Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed to reduce liver fat by computed tomography. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic-resonance-imaging (MRI)-technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Methods Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 gram/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI PDFF in co-localized regions of interest within each of the nine liver segments. Results Compared with placebo, colesevelam increased liver fat by MRI PDFF in all nine segments of the liver with a mean difference of 5.6% (p=0.002). We cross-validated the MRI-PDFF determined fat content with that assessed by co-localized MRS; the latter showed a mean difference of 4.9% (p=0.014) in liver fat between the colesevelam and the placebo-arms. MRI PDFF correlated strongly with MRS determined hepatic fat content (r2=0.96, P<0.0001). Liver biopsy assessment of steatosis, cellular injury and lobular inflammation did not detect any effect of treatment. Conclusion Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR detected increase in liver fat has clinical consequences is not known.

Purpose To describe the spatial distribution of liver fat, using magnetic resonance imaging (MRI)-estimated proton density fat fraction (PDFF), in adults with non-alcoholic fatty liver disease (NAFLD). Materials and Methods This IRB-approved, HIPAA-compliant study prospectively enrolled fifty adults (30 women, 20 men) with biopsy-proven NAFLD. Hepatic PDFF was measured by low-flip-angle multiecho spoiled gradient-recalled-echo MRI at 3T. Three non-overlapping regions of interest were placed within each liver segment. Statistical analyses included Pearson’s correlation, multivariable linear regression, and permutation-based paired tests. Results The study population’s mean whole-liver PDFF was 16.1% (range: 1.6–39.6%). The mean whole-liver PDFF variability was 1.9% (range: 0.7–4.5%). Higher variability was associated with higher PDFF (r=0.34, p=0.0156). The mean PDFF was significantly higher in the right lobe than the left (16.5% vs. 15.3%, p=0.0028). The mean PDFF variability was higher in the left lobe than the right (1.86% vs. 1.28%, p<0.0001). Segment II had the lowest mean segmental PDFF (14.8%); segment VIII had the highest (16.7%). Segments V (0.71%) and VI (0.70%) had the lowest mean segmental PDFF variability; segment II had the highest (1.32%). Conclusion In adult NAFLD there are small but significant differences in fat content and variability between lobes and some of the segments.

Purpose. To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis. Materials and Methods. In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). Using L 1 regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses. Results. The texture-based predicted fibrosis score significantly correlated with qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001) histology. The prediction model for qualitative histology had 0.814–0.976 areas under the curve (AUC), 0.659–1.000 sensitivity, 0.778–0.930 specificity, and 0.674–0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742–0.950 AUC, 0.688–1.000 sensitivity, 0.679–0.857 specificity, and 0.696–0.848 accuracy, depending on the binary classification threshold. Conclusion. CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.

Purpose To explore the cross-sectional and longitudinal relationships between fractional liver fat content, liver volume, and total liver fat burden. Methods In 43 adults with non-alcoholic steatohepatitis participating in a clinical trial, liver volume was estimated by segmentation of magnitude-based low-flip-angle multiecho GRE images. The liver mean proton density fat fraction (PDFF) was calculated. The total liver fat index (TLFI) was estimated as the product of liver mean PDFF and liver volume. Linear regression analyses were performed. Results Cross-sectional analyses revealed statistically significant relationships between TLFI and liver mean PDFF (R2 = 0.740 baseline/0.791 follow-up, P < 0.001 baseline/P < 0.001 follow-up), and between TLFI and liver volume (R2 = 0.352/0.452, P < 0.001/< 0.001). Longitudinal analyses revealed statistically significant relationships between liver volume change and liver mean PDFF change (R2 = 0.556, P < 0.001), between TLFI change and liver mean PDFF change (R2 = 0.920, P < 0.001), and between TLFI change and liver volume change (R2 = 0.735, P < 0.001). Conclusion Liver segmentation in combination with MRI-based PDFF estimation may be used to monitor liver volume, liver mean PDFF, and TLFI in a clinical trial.

Purpose To assess feasibility of and agreement between magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for estimating hepatic proton density fat fraction (PDFF) in children with known or suspected nonalcoholic fatty liver disease (NAFLD). Material and Methods Children were included in this study from two previous research studies in each of which three MRI and three MRS acquisitions were obtained. Sequence acceptability, and MRI- and MRS-estimated PDFF were evaluated. Agreement of MRI- with MRS-estimated hepatic PDFF with MRS was assessed by linear regression and Bland-Altman analysis. Age, sex, BMI Z-score, acquisition time, and artifact score effects on MRI- and MRS-estimated PDFF agreement were assessed by multiple linear regression. Results Eighty-six children (61 boys, 25 girls) were included in this study. Slope and intercept from regressing MRS PDFF on MRI PDFF were 0.969 and 1.591%, respectively, and the Bland-Altman bias and 95% limits of agreement were 1.17% ± 2.61%. MRI motion artifact score was higher in boys than girls (by 0.21, p = 0.021). Higher BMI Z-score was associated with lower agreement between MRS and MRI (p = 0.045). Conclusion Hepatic PDFF estimation by both MRI and MRS is feasible, and MRI- and MRS-estimated PDFF agree closely in children with known or suspected NAFLD.

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