Agents for the treatment of portal hypertension

Patients with end-stage liver disease will suffer from portal hypertension. Portal hypertension can lead to esophageal varices, ascites, hepatorenal syndrome, hyponatremia and hepatic encephalopathy. Treatment of varices is based on decreasing portal pressures with nonselective beta-blockers. They act principally on β1 receptors, resulting in splanchnic vasoconstriction and a reduction in portal inflow. Ascites requires a salt restricted diet and the use of diuretics to remove the excess fluid; it is best to use the diuretics in a ratio of 40 mg of furosemide to 100 mg of spironolactone in order to minimize potassium side effects of the diuretics. As portal hypertension advances, patients may develop worsening splanchnic vasodilation and this will lead to renal insufficiency. Multiple agents have been tried for this, including albumin, octreotide and midodrine. Terlipressin is a vasopressin analog that has been shown in multiple trials to be beneficial for the treatment of hepatorenal syndrome, but has yet to be approved by the FDA in the United States. Hepatic encephalopathy is the result of significant portal blood flow shunting; treatment is based on eliminating the toxic substances from the intestines with either lactulose or rifaximin. Treating patients with end-stage liver disease requires a comprehensive understanding of the complications of portal hypertension and the many agents that are used to counteract these symptoms.