUFAs were also examined. Sensitivity analyses were carried out including participants who responded ≥4 dietary assessments (N=2,828).After fully adjusting for confounders, no significant associations between LPDFF (%) and MUFAs were found. Inverse associations with LPDFF were observed for PUFAs (−5.8% relative difference [95% confidence interval −0.6, −1.9]), per 5% increase in intake, while SFAs were positively associated with LPDFF (5.8% [3.3, 8.3]). Positive associations were observed per 1 SD increase in intake of individual fatty acids SFA stearic acid (4.20% [2.84, 5.57]) and palmitic acid (3.15% [1.78, 4.54]). Negative associations were observed for PUFAs alpha-linoleic acid (−2.32% [−3.47, −1.17]) and docosahexaenoic acid (−2.14% [−3.23, −1.0.3], and for MUFA erucic acid (−2.52% [−3.61, −1.43]). Sensitivity analyses presented similar results, and the associations between PUFAs and liver fat became slightly stronger (−10.73%, [−17.58, −3.32]).This observational study suggests that SFAs and PUFAs are associated with liver fat in opposite directions, independently of energy intake. While total MUFAs did not present significant associations with LPDFF, erucic acid was inversely associated with liver fat, highlighting the value of studying individual fatty acids. These different associations provide valuable information for the design of dietary trials that compare interventions with different types of fatty acids. These further studies would allow a better understanding of the ideal dietary advice to prevent liver steatosis and its global health impact.

Phospholipid metabolism-related genotypes of PLA2R1 and CERS4 contribute to nonobese MASLD.

Abnormal phospholipid metabolism is linked to metabolic dysfunction-associated steatotic liver disease (MASLD) development and progression. We aimed to clarify whether genetic variants of phospholipid metabolism modify these relationships. This case-control study consecutively recruited 600 patients who underwent MRI-based proton density fat fraction examination (240 participants with serum metabonomics analysis, 128 biopsy-proven cases) as 3 groups: healthy control, nonobese MASLD, and obese MASLD, (n = 200 cases each). Ten variants of phospholipid metabolism-related genes [phospholipase A2 Group VII rs1805018, rs76863441, rs1421378, and rs1051931; phospholipase A2 receptor 1 (PLA2R1) rs35771982, rs3828323, and rs3749117; paraoxonase-1 rs662 and rs854560; and ceramide synthase 4 (CERS4) rs17160348)] were genotyped using SNaPshot. The T-allele of CERS4 rs17160348 was associated with a higher risk of both obese and nonobese MASLD (OR: 1.95, 95% CI: 1.20-3.15; OR: 1.76, 95% CI: 1.08-2.86, respectively). PLA2R1 rs35771982-allele is a risk factor for nonobese MASLD (OR: 1.66, 95% CI: 1.11-1.24), moderate-to-severe steatosis (OR: 3.24, 95% CI: 1.96-6.22), and steatohepatitis (OR: 2.61, 95% CI: 1.15-3.87), while the paraoxonase-1 rs854560 T-allele (OR: 0.50, 95% CI: 0.26-0.97) and PLA2R1 rs3749117 C-allele (OR: 1.70, 95% CI: 1.14-2.52) are closely related to obese MASLD. After adjusting for sphingomyelin level, the effect of the PLA2R1 rs35771982CC allele on MASLD was attenuated. Furthermore, similar effects on the association between the CERS4 rs17160348 C allele and MASLD were observed for phosphatidylcholine, phosphatidic acid, sphingomyelin, and phosphatidylinositol. The mutations in PLA2R1 rs35771982 and CERS4 rs17160348 presented detrimental impact on the risk of occurrence and disease severity in nonobese MASLD through altered phospholipid metabolism.

