Long-term pharmacologic therapy of portal hypertension

Beta-blockers modify splanchnic hemodynamics in cirrhotic patients. Nonselective beta-blockers are more effective than selective beta-blockers. Azygos blood flow, as a measure of collateral circulation, including that through varices, is always reduced, but the effects on portal pressure, whether measured directly or by the wedged hepatic venous pressure, are variable. The initial reported correlation between a 25% reduction of resting pulse rate and similar percentage reduction in the wedged free hepatic venous gradient has not been reproduced in subsequent studies. Therefore, to study the effect of changes in hemodynamic indices and the likelihood of variceal bleeding, direct measurements of such indices need to be made in clinical trials. At present, only one primary-prevention trial of propranolol suggests that a hemodynamic index can be used to identify patients given propranolol who will not bleed. Some clinical factors may be important in identifying nonresponders in trials of secondary prevention, but these are not universally recognized. The results of secondary-prevention studies are very heterogeneous, and it is difficult to understand why this is so. However, comparative studies versus sclerotherapy suggest that reductions in rebleeding and mortality are similar. Pharmacologic treatment, including beta-blockade, is ideal for primary prevention of variceal bleeding. The initial results from randomized studies are more homogeneous regarding the benefit of beta-blockers than in the secondary-prevention studies, although there is still doubt about the response in cirrhotics with ascites. No fatal complications due to propranolol administration have been reported in cirrhotic patients, and the complications are reversible. The future of pharmacologic therapy for portal hypertension lies in combination therapy. The addition of vasodilators to beta-blockers appears to potentiate their effect on portal pressure reduction. The results of clinical trials are awaited with great interest.