Influence of liver stiffness heterogeneity on staging fibrosis in patients with nonalcoholic fatty liver disease

Abstract

Background and aims: Despite that hepatic fibrosis often affects the liver globally, spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness (LS) heterogeneity on concordance between MR elastography (MRE)-based fibrosis staging and biopsy staging in patients with NAFLD.

Approach and results: We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3 Tesla MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE-based LS measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE-based fibrosis staging of stage 4 (4.43, kPa; AUROC, 0.89) and stage ≥3 (3.93, kPa; AUROC, 0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of <4. In 86.7% of these discordant cases, variability of LSM was classified as heterogeneous. In MRE-based LSM stage ≥3, 88.9% of discordant cases were classified as heterogeneous. Results of the validation cohort were similar to those of the training cohort.

Conclusions: Discordance between biopsy- and MRE-based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE.

FIGURE 1

Histogram illustrating the distribution of stiffness variability in the training study cohort, where variability was defined as the difference between maximum and minimum LS values (measured in 1‐cm² ROIs), divided by the maximum value and expressed in percentage

FIGURE 2

(A) MRE images demonstrating more heterogenous (right) and less heterogeneous (left) LS patterns. The homogeneous type with advanced LS appears as a uniformly red signal on conventional MRE images. However, in the heterogeneous type, only partial areas show the red signal, indicating advanced LS. (B) Conventional MRE images were converted into three‐dimensional (3D) images by representing the high and low LS regions as contour lines, making it easier to assess the areas with highest and lowest LS visually

FIGURE 3

(A) Left column: graph showing two metrics of LS heterogeneity (variability and overlap, as defined in the text) for each MRE‐based LSM stage in the training cohort. Cases in which histopathology staging was lower than MRE‐based LSM staging are shown in red. Probability distributions of concordant and discordant cases were significantly different, except MRE‐based LSM stage 2. Discordant biopsy results were associated with higher metrics of LS heterogeneity. Right column: similar graph for each histopathological fibrosis stage in the training cohort. Discordant cases, in which MRE‐based LSM stage was lower than pathological fibrosis stage, are shown in red. Probability distributions of concordant and discordant cases were significantly different. (B) Similar graph to (A) in the validation cohort