Magnetic Resonance Imaging-proton Density Fat Research Articles

Proton density fat fraction: magnetic resonance imaging applications beyond the liver.

Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an emerging quantitative imaging biomarker that accurately measures the fat fraction of tissue by correcting factors influencing magnetic resonance signal intensity. Beyond fat quantification, it also measures R2* which is a direct measure of iron concentration. The utilization of MRI-PDFF in liver diseases is well established. In the present review, we focused on applications of MRI-PDFF in different body areas including pancreas, bone, muscle, spleen, testis, visceral, and subcutaneous adipose tissue. Future studies can enable tracking of quantitative fat fraction changes in different organs simultaneously, which can be critical in understanding fat metabolism.

Controlled attenuation parameter in the diagnosis of different liver steatosis groups in children with obesity.

To investigate the utility of the controlled attenuation parameter (CAP), as measured by a liver elastography technique, in predicting varying degrees of liver steatosis in children with obesity. Children with obesity attending the pediatric obesity clinic at the Affiliated Hospital of Hangzhou Normal University from July 2020 to May 2021 were retrospectively analysed. The 71 subjects were divided into four groups according to the degree of liver steatosis obtained by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). The gender, age, CAP, LSM, ALT, AST, BMI, uric acid, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, insulin, and blood 25-hydroxyvitamin D levels of the four groups were compared, and the differences were analysed. Clinical data with significant differences were included in the logistic regression analysis. The receiver operating characteristic (ROC) curve for the CAP for the 71 subjects with different degrees of liver steatosis was plotted to evaluate the diagnostic value. The 71 children were divided into groups according to the degree of hepatic steatosis obtained by MRI-PDFF, and the clinical data for each group were compared. It was found that there was statistical significance for CAP, ALT, and AST in cases of moderate and severe hepatic steatosis (p < 0.05). Logistic regression analysis was conducted between CAP, ALT, AST, and moderate to severe hepatic steatosis in children with obesity, and it was found that CAP was a factor related to moderate to severe hepatic steatosis in children with obesity. The ROC curve indicated that CAP has diagnostic value for NAFLD in children with obesity. There is diagnostic value in the use of CAP for hepatic steatosis in children with obesity, and there is greater diagnostic value in the use of CAP for children with moderate to severe hepatic steatosis.

Optimal Cut-off of Controlled Attenuation Parameter with MRI-PDFF as Reference Standard for the Detection of Liver Steatosis

Background and aims: Controlled attenuation parameter (CAP) is widely available in India for diagnosing liver steatosis. However, data regarding the optimal cut-off values of CAP for diagnosing liver steatosis are scarce. Magnetic resonance imaging proton-density fat fraction (MRI-PDFF) is an accurate technique for quantifying liver steatosis. Thus, this study examined the diagnostic accuracy and the optimal cut-off values of CAP for diagnosing liver steatosis with MRI-PDFF as reference standard.

Value of magnetic resonance imaging-proton density fat fraction and FibroScan in quantitative evaluation of liver fat content in patients with chronic hepatitis B

Value of magnetic resonance imaging-proton density fat fraction and FibroScan in quantitative evaluation of liver fat content in patients with chronic hepatitis B

Deep Learning Techniques for Fatty Liver Using Multi-View Ultrasound Images Scanned by Different Scanners: Development and Validation Study.

