Systemic and splanchnic endothelin-1 plasma levels in liver cirrhosis before and after transjugular intrahepatic portosystemic shunt (TIPS).

AIMS/BACKGROUND: Endothelin-1 (ET-1) may be a mediator for portal hypertension in liver cirrhosis. The aim of the present study was to determine the concentrations of ET-1 in the systemic and splanchnic circulation before and after reduction of portal hypertension by transjugular intrahepatic portosystemic shunt implantation (TIPS). METHODS: Plasma concentrations of immunoreactive ET-1 were measured in peripheral venous blood samples from 25 patients with liver cirrhosis before and at 1, 3, 9 and 15 months after TIPS. Furthermore, acute effects of TIPS on ET-1 were studied in plasma samples from the hepatic vein, the portal vein 30 minutes before and after TIPS and in the femoral artery (only after TIPS) in a subgroup of 15 patients. In addition, the portocaval pressure gradient was determined before and after TIPS. RESULTS: Before TIPS peripheral venous plasma ET-1 concentrations (n=25; median 4.2 pg/ml; range 1.9-14.7) were significantly increased in patients with refractory ascites (n=7; median 7.8, range 3.5 14.7) compared to patients with repetitive bleeding (n=18; median 3.4; range 1.9-7.1) (p=0.003). Furthermore, peripheral ET-1 concentrations correlated with the degree of liver dysfunction according to the Child-Pugh classification (Spearman's r=0.46; p=0.02). Following TIPS, peripheral ET-1 concentrations remained unchanged during a follow-up of 15 months. Before TIPS, a positive gradient of ET-1 concentrations from portalvenous to hepatovenous and peripheral venous levels was found (p<0.03). Immediately after TIPS, arterial ET-1 concentrations reached markedly increased levels in individual patients (88, 92 and 103 pg/ml). Severe systemic reactions to these high levels were not observed. Peripheral venous, hepatovenous and portalvenous ET-1 concentrations did not correlate with portocaval pressure gradients. CONCLUSION: Cirrhotic patients demonstrated unchanged peripheral venous ET-1 concentrations up to 15 months after TIPS. Portal congestion was associated with increased ET-1 levels in the prehepatic splanchnic area. The effect of portal decompression on splanchnic and systemic ET-1 levels deserves further investigation.

Portosystemic hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: clinical, laboratory, psychometric, and electroencephalographic investigations.

A prospective study of hepatic encephalopathy (HE) including neuropsychiatric and psychometric evaluation, electroencephalography, and determination of arterial ammonia levels was performed in 55 cirrhotic patients treated consecutively by transjugular intrahepatic portosystemic shunt (TIPS). The cumulative HE rate increased from 23.6% within the 3-month interval before TIPS to 50. 9% within the first 3-month interval post-TIPS (P = .003). Significant and independent predictors of HE post-TIPS were the presence of HE pre-TIPS and reduced liver function. The cumulative HE rate declined in the second 3-month interval post-TIPS and reached the pre-TIPS level. Chronic forms of HE exceeding grade I were not observed. In a subgroup of 22 nonencephalopathic TIPS patients, the prevalence of subclinical HE did not change after TIPS. Among individual psychometric tests, the block design test gave the highest proportion of pathological results (about 50%), whereas selective reminding gave the lowest (10%-25%). Electroencephalography (EEG) showed a temporary increase of pathological results at 1 month after TIPS, when patients with overt HE (grade I) were included (proportion of 21.1% before vs. 57.1%, P = .005). Arterial ammonia concentration increased from a mean of 94 +/- 26 microgram/dL to 140 +/- 28 microgram/dL at 3 months after TIPS (P < .001). Elevated ammonia levels persisted. TIPS led to a temporary increase of HE incidence within 3 months. The decline of the HE rate beyond 3 months despite a sustained increase of arterial ammonia levels could not entirely be explained by reduction of shunt flow, nor by alteration of liver function. Instead, cerebral adaptation to gut-derived neurotoxins might be anticipated.

Bright basal ganglia in T1-weighted magnetic resonance images are frequent in patients with portal vein thrombosis without liver cirrhosis and not suggestive of hepatic encephalopathy.

BACKGROUND/AIMS: Deposition of paramagnetic substances in basal ganglia, resulting in increased signals in T1-weighted magnetic resonance images (bright basal ganglia), is frequently seen in liver cirrhosis. The present study describes the prevalence of bright basal ganglia and its clinical significance in patients with long-standing portal vein thrombosis in the absence of liver cirrhosis. METHODS: Six patients with angiographically proven complete portal vein thrombosis and cavernomatous transformation without signs of acute or chronic liver disease were studied by magnetic resonance imaging of the brain, neuropsychiatric evaluation, psychometric tests, electroencephalography, and determination of arterial ammonia levels and of serum manganese concentrations from peripheral venous blood. RESULTS: Five out of six patients demonstrated increased signal intensity in the basal ganglia. Overt portal-systemic encephalopathy was not noted prior to or at the time of evaluation. Normal EEG results were recorded in all patients. Only one of the six patients had pathological results in at least two out of four psychometric tests. This latter patient had had a large right-sided brain infarction. Arterial ammonia concentrations were normal in four of the six patients; one patient with increased ammonia levels had concomitant renal insufficiency with azotemia. The other four patients had no relevant concomitant diseases. Serum manganese levels were non-significantly increased compared with a control group (p=0.06), but they were significantly correlated to basal ganglia signal intensity (R=0.88; p=0.02). CONCLUSIONS: Our results demonstrate that bright basal ganglia primarily represent shunt-induced alterations. They are not directly associated with disturbed liver function nor with portal-systemic encephalopathy.