Background & Aims Magnetic-resonance-imaging (MRI) techniques and ultrasound-based transient elastography (TE) can be used in noninvasive diagnosis of fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We performed a prospective study to compare the performance of magnetic resonance elastography (MRE) vs TE for in diagnosis of fibrosis, and MRI-based proton density fat fraction (MRI-PDFF) analysis vs TE-based controlled attenuation parameter (CAP) for diagnosis of steatosis in patients undergoing biopsy to assess NAFLD. Methods We performed a cross-sectional study of 104 consecutive adults (56.7% female) who underwent MRE, TE, and liver biopsy analysis (using the histological scoring system for NAFLD from the nonalcoholic steatohepatitis clinical research network scoring system) from October 2011 through May 2016 at a tertiary medical center. All patients received a standard clinical evaluation, including collection of history, anthropometric examination, and biochemical tests. The primary outcomes were fibrosis and steatosis. Secondary outcomes included dichotomized stages of fibrosis and NASH vs no NASH. Receiver operating characteristic (ROC) curve analyses were used to compare performances of MRE vs TE in diagnosis of fibrosis (stages 1–4 vs 0) and MRI-PDFF vs CAP for diagnosis of steatosis (grades 1–3 vs 0) with respect to findings from biopsy analysis. Results MRE detected any fibrosis (stage 1 or more) with an area under the ROC (AUROC) of 0.82 (95% CI, 0.74–0.91), which was significantly higher than that of TE (AUROC, 0.67; 95% CI, 0.56–0.78). MRI-PDFF detected any steatosis with an AUROC of 0.99 (95% CI, 0.98–1.00), which was significantly higher that of CAP (AUROC, 0.85; 95% CI, 0.75–0.96). MRE detected fibrosis of stages 2, 3, or 4 with AUROC values of 0.89 (95% CI, 0.83–0.96), 0.87 (95% CI, 0.78–0.96), and 0.87 (95% CI, 0.71-1.00); TE detected fibrosis of stages 2, 3, or 4 with AUROC values of 0.86 (95% CI, 0.77–0.95), 0.80 (95% CI, 0.67–0.93), and 0.69 (95% CI, 0.45–0.94). MRI-PDFF identified steatosis of grades 2 or 3 with AUROC values of 0.90 (95% CI, 0.82–0.97) and 0.92 (95% CI, 0.84–0.99); CAP identified steatosis of grades 2 or 3 with AUROC values of 0.70 (95% CI, 0.58–0.82) and 0.73 (95% CI, 0.58–0.89). Conclusions In a prospective, cross-sectional study of more than 100 patients, we found MRE to be more accurate than TE in identification of liver fibrosis (stage 1 or more), using biopsy analysis as the standard. MRI-PDFF is more accurate than CAP in detecting all grades of steatosis in patients with NAFLD.

Ezetimibe inhibits intestinal cholesterol absorption and lowers low-density lipoprotein cholesterol. Uncontrolled studies have suggested that it reduces liver fat as estimated by ultrasound in nonalcoholic steatohepatitis (NASH). Therefore, we aimed to examine the efficacy of ezetimibe versus placebo in reducing liver fat by the magnetic resonance imaging-derived proton density-fat fraction (MRI-PDFF) and liver histology in patients with biopsy-proven NASH. In this randomized, double-blind, placebo-controlled trial, 50 patients with biopsy-proven NASH were randomized to either ezetimibe 10 mg orally daily or placebo for 24 weeks. The primary outcome was a change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Novel assessment by two-dimensional and three-dimensional magnetic resonance elastography was also performed. Ezetimibe was not significantly better than placebo at reducing liver fat as measured by MRI-PDFF (mean difference between the ezetimibe and placebo arms -1.3%, P = 0.4). Compared to baseline, however, end-of-treatment MRI-PDFF was significantly lower in the ezetimibe arm (15%-11.6%, P < 0.016) but not in the placebo arm (18.5%-16.4%, P = 0.15). There were no significant differences in histologic response rates, serum alanine aminotransferase and aspartate aminotransferase levels, or longitudinal changes in two-dimensional and three-dimensional magnetic resonance elastography-derived liver stiffness between the ezetimibe and placebo arms. Compared to histologic nonresponders (25/35), histologic responders (10/35) had a significantly greater reduction in MRI-PDFF (-4.35 ± 4.9% versus -0.30 ± 4.1%, P < 0.019). Conclusions: Ezetimibe did not significantly reduce liver fat in NASH. This trial demonstrates the application of colocalization of MRI-PDFF-derived fat maps and magnetic resonance elastography-derived stiffness maps of the liver before and after treatment to noninvasively assess treatment response in NASH. (Hepatology 2015;61:1239–1250)

