Minimal Hepatic Encephalopathy is Associated with Increased Cerebral Vascular Resistance. A Transcranial Doppler Ultrasound Study

Abstract

Minimal hepatic encephalopathy (MHE) is a subclinical complication of liver cirrhosis with a relevant social impact. Thus, there is urgent need to implement easy to use diagnostic tools for the early identification of affected patients. The aim of this study was to investigate cerebral blood flow, systemic hemodynamics as well as endothelial function of cirrhotic patients with MHE, and to verify their change after treatment with rifaximin. Fifty cirrhotic patients with or without MHE and an equal number of healthy controls underwent transcranial Doppler ultrasound (TCD), abdominal Doppler ultrasound (US), and measurement of flow mediated dilation (FMD). In cirrhotic patients diagnosed with MHE receiving rifaximin, the tests were repeated at the end of treatment. Middle (MCA) and posterior (PCA) cerebral artery resistive (RI) and pulsatility (PI) indices were higher in cirrhotic patients than controls, as well as renal and splenic artery RI. Conversely, FMD was reduced. MCA-RI and PI were even higher in cirrhotic patients with MHE compared to those without; a MCA-RI cut-off of 0.65 showed an accuracy of 74% in discriminating the presence of MHE, with 65% sensitivity and 76% specificity. Rifaximin treatment showed no efficacy in the modulation of cerebral vascular flow. In conclusion, cirrhotic patients with MHE have significantly increased cerebral vascular resistances that are not improved by rifaximin treatment. MCA-RI measurement has a good accuracy for the diagnosis of MHE and can be useful for the early identification of this harmful complication of liver cirrhosis.

Figure 1

Correlations between systemic and splanchnic vascular resistance parameters and flow mediated dilation (FMD) in the study population. Positive correlations are represented in dark green, negative ones in light green. The size of the circle and color intensity are proportional to the correlation coefficient. RI = resistive index; PI = pulsatility index; MCA = middle cerebral artery; PCA = posterior cerebral artery; RA = renal artery; SA = splenic artery; MPV = mean portal vein velocity; FMD = flow mediated dilation.

Figure 2

Receiver operating characteristic (ROC) curve of middle cerebral artery resistive index (MCA-RI) for discriminating the presence or the absence of minimal hepatic encephalopathy (MHE). The cut-off value of 0.65 resulted in the best accuracy (74%), with 65% sensitivity and 76% specificity.

Figure 3

Change in cerebral and splanchnic vascular resistance parameters, flow mediated dilation (FMD), neuropsychological tests results (expressed as rough or standardized values) and ammonia serum level after rifaximin treatment in cirrhotic patients with minimal hepatic encephalopathy (MHE). RI = resistive index; PI = pulsatility index; MCA = middle cerebral artery; PCA = posterior cerebral artery; RA = renal artery; SA = splenic artery; MPV = mean portal vein velocity; FMD = flow mediated dilation; TMT = trail making test; DST = digit symbol test.