Cirrhosis is the most common cause of portal hypertension and varices in the Western world. However, varices can arise in patients with portal hypertension in the absence of cirrhosis or even in the absence of portal hypertension. This short perspective focuses on varices without cirrhosis, including background information and various diagnosis and treatment options.
Non-Cirrhotic Portal Hypertension
Portal hypertension, by convention, is subcategorized into pre-hepatic, hepatic and post-hepatic causes. This can be a very helpful framework to utilize when considering the myriad of causes of non-cirrhotic portal hypertension and varices, though it requires a basic understanding of venous pressure measurements. Direct measurement of portal vein pressure is invasive. Myers and Taylor (1953) first described the measurement of the wedged hepatic venous pressure, which was later validated by Groszmann and is now used to estimate the portal vein pressure. When the balloon occludes the hepatic vein (wedge pressure), it measures the hydrostatic pressure of the column of blood beyond the balloon, which actually represents sinusoidal pressure. The sinusoidal pressure is an indirect measurement of portal vein pressure. The hepatic venous pressure gradient represents the pressure gradient from the portal vein to the inferior vena cava, calculated by subtracting free hepatic venous pressure from the wedged hepatic venous pressure. A hepatic venous pressure gradient of 5 mm Hg or more is consistent with portal hypertension; however, values greater than 10 mm Hg are required for varices to be present (considered to be clinically significant portal hypertension).
A gradient of 12 mm Hg or more can lead to variceal hemorrhage. This framework assesses the gradient across the liver, but it is important to note that resistance to blood flow can occur anywhere from the right atrium to the portal vein. With this in mind, one can categorize a number of causes of non-cirrhotic portal hypertension according to their pressure profiles.
Worldwide, the leading cause of non-cirrhotic portal hypertension is schistosomiasis (230 million infected), a parasitic disease caused by trematode flukes. In Western countries, the leading causes of non-cirrhotic portal hypertension are alcoholic hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, congenital hepatic fibrosis, extrahepatic portal vein thrombosis and Budd-Chiari syndrome. If all causes of portal hypertension have been ruled out, the diagnosis of idiopathic non- cirrhotic portal hypertension can be rendered.1 This diagnosis can account for up to 23 percent of cases of portal hypertension and 10 to 30 percent of variceal bleeds in India, but only 3 to 5 percent of portal hypertension in Western countries. This condition has gone by several names including non-cirrhotic portal fibrosis (India), idiopathic portal hypertension (Japan) and nodular regenerative hyperplasia (Western countries), among others. Patients typically have preserved liver function, splenomegaly and may have variceal hemorrhage. Histologic findings are variable and may include none or some of the following: obliterative portal venopathy of small portal vein branches, paraportal shunts, sinusoidal dilatation and periportal or perisinusoidal fibrosis. A reticulin stain can identify nodular regenerative hyperplasia characterized by micronodular transformation of the liver parenchyma, with central hyperplasia, an atrophic rim and no fibrosis.
Varices without Portal Hypertension
Downhill varices are usually seen in the upper third of the esophagus in contrast to uphill varices associated with portal hypertension that are seen in the lower third of the esophagus. Occasionally, downhill varices may involve the length of the esophagus. Downhill varices are usually caused by superior vena cava obstruction due to bronchogenic carcinoma, mediastinal tumor/fibrosis, caval ligation, thyroid masses or lymphoma. Downhill varices are collaterals that develop to bypass the superior vena cava obstruction. Obstruction of the proximal superior vena cava is associated with varices that span the entire esophagus whereas obstruction of superior vena cava above the azygous inflow is associated with varices in the upper third of the esophagus.2,3 These varices are not treated with non- selective beta-blockers or with banding.
Evaluation of Patient with Esophageal Varices without Evident Cirrhosis
The patient incidentally diagnosed with esophageal varices on upper endoscopy should undergo cross-sectional abdominal imaging with IV contrast. CT or MRI by itself is not sufficiently accurate for the diagnosis of cirrhosis. However, a constellation of findings such as a nodular shrunken liver, ascites, splenomegaly, intra-abdominal varices and a low pre-test probability of a treatable liver condition should dissuade the provider from a liver biopsy. In patients with a normal appearing liver on cross-sectional imaging, patent hepatic and portal veins, and abnormal liver tests, a liver biopsy should be pursued. While transient elastography has demonstrated lower stiffness levels (as expected) in idiopathic non-cirrhotic portal hypertension compared to cirrhosis, this modality is not sufficient for the diagnosis of idiopathic non-cirrhotic portal hypertension. A reticulin stain on liver histology should be requested to assess for nodular regenerative hyperplasia features, which are not obvious on H&E and trichome stains.
In patients with isolated gastric varices without evident cirrhosis, contrast enhanced CT or MRI should be performed to evaluate for splenic vein thrombosis. Splenectomy is the treatment of choice in patients with splenic vein thrombosis and gastric varices. Varices in the upper third or the entire esophagus warrant further evaluation with a CT of the chest.
Management of Non-Cirrhotic Portal Hypertension
For patients with an identifiable cause of non-cirrhotic portal hypertension, such as primary biliary cirrhosis, disease-specific treatment should be initiated. The recently published Baveno VI Consensus Workshop summary reflects on the lack of data regarding prophylaxis for idiopathic non-cirrhotic portal hypertension and recommends following usual esophageal varices prophylaxis, which we agree with.4 Baveno VI guidelines recommend screening for portal vein thrombosis in idiopathic non-cirrhotic portal hypertension with Doppler ultrasound, though there is lack of evidence to support this practice.3 We generally do not include biannual Doppler ultrasound in our management of idiopathic non-cirrhotic portal hypertension.
Dr. Loo has no conflicts to disclose.
Dr. Leise has no conflicts to disclose.
1. Schouten JN, Garcia-Pagan JC, Valla DC, et al. Idiopathic noncirrhotic portal hypertension. Hepatology 2011;54:1071-81.
2. van der Veldt AA, Hadithi M, Paul MA, et al. An unusual cause of hematemesis: Goiter. World Journal of Gastroenterology2006;12:5412-5.
3.Felson B, Lessure AP. Downhill Varices of the Esophagus. Diseases of the Chest 1964;46:740-6.
4. de Franchis R. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. Journal of Hepatology 2015;63:743- 752.