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

  • Jonathan R. DillmanEmail author
  • Suraj D. Serai
  • Andrew T. Trout
  • Ruchi Singh
  • Jean A. Tkach
  • Amy E. Taylor
  • Burns C. Blaxall
  • Lin Fei
  • Alexander G. Miethke
Original Article



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


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.


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).


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.


Autoimmune liver disease Children Liver Magnetic resonance elastography Magnetic resonance imaging Multiparametric Portal hypertension 



This study was partially funded by: (1) a Cincinnati Children’s Hospital Medical Center (CCHMC) Academic and Research Committee grant and (2) the CCHMC Center for Autoimmune Liver Disease. Iron-corrected T1 image processing was performed by Perspectum Diagnostics (Oxford, UK) at no cost through a research agreement.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Deneau M, Jensen MK, Holmen J et al (2013) Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history. Hepatology 58:1392–1400CrossRefGoogle Scholar
  2. 2.
    Singh H, Balouch F, Noble C, Lewindon P (2018) Evolving practice and changing phenotype in pediatric autoimmune liver disease: outcomes from an Australian center. J Pediatr Gastroenterol Nutr 67:80–85CrossRefGoogle Scholar
  3. 3.
    Sun M, Kisseleva T (2015) Reversibility of liver fibrosis. Clin Res Hepatol Gastroenterol 39:S60–S63CrossRefGoogle Scholar
  4. 4.
    Deneau MR, El-Matary W, Valentino PL et al (2017) The natural history of primary sclerosing cholangitis in 781 children: a multicenter, international collaboration. Hepatology 66:518–527CrossRefGoogle Scholar
  5. 5.
    Bloom S, Kemp W, Lubel J (2015) Portal hypertension: pathophysiology, diagnosis and management. Intern Med J 45:16–26CrossRefGoogle Scholar
  6. 6.
    Brancatelli G, Federle MP, Ambrosini R et al (2007) Cirrhosis: CT and MR imaging evaluation. Eur J Radiol 61:57–69CrossRefGoogle Scholar
  7. 7.
    Trout AT, Sheridan RM, Serai SD et al (2018) Diagnostic performance of MR elastography for liver fibrosis in children and young adults with a spectrum of liver diseases. Radiology 2018:172099Google Scholar
  8. 8.
    Banerjee R, Pavlides M, Tunnicliffe EM et al (2014) Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol 60:69–77CrossRefGoogle Scholar
  9. 9.
    Guimaraes AR, Siqueira L, Uppal R et al (2016) T2 relaxation time is related to liver fibrosis severity. Quant Imaging Med Surg 6:103–114CrossRefGoogle Scholar
  10. 10.
    Koinuma M, Ohashi I, Hanafusa K, Shibuya H (2005) Apparent diffusion coefficient measurements with diffusion-weighted magnetic resonance imaging for evaluation of hepatic fibrosis. J Magn Reson Imaging 22:80–85CrossRefGoogle Scholar
  11. 11.
    Yin M, Glaser KJ, Talwalkar JA et al (2016) Hepatic MR elastography: clinical performance in a series of 1,377 consecutive examinations. Radiology 278:114–124CrossRefGoogle Scholar
  12. 12.
    Garteiser P, Doblas S, Van Beers BE (2018) Magnetic resonance elastography of liver and spleen: methods and applications. NMR Biomed 31:e3891CrossRefGoogle Scholar
  13. 13.
    Nedredal GI, Yin M, McKenzie T et al (2011) Portal hypertension correlates with splenic stiffness as measured with MR elastography. J Magn Reson Imaging 34:79–87CrossRefGoogle Scholar
  14. 14.
    Ronot M, Lambert S, Elkrief L et al (2014) Assessment of portal hypertension and high-risk oesophageal varices with liver and spleen three-dimensional multifrequency MR elastography in liver cirrhosis. Eur Radiol 24:1394–1402PubMedGoogle Scholar
  15. 15.
    Lin ZH, Xin YN, Dong QJ et al (2011) Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology 53:726–736CrossRefGoogle Scholar
  16. 16.
    Wai CT, Greenson JK, Fontana RJ et al (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38:518–526CrossRefGoogle Scholar
  17. 17.
    Kim SY, Seok JY, Han SJ, Koh H (2010) Assessment of liver fibrosis and cirrhosis by aspartate aminotransferase-to-platelet ratio index in children with biliary atresia. J Pediatr Gastroenterol Nutr 51:198–202CrossRefGoogle Scholar
  18. 18.
    Chou R, Wasson N (2013) Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review. Ann Intern Med 158:807–820CrossRefGoogle Scholar
  19. 19.
    Sterling RK, Lissen E, Clumeck N et al (2006) Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43:1317–1325CrossRefGoogle Scholar
  20. 20.
    Messroghli DR, Radjenovic A, Kozerke S et al (2004) Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med 52:141–146CrossRefGoogle Scholar
  21. 21.
    Megremis SD, Vlachonikolis IG, Tsilimigaki AM (2004) Spleen length in childhood with US: normal values based on age, sex, and somatometric parameters. Radiology 231:129–134CrossRefGoogle Scholar
  22. 22.
    Xanthakos SA, Podberesky DJ, Serai SD et al (2014) Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr 164:186–188CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jonathan R. Dillman
    • 1
    • 2
    • 3
  • Suraj D. Serai
    • 1
    • 4
  • Andrew T. Trout
    • 1
    • 2
    • 3
  • Ruchi Singh
    • 2
    • 5
  • Jean A. Tkach
    • 1
  • Amy E. Taylor
    • 2
    • 5
  • Burns C. Blaxall
    • 6
  • Lin Fei
    • 7
  • Alexander G. Miethke
    • 2
    • 5
  1. 1.Department of RadiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Center for Autoimmune Liver Disease (CALD)Cincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Department of RadiologyUniversity of Cincinnati College of MedicineCincinnatiUSA
  4. 4.Department of RadiologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  5. 5.Division of Gastroenterology, Hepatology, and Nutrition, Department of PediatricsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  6. 6.Heart Institute, Department of PediatricsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  7. 7.Division of Biostatistics and EpidemiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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