BackgroundFat fraction values obtained from magnetic resonance imaging (MRI) can be used to obtain an accurate diagnosis of fatty liver diseases. However, MRI is expensive and cannot be performed for everyone.ObjectiveIn this study, we aim to develop multi-view ultrasound image–based convolutional deep learning models to detect fatty liver disease and yield fat fraction values.MethodsWe extracted 90 ultrasound images of the right intercostal view and 90 ultrasound images of the right intercostal view containing the right renal cortex from 39 cases of fatty liver (MRI–proton density fat fraction [MRI–PDFF] ≥ 5%) and 51 normal subjects (MRI–PDFF < 5%), with MRI–PDFF values obtained from Good Gang-An Hospital. We obtained combined liver and kidney-liver (CLKL) images to train the deep learning models and developed classification and regression models based on the VGG19 model to classify fatty liver disease and yield fat fraction values. We employed the data augmentation techniques such as flip and rotation to prevent the deep learning model from overfitting. We determined the deep learning model with performance metrics such as accuracy, sensitivity, specificity, and coefficient of determination (R2).ResultsIn demographic information, all metrics such as age and sex were similar between the two groups—fatty liver disease and normal subjects. In classification, the model trained on CLKL images achieved 80.1% accuracy, 86.2% precision, and 80.5% specificity to detect fatty liver disease. In regression, the predicted fat fraction values of the regression model trained on CLKL images correlated with MRI–PDFF values (R2=0.633), indicating that the predicted fat fraction values were moderately estimated.ConclusionsWith deep learning techniques and multi-view ultrasound images, it is potentially possible to replace MRI–PDFF values with deep learning predictions for detecting fatty liver disease and estimating fat fraction values.

Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging.

SummaryBackgroundGlucagon‐like peptide‐1 receptor agonists may be a treatment option in patients with non‐alcoholic fatty liver disease (NAFLD).AimsTo investigate the effects of semaglutide on liver stiffness and liver fat in subjects with NAFLD using non‐invasive magnetic resonance imaging (MRI) methods.MethodsThis randomised, double‐blind, placebo‐controlled trial enrolled subjects with liver stiffness 2.50‐4.63 kPa by magnetic resonance elastography (MRE) and liver steatosis ≥10% by MRI proton density fat fraction (MRI‐PDFF). The primary endpoint was change from baseline to week 48 in liver stiffness assessed by MRE.ResultsSixty‐seven subjects were randomised to once‐daily subcutaneous semaglutide 0.4 mg (n = 34) or placebo (n = 33). Change from baseline in liver stiffness was not significantly different between semaglutide and placebo at week 48 (estimated treatment ratio 0.96 (95% CI 0.89, 1.03; P = 0.2798); significant differences in liver stiffness were not observed at weeks 24 or 72. Reductions in liver steatosis were significantly greater with semaglutide (estimated treatment ratios: 0.70 [0.59, 0.84], P = 0.0002; 0.47 [0.36, 0.60], P < 0.0001; and 0.50 [0.39, 0.66], P < 0.0001) and more subjects achieved a ≥ 30% reduction in liver fat content with semaglutide at weeks 24, 48 and 72, (all P < 0.001). Decreases in liver enzymes, body weight and HbA1c were also observed with semaglutide.ConclusionsThe change in liver stiffness in subjects with NAFLD was not significantly different between semaglutide and placebo. However, semaglutide significantly reduced liver steatosis compared with placebo which, together with improvements in liver enzymes and metabolic parameters, suggests a positive impact on disease activity and metabolic profile. ClinicalTrials.gov identifier: NCT03357380.

Utilization of a Directly Supervised Telehealth-Based Exercise Training Program in Patients With Nonalcoholic Steatohepatitis: Feasibility Study.

BackgroundMost patients with nonalcoholic fatty liver disease (NAFLD) are physically inactive despite the well-known benefits of physical activity. Telehealth offers promise as a novel way to deliver an exercise training program and increase physical activity. However, the feasibility, safety, and efficacy of telehealth-based exercise programs is unknown in patients with NAFLD.ObjectiveThe aim of this study was to determine the feasibility of a directly supervised exercise training program delivered exclusively with telehealth to patients with nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD.MethodsIn response to COVID-19 research restrictions, we adapted an existing clinical trial and delivered 20 weeks of moderate-intensity aerobic training 5 days a week under real-time direct supervision using an audio–visual telehealth platform. Aerobic training was completed by walking outdoors or using a home treadmill. Fitness activity trackers with heart rate monitors ensured exercise was completed at the prescribed intensity with real-time feedback from an exercise physiologist.ResultsThree female patients with biopsy-proven NASH were enrolled with a mean age of 52 (SD 14) years. The mean body mass index was 31.9 (SD 5.1) kg/m2. All patients had metabolic syndrome. All patients completed over 80% of exercise sessions (mean 84% [SD 3%]) and no adverse events occurred. Body weight (mean –5.1% [SD 3.7%]), body fat (mean –4.4% [SD 2.3%]), and waist circumference (mean –1.3 in. [SD 1.6 in.]) all improved with exercise. The mean relative reduction in magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was 35.1% (SD 8.8%). Mean reductions in hemoglobin A1c and Homeostatic Model Assessment for Insulin Resistance were also observed (–0.5% [SD 0.2%] and –4.0 [SD 1.2], respectively). The mean peak oxygen consumption (VO2peak) improved by 9.9 (SD 6.6) mL/kg/min.ConclusionsThis proof-of-concept study found that supervised exercise training delivered via telehealth is feasible and safe in patients with NASH. Telehealth-based exercise training also appears to be highly efficacious in patients with NASH, but this will need to be confirmed by future large-scale trials.Trial RegistrationClinicalTrials.gov NCT03518294; https://clinicaltrials.gov/ct2/show/NCT03518294

