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Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease.

ABSTRACT: Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two-dimensional (2D) MRE in children with NAFLD. MR elastograms were analyzed manually at two reading centers, and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross-validated. In 90 children with a mean age of 13.1?±?2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r?=?0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ??=?0.53; center 2, ??=?0.55; and automated analysis, ??=?0.52; P?

SUBMITTER: Schwimmer JB

PROVIDER: S-EPMC5650504 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease.

Schwimmer Jeffrey B JB Behling Cynthia C Angeles Jorge Eduardo JE Paiz Melissa M Durelle Janis J Africa Jonathan J Newton Kimberly P KP Brunt Elizabeth M EM Lavine Joel E JE Abrams Stephanie H SH Masand Prakash P Krishnamurthy Rajesh R Wong Kelvin K Ehman Richard L RL Yin Meng M Glaser Kevin J KJ Dzyubak Bogdan B Wolfson Tanya T Gamst Anthony C AC Hooker Jonathan J Haufe William W Schlein Alexandra A Hamilton Gavin G Middleton Michael S MS Sirlin Claude B CB

Hepatology (Baltimore, Md.) 20171009 5

Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two-dimensional (2D ...[more]

PMID: 28493388

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Project description:BACKGROUND:A recent retrospective study confirmed that hepatic stiffness and splenic stiffness measured with magnetic resonance elastography (MRE) are strongly associated with the presence of esophageal varices. In addition, strong correlations have been reported between splenic stiffness values measured with MRE and hepatic venous pressure gradients in animal models. However, most studies have been conducted on adult populations, and previous pediatric MRE studies have only demonstrated the feasibility of MRE in pediatric populations, while the actual clinical application of spleen MRE has been limited. AIM:To assess the utility of splenic stiffness measurements by MRE to predict gastroesophageal varices in children. METHODS:We retrospectively reviewed abdominal MRE images taken on a 3T system in pediatric patients. Patients who had undergone Kasai operations for biliary atresia were selected for the Kasai group, and patients with normal livers and spleens were selected for the control group. Two-dimensional spin-echo echo-planar MRE acquisition centered on the liver, with a pneumatic driver at 60 Hz and a low amplitude, was performed to obtain hepatic and splenic stiffness values. Laboratory results for aspartate aminotransferase to platelet ratio index (APRI) were evaluated within six months of MRE, and the normalized spleen size ratio was determined with the upper normal size limit. All Kasai group patients underwent gastroesophageal endoscopy during routine follow-up. The Mann-Whitney U test, Kendall's tau b correlation and diagnostic performance analysis using the area under the curve (AUC) were performed for statistical analysis. RESULTS:The median spleen MRE value was 5.5 kPa in the control group (n = 9, age 9-18 years, range 4.7-6.4 kPa) and 8.6 kPa in the Kasai group (n = 22, age 4-18 years, range 5.0-17.8 kPa). In the Kasai group, the APRI, spleen size ratio and spleen MRE values were higher in patients with portal hypertension (n = 11) than in patients without (n = 11) (all P < 0.001) and in patients with gastroesophageal varices (n = 6) than in patients without (n = 16) (all P < 0.05), even though their liver MRE values were not different. The APRI (? = 0.477, P = 0.007), spleen size ratio (? = 0.401, P = 0.024) and spleen MRE values (? = 0.426, P = 0.016) also correlated with varices grades. The AUC in predicting gastroesophageal varices was 0.844 at a cut-off of 0.65 (100% sensitivity and 75% specificity) for the APRI, and 0.844 at a cut-off of 9.9 kPa (83.3% sensitivity and 81.3% specificity) for spleen MRE values. CONCLUSION:At a cut-off of 9.9 kPa, spleen MRE values predicted gastroesophageal varices as well as the APRI and spleen size ratio in biliary atresia patients after the Kasai operation. However, liver MRE values were not useful for this purpose.

Project description:UnlabelledRetrospective studies have shown that two-dimensional magnetic resonance elastography (2D-MRE), a novel MR method for assessment of liver stiffness, correlates with advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Prospective data on diagnostic accuracy of 2D-MRE in the detection of advanced fibrosis in NAFLD are needed. The aim of this study is to prospectively assess the diagnostic accuracy of 2D-MRE, a noninvasive imaging biomarker, in predicting advanced fibrosis (stage 3 or 4) in well-characterized patients with biopsy-proven NAFLD. This is a cross-sectional analysis of a prospective study including 117 consecutive patients (56% women) with biopsy-proven NAFLD who underwent a standardized research visit: history, exam, liver biopsy assessment (using the nonalcoholic steatohepatitis Clinical Research Network histological scoring system), and 2D-MRE from 2011 to 2013. The radiologist and pathologist were blinded to clinical and pathology/imaging data, respectively. Receiver operating characteristics (ROCs) were examined to assess the diagnostic test performance of 2D-MRE in predicting advanced fibrosis. The mean (± standard deviation) of age and body mass index was 50.1 (± 13.4) years and 32.4 (± 5.0) kg/m(2), respectively. The median time interval between biopsy and 2D-MRE was 45 days (interquartile range: 50 days). The number of patients with fibrosis stages 0, 1, 2, 3, and 4 was 43, 39, 13, 12, and 10, respectively. The area under the ROC curve for 2D-MRE discriminating advanced fibrosis (stage 3-4) from stage 0-2 fibrosis was 0.924 (P < 0.0001). A threshold of >3.63 kPa had a sensitivity of 0.86 (95% confidence interval [CI]: 0.65-0.97), specificity of 0.91 (95% CI: 0.83-0.96), positive predictive value of 0.68 (95% CI: 0.48-0.84), and negative predictive value of 0.97 (95% CI: 0.91-0.99).ConclusionsMRE is accurate in predicting advanced fibrosis and may be utilized for noninvasive diagnosis of advanced fibrosis in patients with NAFLD.

