Portal hypertension, which is most often caused by cirrhosis, is seen frequently in medical practice. Noncirrhotic portal hypertension is much rarer, particularly in the developed world.
A 54-year-old man presented to the emergency department with a 1-month history of edema in the lower legs and a 1-week history of upper abdominal pain. He also reported intermittent nausea, early satiety, and diarrhea but did not have fevers, chills, or vomiting. A new Clinical Problem-Solving article summarizes.
Q: What serum–ascites albumin gradient (SAAG) is consistent with portal hypertension?
A: A SAAG of 1.1 g per deciliter or higher is consistent with portal hypertension. Other causes of high SAAG include heart failure (although heart failure is usually associated with higher levels of ascitic fluid protein), hepatic vein obstruction (Budd–Chiari syndrome), and myxedema. Myxedema ascites is also characterized by a high level of ascitic fluid protein (>2.5 g deciliter).
Q: What are some of the causes of noncirrhotic portal hypertension?
A: Numerous conditions may cause portal hypertension in the absence of cirrhosis by distorting hepatic architecture or increasing intrahepatic vascular resistance at the prehepatic, intrahepatic, or posthepatic level. Conditions that cause noncirrhotic portal hypertension at the prehepatic level include portal vein or splenic vein thrombosis and splanchnic arteriovenous malformation. Conditions that cause changes at the intrahepatic level include hepatic vasculitis, HIV infection, and infiltrative disease (medications may also cause changes at the intrahepatic level). The Budd–Chiari syndrome, inferior vena cava obstruction, and restrictive cardiac disease may cause changes at the posthepatic level. Vitamin A toxicity may also cause portal hypertension. Worldwide, schistosomiasis is the most common cause of noncirrhotic portal hypertension and is mediated by local inflammation and the microvascular obstruction caused by schistosoma larvae. Vinyl chloride, copper, and arsenic have also been reported to cause noncirrhotic portal hypertension.
Figure 2. Selected Causes of Portal Hypertension in the Absence of Cirrhosis.
Morning Report Questions
Q: What doses of vitamin A are associated with hepatic toxicity?
A: Liver injury, including noncirrhotic portal hypertension and cirrhosis, is a recognized complication of excessive consumption of vitamin A and may occur at doses as low as 25,000 IU daily. (The U.S. recommended daily allowance is 3000 IU per day.) In one case series of 41 patients with vitamin A–related liver toxicity, daily intakes ranged from 20,000 to 400,000 IU for an average of 7.1 years, although single ingestions of more than 500,000 IU have been reported to provoke noncirrhotic portal hypertension.
Q: How does excess vitamin A ingestion cause liver damage?
A: Vitamin A is stored primarily as retinol in hepatic stellate cells and may cause portal hypertension when the cells become engorged, obstructing blood flow through the liver sinusoids. Excess vitamin A also causes hepatocyte injury and necrosis in hepatocytes. Hepatic stellate cells participate in the deposition of extracellular matrix; their continued activation may lead to cirrhosis. Vitamin A overuse is best identified by obtaining a detailed history rather than by measuring retinol levels, since serum levels poorly reflect total body stores. In many reported cases, vitamin A–induced portal hypertension resolves within months to years after vitamin A has been withdrawn, although in several instances there has been progression to liver failure.
Figure 1. Liver-Biopsy Specimen.
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