Complications of cirrhosis. I. Portal hypertension

Increased resistance to portal blood flow is the primary factor in the path ophysiology of portal hypertension, and is mainly determined by the morphol ogical changes occurring in chronic liver diseases. This is aggravated by a dynamic component, due to the active - reversible - contraction of differe nt elements of the porto-hepatic bed. A decreased synthesis of NO in the in trahepatic circulation is the main determinant of this dynamic component. T his provides a rationale for the use of vasodilators to reduce intrahepatic resistance and portal pressure. Another factor contributing to aggravate t he portal hypertension is a significant increase in portal blood flow, caus ed by arteriolar splanchnic vasodilation and hyperkinetic circulation. Spla nchnic arteriolar vasodilation is a multifactorial phenomenon, which may in volve local (endothelial) mechanisms as well as neurogenic and humoral path ways. Most pharmacological treatments have been aimed at correcting the inc reased 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 (HV PG) during maintenance therapy are useful to identify those patients who ar e going to have a variceal bleeding or rebleeding. The wide individual vari ation 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 a s surrogate indicators of the HVPG response. In the clinical management of portal hypertension, beta-blockers are at present the only accepted treatme nt for the prevention of variceal bleeding. Whether the association of isos orbide-5-mononitrate will improve the high efficacy of beta-blockers is que stionable. The efficacy of more aggressive techniques, such as endoscopic b and ligation, should be further tested against beta-blockers in patients wi th a high risk of bleeding. In the treatment of acute variceal bleeding, ad ministration of somatostatin dr terlipressin is an established therapy. It may be used alone or, preferably, as an initial treatment before sclerother apy or endoscopic band ligation. No more than two sessions of endoscopic tr eatment should be used to control the bleeding. If the bleeding is not easi ly controlled, other alternatives such as transjugular intrahepatic portosy stemic shunts (TIPS) or derivative surgery should be considered, the former being the best in patients with poor liver function. Recent studies sugges t that early measurement of HVPG during variceal bleeding may be used as a guide for therapeutic decisions in the treatment of patients with acute var iceal bleeding. Those patients with a high HVPG have a high risk of poor ev olution, and may be candidates for more intensive and aggressive therapy, s uch as surgery or TIPS. Those with lower HVPG have a very high probability of an uneventful evolution, and may thus be managed more conservatively usi ng medical and endoscopic treatments. Pharmacological agents (propranolol o r nadolol), endoscopic treatment (preferably banding ligation) or surgery c an be used to prevent rebleeding. A pending task for the new millennium is to assess whether the early treatment of asymptomatic, compensated cirrhoti c patients with portal pressure reducing agents can prevent the development of esophageal varices and of other complications of portal hypertension.