Usefulness of Controlled Attenuation Parameter for Identification and Grading of Nonalcoholic Fatty Liver Disease in Adolescents with Obesity.

To identify controlled attenuation parameter (CAP) based cutoffs for diagnosing and grading hepatic steatosis in adolescents with overweight/obesity, using magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as the reference method. Adolescents with overweight/obesity were included. Fasting glucose, insulin, aspartate aminotransferase, and alanine aminotransferase were estimated. Hepatic steatosis (S) was assessed by MRI-PDFF, and graded as S0, S1, S2, and S3 with fat fraction cutoffs of < 6.0%, ≥ 6.0% to < 17.5%, ≥ 17.5% to < 23.3%, and ≥ 23.3%, respectively. CAP and liver stiffness measure (LSM) were assessed using FibroScan. Receiver operating characteristic (ROC) curves were used to estimate the CAP scores predicting various grades of hepatic steatosis. A total of 108 adolescents aged 12.4 ± 1.9 y, with mean BMI of 26.7 ± 4.9kg/m2 were included. S0, S1, S2, and S3 steatosis by MRI-PDFF was identified in 15, 70, 13, and 10 adolescents, respectively. A moderate positive correlation was observed between CAP score and MRI-estimated hepatic fat (r = 0.528, p < 0.001). The optimal CAP cutoffs for identifying ≥ S1, ≥ S2, and S3 steatosis were 271 [area under ROC (AUROC) 0.745 (0.630-0.859)], 296 [AUROC 0.820 (0.728-0.911)], and 309dB/m [AUROC 0.836 (0.729-0.944)], respectively. CAP score had a good discriminative ability to diagnose fatty liver in adolescents with overweight or obesity.

Hepatic Fat Reduction Due to Resmetirom in Patients With Nonalcoholic Steatohepatitis Is Associated With Improvement of Quality of Life

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with adverse clinical outcomes and impaired health-related quality of life (HRQL). Patients with biopsy-proven non-cirrhotic NASH with hepatic fat fraction of ≥10% by magnetic resonance imaging-proton density fat fraction were enrolled in a phase 2, multicenter, double-blind, randomized, placebo-controlled study of resmetirom. HRQL was assessed using Short Form-36 throughout 36 weeks of treatment. One hundred twenty-five NASH patients were enrolled (50 ± 11 years old, 50% male, 94% white, body mass index 35 ± 6 kg/m2, 39% with diabetes mellitus). Of these, 84 patients received 80 mg of resmetirom daily, and 41 received placebo. At baseline, HRQL scores were not different from general population norms (Physical Component Summary [PCS] 47.9 ± 9.3 vs 50, Mental Component Summary 50.4 ± 10.0 vs 50; all P > .05). By treatment week 12, patients who received resmetirom experienced improvement of Bodily Pain and Short Form-6D utility scores (P < .05); no HRQL improvement was noted in placebo (all P > .05). Improvement in PCS continued up to week 36 of treatment with resmetirom, again with no improvement in placebo group (all P > .05). Adjusted for the baseline score and clinicodemographic confounders, meeting the endpoint of a decrease in proton density fat fraction of ≥30% by week 12 (met by 54 of 116 treatment completers; 47 of 54 on resmetirom) was independently associated with greater improvements in Physical Functioning and PCS scores at week 36 (P < .05). Patients with improvement in NASH and fibrosis on liver biopsy also showed improvement in components of HRQL. Patients with NASH treated who improved their hepatic fat fraction and/or Nonalcoholic Fatty Liver Disease Activity Score on serial liver biopsy experienced improvement of HRQL. Further studies are needed to confirm long-term sustainability of that improvement. gov #NCT02912260.

