Identification of minimal hepatic encephalopathy in patients with cirrhosis based on white matter imaging and Bayesian data mining

Abstract

Background and purpose: White matter abnormalities have been demonstrated to play an important role in minimal hepatic encephalopathy. In this study, we aimed to evaluate whether WM diffusion tensor imaging can be used to identify minimal hepatic encephalopathy among patients with cirrhosis.

Materials and methods: Our study included 65 patients with cirrhosis with covert hepatic encephalopathy (29 with minimal hepatic encephalopathy and 36 without hepatic encephalopathy). Participants underwent DTI, from which we generated mean diffusivity and fractional anisotropy maps. We used a Bayesian machine-learning technique, called Graphical-Model-based Multivariate Analysis, to determine WM regions that characterize group differences. To further test the clinical significance of these potential biomarkers, we performed Cox regression analysis to assess the potential of these WM regions in predicting survival.

Results: In mean diffusivity or fractional anisotropy maps, 2 spatially distributed WM regions (predominantly located in the bilateral frontal lobes, corpus callosum, and parietal lobes) were consistently identified as differentiating minimal hepatic encephalopathy from no hepatic encephalopathy and yielded 75.4%-81.5% and 83.1%-92.3% classification accuracy, respectively. We were able to follow 55 of 65 patients (median = 18 months), and 15 of these patients eventually died of liver-related causes. Survival analysis indicated that mean diffusivity and fractional anisotropy values in WM regions were predictive of survival, in addition to the Child-Pugh score.

Conclusions: Our findings indicate that WM DTI can provide useful biomarkers differentiating minimal hepatic encephalopathy from no hepatic encephalopathy, which would be helpful for minimal hepatic encephalopathy detection and subsequent treatment.

Fig 1.

Two white matter ROIs generated by GAMMA, which characterize group differences on the MD map on the basis of voxelwise thresholds of the following: 0 SD (A), 0.25 SD (B), 0.50 SD (C), 0.75 SD (D), and 1.0 SD (E) above the mean voxelwise MD value. Green and red indicate the 2 ROIs generated by GAMMA.

Fig 2.

The 2 white matter ROIs generated by GAMMA, which characterize group differences in the FA on the basis of voxelwise thresholds of the following: 0 SD (A), 0.25 SD (B), 0.50 SD (C), 0.75 SD (D), and 1.0 SD (E) below the mean voxelwise FA value. Green and red indicate the 2 ROIs.