Quantitative Liver MRI-Biopsy Correlation in Pediatric and Young Adult Patients With Nonalcoholic Fatty Liver Disease: Can One Be Used to Predict the Other?

Abstract

Objective: The purpose of this study is to determine the relationships between quantitative liver MRI measurements and liver biopsy findings in pediatric and young adult patients with nonalcoholic fatty liver disease (NAFLD).

Materials and methods: Data were obtained from a registry that prospectively enrolls pediatric and young adult patients with biopsy-confirmed NAFLD at our tertiary medical center with parent or guardian and subject informed consent, as appropriate. Patients enrolled between November 2007 and June 2016 with a quantitative liver MRI examination within 6 months of biopsy were included (n = 69). Liver stiffness (kilopascals), volume (milliliters), and fat fraction (percentage) were extracted from MRI records. Multiple linear regression was used to determine the relationships between NAFLD activity score and quantitative MRI measures, and between MRI liver stiffness and histopathologic scores (steatosis, lobular inflammation, portal inflammation, hepatocyte ballooning, and fibrosis). Histopathologic data were extracted from medical records, with severity graded by hepatopathologists using Non-alcoholic Steatohepatitis (NASH) Clinical Research Network criteria. Ordinal logistic regression was used to assess the relationship between categoric NAFLD severity (simple steatosis vs NASH vs NASH with significant fibrosis) and MRI measures.

Results: The mean (± SD) patient age at the time of MRI was 14.3 ± 2.8 years (range, 8-21 years); 25 (36.2%) patients were female. Liver biopsy was performed within a mean of 64.4 days of the MRI examination. There was a positive correlation between histopathologic steatosis and MRI liver fat fraction (ρ = 0.57; p < 0.0001). MRI fat fraction was the only significant imaging predictor of NAFLD activity score (p = 0.017). Fibrosis score was the only significant histopathologic predictor of MRI liver stiffness (p = 0.001). MRI liver volume was the only imaging predictor of categoric NAFLD severity (odds ratio = 1.001; 95% CI, 1.000-1.002; p = 0.007).

Conclusion: There was significant positive correlation between histopathologic and MRI liver fat measurements in our cohort. MRI liver stiffness did not predict the severity of fatty liver disease in children and young adults.

Keywords: MRI; biopsy; children; nonalcoholic fatty liver disease; quantitative.

Fig. 1

16-year-old boy with chronically elevated liver enzyme levels due to nonalcoholic steatohepatitis (histologic steatosis grade = 3, lobular inflammation score = 3, portal inflammation score = 2, fibrosis stage = 1, and nonalcoholic fatty liver disease activity score = 7). A, Axial proton density fat fraction parametric MR image shows that liver has much higher signal intensity than spleen or skeletal muscle. Liver fat fraction measurement was 39%. B, Axial MR elastography image shows mean liver stiffness of 2.1 kPa. Overall liver stiffness based on mean of four images through mid liver was 2.0 kPa. C, Volume-rendered image of liver acquired from T2-weighted MRI series shows total liver volume of 2562.66 mL. D, Histologic image (H and E, ×4) shows prominent macrovesicular steatosis involving greater than 70% of liver parenchyma, as well as mild-to-moderate portal inflammation and foci of lobular inflammation. E, Histologic image (Masson trichrome, ×10) shows mild portal fibrosis, appearing blue.

Fig. 2

Tukey box plot of relationship between histopathologic liver steatosis score (0–3) and MRI liver fat fraction. Squares represent statistical outliers, horizontal lines within boxes represent medians, and vertical lines and whiskers represent lowest and highest observations still within 1.5 interquartile ranges of lower and upper quartiles, respectively.

Fig. 3

Tukey box plot of relationship between histopathologic liver fibrosis score (0–4) and liver stiffness determined by MR elastography. Circle represents statistical outlier, horizontal lines within boxes represent medians, and vertical lines and whiskers represent lowest and highest observations still within 1.5 interquartile ranges of lower and upper quartiles, respectively. Only one patient had fibrosis score of 4, and this patient reflects outlier seen in fibrosis score (3/4).

Fig. 4

Tukey box plots showing MRI values for each categoric nonalcoholic fatty liver disease (NAFLD) histopathologic severity cohort: simple steatosis (NAFLD activity score 0–4), likely nonalcoholic steatohepatitis (NASH; NAFLD activity score 5–8), and NASH with significant fibrosis (fibrosis score ≥ 2). A–C, Box plots show liver volume (A), fat fraction (B), and stiffness (C) for each categoric NAFLD histopathologic severity cohort. There were significant differences between cohorts for liver volume (p = 0.0005; 32 vs 18 vs 19 subjects) and liver fat fraction (p = 0.004; 26 vs 16 vs 12 subjects). There was no difference in liver stiffness between cohorts (p = 0.09; 31 vs 18 vs 19 subjects). Circles, squares, and triangles represent statistical outliers, horizontal lines within boxes represent medians, and vertical lines and whiskers represent lowest and highest observations still within 1.5 interquartile ranges of lower and upper quartiles, respectively.

Fig. 5

ROC curve for discriminating simple steatosis and nonalcoholic steatohepatitis (NASH) from NASH with significant fibrosis based on MRI liver volume. AUC is 0.774.