Reliability of Performing Multiparametric Ultrasound in Adult Livers.

The aim of the study was to test inter-observer and intra-observer reliability of measuring multiparametric ultrasound in adult livers. We prospectively measured shear wave velocity (SWV, m/s), shear wave dispersion slope (SWD, m/s/kHz), attenuation coefficient (ATI, dB/cm/MHz), normalized local variance (NLV), and echo intensity ratio of liver to kidney (L/K ratio) in 21 adults who underwent liver magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Intraclass correlation coefficient and 95% Bland-Altman limits of agreement (95% LOA) were used to analyze intra- and inter-observer reproducibility. Based on liver MRI-PDFF, 21 participants (8 men and 13 women, mean age 55 years) were divided into group 1 (11 normal livers, MRI-PDFF <5%) and group 2 (10 steatotic livers, MRI-PDFF ≥5%). ICCs for intra-observer repeatability and inter-observer reproducibility in measuring multiple ultrasound parameters in both normal and steatotic livers were above 0.75. However, 95% confidence interval for measuring SWD in all livers and L/K ratio in normal livers was 0.38-0.90 and 0.47-0.91, respectively. Differences in SWV, SWD, ATI, NLV, L/K ratio, and MRI-PDFF between participants with and without hepatic steatosis were significant (p < .05), whereas serum biomarkers and body mass index were not (p > .05), based on a two-tailed t-test. The results suggest that the repeatability and reproducibility for measuring liver SWV, ATI, and NLV are moderate to excellent, while those for SWD and L/K ratio are poor. Standardized machine settings, scanning protocols, and operator training are suggested in performing multiparametric ultrasound of the liver.

Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: A randomized phase 2 trial

Increased consumption of the lipogenic sugar fructose promotes the current epidemic of metabolic disease. Ketohexokinase (KHK) catalyzes the first committed step in fructose metabolism. In animal models, KHK inhibition decreases hepatic de novo lipogenesis and steatosis and corrects many metabolic abnormalities associated with insulin resistance. The consequences of inhibiting fructose metabolism in humans have not been tested. This randomized, double-blind, placebo-controlled, phase 2a study (NCT03256526) assessed the effect of the reversible KHK inhibitor PF-06835919 on metabolic parameters in participants with non-alcoholic fatty liver disease (NAFLD). Adults with NAFLD (>6% whole liver fat [WLF] by magnetic resonance imaging-proton density fat fraction) received once-daily oral placebo or PF-06835919 75mg or 300mg for 6weeks. Randomization (1:1:1) was via computer-generated randomization code with random permuted blocks. Endpoints included WLF (primary endpoint), safety/tolerability, and metabolic parameters. Overall, 158 participants were screened and 53 randomized; 48 completed the trial (placebo, n= 17; PF-06835919 75mg, n= 17; PF-06835919 300mg, n= 14). Compared with placebo, significant reductions in WLF were observed in participants receiving PF-06835919 300mg (difference of -18.73%; p= 0.04), but not with 75mg. In addition, inhibition of KHK resulted in improvement in inflammatory markers. The incidence of treatment-emergent adverse events (AEs) was low and similar across treatment groups (26.3%, 23.5%, and 29.4% of participants in the placebo and PF-06835919 75mg and 300mg groups, respectively). No serious AEs were reported. Data suggest that KHK inhibition may be clinically beneficial in the treatment of adults with NAFLD and insulin resistance. This study was sponsored by Pfizer Inc.