Diagnosis and non-invasive assessment of MASLD in type 2 diabetes and obesity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease and an important cause of cirrhosis and hepatocellular carcinoma. It is strongly associated with type 2 diabetes and obesity. Because of the huge number of patients at risk of MASLD, it is imperative to use non-invasive tests appropriately. To provide a narrative review on the performance and limitations of non-invasive tests, with a special emphasis on the impact of diabetes and obesity. We searched PubMed and Cochrane databases for articles published from 1990 to August 2023. Abdominal ultrasonography remains the primary method to diagnose hepatic steatosis, while magnetic resonance imaging proton density fat fraction is currently the gold standard to quantify steatosis. Simple fibrosis scores such as the Fibrosis-4 index are well suited as initial assessment in primary care and non-hepatology settings to rule out advanced fibrosis and future risk of liver-related complications. However, because of its low positive predictive value, an abnormal test should be followed by specific blood (e.g. Enhanced Liver Fibrosis score) or imaging biomarkers (e.g. vibration-controlled transient elastography and magnetic resonance elastography) of fibrosis. Some non-invasive tests of fibrosis appear to be less accurate in patients with diabetes. Obesity also affects the performance of abdominal ultrasonography and transient elastography, whereas magnetic resonance imaging may not be feasible in some patients with severe obesity. This article highlights issues surrounding the clinical application of non-invasive tests for MASLD in patients with type 2 diabetes and obesity.

Assessment of Hepatic Steatosis Using Ultrasound-Based Techniques: Focus on Fat Quantification

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, affecting more than 30% of the global population, and is associated with increased liver-related morbidity and mortality, and extrahepatic complications. With the increasing prevalence of MASLD, there is an urgent need for accessible, non-invasive methods to detect hepatic steatosis. Currently, liver biopsy and magnetic resonance imaging proton density fat fraction are considered reference standards for diagnosing hepatic steatosis; however, their invasiveness and limited accessibility limit their widespread use. Ultrasonography (US) is a promising alternative owing to its cost-effectiveness and widespread accessibility. Recently, quantitative US techniques have been developed and commercialized by several vendors to measure steatosis by detecting changes in various acoustic properties associated with hepatic steatosis, making it readily accessible. Controlled attenuation parameter (CAP), which evaluates hepatic steatosis using the attenuation of the US beam, is the most widely studied algorithm as a non-imaging technique. Several other algorithms are also available on B-mode ultrasound systems, and their diagnostic performance is comparable to or better than that of the CAP. Therefore, we aimed to review current US-based methods for detecting and grading hepatic steatosis, discussing their diagnostic performance and utilization.

Evaluating Sex-specific Differences in Abdominal Fat Volume and Proton Density Fat Fraction at MRI Using Automated nnU-Net-based Segmentation.

Sex-specific abdominal organ volume and proton density fat fraction (PDFF) in people with obesity during a weight loss intervention was assessed with automated multiorgan segmentation of quantitative water-fat MRI. An nnU-Net architecture was employed for automatic segmentation of abdominal organs, including visceral and subcutaneous adipose tissue, liver, and psoas and erector spinae muscle, based on quantitative chemical shift-encoded MRI and using ground truth labels generated from participants of the Lifestyle Intervention (LION) study. Each organ's volume and fat content were examined in 127 participants (73 female and 54 male participants; body mass index, 30-39.9 kg/m2) and in 81 (54 female and 32 male participants) of these participants after an 8-week formula-based low-calorie diet. Dice scores ranging from 0.91 to 0.97 were achieved for the automatic segmentation. PDFF was found to be lower in visceral adipose tissue compared with subcutaneous adipose tissue in both male and female participants. Before intervention, female participants exhibited higher PDFF in subcutaneous adipose tissue (90.6% vs 89.7%; P < .001) and lower PDFF in liver (8.6% vs 13.3%; P < .001) and visceral adipose tissue (76.4% vs 81.3%; P < .001) compared with male participants. This relation persisted after intervention. As a response to caloric restriction, male participants lost significantly more visceral adipose tissue volume (1.76 L vs 0.91 L; P < .001) and showed a higher decrease in subcutaneous adipose tissue PDFF (2.7% vs 1.5%; P < .001) than female participants. Automated body composition analysis on quantitative water-fat MRI data provides new insights for understanding sex-specific metabolic response to caloric restriction and weight loss in people with obesity. Keywords: Obesity, Chemical Shift-encoded MRI, Abdominal Fat Volume, Proton Density Fat Fraction, nnU-Net ClinicalTrials.gov registration no. NCT04023942 Supplemental material is available for this article. Published under a CC BY 4.0 license.

Diagnostic performance of quantitative ultrasonography for hepatic steatosis in a health screening program: a prospective single-center study.