Project description:Background & aimsSingle measurements of liver stiffness (LS) by magnetic resonance elastography (MRE) have been associated with outcomes of patients with primary sclerosing cholangitis (PSC), but the significance of changes in LS over time are unclear. We investigated associations between changes in LS measurement and progression of PSC.MethodsWe performed a retrospective review of 204 patients with patients who underwent 2 MREs at a single center between January 1, 2007 and December 31, 2018. We collected laboratory data and information on revised Mayo PSC risk and model for end-stage liver disease scores, the PSC risk estimate tool, and levels of aspartate transferase at the time of each MRE. The ΔLS/time was determined by the change in LS between the second MRE compared to the first MRE divided by the time between examinations. The primary endpoint was development of hepatic decompensation (ascites, variceal hemorrhage or hepatic encephalopathy).ResultsThe median LS measurement was 2.72 kPa (interquartile range, 2.32-3.44 kPa) and the overall change in LS was 0.05 kPa/y. However, ΔLS/y was 10-fold higher in patients anticipated to have cirrhosis (0.31 kPa/y) compared to patients with no fibrosis (0.03 kPa/y). The median LS increased over time in patients who ultimately developed hepatic decompensation (0.60 kPa/y; interquartile range, 0.21-1.26 kPa/y) vs but remained static in patients who did not (reduction of 0.04/y; interquartile range, reductions of 0.26 to 0.17 kPa/y) (P < .001). The ΔLS/y value associated with the highest risk of hepatic decompensation was Δ0.34 kPa/y (hazard ratio [HR], 13.29; 95% CI, 0.23-33.78). After we adjusted for baseline LS and other risk factors, including serum level of alkaline phosphatase and the Mayo PSC risk score, ΔLS/y continued to be associated with hepatic decompensation. The optimal single LS cut-off associated with the hepatic decompensation was 4.32 kPa (HR, 60.41; 95% CI, 17.85-204.47). A combination of both cut-off values was associated with risk of hepatic decompensation (concordance score, 0.93; 95% CI, 0.88-0.98) CONCLUSIONS: A single LS measurement and changes in LS over time are independently associated with hepatic decompensation in patients with PSC. However, changes in LS occur slowly in patients without advanced fibrosis or hepatic decompensation.

Project description:Skeletal muscle stiffness is altered after spinal cord injury (SCI). Assessing muscle stiffness is essential for rehabilitation and pharmaceutical interventions design after SCI. The study used magnetic resonance elastography to assess the changes in stiffness after chronic SCI compared to matched able-bodied controls and determine its association with muscle size, spasticity, and peak torque in persons with SCI. Previous studies examined the association between muscle stiffness and spasticity, however, we are unaware of other studies that examined the effects of muscle composition on stiffness after SCI. Ten participants (one female) with chronic SCI and eight (one female) matched able-bodied controls participated in this cross-sectional study. Magnetic resonance elastography was utilized to monitor stiffness derived from shear waves propagation. Modified Ashworth scale was used to evaluate spasticity scores in a blinded fashion. Peak isometric and isokinetic torques were measured using a biodex dynamometer. Stiffness values were non-significantly lower (12.5%; P = 0.3) in the SCI group compared to able-bodied controls. Moreover, stiffness was positively related to vastus lateralis whole muscle cross-sectional area (CSA) (r2 = 0.64, P < 0.005) and vastus lateralis absolute muscle CSA after accounting for intramuscular fat (r2 = 0.78, P < 0.0007). Stiffness was also positively correlated to both isometric (r2= 0.55-0.57, P < 0.05) and isokinetic peak (r2= 0.46-0.48, P < 0.05) torques. Our results suggest that larger clinical trial is warranted to confirm the preliminary findings that muscle stiffness is altered after SCI compared to healthy controls. Stiffness appeared to be influenced by infiltration of intramuscular fat and modestly by the spasticity of the paralyzed muscles. The preliminary data indicated that the relationship between muscle stiffness and peak torque is not altered with changing the frequency of pulses or angular velocities. All study procedures were approved by the Institutional Review Board at the Hunter Holmes McGuire VA Medical Center, USA (IRB #: 02314) on May 3, 2017.

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Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease.

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Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease.

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