Diagnostic performance of quantitative magnetic resonance imaging biomarkers for predicting portal hypertension in children and young adults with autoimmune liver disease

Abstract

Background: Primary sclerosing cholangitis, autoimmune hepatitis and autoimmune sclerosing cholangitis are forms of chronic, progressive autoimmune liver disease (AILD) that can affect the pediatric population.

Objective: To determine whether quantitative MRI- and laboratory-based biomarkers are associated with conventional imaging findings of portal hypertension (radiologic portal hypertension) in children and young adults with AILD.

Materials and methods: Forty-four patients with AILD enrolled in an institutional registry underwent a research abdominal MRI examination at 1.5 tesla (T). Five quantitative MRI techniques were performed: liver MR elastography, spleen MR elastography, liver iron-corrected T1 mapping, liver T2 mapping, and liver diffusion-weighted imaging (DWI, quantified as apparent diffusion coefficients). Two anatomical sequences were used to document splenomegaly, varices and ascites. We calculated aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores - laboratory-based biomarkers of liver fibrosis. We used receiver operating characteristic (ROC) curve analyses to establish the diagnostic performance of quantitative MRI and laboratory biomarkers for indicating the presence of radiologic portal hypertension.

Results: Twenty-three (52%) patients were male; mean age was 15.2±4.0 years. Thirteen (30%) patients had radiologic portal hypertension. Liver and spleen stiffness demonstrated the greatest diagnostic performance for indicating the presence of portal hypertension (area-under-the-ROC-curve [AUROC]=0.98 and 0.96, respectively). The APRI and FIB-4 scores also demonstrated good diagnostic performance (AUROC=0.87 and 0.88, respectively).

Conclusion: MRI-derived measures of liver and spleen stiffness as well as laboratory-based APRI and FIB-4 scores are highly associated with imaging findings of portal hypertension in children and young adults with AILD and thus might be useful for predicting portal hypertension impending onset and directing personalized patient management.

Keywords: Autoimmune liver disease; Children; Liver; Magnetic resonance elastography; Magnetic resonance imaging; Multiparametric; Portal hypertension.

Fig. 1

Autoimmune liver disease in a 7-year-old boy. a, b Coronal single-shot fast spin-echo (a) and axial T2-weighted fast spin-echo fat-saturated (b) MR images show areas of geographic liver signal hyperintensity, marked splenomegaly (with an area of splenic infarction) and ascites. c, d MR elastography images of the liver (c) and spleen (d) show abnormally increased stiffness (4.8 kPa and 7.4 kPa, respectively). Note that the splenic region-of-interest was drawn to avoid the area of splenic infarction. e, f Iron-corrected T1 (cT1) (e) and T2 (f) maps show heterogeneous appearance of the liver with areas of focally increased T1 (mean=1,003.4 ms) and T2 (mean=66.0 ms) values, particularly in the right lobe. The T2 map shows mild motion artifacts. g Diffusion-weighted imaging apparent diffusion coefficient (ADC) map shows that the liver is diffusely hypointense, with lower than expected mean ADC value (0.93×10⁻³ mm²/s)

Fig. 2

Liver stiffness and splenomegaly. a Tukey box plot compares liver stiffness in registry participants with and without splenomegaly. b Receiver operating characteristic curve shows the diagnostic performance of liver stiffness for indicating the presence of splenomegaly (AUROC=0.87)

Fig. 3

Liver and spleen stiffness, and portal hypertension. a Tukey box plot compares liver stiffness in registry participants with and without portal hypertension. b Receiver operating characteristic curve shows the diagnostic performance of liver stiffness for indicating the presence of radiologic portal hypertension (AUROC=0.98). c Tukey box plot compares spleen stiffness in registry participants with and without portal hypertension. d Receiver operating characteristic curve shows the diagnostic performance of spleen stiffness for indicating the presence of radiologic portal hypertension (AUROC=0.96). PTLHTN portal hypertension

Fig. 4

Fibrosis-4 score performance and portal hypertension. a Tukey box plot compares fibrosis-4 (FIB-4) score in registry participants with and without radiologic portal hypertension. b Receiver operating characteristic curve shows the diagnostic performance of the FIB-4 score for indicating the presence of radiologic portal hypertension (AUROC=0.88). PTL HTN portal hypertension