This study compared the diagnostic performance of quantitative ultrasonography (QUS) with that of conventional ultrasonography (US) in assessing hepatic steatosis among individuals undergoing health screening using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) as the reference standard. This single-center prospective study enrolled 427 participants who underwent abdominal MRI and US. Measurements included the attenuation coefficient in tissue attenuation imaging (TAI) and the scatter-distribution coefficient in tissue scatter-distribution imaging (TSI). The correlation between QUS and MRI-PDFF was evaluated. The diagnostic capabilities of QUS, conventional B-mode US, and their combined models for detecting hepatic fat content of ≥5% (MRI-PDFF ≥5%) and ≥10% (MRI-PDFF ≥10%) were compared by analyzing the areas under the receiver operating characteristic curves. Additionally, clinical risk factors influencing the diagnostic performance of QUS were identified using multivariate linear regression analyses. TAI and TSI were strongly correlated with MRI-PDFF (r=0.759 and r=0.802, respectively; both P&lt;0.001) and demonstrated good diagnostic performance in detecting and grading hepatic steatosis. The combination of QUS and B-mode US resulted in the highest areas under the ROC curve (AUCs) (0.947 and 0.975 for detecting hepatic fat content of ≥5% and ≥10%, respectively; both P&lt;0.05), compared to TAI, TSI, or B-mode US alone (AUCs: 0.887, 0.910, 0.878 for ≥5% and 0.951, 0.922, 0.875 for ≥10%, respectively). The independent determinants of QUS included skinliver capsule distance (β=7.134), hepatic fibrosis (β=4.808), alanine aminotransferase (β=0.202), triglyceride levels (β=0.027), and diabetes mellitus (β=3.710). QUS is a useful and effective screening tool for detecting and grading hepatic steatosis during health checkups.

Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis

ObjectiveIn nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers.MethodsIn this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistical approach.ResultsIn total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2.ConclusionMRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling.Clinical relevance statementLiver fibrosis may be considered a cardiovascular risk factor in patients without cirrhosis. Further research on the mechanisms that link liver fibrosis to left ventricular concentricity may reveal potential therapeutic targets in patients with non-alcoholic fatty liver disease (NAFLD).Key PointsPreviously, studies on liver fibrosis and cardiac remodeling have focused on advanced stages of liver fibrosis.Liver fibrosis is associated with left ventricular (LV) concentricity and may relate to interleukin-1 receptor type 2.Interleukin-1 signaling is a potential mechanistic interlink between early liver fibrosis and LV remodeling.

Age and BMI have different effects on subcutaneous, visceral, liver, bone marrow, and muscle adiposity, as measured by CT and MRI.

We analyzed quantitative computed tomography (CT) and chemical shift-encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots. In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2-L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements. Of the 168 men, 29% had normal BMI (<24.0 kg/m2), 47% had overweight (24.0-27.9 kg/m2), and 24% had obesity (≥ 28.0 kg/m2). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes. Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT.

Sodium quantification in skeletal muscle: comparison between Cartesian gradient-echo and radial ultra-short echo time 23Na MRI techniques

BackgroundClinical magnetic resonance imaging (MRI) studies often use Cartesian gradient-echo (GRE) sequences with ~2-ms echo times (TEs) to monitor apparent total sodium concentration (aTSC). We compared Cartesian GRE and ultra-short echo time three-dimensional (3D) radial-readout sequences for measuring skeletal muscle aTSC.MethodsWe retrospectively evaluated 211 datasets from 112 volunteers aged 62.3 ± 12.1 years (mean ± standard deviation), acquired at 3 T from the lower leg. For 23Na MRI acquisitions, we used a two-dimensional Cartesian GRE sequence and a density-adapted 3D radial readout sequence with cuboid field-of-view (DA-3D-RAD-C). We calibrated the 23Na MR signal using reference tubes either with or without agarose and subsequently performed a relaxation correction. Additionally, we employed a six-echo 1H GRE sequence and a multi-echo spin-echo sequence to calculate proton density fat fraction (PDFF) and water T2. Paired Wilcoxon signed-rank test, Cohen dz for paired samples, and Spearman correlation were used.ResultsRelaxation correction effectively reduced the differences in muscle aTSC between the two acquisition and calibration methods (DA-3D-RAD-C using NaCl/agarose references: 20.05 versus 19.14 mM; dz = 0.395; Cartesian GRE using NaCl/agarose references: 19.50 versus 18.82 mM; dz = 0.427).Both aTSC of the DA-3D-RAD-C and Cartesian GRE acquisitions showed a small but significant correlation with PDFF as well as with water T2.ConclusionsDifferent 23Na MRI acquisition and calibration approaches affect aTSC values. Applying relaxation correction is advised to minimize the impact of sequence parameters on quantification, and considering additional fat correction is advisable for patients with increased fat fractions.Relevance statementThis study highlights relaxation correction’s role in improving sodium MRI accuracy, paving the way for better disease assessment and comparability of measured sodium signal in patients.Key points• Differences in MRI acquisition methods hamper the comparability of sodium MRI measurements.• Measured sodium values depend on used MRI sequences and calibration method.• Relaxation correction during postprocessing mitigates these discrepancies.• Thus, relaxation correction enhances accuracy of sodium MRI, aiding its clinical use.Graphical

