Portal Hypertension

Portal hypertension results mainly from increased resistance to blood flow in the portal vein. Causes may be classified as prehepatic (as in portal vein thrombosis), intrahepatic (as in cirrhosis or schistosomiasis), and post-hepatic (as in hepatic venous obstruction) (1). Cirrhosis is the most common cause of intrahepatic resistance (see table Most Common Causes of Portal Hypertension for other causes). Increased flow volume is a rare cause, although it often contributes to portal hypertension in cirrhosis and in hematologic disorders that cause massive splenomegaly.

In cirrhosis, tissue fibrosis and regeneration increase resistance in the sinusoids and terminal portal venules. However, other potentially reversible factors contribute; they include contractility of sinusoidal lining cells, production of vasoactive substances (eg, endothelins, nitric oxide), various systemic mediators of arteriolar resistance, and possibly swelling of hepatocytes. Other causes of and contributing factors to cirrhosis may affect the prehepatic blood vessels (eg, portal venous thrombosis), the pre- or postsinusoidal vasculature within the liver itself (eg, presinusoidal fibrosis in schistosomiasis), or the posthepatic blood vessels or the heart itself (eg, hepatic vein thrombosis)., tissue fibrosis and regeneration increase resistance in the sinusoids and terminal portal venules. However, other potentially reversible factors contribute; they include contractility of sinusoidal lining cells, production of vasoactive substances (eg, endothelins, nitric oxide), various systemic mediators of arteriolar resistance, and possibly swelling of hepatocytes. Other causes of and contributing factors to cirrhosis may affect the prehepatic blood vessels (eg, portal venous thrombosis), the pre- or postsinusoidal vasculature within the liver itself (eg, presinusoidal fibrosis in schistosomiasis), or the posthepatic blood vessels or the heart itself (eg, hepatic vein thrombosis).

Portal Circulation

3D Model

Over time, portal hypertension creates portosystemic venous collaterals. They may slightly decrease portal vein pressure but can cause complications. Engorged serpentine submucosal vessels (varices) in the distal esophagus and sometimes in the gastric fundus can rupture, causing sudden, catastrophic gastrointestinal bleeding. Bleeding rarely occurs unless the portal pressure gradient is > 12 mm Hg. Gastric mucosal vascular congestion (portal hypertensive gastropathy) can cause acute or chronic bleeding independent of varices. Visible abdominal wall collaterals are common; veins radiating from the umbilicus (caput medusae) are much rarer and indicate extensive flow in the umbilical and periumbilical veins. Collaterals around the rectum can cause rectal varices that can bleed.

Portosystemic collaterals shunt blood away from the liver. Thus, less blood reaches the liver when portal flow increases (diminished hepatic reserve). In addition, toxic substances from the intestine, including ammonia, are shunted directly to the systemic circulation, contributing to portosystemic encephalopathy. Venous congestion within visceral organs due to portal hypertension contributes to ascites via altered Starling forces. Splenomegaly and hypersplenism commonly occur as a result of increased splenic vein pressure. Thrombocytopenia, leukopenia, and, less commonly, hemolytic anemia may result.

Portal hypertension is often associated with a hyperdynamic circulation. Mechanisms are complex and seem to involve altered sympathetic tone, production of nitric oxide and other endogenous vasodilators, and enhanced activity of humoral factors (eg, Portal hypertension is often associated with a hyperdynamic circulation. Mechanisms are complex and seem to involve altered sympathetic tone, production of nitric oxide and other endogenous vasodilators, and enhanced activity of humoral factors (eg,glucagon).

Portal hypertension is asymptomatic; symptoms and signs result from its complications. The most dangerous is acute variceal bleeding. Patients typically present with sudden painless upper gastrointestinal bleeding, often massive. Bleeding from portal hypertensive gastropathy is often subacute or chronic. Ascites, splenomegaly, or portosystemic encephalopathy may be present.

