Gianfranco Finucci

Prognostic Usefulness of Hepatic Vein Catheterization in Patients With Cirrhosis and Esophageal Varices

Clinical and anamnestic data, Pugh score, and size of esophageal varices were obtained in 129 cirrhotics. Hepatic vein catheterization was performed to measure hepatic venous pressure gradient (HVPG), indocyanine green (ICG) intrinsic hepatic clearance, and hepatic plasma flow. During a follow-up period of up to 60 months, 44 patients experienced gastrointestinal bleeding and 54 died. Applying Cox regression analysis, ICG intrinsic hepatic clearance, Pugh score, previous variceal bleeding, and HVPG were the only significant prognostic determinants of survival. In addition, Coxs regression analysis showed that HVPG, Pugh score, size of varices, and previous variceal bleeding all contained significant prognostic information regarding risk of gastrointestinal bleeding. The models were validated using a split-sample technique, and prognostic indexes for death and gastrointestinal bleeding were calculated. The prognostic index predicting death had significantly improved prognostic accuracy over a prognostic index calculated excluding the data obtained from hepatic vein catheterization (P less than 0.05). In conclusion, prognostic accuracy in cirrhosis with portal hypertension is significantly improved by information obtained from hepatic vein catheterization.

Left Ventricular Diastolic Function in Liver Cirrhosis

BACKGROUND Left ventricular systolic abnormalities have been reported in liver cirrhosis (LC). Diastolic function in cirrhotics, on the contrary, does not seem to have been studied so far. METHODS Diastolic function was evaluated in 42 cirrhotic patients and in 16 controls by means of Doppler echocardiography. RESULTS Compared with the controls, cirrhotics had increased left ventricular end-diastolic and left atrial volume, stroke volume, late diastolic flow velocity (peak A) (71 + or - 17 cm/sec versus 56 +/- 18; p <0.01), time from onset of mitral inflow to the early peak (time E) (86 + or - 11 msec versus 72 +/- 14; p < 0.003), and deceleration time (DT) (194 +/- 40 msec versus 159 +/- 27; p < 0.001) and decreased ratio of peak E to peak A filling velocities (1.02 +/ - 0.35 versus 1.22 +/- 0.25; p < 0.02). Patients with tense ascites had a higher E/A ratio (p < 0.03) and a shorter DT (p < 0.03) than patients with mild or no ascites. CONCLUSIONS The impaired left ventricular relaxation in the presence of high stroke volume suggests a myocardial involvement in LC. The pseudo normalization of the E/A ratio and DT in patients with tense ascites could reflect loading conditions masking the relaxation abnormality.

Effect of Somatostatin on Splanchnic Hemodynamics in Patients with Liver Cirrhosis and Portal Hypertension

The effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis is not clearly defined, as some authors report a decrease in portal pressure and in liver blood flow during intravenous administration of this hormone, while others do not. In 19 subjects with liver cirrhosis and portal hypertension the following parameters were measured before and during intravenous administration of somatostatin (7.5 micrograms/min): porto-hepatic gradient, estimated hepatic blood flow, specific splenic blood flow, cardiac index. Estimated hepatic blood flow decreased significantly during somatostatin infusion (p less than 0.05), averaging a 13% decrease; porto-hepatic gradient, splenic specific blood flow and cardiac index did not vary significantly. These data indicate that somatostatin infused at a dose of 7.5 micrograms/min induces a slight decrease in liver blood flow without affecting portal hypertension.

Effects of isosorbide dinitrate on portal hypertension in alcoholic cirrhosis

It has recently been reported that vasodilators lower portal pressure in patients with cirrhosis. This effect, however, is not definitively proven. The effect of isosorbide dinitrate (5 mg sublingually) on splanchnic and systemic hemodynamics was investigated in 13 patients with alcoholic cirrhosis and portal hypertension. The administration of isosorbide dinitrate reduced hepatic venous pressure gradient by 34% (P less than 0.001), mean arterial pressure by 30% (P less than 0.001), cardiac index by 17% (P less than 0.001) and systemic vascular resistance by 11% (P = 0.05). Hepatic blood flow was not affected by the treatment. Significant correlations were found between the decrease in hepatic venous pressure gradient and that of cardiac index (P less than 0.05) and mean arterial pressure (P less than 0.05). These data indicate that isosorbide dinitrate lowers portal pressure in patients with cirrhosis. Decrease in cardiac output, rise in splanchnic arterial vascular resistance and decrease in porto-hepatic resistance seem to participate in determining the effect.

