Background & Aims We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. Methods We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. Results At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0–1 vs 2–3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91–0.98), and grade 0–2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93–0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2–3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs. placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71–0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63–0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity. Conclusions Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.

Magnetic resonance elastography (MRE), an advanced MR-based imaging technique, and acoustic radiation force impulse (ARFI), an ultrasound-based imaging technique, have been shown to be accurate for diagnosing nonalcoholic fatty liver disease (NAFLD) fibrosis. However, no head-to-head comparisons between MRE and ARFI for diagnosing NAFLD fibrosis have been performed. We aimed to compare MRE versus ARFI head-to-head for diagnosing fibrosis in well-characterized patients with biopsy-proven NAFLD. Methods This cross-sectional analysis of a prospective cohort involved 125 patients (54.4% female) who underwent MRE, ARFI, and contemporaneous liver biopsies scored using the Nonalcoholic Steatohepatitis Clinical Research Network histological scoring system. MRE versus ARFI’s performances for diagnosing fibrosis were evaluated using area under receiver operating characteristic curves (AUROCs). Results The mean (±SD) age and BMI were 48.9 (±15.4) years and 31.8 (±7.0) kg/m2, respectively. For diagnosing any fibrosis (≥ stage 1), MRE’s AUROC was 0.799 (95% CI, 0.723–0.875), significantly (p=0.012) higher than ARFI’s AUROC of 0.664 (95% CI, 0.568–0.760). In stratified analysis by presence/absence of obesity, MRE was superior to ARFI for diagnosing any fibrosis in obese patients (p<0.001) but not in non-obese patients (p=0.722). MRE’s AUROCs for diagnosing ≥ stages 2, 3, and 4 fibrosis were 0.885 (95% CI, 0.816–0.953), 0.934 (95% CI, 0.863–1.000), and 0.882 (95% CI, 0.729–1.000), and ARFI’s AUROCs were 0.848 (95% CI, 0.776–0.921), 0.896 (95% CI, 0.824–0.968), and 0.862 (95% CI, 0.721–1.000). MRE had higher AUROCs than ARFI for discriminating dichotomized fibrosis stages at all dichotomization cut-points, but the AUROC differences decreased as the cut-points (fibrosis stages) increased. Conclusions MRE is more accurate than ARFI for diagnosing any fibrosis in all NAFLD patients and obese NAFLD patients, although not in non-obese NAFLD patients.

Background & Aims Liver biopsy analysis is the standard method used to diagnose nonalcoholic fatty liver disease (NAFLD). Advanced magnetic resonance imaging is a noninvasive procedure that can accurately diagnose and quantify steatosis, but is expensive. Conventional ultrasound is more accessible but identifies steatosis with low levels of sensitivity, specificity, and quantitative accuracy, and results vary among operators. A new quantitative ultrasound (QUS) technique can identify steatosis in animal models. We assessed the accuracy of QUS in the diagnosis and quantification hepatic steatosis, comparing findings with those from MRI proton density fat fraction (MRI-PDFF) analysis as a reference. Methods We performed a prospective, cross-sectional analysis of a cohort of adults (n=204) with NAFLD (MRI-PDFF≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and QUS analyses of the liver on the same day at the University of California, San Diego, from February 2012 through March 2014. QUS parameters and backscatter coefficient (BSC) values were calculated. Patients were randomly assigned to training (n=102; mean age, 51±17 years; mean body mass index, 31±7 kg/m2) and validation (n=102; mean age, 49±17 years; body mass index, 30±6 kg/m2) groups; 69% of patients in each group had NAFLD. Results BSC (range 0.00005–0.25 1/cm-sr) correlated with MRI-PDFF (Spearman’s ρ=0.80; P<.0001). In the training group, the BSC analysis identified patients with NAFLD with an area under the curve value of 0.98 (95% confidence interval, 0.95–1.00; P<.0001). The optimal BSC cutoff value identified patients with NAFLD in the training and validation groups with 93% and 87% sensitivity, 97% and 91% specificity, 86% and 76% negative predictive values, and 99% and 95% positive predictive values, respectively. Conclusions QUS measurements of BSC can accurately diagnose and quantify hepatic steatosis, based on a cross-sectional analysis that used MRI-PDFF as the reference. With further validation, QUS could be an inexpensive, widely available method to screen the general or at-risk population for NAFLD.

OBJECTIVE. The purpose of this study is to evaluate the per-patient diagnostic performance of an abbreviated gadoxetic acid-enhanced MRI protocol for hepatocellular carcinoma (HCC) surveillance. MATERIALS AND METHODS. A retrospective review identified 298 consecutive patients at risk for HCC enrolled in a gadoxetic acid-enhanced MRI-based HCC surveillance program. For each patient, the first gadoxetic acid-enhanced MRI was analyzed. To simulate an abbreviated protocol, two readers independently read two image sets per patient: set 1 consisted of T1-weighted 20-minute hepatobiliary phase and T2-weighted single-shot fast spin-echo (SSFSE) images; set 2 included diffusion-weighted imaging (DWI) and images from set 1. Image sets were scored as positive or negative according to the presence of at least one nodule 10 mm or larger that met the predetermined criteria. Agreement was assessed using Cohen kappa statistics. A composite reference standard was used to determine the diagnostic performance of each image set for each reader. RESULTS. Interreader agreement was substantial for both image sets (κ = 0.72 for both) and intrareader agreement was excellent (κ = 0.97-0.99). Reader performance for image set 1 was sensitivity of 85.7% for reader A and 79.6% for reader B, specificity of 91.2% for reader A and 95.2% for reader B, and negative predictive value of 97.0% for reader A and 96.0% for reader B. Reader performance for image set 2 was nearly identical, with only one of 298 examinations scored differently on image set 2 compared with set 1. CONCLUSION. An abbreviated MRI protocol consisting of T2-weighted SSFSE and gadoxetic acid-enhanced hepatobiliary phase has high negative predictive value and may be an acceptable method for HCC surveillance. The inclusion of a DWI sequence did not significantly alter the diagnostic performance of the abbreviated protocol.

SUMMARY Background Ectopic fat deposition in the pancreas and its association with hepatic steatosis have not previously been examined in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). Aim To quantify pancreatic fat using a novel magnetic resonance imaging (MRI) technique and determine whether it is associated with hepatic steatosis and/or fibrosis in patients with NAFLD. Methods This is a cross-sectional study including 43 adult patients with biopsy-proven NAFLD who underwent clinical evaluation, biochemical testing and MRI. The liver biopsy assessment was performed using the NASH-CRN histological scoring system, and liver and pancreas fat quantification was performed using a novel, validated MRI biomarker; the proton density fat fraction. Results The average MRI-determined pancreatic fat in patients with NAFLD was 8.5% and did not vary significantly between head, body, and tail of the pancreas. MRI-determined pancreatic fat content increased significantly with increasing histology-determined hepatic steatosis grade; 4.6% in grade 1; 7.7% in grade 2; 13.0% in grade 3 (P = 0.004) respectively. Pancreatic fat content was lower in patients with histology-determined liver fibrosis than in those without fibrosis (11.2% in stage 0 fibrosis vs. 5.8% in stage 1–2 fibrosis, and 6.9% in stage 3–4 fibrosis, P = 0.013). Pancreatic fat did not correlate with age, body mass index or diabetes status. Conclusions In patients with NAFLD, increased pancreatic fat is associated with hepatic steatosis. However, liver fibrosis is inversely associated with pancreatic fat content. Further studies are needed to determine underlying mechanisms to understand if pancreatic steatosis affects progression of NAFLD.