1Liver Clinic, Department of Gastroenterology.
Factors other than elevated levels of ammonia may be implicated in hepatic encephalopathy (HE) pathophysiology, including abnormal cerebral hemodynamics. Transcranial Doppler ultrasonography (TCD) evaluates cerebrovascular structural integrity and reactivity, through pulsatility index (PI) and breath-holding index (BHI), respectively. Aim: to evaluate cerebral hemodynamics by TCD in patients with compensated and decompensated cirrhosis, and patients with and without HE.
We studied 90 subjects by TCD measuring PI and BHI in the middle cerebral artery: 30 with cirrhosis and no HE, 30 with cirrhosis and low-grade HE, and 30 healthy subjects. Critical flicker frequency, psychometric hepatic encephalopathy score) and West-Haven criteria were performed to assess MHE and HE respectively.
PI increased in decompensated cirrhotics (Child≥7) when compared to compensated cirrhotics, and healthy subjects (median [IQR] 1.07[0.95-1.21]vs 0.90[0.83-1.05]vs 0.87[0.78-0.96]; P<0.001). A reverse relationship was observed for BHI among the three groups: 0.82[0.45-1.11] vs 1.20[0.82-1.52] vs 1.28[1.06-1.68]; P<0.001). Similar findings were observed in decompensation (MELD score ≥14). Patients with HE showed higher PI and lower BHI (1.05[1.00-1.16] and 0.89[0.59-1.15]), when compared to patients without HE (0.96[0.83-1.13] and 1.00[0.60-1.53]), or controls (0.87[0.78-0.96] and 1.28[1.06-1.68]) (p<0.001 for PI, and p=0.007 for BHI). In multivariate regression models only PI predicted HE, but it was outperformed by MELD-sodium, and TNF-α.
These results indicate that cerebral hemodynamics are altered in patients with cirrhosis, in relation to severity of disease and HE. Findings on impaired PI and BHI suggest that structural vascular damage and loss of vascular autoregulation are implicated in the pathophysiology of HE.