Potent suppression of hydrophobic bile acids by aldafermin, an FGF19 analogue, across metabolic and cholestatic liver diseases

SummaryBackground & AimsHigher serum bile acid levels are associated with an increased risk of cirrhosis and liver-related morbidity and mortality. Herein, we report secondary analyses of aldafermin, an engineered analogue of the gut hormone fibroblast growth factor 19, on the circulating bile acid profile in prospective, phase II studies in patients with metabolic or cholestatic liver disease.MethodsOne hundred and seventy-six patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis and elevated liver fat content (≥8% by magnetic resonance imaging-proton density fat fraction) received 0.3 mg (n = 23), 1 mg (n = 49), 3 mg (n = 49), 6 mg (n = 28) aldafermin or placebo (n = 27) for 12 weeks. Sixty-two patients with primary sclerosing cholangitis (PSC) and elevated alkaline phosphatase (>1.5× upper limit of normal) received 1 mg (n = 21), 3 mg (n = 21) aldafermin or placebo (n = 20) for 12 weeks. Serum samples were collected on day 1 and week 12 for determination of bile acid profile and neoepitope-specific N-terminal pro-peptide of type III collagen (Pro-C3), a direct measure of fibrogenesis.ResultsTreatment with aldafermin resulted in significant dose-dependent reductions in serum bile acids. In particular, bile acids with higher hydrophobicity indices, such as deoxycholic acid, lithocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, and glycocholic acid, were markedly lowered by aldafermin in both NASH and PSC populations. Moreover, aldafermin predominantly suppressed the glycine-conjugated bile acids, rather than the taurine-conjugated bile acids. Changes in levels of bile acids correlated with changes in the novel fibrogenesis marker Pro-C3, which detects a neo-epitope of the type III collagen during its formation, in the pooled NASH and PSC populations.ConclusionsAldafermin markedly reduced major hydrophobic bile acids that have greater detergent activity and cytotoxicity. Our data provide evidence that bile acids may contribute to sustaining a pro-fibrogenic microenvironment in the liver across metabolic and cholestatic liver diseases.Lay summaryAldafermin is an analogue of a gut hormone, which is in development as a treatment for patients with chronic liver disease. Herein, we show that aldafermin can potently and robustly suppress the toxic, hydrophobic bile acids irrespective of disease aetiology. The therapeutic strategy utilising aldafermin may be broadly applicable to other chronic gastrointestinal and liver disorders.Clinical Trials RegistrationThe study is registered at Clinicaltrials.govNCT02443116 and NCT02704364.

Usefulness of US attenuation imaging for the detection and severity grading of hepatic steatosis in routine abdominal ultrasonography

PurposeTo assess the diagnostic performance of ultrasound (US) attenuation imaging (ATI) for diagnosis and grading of hepatic steatosis with comparison to magnetic resonance imaging-proton density fat fraction (MRI-PDFF) using mDIXON-Quant sequence. MethodsTotal 100 patients who underwent abdominal US ATI and MRI-PDFF within one month were included. Subjects were divided into three groups according to MRI-PDFF; Group 1 (no fatty liver), Q < 5.1%; Group 2 (mild fatty liver), 5.1% ≤ Q < 14.1%; and Group 3 (moderate fatty liver), Q ≥ 14.1%. US attenuation coefficients (AC) of enrolled patients were measured and correlated with MRI-PDFF. And their diagnostic performances were assessed. AC, MRI-PDFF, and liver function tests were compared among all groups. ResultsMean AC value of each group was as follows: Group 1 = 0.58 ± 0.11 dB/cm/MHz, Group 2 = 0.68 ± 0.08 dB/cm/MHz, and Group 3 = 0.77 ± 0.06 dB/cm/MHz. Mean AC value of each group of hepatic steatosis showed statistically significant difference (p < 0.001). There was a significant correlation between AC and MRI-PDFF in Pearson correlation (r = 0.751, p < 0.001). The area under the ROC curve (AUROC) of AC was 0.914 with sensitivity of 91.5%, and specificity of 80.0% for detection of mild fatty liver, and 0.935 for detection of moderate fatty liver with sensitivity of 93.3%, and specificity of 87.1%. ConclusionAC using ultrasound ATI showed high diagnostic performance and provided discriminative values for severity grading of fatty liver disease.

Comparison of sonographic hepatorenal ratio and the degree of hepatic steatosis in magnetic resonance imaging-proton density fat fraction.

