Chapter 10 Portal hypertension and gastrointestinal bleeding
1 Patients with cirrhosis who develop large esophageal varices as a consequence of portal hypertension have a 25% to 35% risk of a variceal hemorrhage and a 15% to 20% mortality rate associated with each bleeding episode. Mortality depends on the clinical status of the patient and the severity of the bleeding episode.
2 Nonselective beta-adrenergic blockers are effective and are a first-line therapy for the primary prevention of variceal hemorrhage in patients with cirrhosis and portal hypertension. Endoscopic variceal ligation is an excellent alternative, especially for patients with varices who have contraindications to or cannot tolerate beta blockers.
3 Endoscopic therapy (variceal band ligation) and pharmacologic therapy (somatostatin/octreotide/vapreotide, terlipressin) are effective in controlling acute bleeding episodes. The combination of endoscopic and pharmacologic therapy offers an advantage over the use of either therapy alone.
4 Endoscopic variceal band ligation is the endoscopic treatment of choice for the prevention of recurrent variceal bleeding.
5 Pharmacologic maintenance therapy with nonselective beta-adrenergic blockers is effective for the prevention of recurrent variceal bleeding in selected patients, defined by a hemodynamic response to therapy. Serial measurement of portal pressure is helpful in assessing the effectiveness and making changes in therapy when indicated.
6 The combination of endoscopic and pharmacologic treatment is the preferred option for prevention of recurrent variceal bleeding.
7 For patients in whom medical therapy fails to prevent recurrent variceal hemorrhage, options include transjugular intrahepatic portosystemic shunt (TIPS), surgical portosystemic shunt, and liver transplantation. Selection of the appropriate rescue procedure is dictated by the clinical status of the patient, the availability of expertise for performance of the procedure, and, in the case of liver transplantation, appropriateness of the candidate and availability of a donor organ.
Portal Hypertension: Overview
Pathophysiology
1. 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.
2. 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.
3. Hepatic resistance may be modified by changes in perivenular and presinusoidal myofibroblasts as well as the smooth muscle component of portocollateral vessels.
4. Portal hypertension is exacerbated by the development of systemic vasodilatation, which leads to plasma volume expansion, an increase in cardiac output, and 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.
Pharmacotherapy
1. Two classes of drugs—vasoconstrictors and vasodilators—are used for treatment of portal hypertension.
2. 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.
3. Vasodilators (nitroglycerin, long-acting nitrates, angiotensin inhibitors [losartan, irbesartan]), prazosin) alter resistance by inducing changes in the intrahepatic perivenular and perisinusoidal myofibroblasts as well as the smooth muscle component of portocollateral vessels.
Epidemiology of Esophagogastric Variceal Hemorrhage
1. Some 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 secondary to hepatitis C, the risk of varices is somewhat less; 30% will develop esophageal varices within 6 years of the initial diagnosis of cirrhosis.
2. Some 25% to 35% of patients with cirrhosis and large esophageal varices will experience an episode of variceal bleeding; most bleeding episodes occur within the first year after the diagnosis of varices.
3. In patients with cirrhosis who survive the initial episode of esophagogastric variceal hemorrhage (EVH) with conservative medical management, the risk of recurrent EVH is 65% to 70%; most episodes of recurrent bleeding occur within 6 months of the index hemorrhage.
4. EVH accounts for approximately one third 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.
Predictive Value of Portal Hemodynamic Measurements
1. Measurement of the hepatic venous pressure gradient (HVPG) is an easy and reproducible method for estimating PVPG. HVPG is the difference between the wedged or occluded hepatic venous pressure and the free hepatic venous pressure. HVPG has a high correlation with PVPG in patients with cirrhosis when hepatic resistance is sinusoidal or postsinusoidal, as in patients with alcoholic cirrhosis. HVPG tends to underestimate PVPG when the defect is presinusoidal, as in primary biliary cirrhosis.
3. 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.
4. The risk of recurrent EVH correlates with the level of HVPG: the higher the HVPG, the greater the risk of recurrent EVH.
5. HVPG is also prognostic for survival: the higher the HVPG, the worse the survival. HVPG also predicts the development of hepatic decompensation and the development of hepatocellular carcinoma.
6. Serial measurements of HVPG are predictive of the risk of recurrent EVH. Patients who have a decrease in HVPG to a level less than 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.
Prevention of Initial Variceal Hemorrhage
Pharmacologic
1. For patients with large esophageal varices and no prior history of variceal hemorrhage, nonselective beta-adrenergic blockers have been shown to decrease the risk of initial variceal bleeding by approximately 40% and are the treatment of choice for the primary prevention of variceal hemorrhage.
2. Nonselective beta blockers (propranolol, nadolol, timolol) should be offered to compliant patients who have no contraindications to the use of beta blockers, such as severe chronic obstructive lung disease or congestive heart failure.
3. For patients unable to tolerate beta blocker therapy, no drugs given as monotherapy have shown benefit.
4. In routine practice, the dose of the nonselective beta blocker should be achieved by a stepwise increase in dosage, adjusted to patient tolerance. If portal hemodynamic studies are readily available, serial measurements of HVPG in response to beta blocker therapy may be of value in determining the therapeutic dose and potential clinical benefit of beta blockers.
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