3 Natural history. Clinical-haemodynamic correlations. Prediction of the risk of bleeding

We conducted a prospective study of 321 patients with cirrhosis of the liver and esophageal varices with no history of bleeding to see whether a comprehensive analysis of their clinical features and of the endoscopic appearances of their varices could help to identify those at highest risk for bleeding. Varices were classified endoscopically as suggested by the Japanese Research Society for Portal Hypertension. Patients were followed for 1 to 38 months (median, 23), during which 85 patients (26.5 percent) bled. Multiple regression analysis (Cox's model) revealed that the risk of bleeding was significantly related to the patient's modified Child class (an index of liver dysfunction based on serum albumin concentration, bilirubin level, prothrombin time, and the presence of ascites and encephalopathy), the size of the varices, and the presence of red wale markings (longitudinal dilated venules resembling whip marks) on the varices. A prognostic index based on these variables was devised that enabled us to identify a subset of patients with a one-year incidence of bleeding exceeding 65 percent. The index was prospectively validated on an independent sample of 75 patients with varices and no history of bleeding. We conclude that our prognostic index, which identifies groups of patients with one-year probabilities of bleeding ranging from 6 to 76 percent, can be used to identify candidates for prophylactic treatment.

The aim of the study was to investigate the incidenc, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. The study is a follow-up investigation in 234 nonazotemic patients with cirrhosis and ascites. Thirty-nine variables obtained at inclusion were analyzed as possible predictors of hepatorenal syndrome occurrence (Kaplan-Meier method, Mantel-Cox test, and step-wise Cox regression procedure). The probability of hepatorenal syndrome occurrence was 18% at 1 year and 39% at 5 years. Sixteen variables had predictive value for hepatorenal syndrome occurrence in the univariate analysis: history of ascites, hepatomegaly, nutritional status, blood urea nitrogen level, serum creatinine concentration, serum sodium and potassium concentration, serum and urine osmolality, urinary sodium excretion, free water clearance after a water load, glomerular filtration rate, arterial pressure, plasma renin activity, plasma norepinephrine concentration, and esophageal varices. Neither etiology (alcoholic vs. nonalcoholic) nor the Child-Pugh score had predictive value. A multivariate analysis disclosed only three independent predictors of hepatorenal syndrome occurrence: low serum sodium concentration, high plasma renin activity, and absence of hepatomegaly. The hepatorenal syndrome is a relatively frequent complication in cirrhotic patients with ascites that is associated with an extremely short survival. Liver size, plasma renin activity, and serum sodium concentration are predictors of hepatorenal syndrome occurrence in these patients.

In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.