Portal hypertension and iron depletion in patients with genetic hemochromatosis

Abstract

Clinically, portal hypertension has been considered to be less common and less severe in patients with cirrhosis resulting from iron overload in homozygotes for genetic hemochromatosis than in patients with cirrhosis of other causes. To characterize the prevalence and progression of portal hypertension in genetic hemochromatosis (GH), 120 cirrhosis and iron-overloaded patients were compared with a control group of 120 patients with postnecrotic cirrhosis (PNC) who were matched for gender, age, Child's class, and alcohol abuse. Gastroesophageal endoscopy and abdominal ultrasonography were performed at diagnosis and repeated every 12 months and every 6 months, respectively, to evaluate the presence and severity of varices, the caliber of the portal vein and its collaterals, and splenic size. At diagnosis a similar frequency of varices was observed in patients with GH (25%) and in PNC (24%), as well as of portal vein abnormalities and spleen enlargement. During the follow-up period, all but two of the patients with GH were treated by phlebotomy and depleted of excess iron. After a mean of 6 +/- 4.3 (SD) years of observations (range, 2 to 10 years), varices were improved or completely reversed in 26% of patients with cirrhosis and GH but in only 5% of those with PNC (P < .01). Bleeding from varices was observed in only one patient with GH but in five patients with PNC, Of 22 patients with GH in whom portal hypertension was unmodified or worsened, 16 had coexistent hepatic viral infection, The hazard risk for the development of de novo (i.e., a new occurrence) varices was 17 times higher in patients with PNC than in patients with GH (P < .001). The natural history of portal hypertension in patients with GH was substantially improved by phlebotomy therapy except in the presence of a coexistent hepatic viral infection, These results emphasize the need for intensive phlebotomy therapy even in patients diagnosed after the development of cirrhosis.