• Primarily history and physical examination

• Sometimes ultrasound, CT, endoscopy, or direct transjugular measurement of portal venous pressure gradient

Portal hypertension is assumed to be present when a patient with chronic liver disease has collateral circulation, splenomegaly, ascites, or portosystemic encephalopathy. Proof requires measurement of the hepatic venous pressure gradient, which approximates portal pressure, by a transjugular catheter; however, this procedure is invasive and usually not performed. Imaging may help when cirrhosis is suspected. Ultrasound or CT often reveals dilated intra-abdominal collaterals, and Doppler ultrasound can determine portal vein patency and flow.

Esophagogastric varices and portal hypertensive gastropathy are best diagnosed by endoscopy, which may also identify predictors of esophagogastric variceal bleeding (eg, red markings on a varix).

• Ongoing endoscopic therapy and surveillance

• Nonselective beta-blockers with or without isosorbide mononitrateNonselective beta-blockers with or without isosorbide mononitrate

• Sometimes portal vein shunting

When possible, the underlying disorder is treated.

In patients with esophagogastric varices that have bled, combined endoscopic treatment and pharmacotherapy decreases mortality and reduces risk of rebleeding better than either therapy used alone. A series of endoscopic banding sessions are performed to obliterate residual varices, then periodic endoscopic surveillance is performed to identify and treat recurrent varices. Long-term pharmacotherapy usually involves nonselective beta-blockers; these medications lower portal pressure primarily by diminishing portal flow, although the effects vary. Agents include propranolol, nadolol, timolol, and carvedilol, with dosage titrated to decrease heart rate by approximately 25%. In patients with compensated cirrhosis, carvedilol is the preferred first-line beta-blocker, with initial dosing and uptitration as tolerated by blood pressure (In patients with esophagogastric varices that have bled, combined endoscopic treatment and pharmacotherapy decreases mortality and reduces risk of rebleeding better than either therapy used alone. A series of endoscopic banding sessions are performed to obliterate residual varices, then periodic endoscopic surveillance is performed to identify and treat recurrent varices. Long-term pharmacotherapy usually involves nonselective beta-blockers; these medications lower portal pressure primarily by diminishing portal flow, although the effects vary. Agents include propranolol, nadolol, timolol, and carvedilol, with dosage titrated to decrease heart rate by approximately 25%. In patients with compensated cirrhosis, carvedilol is the preferred first-line beta-blocker, with initial dosing and uptitration as tolerated by blood pressure (1). Beta blockers are generally given at doses lower than are used for heart failure unless concomitant systemic arterial hypertension or heart disease exists. Adding isosorbide mononitrate may further reduce portal pressure (). Beta blockers are generally given at doses lower than are used for heart failure unless concomitant systemic arterial hypertension or heart disease exists. Adding isosorbide mononitrate may further reduce portal pressure (2, 3).

In patients with esophagogastric varices that have not yet bled (ie, for primary prophylaxis), outcomes are similar with beta-blocker therapy or endoscopic therapy.

Patients who do not adequately respond to either treatment should be considered for transjugular intrahepatic portosystemic shunting (TIPS) or, less frequently, a surgical portacaval shunt. In TIPS, the shunt is created by placing a stent between the portal and hepatic venous circulation within the liver (1). Although TIPS may result in fewer immediate deaths than surgical shunting, particularly during acute bleeding, maintenance of patency may require repeat procedures because the stent may become stenosed or occluded over time. Long-term benefits are unknown. Liver transplantation may be indicated for some patients.

For bleeding due to portal hypertensive gastropathy, beta-blockers can be used to decrease portal pressure. A shunt should be considered if medications are ineffective, but results may be less successful than for esophagogastric variceal bleeding.

Because it rarely causes clinical problems, hypersplenism requires no specific treatment, and splenectomy should be avoided.

Mortality during acute variceal hemorrhage is approximately 15 to 20% and 6-week mortality ranges up to 43% (1, 2, 3). Prognosis is predicted by the degree of hepatic reserve and the degree of bleeding. For survivors, the bleeding risk within the next 1 year is up to 60% without prophylaxis (4). Ongoing endoscopic or pharmacotherapy lowers the rebleeding risk but decreases long-term mortality (> 60% at 5 years [5]) only marginally. For treatment of acute bleeding, see Overview of Gastrointestinal Bleeding and Varices: Treatment.