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Relationship Between Histological Features of Non-alcoholic Fatty Liver Disease and Ectopic Fat on Magnetic Resonance Imaging in Children and Adolescents.

ABSTRACT: Objectives: To investigate the association between ectopic fat content in the liver and pancreas, obesity-related metabolic components, and histological findings of non-alcoholic fatty liver disease (NAFLD) in children. Methods: This cross-sectional study investigated 63 children with biopsy-proven NAFLD who underwent magnetic resonance imaging (MRI), anthropometry, laboratory tests, and body composition analysis. Clinical and metabolic parameters, MRI-measured hepatic fat fraction (HFF) and pancreatic fat fraction (PFF), and histological findings were analyzed. Results: In a total of 63 children (48 boys, median age 12.6 years, median body mass index z-score 2.54), HFF was associated with histological steatosis [10.4, 23.7, and 31.1% in each steatosis grade, P < 0.001; Spearman's rho coefficient (rs) = 0.676; P < 0.001] and NAFLD activity score (rs = 0.470, P < 0.001), but not with lobular inflammation, hepatocyte ballooning, and hepatic fibrosis. PFF was not associated with any histological features of the liver. Waist circumference-to-height ratio and body fat percentage were associated with the steatosis grade (P = 0.006 and P = 0.004, respectively). Alanine aminotransferase was not associated with steatosis but was associated with lobular inflammation (P = 0.008). Lobular inflammation was also associated with high total cholesterol and low-density lipoprotein cholesterol and metabolic syndrome (P = 0.015, P = 0.036, and P = 0.038, respectively). Conclusions: Hepatic steatosis on MRI was only associated with the histological steatosis grade, while elevated serum levels of liver enzymes and lipids were related to the severity of lobular inflammation. Therefore, MRI should be interpreted in conjunction with the anthropometric and laboratory findings in pediatric patients.

SUBMITTER: Lee EH

PROVIDER: S-EPMC8222518 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background & aimsThe diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease.MethodsSeventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ?2 and/or Fibrosis ?2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed.ResultsMagnetic resonance success rate was 95% vs 59% for transient elastography (P<.0001). Fibrosis stage on biopsy correlated with liver inflammation and fibrosis (rs =.51, P<.0001). The area under the receiver operating curve using liver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (P<.05) with an area under the receiver operating characteristic curve of 0.83 for the diagnosis of ballooning. Patients with steatosis had lower liver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (P<.0001); area under the receiver operating characteristic curve for the diagnosis of non-alcoholic steatohepatitis was 0.80. Liver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (P<.0001). The area under the receiver operating characteristic curve of liver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0.89.ConclusionsMultiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non-alcoholic fatty liver disease histological parameters, and can potentially identify patients with non-alcoholic steatohepatitis and cirrhosis.

Project description:Background & aimsPatients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) often require histologic assessment via liver biopsy. Magnetic resonance imaging (MRI)-based methods for measuring liver triglycerides based on proton density fat fraction (PDFF) are increasingly used as a noninvasive tool to identify patients with hepatic steatosis and to assess for change in liver fat over time. We aimed to determine whether MRI-PDFF accurately reflects a variety of liver histology features in patients with NAFLD or NASH.MethodsWe performed a retrospective analysis of pooled data from 3 phase 2a trials of pharmacotherapies for NAFLD or NASH. We collected baseline clinical, laboratory, and histopathology data on all subjects who had undergone MRI analysis in 1 of the trials. We assessed the relationship between liver PDFF values and liver histologic findings using correlation and area under the receiver operating characteristic (AUROC) analyses. As an ancillary analysis, we also simulated a clinical trial selection process and calculated subject exclusion rates and differences in population characteristics caused by PDFF inclusion thresholds of 6% to 15%.ResultsIn 370 subjects, the mean baseline PDFF was 17.4% ± 8.6%. Baseline PDFF values correlated with several histopathology parameters, including steatosis grade (r = 0.78; P < .001), NAFLD activity score (NAS, r = 0.54; P < .001), and fibrosis stage (r = -0.59; P < .001). However, PDFF did not accurately identify patients with NAS ≥ 4 (AUROC = 0.72) or fibrosis stage ≥3 (AUROC = 0.66). In a theoretical trial of these subjects, exclusion rates increased as PDFF minimum threshold level increased. There were no significant differences in cohort demographics when PDFF thresholds ranging from 6% to 15% were used, and differences in laboratory and histopathology data were small.ConclusionsIn an analysis of patients with NAFLD or NASH, we determined that although The MRI-PDFF correlated with steatosis grade and NAS, and inversely with fibrosis stage, it was suboptimal in identification of patients with NAS >4 or advanced fibrosis. Although MRI-PDFF is an important imaging biomarker for continued evaluation of this patient population, liver biopsy analysis is still necessary.

Project description:PURPOSE:Cardiac magnetic resonance fingerprinting (cMRF) has been recently introduced to simultaneously provide T1 , T2 , and M0 maps. Here, we develop a 3-point Dixon-cMRF approach to enable simultaneous water specific T1 , T2 , and M0 mapping of the heart and fat fraction (FF) estimation in a single breath-hold scan. METHODS:Dixon-cMRF is achieved by combining cMRF with several innovations that were previously introduced for other applications, including a 3-echo GRE acquisition with golden angle radial readout and a high-dimensional low-rank tensor constrained reconstruction to recover the highly undersampled time series images for each echo. Water-fat separation of the Dixon-cMRF time series is performed to allow for water- and fat-specific T1 , T2 , and M0 estimation, whereas FF estimation is extracted from the M0 maps. Dixon-cMRF was evaluated in a standardized T1 -T2 phantom, in a water-fat phantom, and in healthy subjects in comparison to current clinical standards: MOLLI, SASHA, T2 -GRASE, and 6-point Dixon proton density FF (PDFF) mapping. RESULTS:Dixon-cMRF water T1 and T2 maps showed good agreement with reference T1 and T2 mapping techniques (R2 > 0.99 and maximum normalized RMSE ~5%) in a standardized phantom. Good agreement was also observed between Dixon-cMRF FF and reference PDFF (R2 > 0.99) and between Dixon-cMRF water T1 and T2 and water selective T1 and T2 maps (R2 > 0.99) in a water-fat phantom. In vivo Dixon-cMRF water T1 values were in good agreement with MOLLI and water T2 values were slightly underestimated when compared to T2 -GRASE. Average myocardium septal T1 values were 1129 ± 38 ms, 1026 ± 28 ms, and 1045 ± 32 ms for SASHA, MOLLI, and the proposed water Dixon-cMRF. Average T2 values were 51.7 ± 2.2 ms and 42.8 ± 2.6 ms for T2 -GRASE and water Dixon-cMRF, respectively. Dixon-cMRF FF maps showed good agreement with in vivo PDFF measurements (R2 > 0.98) and average FF in the septum was measured at 1.3%. CONCLUSION:The proposed Dixon-cMRF allows to simultaneously quantify myocardial water T1 , water T2 , and FF in a single breath-hold scan, enabling multi-parametric T1 , T2 , and fat characterization. Moreover, reduced T1 and T2 quantification bias caused by water-fat partial volume was demonstrated in phantom experiments.

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Relationship Between Histological Features of Non-alcoholic Fatty Liver Disease and Ectopic Fat on Magnetic Resonance Imaging in Children and Adolescents.

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