Portal Hypertension and Gastrointestinal Bleeding

Portal hypertension is defined as an increase in the portal venous pressure gradient (PVPG) and is a function of portal venous blood flow and hepatic and portocollateral resistance.

In patients with cirrhosis, portal hypertension is initiated by an increase in hepatic and portocollateral resistance. This resistance is modulated by an increase in levels of intrahepatic endothelin, a potent vasoconstrictor, and a decrease in levels of intrahepatic nitric oxide, a vasodilator.

Hepatic resistance may be modified by changes in perivenular and presinusoidal myofibroblasts as well as the smooth muscle component of portocollateral vessels.

Portal hypertension is exacerbated by the development of systemic vasodilatation, which leads to plasma volume expansion, an increase in cardiac output, and a hyperdynamic circulation. Systemic vasodilatation is a result of an increase in systemic levels of nitric oxide and, to a lesser extent, increased circulatory levels of glucagon, prostaglandins, tumor necrosis factor (TNF) alpha, and other cytokines and alterations in the autonomic nervous system. Angiogenic factors modulate the development of collateral vessels secondary to increased portal vein pressure.

Any increase in portal blood flow or hepatic or portocollateral resistance will increase portal pressure. Conversely, any decrease in portal blood flow or hepatic resistance will decrease portal pressure. This forms the basis for the pharmacologic treatment of portal hypertension.

Two classes of drugs—vasoconstrictors and vasodilators—are used for treatment of portal hypertension.

Vasoconstrictors (vasopressin, somatostatin, nonselective beta blockers) produce a decrease in splanchnic blood flow that leads to a reduction in portal venous blood flow and portal pressure. Carvedilol is a nonselective beta blocker with intrinsic anti-alpha-1 adrenergic activity. Clinical studies demonstrate a greater reduction in portal pressure with carvedilol when compared with propranolol or nadolol when used as monotherapy.

Vasodilators (nitroglycerin, long-acting nitrates, angiotensin inhibitors [losartan, irbesartan]) alter resistance by inducing changes in the intrahepatic perivenular and perisinusoidal myofibroblasts as well as the smooth muscle component of portocollateral vessels.

Combined use of vasoconstrictors and vasodilators offers the potential benefit of additive reductions in portal pressure, but their use may be limited by the side effects of treatment (i.e., systemic hypotension).

Patients with cirrhosis can be classified as compensated or decompensated. Decompensation is defined as the appearance of ascites, variceal hemorrhage, hepatic encephalopathy, or jaundice. Five stages have been proposed to account for the increased mortality associated with progressive decompensation. For patients with compensated cirrhosis, the 5-year mortality rate is 1.5% compared with 88% for patients with multiple complications of cirrhosis (stage 5) ( Fig. 12.1 ). Therefore, a goal of therapy is to inhibit progression from compensated to decompensated cirrhosis.

Approximately 50% of patients with alcoholic cirrhosis will develop esophageal varices within 2 years of diagnosis, and 70% to 80% will do so within 10 years. In patients with cirrhosis due to chronic hepatitis C, the risk of varices is somewhat less; 30% will develop esophageal varices within 6 years of the initial diagnosis of cirrhosis.

Of patients with cirrhosis and large esophageal varices, 25% to 35% will experience an episode of variceal bleeding; most bleeding episodes occur within the first year after identification of varices.

In patients with cirrhosis who survive the initial episode of esophagogastric variceal hemorrhage (EVH) with medical management, the risk of recurrent EVH is 65% to 70%; most episodes of recurrent bleeding occur within 6 months of the index hemorrhage.

EVH accounts for approximately 1/3 of deaths in patients with cirrhosis and portal hypertension ; the mortality rate for each episode of EVH is 15% to 20%, depending on the clinical status of the patient.

Treatment to prevent recurrent EVH should be initiated immediately following control of the acute EVH.

Large esophageal varices

The presence of endoscopic red color signs (red weals, cherry-red spots, hematocystic spots); these are essentially small varices on the surface of large varices.

Hepatic decompensation as evaluated by the Child-Turcotte-Pugh score or the Model for End-stage Liver Disease (MELD) score; ascites is a particular risk factor (see Chapter 11 , Chapter 33 ).

Active alcohol consumption in patients with alcoholic liver disease

Measurement of the HVPG is an easy and reproducible method for estimating portal pressure. HVPG is the difference between the wedged or occluded hepatic venous pressure and the free hepatic venous pressure. HVPG has a high correlation with portal pressure in patients with cirrhosis when hepatic resistance is sinusoidal or postsinusoidal, as in patients with alcoholic cirrhosis. HVPG tends to underestimate portal pressure when the defect is presinusoidal, as in primary biliary cholangitis.

An HVPG of 10 mm Hg or greater is necessary for esophageal varices to form and bleed.

According to Laplace’s law, variceal wall tension ( T ) is a function of the transmural pressure ( TP ) times the radius ( r ) of the varix divided by the variceal wall thickness ( w ):

This calculation combines measurements of variceal size and pressure and has the highest predictive value for determining the risk of EVH.

The risk of recurrent EVH correlates with the level of HVPG: The higher the HVPG, the greater the risk of recurrent EVH.

HVPG also predicts survival: The higher the HVPG, the lower the survival. HVPG also predicts the development of hepatic decompensation and the development of hepatocellular carcinoma.

Serial measurements of HVPG are predictive of the risk of recurrent EVH. Patients who achieve a decrease in HVPG to a level <12 mm Hg either spontaneously or in response to pharmacologic therapy are not at risk for recurrent EVH and other complications of portal hypertension. Patients in whom HVPG decreases by 20% or more over the first few months after the index hemorrhage, usually in response to pharmacologic therapy, have a marked decrease in the risk of recurrent EVH, whereas patients who have less than a 20% decrease in HVPG while receiving pharmacologic therapy maintain a high risk of recurrent EVH.