Relationship between Femoral Proximal Bone Quality Assessment by MRI IDEAL-IQ Sequence and Body Mass Index in Elderly Men.

Bone assessment using the MRI DEAL-IQ sequence may have the potential to serve as a substitute for evaluating bone strength by quantifying the bone marrow hematopoietic region (R2*) and marrow adiposity (proton density fat fraction: PDFF). Higher body mass index (BMI) is associated with increased bone mineral density (BMD) in the proximal femur; however, the relationship between BMI and R2* or PDFF remains unclear. Herein, we investigated the correlation between BMI and MRI IDEAL-IQ based R2* or PDFF of the proximal femur. A retrospective single-cohort study was conducted on 217 patients diagnosed with non-metastatic prostate cancer between September 2019 and December 2022 who underwent MRI. The correlation between BMI and R2* or PDFF of the proximal femur was analyzed using Spearman's rank correlation test. Among 217 patients (median age, 74 years; median BMI, 23.8 kg/m2), there was a significant positive correlation between BMI and R2* at the right and left proximal femur (r = 0.2686, p < 0.0001; r = 0.2755, p < 0.0001, respectively). Furthermore, BMI and PDFF showed a significant negative correlation (r = -0.239, p = 0.0004; r = -0.2212, p = 0.001, respectively). In elderly men, the increased loading on the proximal femur due to elevated BMI was observed to promote a decrease in bone marrow adiposity in the proximal femur, causing a tendency for a transition from fatty marrow to red marrow with hematopoietic activity. These results indicate that the MRI IDEAL-IQ sequence may be valuable for assessing bone quality deterioration in the proximal femur.

Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease.

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with βFLI→SBP = 0.081, P < 0.001 versus βSBP→FLI = 0.020, P = 0.031; βFLI→DBP = 0.082, P < 0.001 versus βDBP→FLI = -0.006, P = 0.480 for CEMC, and βFLI→SBP = 0.057, P < 0.001 versus βSBP→FLI = -0.001, P = 0.727; βFLI→DBP = 0.061, P < 0.001, versus βDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.

Modelling and assessment of glucose-lactate kinetics in youth withoverweight, obesityand metabolic dysfunction-associated steatotic liver disease: A pilot study.

In this study, we investigated glucose and lactate kinetics during a 75 g oral glucose tolerance test (OGTT) in 23 overweight and obese adolescents and assessed putative differences among participants with and without metabolic dysfunction-associated steatotic liver disease (MASLD). We enrolled 23 young people (six girls) with obesity [body mass index 33 (29-37)]. Glucose-lactate kinetics parameters (disposal glucose insulin sensitivity, SID; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, kL) and lactate production rate (LPR) were estimated using the oral glucose-lactate minimal model. MASLD presence was assessed using the proton density fat fraction. We analysed glucose, lactate and LPR time to peak, peak values and area under the curve and evaluated differences using the Wilcoxon test. MASLD and no-MASLD participants were compared using the Mann-Whitney test. Correlations between parameters were assessed using the Spearman correlation coefficient (ρ). We also tested the performance of two (4 or 3 h OGTT) protocols in estimating oral glucose-lactate minimal model and LPR parameters. Glucose peaks 30 min earlier than lactate (p = .0019). This pattern was present in the no-MASLD group (p < .001). LPR peaks 30 min later in the MASLD group (p = .02). LPR and kL were higher in MASLD, suggesting higher glycolysis and lactate utilization. SID and fr correlate significantly (ρ = -0.55, p = .008). SID and fr were also correlated with the body mass index, (ρ = -0.45, p = .04; and ρ = 0.45; p = .03). The protocol duration did not influence the estimates of the parameters. Youth with MASLD showed a delayed glucose metabolism, possibly because of greater utilization of the underlying substrates. A 3-h OGTT may be used to assess lactate metabolism effectively.

