Alberto Monescillo

Circulatory function and hepatorenal syndrome in cirrhosis

The pathogenic mechanism of hepatorenal syndrome is not well established. We investigated the circulatory function in cirrhosis before and after the development of hepatorenal syndrome. Systemic and hepatic hemodynamics and the activity of endogenous vasoactive systems were measured in 66 patients who had cirrhosis with tense ascites and normal serum creatinine levels; measurements were repeated at follow‐up in 27 cases in whom hepatorenal syndrome had developed. At baseline, mean arterial pressure and cardiac output were significantly higher, and hepatic venous pressure gradient, plasma renin activity, and norepinephrine concentration were significantly lower in patients who did not develop hepatorenal syndrome compared with those presenting with this complication. Peripheral vascular resistance was decreased to the same extent in the two groups. Plasma renin activity and cardiac output were the only independent predictors of hepatorenal syndrome. Hepatorenal syndrome occurred in the setting of a significant reduction in mean arterial pressure (83 ± 9 to 75 ± 7 mmHg; P < .001), cardiac output (6.0 ± 1.2 to 5.4 ± 1.5 L/min; P < .01), and wegded pulmonary pressure (9.2 ± 2.6 to 7.5 ± 2.6 mmHg; P < .001) and an increase in plasma renin activity (9.9 ± 5.2 to 17.5 ± 11.4 ng/mL · hr; P < .001), norepinephrine concentration (571 ± 241 to 965 ± 502 pg/mL; P < .001), and hepatic venous pressure gradient. No changes were observed in peripheral vascular resistance. In conclusion, these data indicate that hepatorenal syndrome is the result of a decrease in cardiac output in the setting of a severe arterial vasodilation. (HEPATOLOGY 2005.)

Terlipressin and Albumin vs Albumin in Patients With Cirrhosis and Hepatorenal Syndrome : A Randomized Study

BACKGROUND & AIMS Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. METHODS Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. RESULTS Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. CONCLUSIONS As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.

Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration.

Hyponatraemia is common in patients with advanced cirrhosis and is associated with remarkable changes in brain cells, particularly a reduction in myoinositol and other intracellular organic osmolytes related to the hypo‐osmolality of the extracellular fluid. It has been recently suggested that hyponatraemia may be an important factor associated with the development of overt hepatic encephalopathy (HE). To test this hypothesis, we retrospectively analysed the incidence and predictive factors of overt HE using a database of 70 patients with cirrhosis included in a prospective study comparing transjugular intrahepatic portosystemic shunts (TIPS) vs large‐volume paracentesis in the management of refractory of ascites. Variables used in the analysis included age, sex, previous history of HE, treatment assignment (TIPS vs large volume paracentesis plus albumin), treatment with diuretics, serum bilirubin, serum creatinine and serum sodium concentration. Laboratory parameters were measured at entry, at 1 month and every 3 months during follow‐up and at the time of development of HE in patients who developed this complication. During a mean follow‐up of 10 months, 50 patients (71%) developed 117 episodes of HE. In the whole population of patients, the occurrence of HE was independently associated with serum hyponatraemia, serum bilirubin and serum creatinine. In conclusion, in patients with refractory ascites, the occurrence of HE is related to the impairment of liver and renal function and presence of hyponatraemia.

Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal rebleeding after recent variceal hemorrhage

Variceal hemorrhage continues to be a major cause of morbidity and mortality in cirrhotic patients. Transjugular intrahepatic portosystemic shunt (TIPS) is gaining wide acceptance as a treatment for several complications of portal hypertension. The aim of the current randomized study was to compare the transjugular shunt and endoscopic sclerotherapy (ES) for the prevention of variceal rebleeding (VB) in cirrhotic patients. Forty-six consecutive cirrhotic patients with variceal bleeding were randomly allocated to receive either transjugular shunt (22 patients) or ES (24 patients) 24 hours after control of bleeding. VB (50% vs. 9%) and early (first 6 weeks) VB (33% vs. 5%) were significantly more frequent in sclerotherapy patients; the actuarial probability of being free of VB was higher in the shunt group (P <.002). Eight patients (33%) of the sclerotherapy group and 3 patients (15%) of the shunt group died; the actuarial probability of survival was higher for the shunted patients (P <.05); 6 patients in the sclerotherapy group and none in the shunt group died from VB (P <.05). No difference was found in the proportion of patients with clinically evident hepatic encephalopathy (HE). These results show that the transjugular shunt is more effective than sclerotherapy in the prevention of both early and long-term VB. Moreover, a significant improvement in survival was found in the shunt group.