Hemodynamic changes of systemic, hepatic, and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis

Triglycyl-lysin-vasopressin is a long-acting vasopressin derivative which is under consideration for the treatment of acute variceal bleeding in cirrhosis. However, its splanchnic hemodynamic effects have not been investigated thoroughly. In 11 patients with alcoholic cirrhosis, systemic and splanchnic hemodynamics were evaluated before and 20–40 min after intravenous administration of 2 mg triglycyl-lysin-vasopressin. Following the drug administration, heart rate decreased by 10% and cardiac index by 22% on the average, respectively; mean arterial pressure increased by 14% and systemic vascular resistence index by 48%. Hepatic venous pressure gradient showed a marked and persistent fall, averaging 31%. Hepatic and splenic blood flow decreased by 31% and 56%, respectively. A significant correlation was found between the decrease in hepatic venous pressure gradient and in splenic blood flow. By contrast, the decrease in the hepatic venous pressure gradient was not significantly correlated to the decrease in hepatic blood flow or in cardiac index. We conclude that in patients with alcoholic cirrhosis, triglycyl-lysin-vasopressin decreases portal pressure as well as hepatic and splenic blood flows. The decrease in portal pressure was due to the decrease in splanchnic blood inflow and not to the decrease in cardiac index.

Long-term effect of nadolol on quantitative liver function tests in patients with cirrhosis.

SummaryNadolol, a non-cardioselective beta adrenoreceptor blocking agent, has been reported to decrease portal pressure without affecting liver function in cirrhotic patients treated for 1 month. There were no data about the long-term effects of nadolol on liver function.In 11 patients with cirrhosis and portal hypertension galactose eliminating capacity, aminopyrine metabolic capacity, ICG clearance and IGC intrinsic hepatic clearance according to the “parallel tube” model were measured before and after 6 months of treatment with nadolol at a dose reducing resting heart rate by approximately 25%. No significant variation in any of these parameters was found.Thus 6 months of continuous oral administration of nadolol did not further impair liver function in cirrhotics.

Clinical Significance of Cholelithiasis in Patients with Decompensated Cirrhosis

There is general agreement that the prevalence of gallstones in cirrhotics is high (at least twice that in the general population), but the pathogenetic link between cirrhosis and cholelithiasis is still uncertain. The influence of cholelithiasis on survival in cirrhotics is also unknown. During an 8-year period, we observed 90 patients affected by decompensated cirrhosis: 36 of them (40%) turned out by cholecystographic/cholangiographic or ultrasonographic examination to have cholelithiasis. We were not able to demonstrate any correlation between cholelithiasis and sex, age of patients, etiology of cirrhosis severity of the illness, degree of portal hypertension, previous gastrointestinal bleeding, number of pregnancies, or levels of serum cholesterol, bilirubin, and triglycerides. During the follow-up observation, (range, 1–91 months), 30 patients died. Survival curves analyzed by the log-rank test did not show any difference between patients with or without gallstones. We therefore confirm that cirrhosis is a lithogenic condition, but we were not able to explain the reasons for the close relationship between cholelithiasis and cirrhosis. Gallstones, however, did not affect the survival of these patients.

EVALUATION OF SPLANCHNIC ANGIOGRAPHY AS A PROGNOSTIC INDEX OF SURVIVAL IN PATIENTS WITH CIRRHOSIS

Prognostic evaluation of advanced liver disease is usually made on the basis of the common clinical and biochemical data included in the Child-Turcotte classification. The aim of this study was to evaluate the contribution of data from splanchnic angiography as a guide to prognosis in patients with cirrhosis. Over an 8-year period 219 patients with cirrhosis were investigated by splanchnic angiography and followed up prospectively. At the end of the study 95 patients had died (43.4%). Median survival time was 68 months. In addition to several clinical and biochemical data, hepatic portal venous perfusion and the presence of caudad hepatofugal veins as assessed by angiography were significant predictors of survival. Incorporating all nonangiographic variables in a Coxs multiple regression analysis, a clinicobiochemical set of prognostic covariates (ascites, s-albumin, gammaglobulins, s-alkaline phosphatase, and sex) was selected. When adding to this model each of the angiographic variables, only portal perfusion resulted in an independent predictor of survival. In conclusion, in cirrhotics the angiographic evaluation of portal perfusion improved the prognostic information obtained from clinical and biochemical data.