Influence of Gd-EOB-DTPA on proton-density fat fraction in the liver using chemical shift-encoded magnetic resonance imaging at 3-T.

Non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), have become increasingly prevalent owing to the rise in metabolic syndromes. Accurate assessment of hepatic fat deposition and inflammation is crucial for diagnosing and managing NAFLD/NASH. We investigated the influence of Gd-EOB-DTPA, (EOB) on proton-density fat fraction (PDFF) measurements using chemical shift-encoded magnetic resonance imaging (CSE-MRI) at 3-T. In total, 431 patients who underwent EOB contrast-enhanced MRI were included. PDFF measurements were obtained from pre- and post-contrast CSE-MRI. Linear regression and Bland-Altman analyses were performed to assess the correlation and agreement between pre- and post-EOB PDFF measurements. Relative enhancement (RE) of the liver was calculated as an EOB uptake index. There was a significant decrease in PDFF following EOB administration compared with the pre-contrast values (P < 0.0001), which was observed across all PDFF ranges (< 10% and ≥ 10%). Linear regression analysis revealed high correlation between pre- and post-EOB PDFF measurements. Bland-Altman analysis indicated a small bias between pre- and post-EOB PDFF values. Subgroup analysis based on RE showed a significant difference in ΔPDFF between patients with high RE (> 120%) and those with lower RE levels. EOB administration resulted in a slight decrease in PDFF measurements obtained using CSE-MRI at 3-T. We were able to generalize and clarify that the PDFF of the liver on 3D CSE-MRI at 3-T was slightly decreased after EOB administration as we used a larger group of patients compared to previous studies.

Controlled attenuation parameter (CAP): the clinical value based on MRI-PDFF in children with obesity.

Controlled attenuation parameter (CAP) is a noninvasive and quantitative method to evaluate hepatic steatosis, which is not well evaluated in children. The aim ofthis study was to examine the diagnostic value of CAP forhepatic steatosis in children with obesity based on MR proton density fat fraction (PDFF). About 108 pediatric patients with nonalcoholic fatty liver disease (NAFLD) who were assessed for PDFF, CAP, and other laboratory results were enrolled. In this study, pediatric patients were separated for the obese group (n=80) and the severe obese group (n=28). Hepatic steatosis grades (0-3) were classified according to PDFF using cutoff values of 6.4 , 17.4, and 22.1 %. There are significant differences in CAP between the obese and severe obese groups (p<0.05). CAP showed a good correlation with PDFF in pediatric patients with NAFLDfor diagnosing hepatic steatosis using a cutoff valueof 265 dB/m (p<0.001). Meanwhile, ALT significantly outperforms CAP in receiver-operating curve (ROC) analysis for diagnosing hepatic steatosis grades. The diagnostic accuracy of CAP for steatosis is 77.8 %, and the diagnostic accuracy of ALT for steatosis is 83.3 %. While CAP holds promise as a diagnostic tool for pediatric NAFLD, its diagnostic performance warrants some caution. The potential of CAP is evident; however, ALTemerges as a simpler and more accurate measure for detecting hepatic steatosis in children. Further research is essential to determine the optimal role of CAP in pediatric NAFLD diagnosis and management.

Relationship between paraspinal muscle properties and bone mineral density based on QCT in patients with lumbar disc herniation

ObjectiveIncreasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH).MethodsA total of 383 patients (aged 24–76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors.ResultsAmong the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05).ConclusionIn patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.

Prognostic significance of low hepatic fat content in advanced chronic liver disease: MRI-PDFF insights

