Current management of portal hypertension.

The management of portal hypertension should be based on an updated knowledge of its natural history. Portal hypertension is an almost unavoidable complication of cirrhosis, and it is responsible for the more lethal complications of this syndrome: gastro-esophageal varices and massive gastrointestinal bleeding, ascites, hepatorenal syndrome, and hepatic encephalopathy. Appearance of these complications represents the major cause of death and liver transplantation in patients with cirrhosis. The prevalence of esophageal varices is very high: when cirrhosis is diagnosed, varices are present in about 40% of compensated patients and in 60% of those with ascites [1,2]. After initial diagnosis of cirrhosis, the expected incidence of newly developed varices is about 5% per year [3]. Once developed, varices increase in size from small to large at an overall rate of 10–15% per year [3]. Progression of liver failure seems to be the factor with the greatest influence on overall growth [4]. On the other side, improvement in liver function and abstinence from alcohol may result in decrease or even disappearance of varices [5]. Once diagnosed, the overall incidence of variceal bleeding is to the order of 25% at 2 years in non-selected patients [6]. Many efforts have been made to define risk criteria for the development of variceal bleeding. The most important predictive factors related to the risk of bleeding are variceal size,presence of red weal marks in the varices, and severity of liver dysfunction expressed by the Child–Pugh classification. These risk indicators have been combined in the north Italian endoscopic club (NIEC) index [7] which allows to classify patients into different groups with predicted 1-year bleeding risk ranging from 6 to 76%. However, the predictive power of this index is far from satisfactory. In a recent report, variceal size was found to be the best predictor of variceal bleeding, and this is the variable used to decide whether a patient should be given prophylactic therapy or not. The risk of variceal bleeding is about 7% at 2 years in patients with small varices (less than 5 mm), and increases to 30% at 2 years in patients with large varices [6]. Variceal size and red color signs are associated with increased bleeding risk probably because they contribute to marked increase in the tension of the wall of the varices, the decisive factor determining variceal rupture [8]. According to Frank’s modification of Laplace’s law, variceal wall tension is directly proportional to the transmural variceal pressure (the gradient between intravariceal and esophageal luminal pressures) and the radius of the varix, and inversely proportional to the thickness of the variceal wall. While variceal size is a function of variceal radius, red weal marks may represent areas of reduced wall thickness. Hepatic venous pressure gradient (HVPG) may constitute a good surrogate marker of transmural variceal pressure [9]. Indeed, cross-sectional and longitudinal studies demonstrated that variceal bleeding does not occur if HVPG remains below 12 mmHg [5,9–12]. It has been reported that 30–50% of cirrhotic patients with an acute variceal bleeding episode will die within 6 weeks [2], but it is likely that this figure overestimates the current mortality from variceal bleeding [13]. A more accurate, current figure may be a mortality of 20% at 6 weeks. Immediate mortality from uncontrolled bleeding is in the range of 5–8% [2,6]. Active bleeding at endoscopy [14], bacterial infection [15] and HVPG .20 mmHg measured early after admission [16] are significant prognostic indicators of failure to control bleeding. It is important to emphasize that variceal bleeding ceases spontaneously in 40–50% of patients. This is probably influenced by the fact that hypovolemia leads to reflex splanchnic vasoconstriction with reduced portal pressure and blood flow, a beneficial response that is nullified by blood transfusion [17,18]. The incidence of early rebleeding ranges between 30 and 40% within the first 6 weeks [6]. The risk peaks in the first 5 days with 40% of all rebleeding episodes occurring in this very early period [19]. Bleeding gastric varices, active bleeding at emergency endoscopy, low serum albumin levels, renal failure Journal of Hepatology 38 (2003) S54–S68