Complications of cirrhosis. I. Portal hypertension.

Increased resistance to portal blood flow is the primary factor in the pathophysiology of portal hypertension, and is mainly determined by the morphological changes occurring in chronic liver diseases. This is aggravated by a dynamic component, due to the active-reversible- contraction of different elements of the porto-hepatic bed. A decreased synthesis of NO in the intrahepatic circulation is the main determinant of this dynamic component. This provides a rationale for the use of vasodilators to reduce intrahepatic resistance and portal pressure. Another factor contributing to aggravate the portal hypertension is a significant increase in portal blood flow, caused by arteriolar splanchnic vasodilation and hyperkinetic circulation. Splanchnic arteriolar vasodilation is a multifactorial phenomenon, which may involve local (endothelial) mechanisms as well as neurogenic and humoral pathways. Most pharmacological treatments have been aimed at correcting the increased portal blood inflow by the use of splanchnic vasoconstrictors, such as beta-blockers, vasopressin derivatives and somatostatin. Several studies have demonstrated that changes in the hepatic venous pressure gradient (HVPG) during maintenance therapy are useful to identify those patients who are going to have a variceal bleeding or rebleeding. The wide individual variation in the HVPG response to pharmacological treatment makes it desirable to schedule follow-up measurements of HVPG during pharmacological therapy. A priority for research in the forthcoming years is to develop accurate non-invasive methods to assess prognosis, which can be used to substitute or as surrogate indicators of the HVPG response. In the clinical management of portal hypertension, beta-blockers are at present the only accepted treatment for the prevention of variceal bleeding. Whether the association of isosorbide-5-mononitrate will improve the high efficacy of beta-blockers is questionable. The efficacy of more aggressive techniques, such as endoscopic band ligation, should be further tested against beta-blockers in patients with a high risk of bleeding. In the treatment of acute variceal bleeding, administration of somatostatin or terlipressin is an established therapy. It may be used alone or, preferably, as an initial treatment before sclerotherapy or endoscopic band ligation. No more than two sessions of endoscopic treatment should be used to control the bleeding. If the bleeding is not easily controlled, other alternatives such as transjugular intrahepatic portosystemic shunts (TIPS) or derivative surgery should be considered, the former being the best in patients with poor liver function. Recent studies suggest that early measurement of HVPG during variceal bleeding may be used as a guide for therapeutic decisions in the treatment of patients with acute variceal bleeding. Those patients with a high HVPG have a high risk of poor evolution, and may be candidates for more intensive and aggressive therapy, such as surgery or TIPS. Those with lower HVPG have a very high probability of an uneventful evolution, and may thus be managed more conservatively using medical and endoscopic treatments. Pharmacological agents (propranolol or nadolol), endoscopic treatment (preferably banding ligation) or surgery can be used to prevent rebleeding. A pending task for the new millennium is to assess whether the early treatment of asymptomatic, compensated cirrhotic patients with portal pressure reducing agents can prevent the development of esophageal varices and of other complications of portal hypertension.