Introduction and ObjectivesThe mechanisms of hepatic fat loss in late-stage metabolic dysfunction-associated fatty liver disease (MASLD) are enigmatic and the prognostic significance of low hepatic fat content (LHF) in chronic liver disease (CLD) is unknown. Proton density fat fraction (PDFF), measured by magnetic resonance imaging (MRI), is considered the most accurate noninvasive method for quantifying hepatic fat content. This study aimed to address these issues by evaluating PDFF. Patients and MethodsThis is a single-center, retrospective study involving 762 patients with CLD, measuring liver stiffness (LS) using MR elastography and PDFF using MRI. LHF was defined as a PDFF ≤ 2.7 % and hepatic reserve function was assessed using the albumin-bilirubin (ALBI) score. Multivariate analysis explored associations between variables. ResultsLHF was 27 % in the entire cohort, and PDFF was significantly decreased with LS ≥ 5.5 kPa (p < 0.05). On the multivariate analysis, low body mass index and ALBI score were independently associated with LHF (p < 0.05). In advanced CLD (n = 288), ALBI score and PDFF showed a significant negative correlation regardless of etiology (MASLD/non-MASLD: r= -0.613/-0.233), and the prevalence of LHF increased with progression of ALBI grade (p < 0.01 each). In addition, lower PDFF was associated with increased liver-related and all-cause mortality (p < 0.01), and Cox proportional hazards models extracted LHF as an independent prognostic factor, along with ALBI score and hepatocellular carcinoma (p < 0.05 each). ConclusionsIn ACLD, hepatic reserve dysfunction contributed to hepatic fat loss independent of nutritional status, suggesting that LHF may be a poor prognostic factor in all etiologies.

Dietary Effect on Peripheral and Cerebral Vascular Function in Adults with Non-Alcoholic Fatty Liver Disease

Objective: Non-alcoholic fatty liver disease (NAFLD) is a recognized independent risk factor for cardiovascular and cerebrovascular dysfunction. The present study evaluated the effect of dietary interventions on peripheral and cerebral vascular function in individuals with NAFLD. Methods: We studied 30 middle-aged adults (55±9 years) with NAFLD or with elevated NAFLD risk (with prediabetes symptoms). Liver fat content was assessed via 1H magnetic resonance spectroscopy. NAFLD was defined as liver fat proton density fat fraction (PDFF) exceeding 5%. Participants were randomly assigned to a low-carbohydrate diet (carbohydrate intake &lt;30 g/d) or a low-calorie diet (30% calorie intake reduction). Arterial stiffness (via brachial-ankle pulse wave velocity-baPWV), carotid artery intima-media thickness (IMT), endothelium-dependent vasodilation (via flow-mediated dilation-FMD), cerebrovascular reactivity (CVR) in the middle cerebral artery (MCA), and blood concentrations of cardiovascular risk factors were measured before and after a two-week dietary intervention. Results: Participants with NAFLD represented 70% of the current cohort. Following the dietary interventions, participants had significant reductions in body weight (95%CI [-3.22, -1.41 kg]) and fat mass (95%CI [-1.64, -0.56 kg]), accompanied by decreased liver fat content (95%CI [-2.62, -0.79%]). These changes were only evident in the NAFLD group with no significant differences between the two dietary interventions. Systolic and diastolic blood pressure as well as pulse pressure significantly decreased in both NAFLD and non-NAFLD groups. Total cholesterol (95%CI [-22.2, -1.5 mg/dL]) and triglyceride (95%CI [-30.4, -0.9 mg/dL]) concentrations decreased in those with NAFLD assigned to the low-carbohydrate diet. baPWV decreased (95%CI [-78.6, -12.4 cm/s]) only in individuals with NAFLD assigned to the low-calorie diet. FMD significantly increased (95%CI [0.5, 5.1%]) only in individuals with NAFLD assigned to the low-carbohydrate diet. Lower baseline liver fat content was associated with greater improvement in FMD (r=-0.60, p=0.008) in the NAFLD group. Carotid IMT and cerebrovascular parameters (e.g., pulsatility index, CVR, MCA blood flow velocity) remained unchanged in any groups. Changes in vascular function were not associated with the corresponding changes in liver fat content. Conclusion: The two-week dietary intervention involving either a low-carbohydrate or low-calorie diet elicited significant reductions in liver fat content and improvements in peripheral arterial stiffness and endothelium-dependent vasodilation in adults with NAFLD. UT Aging Initiatives. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of Resmetirom, a Liver-Directed, Thyroid Hormone Receptor Beta-Selective Agonist, in Managing Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis

BackgroundResmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH. MethodsElectronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis. ResultsThree randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD −27.76% [95%CI: −32.84, −22.69]; for resmetirom 100 mg: MD −36.01% [95%CI: −41.54, −30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD −21.45 dBm [95%CI: −29.37, −13.52]; for resmetirom 100 mg: MD −25.51 dBm [95%CI: −33.53, −17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable. ConclusionResmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.