MR elastography for the assessment of hepatic fibrosis in patients with chronic hepatitis B infection: does histologic necroinflammation influence the measurement of hepatic stiffness?

Abstract

Purpose: To determine the diagnostic performance of magnetic resonance (MR) elastography for the staging of hepatic fibrosis and to evaluate the influence of necroinflammation on hepatic stiffness in patients with chronic hepatitis B virus (HBV) infection by using histopathologic findings as the reference standard.

Materials and methods: One hundred thirteen consecutive patients with chronic HBV infection were recruited prospectively in this institutional review board-approved study after providing written informed consent between March 2012 and October 2013. The stiffness measurements were obtained by using two-dimensional gradient-echo MR elastography with a 3.0-T MR system. The METAVIR scoring system was used for the assessment of fibrosis ("F" stage) and necroinflammation ("A" grade). The predictive ability of MR elastography was evaluated by using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). Multiple linear regression analyses were conducted to determine the relationship between hepatic stiffness and the variables that showed a significant association in the univariate analysis or those that were of interest for comparison with earlier work (histologic scores, sex, age, aspartate aminotransferase level, and aspartate aminotransferase/alanine aminotransferase ratio).

Results: MR elastography showed excellent performance for characterization of ≥ F1, ≥ F2, ≥ F3, and F4 findings, with AUC values of 0.961, 0.986, 1.000, and 0.998, respectively. It showed a moderate capability for evaluation of necroinflammatory activity of ≥ A1, ≥ A2, and A3 (AUC = 0.806, 0.834, and 0.906, respectively). Multiple linear regression analysis showed that fibrosis, necroinflammation, and sex were independently associated with hepatic stiffness (β = 0.799, 0.277, and 0.070, respectively; P < .05). For pairwise comparisons, log-transformed hepatic stiffness showed no difference between (a) groups F0/A2-3 and F1/A0-1 and (b) groups F1/A2-3 and F2/A0-1 (P > .99 and P = .486, respectively).

Conclusion: MR elastography demonstrated excellent performance for distinguishing the stages of hepatic fibrosis in patients with chronic HBV infection. For hepatic tissue with ≤ F2 fibrosis, necroinflammation can account for a substantial fraction of the increase in hepatic stiffness.

Figure 1:

Flowchart shows the study enrollment process during the 19-month study period. “Treatment naive” indicates that no antiviral or other hepatic disease–related thearpy was administered. MRE = MR elastography.

Figure 2:

MR elastography magnitude images (left) and MR elastograms (right) in a 30-year-old man with fibrosis stage F0 and necroinflammation grade A1. A, Green outlined area indicates the automated ROI. B, Corresponding axial elastogram shows the same automated ROI. The recorded stiffness was 2.26 kPa ± 0.29. C, Red outlined area indicates the reader-defined ROI, excluding areas of interference, portal areas, and blood vessels. D, Reader-defined ROI is shown on the elastogram, and the reported stiffness was 2.34 kPa ± 0.19.

Figure 3:

Bland-Altman plot used to compare the stiffness measurements from the reader and the automated algorithm. The 95% confidence limits of the bias are shown as two dotted lines. SD = standard deviation.

Figure 4:

Box and whisker plot depicts hepatic stiffness according to fibrosis stage and necroinflammation grade. The boxes indicate the lower and upper quartiles for each group, and the dark horizontal line in the middle of the box is the median (50%) percentile. The whiskers are the lowest and highest values in distribution.

Figure 5:

Forest plot shows pooled AUC values for MR elastography with 95% CIs (whiskers) for the prediction of hepatic fibrosis (grades ≥F1, ≥F2, ≥F3, and F4) and necroinflammatory grade (grades ≥A1, ≥A2, and A3).