Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease

Abstract

BACKGROUND. Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. OBJECTIVE. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. METHODS. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]). The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI examination that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within 6 months of that examination. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (in kilopascals) for each examination. Laboratory markers of liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] score) were recorded. For investigational purposes, one pathologist, blinded to clinical and MRI data, determined histologic Metavir liver fibrosis stage. The Spearman rank order correlation coefficient was calculated between MRE liver stiffness and Metavir liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating Metavir F0-F1 from F2-F4 fibrosis), and sensitivity and specificity were calculated using the Youden index. RESULTS. The study included 46 patients (median age, 16.6 years [IQR, 13.7-17.8 years]; 20 female patients, 26 male patients); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR, 2.2-4.0 kPa). MRE liver stiffness and Metavir fibrosis stage showed strong positive correlation (ρ = 0.68). For identifying advanced liver fibrosis, MRE liver stiffness had an AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had an AUC of 0.72, with sensitivity of 64.0% and specificity of 80.0%; and FIB-4 score had an AUC of 0.71, with sensitivity of 60.0% and specificity of 85.0%. CONCLUSION. MRE liver stiffness measurements were associated with histologic liver fibrosis severity. CLINICAL IMPACT. The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD. TRIAL REGISTRATION. ClinicalTrials.gov NCT03175471.

Keywords: MR elastography; children; fibrosis; histology; liver.

Fig. 1—

Flow diagram shows patient selection for study. AIH = autoimmune hepatitis, PSC = primary sclerosing cholangitis, ASC = autoimmune sclerosing cholangitis, AILD = autoimmune liver disease.

Fig. 2—

18-year-old woman with primary sclerosing cholangitis and Metavir stage 0 fibrosis on liver biopsy. A, Coronal maximum-intensity-projection MRCP image shows stricture of distal common bile duct (solid arrow) with dilatation of more proximal biliary tree (dashed arrows). B, Axial T2-weighted fast spin-echo MR image with fat suppression shows morphologically normal liver with diffuse mild hyperintensity; spleen is enlarged. C, Axial MR elastogram shows homogeneous appearance of liver without abnormal stiffening (mean liver stiffness, 1.79 kPa). Scale is in kilopascals. D, Digital micrograph (Masson trichrome stain, ×1) of tissue specimen from percutaneous liver biopsy shows no significant liver fibrosis.

Fig. 3—

7-year-old boy with autoimmune sclerosing cholangitis and Metavir stage III fibrosis on liver biopsy. A, Coronal maximum-intensity-projection MRCP image shows multiple intrahepatic strictures (dotted arrows), narrowing of common bile duct (solid arrow), and mild dilatation of central biliary tree (dashed arrow). B, Axial T2-weighted fast spin-echo MR image with fat suppression shows enlarged liver with increased T2-weighted signal intensity. C, Axial MR elastogram shows heterogeneous appearance of liver with abnormal stiffening (mean liver stiffness, 6.55 kPa). Scale is in kilopascals. D, Digital micrograph (Masson trichrome stain, ×1) of tissue specimen from percutaneous liver biopsy shows abnormally increased fibrosis (blue areas).

Fig. 4—

Histogram depicts MR elastography liver stiffness measurements (rounded to nearest integer) stratified by specific autoimmune liver disease diagnosis. PSC = primary sclerosing cholangitis, ASC = autoimmune sclerosing cholangitis, AIH = autoimmune hepatitis.

Fig. 5—

Scatterplots show associations between histologic liver fibrosis scores and MR elastography (MRE) liver stiffness values. PSC = primary sclerosing cholangitis, ASC = autoimmune sclerosing cholangitis, AIH = autoimmune hepatitis. A, Scatterplot shows positive association between Metavir histologic liver fibrosis score and MRE liver stiffness (ρ = 0.68 in entire sample). Solid lines = lines of best fit, dotted lines = 95% confidence limits for lines of best fit. B, Scatterplot shows positive association between Ishak histologic liver fibrosis score and MRE liver stiffness (ρ = 0.67 in entire sample). Solid lines = lines of best fit, dotted lines = 95% confidence limits for lines of best fit. C and D, Tukey box plots of entire sample show increase in MRE liver stiffness with increasing Metavir (C) and Ishak (D) histologic liver fibrosis scores. Lines in center of boxes represent median, top and bottom of boxes represent IQR, and top and bottom of whiskers represent maximum and minimum values.