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.

The neurogliovascular unit in hepatic encephalopathy

“…The cause of these energy disturbances is likely multifactorial. Several studies show that in HE associated with ALF and CLD, and even in subclinical HE, cerebral blood flow and oxygen metabolism are reduced (figure 2A) (44,45). Secondly, ammonia can directly inhibit the Krebs cycle enzymes αketoglutarate dehydrogenase, isocitrate dehydrogenase and pyruvate dehydrogenase, limiting the effectiveness of oxidative phosphorylation (figure 2B) (28).…”

“…2 A). 44 , 45 Secondly, ammonia can directly inhibit the Krebs cycle enzymes α-ketoglutarate dehydrogenase, isocitrate dehydrogenase and pyruvate dehydrogenase, limiting the effectiveness of oxidative phosphorylation ( Fig. 2 B).…”

The Importance of Neuromonitoring in Non Brain Injured Patients

“…TCD has considerable diagnostic potential in the ED and the ICU. Hepatic encephalopathy is a complication which occurs in up to 70% of patients with liver cirrhosis, and that manifests with psychomotor, attentive, and executive alterations [ 35 ].…”

“…Higher vascular resistances and pulsatility index in the middle and posterior cerebral arteries of cirrhotic patients have been reported in comparison to controls, with 74% accuracy of the middle cerebral artery resistive index for discriminating the presence of hepatic encephalopathy [ 35 ].…”

Peripheral endothelial and microvascular damage in liver cirrhosis: A systematic review and meta‐analysis

“…Of the 20 studies included in this systematic review, 10 studies evaluated endothelial function via VOP, [20][21][22][24][25][26][27][28][29][30] 6 via FMD, 12,15,[31][32][33][34] 2 via NIRS, 11,23 1 via LDF, 35 and 1 via nailfold video-capillaroscopy. 19 Among the studies that used VOP, 3 studies assessed only endothelial-dependent vasodilation (FBF after acetylcholine infusion or after a typical post-occlusion reactive hyperemia protocol), 22,24,30 4 studies assessed only endothelialindependent vasodilation (FBF after infusion of selective endothelin type-A receptor antagonist, BQ123, or after infusion of nitroglycerin), 21,[27][28][29] and 3 studies evaluated both endothelialdependent and endothelial-independent vasodilation (FBF after infusion of acetylcholine, bradykinin, methacholine, or sodium nitroprusside).…”