Portal Hypertension and Esophageal Varices

1

Describe the common causes of upper gastrointestinal bleeding (UGIB) in US populations

Peptic ulcer disease is the number one cause of UGIB in the United States. The gram-negative bacteria Helicobacter pylori plays a significant role in the pathogenesis for many. Esophageal varices (EV) related to portal hypertension (PH) is another leading cause, followed by a number of disorders including Mallory-Weiss tears, and arteriovenous malformations.

2

What is the definition of PH?

An hepatic venous pressure gradient (HVPG) >5 mm Hg defines PH. HVPG is measured between the portal vein and the inferior vena cava. In practice, the pressure is measured free and in a wedged fashion in the hepatic veins. PH becomes significant when the HVPG becomes >10 mm Hg. It should be noted that HVPG is not commonly tested or utilized in many US centers.

3

What are the causes of PH?

Chronic injury to the liver from a variety of sources leads to increased resistance to portal blood flow. In the United States, this resistance is most commonly within the liver and the most common cause (>90%) is chronic alcohol abuse. Structural changes include distortion of liver microcirculation from fibrosis and vascular occlusion. The resistance can also be prehepatic (e.g., portal vein thrombosis) or posthepatic (e.g., Budd-Chiari syndrome). Worldwide causes of cirrhosis include schistosomiasis and other infectious sequelae.

One way to stratify patients with cirrhosis is by characterizing them as either with compensated cirrhosis (i.e., those who do not have ascites, encephalopathy, jaundice, or variceal hemorrhage) versus decompensated.

4

How is PH diagnosed?

PH is often asymptomatic until complications develop. Clinical signs may include abdominal wall collateral vessels, splenomegaly, and thrombocytopenia. Thus, the diagnosis of cirrhosis is a clinical one; however, imaging studies may reveal the characteristic nodular liver, ascites, and/or the existence of EV. Up to 60% of patients with newly diagnosed cirrhosis present with clinically significant PH. Additional diagnostic confirmation can be accomplished by obtaining an HVPG measurement if needed.

5

Describe screening and prevention strategies for patients with known PH

Among asymptomatic patients with cirrhosis, approximately 85% will have an elevated HVPG and 40% of these will have EV. Some literature suggests that gastroesophageal varices are present in almost half of patients with cirrhosis at the time of diagnosis. Given the 6-week mortality with each episode of variceal hemorrhage is approximately 15%–20%, it is prudent to offer screening and prevention strategies for such patients. The recommended screening method to determine the presence and size of gastroesophageal varices is esophagogastroduodenoscopy. The current consensus is that every known cirrhotic be endoscopically screened for varices at the time of diagnosis. The rationale behind screening is the existence of effective therapies that reduce the likelihood of first and subsequent bleeding episodes.

6

Describe the Child-Turcotte-Pugh classification of cirrhosis

Gastroesophageal varices occur with the highest rate in patients with Child’s class B or C cirrhosis, and the mortality for any given episode of variceal hemorrhage is higher in class B or C cirrhotics. (The table below is available from multiple sources. Class A= 5–6 points, Class B= 7–9 points, and Class C = 10–15 points.)

7

What is the pathogenesis of PH leading to varices, variceal hemorrhage, and portosystemic collaterals?

Increased resistance to portal blood flow results from cirrhosis, and this leads to increases in portal venous pressure as stated. This results in decreased vasodilating factors (e.g., nitric oxide [NO]) and increased angiogenic factors (e.g., vascular endothelial growth factor) and the formation of new vessels. Splanchnic vasodilation occurs leading to increased portal blood flow, which completes a cycle by increasing portal venous pressure. Dilation of preexisting vessels leads to formation of varices and/or collaterals. Collaterals develop at watershed zones between the portal venous drainage (e.g., stomach, small bowel, large bowel, and spleen) and systemic venous drainage (e.g., esophagus, distal rectum). Collaterals can also develop from recanalization of embryonic connections (e.g., umbilical vein, persistent ductus venosus).

Note: EV refers to esophageal varices, but it should be noted that gastric varices are present in 20% of patients with cirrhosis, either in isolation or in combination with EV. In this chapter, the term EV and gastroesophageal varices may be used interchangeably with this caveat.

8

Describe how the HVPG and Child’s classification help in both risk assessment and management of bleeding from EV in patients with cirrhosis and PH?

In cirrhotic patients with an HVPG >10 mm Hg, a higher risk of complications such as ascites and varices exist. In addition, these patients have double the risk of developing EV (50% at 5 years) when compared to patients with HVPG below this threshold (25% at 5 years). With an HVPG >12 mm Hg, there is an increased risk of EV rupture and bleeding. As stated previously, patients with decompensated cirrhosis, Child’s class B and C, carry the highest rate of EV formation and a higher mortality for any given episode of variceal hemorrhage.