Background & Aims Little is known about the heritability of hepatic fibrosis, and the heritability of hepatic steatosis has not been systematically assessed in adults. We investigated the heritability of hepatic fibrosis and steatosis in a community-dwelling twin cohort. Methods We performed a cross-sectional analysis of a cohort of well-characterized twins residing in Southern California including 60 pairs of twins (42 monozygotic and 18 dizygotic; average age, 45.7±22.1 years; average body mass index, 26.4±5.7 kg/m2). We collected data on medical history, physical examinations, fasting laboratory test results, and liver health; all participants underwent an advanced magnetic resonance imaging (MRI) examination of the liver from January 2012 through January 2015. Hepatic steatosis was quantified non-invasively by MRI and determined based on the proton-density fat fraction (MRI-PDFF); liver fibrosis was measured based on stiffness measured by magnetic resonance elastography. Results Twenty-six of the 120 subjects (21.7%) had non-alcoholic fatty liver disease (defined as MRI-PDFF ≥ 5% after exclusion of other causes of hepatic steatosis). The presence of hepatic steatosis correlated between monozygotic twins (r2=0.70, P<.0001) but not between di-zygotic twins (r2=0.36, P=0.2). The level of liver fibrosis also correlated between monozygotic twins (r2=0.48, P<.002) but not between dizygotic twins (r2=.12, P=.7). In multivariable models adjusted for age, sex, and ethnicity, the heritability of hepatic steatosis (based on MRI-PDFF) was 0.52 (95% confidence interval, 0.31–0.73; P<1.1x10−11) and the heritability of hepatic fibrosis (based on liver stiffness) was 0.5 (95% confidence interval, 0.28–0.72; P<6.1 x 10−11). Conclusions A study of twins provides evidence that hepatic steatosis and hepatic fibrosis are heritable traits.

The cut-point of CAP for presence of hepatic steatosis (MRI-PDFF ≥ 5%) was 288 dB/m. The diagnostic accuracy of CAP for the detection of hepatic steatosis is more reliable when the IQR of CAP is <30 dB/m. These data have implications for the clinical use of CAP in the assessment of NAFLD. (Hepatology 2018;67:1348-1359).

The presence of cirrhosis in nonalcoholic-fatty-liver-disease (NAFLD) is the most important predictor of liver-related mortality. Limited data exist concerning the diagnostic accuracy of gut-microbiome-derived signatures for detecting NAFLD-cirrhosis. Here we report 16S gut-microbiome compositions of 203 uniquely well-characterized participants from a prospective twin and family cohort, including 98 probands encompassing the entire spectrum of NAFLD and 105 of their first-degree relatives, assessed by advanced magnetic-resonance-imaging. We show strong familial correlation of gut-microbiome profiles, driven by shared housing. We report a panel of 30 features, including 27 bacterial features with discriminatory ability to detect NAFLD-cirrhosis using a Random Forest classifier model. In a derivation cohort of probands, the model has a robust diagnostic accuracy (AUROC of 0.92) for detecting NAFLD-cirrhosis, confirmed in a validation cohort of relatives of proband with NAFLD-cirrhosis (AUROC of 0.87). This study provides evidence for a fecal-microbiome-derived signature to detect NAFLD-cirrhosis.