Increased flow-mediated vasodilation in cirrhotic patients with ascites: relationship with renal resistive index.

BACKGROUND: Peripheral vasodilation is the key factor in the development of hyperdynamic circulation, sodium retention and functional renal failure in patients with cirrhosis. Brachial artery flow-mediated dilation (FMD) after transient vascular occlusion is a non-invasive method to assess the shear stress-induced arterial vasodilation. AIMS: To evaluate FMD in cirrhotic patients with and without ascites and to assess the relationship between FMD and intrarenal resistances. METHODS: Flow-mediated dilation was determined in 32 cirrhotic patients (22 with ascites) and 12 healthy controls and correlated with the intrarenal resistive index (RI) assessed by Doppler exploration. RESULTS: Basal diameter of the brachial artery was similar in healthy controls and in cirrhotic patients, whereas FMD was significantly higher in patients with cirrhosis and ascites [29.5% (range 10.3-50%)] than in pre-ascitic patients [17.3% (range 2.4-48.5%)] and healthy control subjects [11.6% (range 5.1-17.8%)] (P<0.001). Intrarenal RI was significantly higher in patients with cirrhosis than in healthy subjects, and a direct relationship existed between FMD and intrarenal RI (r=0.66; P<0.00001). CONCLUSIONS: These findings in vivo demonstrate that cirrhotic patients with ascites have an enhanced shear stress-induced peripheral vasodilation, which is closely related to intrarenal vasoconstriction.

Diastolic dysfunction is associated with poor survival in patients with cirrhosis with transjugular intrahepatic portosystemic shunt.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a treatment for portal hypertension-related complications. Accurate prediction of the outcome of patients treated with TIPS is important, because some patients have very short survival. Diastolic dysfunction is frequently observed in patients with cirrhosis. AIM: To investigate whether or not diastolic dysfunction can predict the outcome after TIPS. METHODS: Echocardiography with Doppler exploration was performed before and 28 days after TIPS insertion in 32 patients with cirrhosis. Several echocardiographic measures, including the early maximal ventricular filling velocity/late filling velocity (E/A) ratio as indicative of diastolic function, as well as laboratory, clinical and demographic variables were evaluated as predictors of survival. RESULTS: Univariate analysis revealed that the presence of diastolic dysfunction observed 28 days after TIPS (E/A ratio 1 survived. CONCLUSIONS: Diastolic dysfunction estimated using E/A ratio is a promising predictor of death in patients with cirrhosis who are treated with TIPS.

Effect of potassium canrenoate, an anti-aldosterone agent, on incidence of ascites and variceal progression in cirrhosis.

BACKGROUND & AIMS: Because aldosterone-dependent sodium and water retention contribute to portal hypertension, the safety and effect of an antialdosteronic drug (Kcanrenoate) have been evaluated on the occurrence of de novo appearance of ascites and the development of esophageal varices or the progression of small varices. METHODS: Inclusion criteria were as follows: Child-Pugh A viral pre-ascitic cirrhosis, with either F1 esophageal varices or no varices, but endoscopic and/or ultrasound evidence of portal hypertension. Thirteen Italian Liver Units prospectively enrolled 120 patients randomized to receive double-blind either Kcanrenoate (100 mg/day; 66 patients) or placebo (54 patients). Endoscopy and sonography were performed at entry and at 52 weeks unless the patient developed ascites earlier, whereas laboratory examinations were performed at entry and every 3 months thereafter. An intention-to-treat analysis was performed, with each end point assessed by the Fisher exact test; the cumulative risk for the appearance of any end point was analyzed by the adjusted log-rank test (Tarone-Ware), with censoring for drop-outs. RESULTS: The progression of variceal status or appearance of ascites, analyzed independently, was not significantly more frequent on placebo (24.1% and 9.2%, respectively) than on Kcanrenoate (12.1% and 1.5%, respectively), whereas the cumulative occurrence of end points was decreased on Kcanrenoate (17.6% vs 38.3% with placebo; P < .05, Tarone-Ware test). The incidence of adverse events was negligible and did not differ between groups. CONCLUSIONS: This preliminary study shows that 100 mg/day of Kcanrenoate is well tolerated and does not reduce the individual incidence of ascites and/or the appearance or progression of esophageal varices in preascitc cirrhosis, but may decrease their 1-year cumulative occurrence.

Nadolol is superior to isosorbide mononitrate for the prevention of the first variceal bleeding in cirrhotic patients with ascites.

BACKGROUND/AIMS: beta-blockers effectively prevent first variceal bleeding (FVB) in cirrhotic patients. In patients with ascites, however, their use might be precluded by a high rate of contraindications and side effects. We compared the efficacy and applicability of nadolol and isosorbide-mononitrate (IsMn) in preventing FVB in a population of cirrhotic patients at high risk of variceal bleeding with ascites, who can be frequently intolerant to beta-blockers. METHODS: A total of 80 consecutive cirrhotic patients with ascites and esophageal varices (25% average risk of bleeding at 1 year) were considered, 28 were excluded due to contraindications and 52 were randomly assigned to receive nadolol (n=25) or IsMn (n=27). RESULTS: Frequency of contraindications was greater for beta-blockers than IsMn (35 versus 0%, P=0.001). During 21.3+/-11.6 months of follow-up, side effects forced six patients taking nadolol and four taking IsMn to stop treatment. Bleeding occurred in two patients taking nadolol and ten taking IsMn. The probability of bleeding was significantly lower in the nadolol group (P<0.05), whereas overall survival was similar (seven patients on IsMn and eight on nadolol died, P=0.3). CONCLUSIONS: In patients with ascites IsMn is tolerated but ineffective while nadolol is effective but less tolerated.