Objectives: Conventional ultrasonography can provide only semi-quantitative assessment of hepatic steatosis. The aim of this study was to assess sonographic hepatorenal ratio to quantify the severity of fatty liver. Methods: We performed a retrospective analysis of 179 patients with various liver diseases who underwent abdominal magnetic resonance imaging and ultrasonography on the same day. The hepatorenal ratio was calculated by the ratio between the mean echo intensity in regions of interests of the liver and regions of interests of the right renal cortex. Magnetic resonance imaging-proton density fat fraction was used as standard reference for steatosis grading. The effect of fibrosis measured by magnetic resonance elastography on the degree of correlation was also assessed. Results: The hepatorenal ratio was highly correlated with magnetic resonance imaging-proton density fat fraction (Spearman’s coefficient = 0.83) (p <0.001). High correlation of hepatorenal ratio with magnetic resonance imaging-proton density fat fraction was observed in patients with less than stage 2 fibrosis (p <0.001), whereas moderate correlation of hepatorenal ratio with magnetic resonance imaging-proton density fat fraction was found in patients with ≥ stage 2 fibrosis or higher (p <0.001). The hepatorenal ratio cutoff point for prediction of grade 1 hepatic steatosis was 1.18 with sensitivity of 90.0% and specificity of 80.0%. The hepatorenal ratio cutoff point for prediction of grade 2 and grade 3 hepatic steatosis was 1.55 and 1.60, respectively, with sensitivity greater than 90% and specificity greater than 80%. Conclusions: The hepatorenal ratio could become an effective quantitative tool for hepatic steatosis alternative to magnetic resonance imaging-proton density fat fraction. Application should be careful in the group of patients with stage 2 liver fibrosis or higher.

Optimal Threshold of Controlled Attenuation Parameter for Detection of HIV-Associated NAFLD With Magnetic Resonance Imaging as the Reference Standard.

Controlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard. Patients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%). Seventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%. The optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD.

Differences in multi-echo chemical shift encoded MRI proton density fat fraction estimation based on multifrequency fat peaks selection in non-alcoholic fatty liver disease patients

To compare the performance of multi-echo chemical-shift-encoded (MECSE) magnetic resonance imaging (MRI) proton density fat fraction (PDFF) estimation, considering three different fat frequency peak combinations, for the quantification of steatosis in patients with non-alcoholic fatty liver disease (NAFLD). The present study was a prospective cross-sectional research of 121 patients with metabolic syndrome and evidence of hepatic steatosis on ultrasound, who underwent a 3 T MRI examination. All patients were studied with a multifrequency MECSE sequence. The PDFF was calculated using six peaks (MECSEp123456), three peaks (MECSEp456), and a single peak (MECSEp5) model. The two simpler fat peak models were compared to the six peaks model, which was considered the reference standard. Linearity was evaluated using linear regression while agreement was described using Bland-Altman analysis. The mean age was 47 (±9) years and BMI was 29.9 (±2.9) kg/m2. Steatosis distribution was 15%/31%/54% (S1/S2/S3, respectively). Compared to MECSEp123456, both models provided linear PDFF measurements (R2= 0.99 and 0.97, MECSEp456 and MECSEp5 respectively). Regression slope (0.92; p<0.001) and mean Bland-Altman bias (-1.5%; 95% limits of agreement: -3.19%, 0.22%) indicated minimal underestimation by using PDFF-MECSEp456. Nonetheless, mean differences in PDFF estimations varied from -1.5% (MECSEp456,p=0.006) to -2.2% (MECSEp5,p<0.001) when compared to full six fat frequencies model. Although simpler spectral fat MECSE analysis shows a linear relationship with the standard six peaks model, their variation in estimated PDFF values introduces a low but clinically significant bias in fat quantification and steatosis grading in NAFLD patients.

Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis

Aldafermin, an engineered analog of fibroblast growth factor 19, inhibits bile acid synthesis and regulates metabolic homeostasis. We report results from a 24-week, phase 2 study, with serial liver biopsies, of patients with nonalcoholic steatohepatitis (NASH). We performed a double-blind study of 78 patients with NASH at 9 centers in the United States. Key inclusion criteria were biopsy-proven NASH with Nonalcoholic Fatty Liver Disease Activity Score ≥4, stage 2 or 3 fibrosis by NASH Clinical Research Network classification, and absolute liver fat content ≥8%, measured by magnetic resonance imaging-proton density fat fraction. Patients were randomly assigned (1:2) to groups given subcutaneous placebo (n= 25) or aldafermin 1 mg (n= 53) daily for 24 weeks. The primary outcome was change in absolute liver fat content from baseline at week 24. Secondary outcomes included serum markers and histologic measures of fibrosis improvement and NASH resolution. At week 24, the aldafermin group had a significant reduction in absolute liver fat content (reduction of 7.7%) compared with placebo (reduction of 2.7%; difference, reduction of 5.0%; 95% confidence interval, reduction of 8.0%-1.9%; P= .002). Aldafermin produced significantly greater decreases in levels of 7α-hydroxy-4-cholesten-3-one, bile acids, alanine and aspartate aminotransferases, and neoepitope-specific N-terminal pro-peptide of type III collagen (Pro-C3) than placebo. Fibrosis improvement (≥1 stage) with no worsening of NASH was achieved in 38% of patients receiving aldafermin vs 18% of patients receiving placebo (P= .10). NASH resolution with no worsening of fibrosis was observed in 24% of patients given aldafermin vs 9% of patients given placebo (P= .20). Discontinuations due to adverse events occurred in no patients in the aldafermin group and 4% of patients in the placebo group. In a phase 2 trial of patients with NASH, aldafermin reduced liver fat and produced a trend toward fibrosis improvement. ClinicalTrials.gov, Number: NCT02443116.

LPCN 1144 Resolves NAFLD in Hypogonadal Males

Hypogonadism affects hepatic lipid metabolism and is expected to promote nonalcoholic fatty liver disease (NAFLD). The aims of this study were to determine (1) the prevalence of NAFLD in hypogonadal males and (2) the impact of correction of hypogonadism by LPCN 1144 (Lipocine, Inc., Salt Lake City, UT), an oral testosterone prodrug, on NAFLD in this population. Data were derived from a multicenter open‐label single‐arm trial of LPCN 1144 for hypogonadal males, in which a subset (n = 36) had serial magnetic resonance imaging–proton density fat fraction measurements (National Clinical Trial 03868059). NAFLD prevalence, defined by magnetic resonance imaging–proton density fat fraction ≥5%, was 66%. Eighty‐one percent of those with baseline liver fat (BL) ≥5% had improvement in liver fat content, and NAFLD resolved in 33% of subjects at 8 weeks (mean relative reduction: 45%) and 48% (mean relative reduction: 55%) after 16 weeks of LPCN 1144 therapy. The reduction in liver fat was greater in those with higher BL (BL ≥5%: 71%; BL ≥8%: 80%; and BL ≥10%: 75%). Normalization rate of alanine aminotransferase and gamma‐glutamyltransferase greater than the upper limit of normal range were 100% and 50% of treated patients, respectively. LPCN 1144 was not associated with major adverse events. Conclusion: Treatment with LPCN 1144 (oral T prodrug) in hypogonadal males with NAFLD resolved NAFLD in approximately half of the affected patients without any safety signals. Further studies are needed to validate its use in hypogonadal males with nonalcoholic steatohepatitis.

AS077 - Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to predict treatment response on NASH liver biopsy: a secondary analysis of the resmetirom randomized placebo-controlled phase 2 clinical trial

AS077 - Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to predict treatment response on NASH liver biopsy: a secondary analysis of the resmetirom randomized placebo-controlled phase 2 clinical trial

Exam 2: Prospective, Same-Day, Direct Comparison of Controlled Attenuation Parameter With the M vs the XL Probe in Patients With Nonalcoholic Fatty Liver Disease, Using Magnetic Resonance Imaging—Proton Density Fat Fraction as the Standard

Exam 2: Prospective, Same-Day, Direct Comparison of Controlled Attenuation Parameter With the M vs the XL Probe in Patients With Nonalcoholic Fatty Liver Disease, Using Magnetic Resonance Imaging—Proton Density Fat Fraction as the Standard