DOES HEPATIC VEIN OUTFLOW OBSTRUCTION CONTRIBUTE TO THE PATHOGENESIS OF HEPATOCELLULAR-CARCINOMA

Hepatocellular carcinoma (HCC) is one of the more common malignant dis eases in the world. Here we have investigated role of hepatic venous o utflow obstruction in the development of HCC. During a IO-year period from November 1986 to December 1996, 1,748 patients with clinical evid ence of either portal hypertension, hepatic venous outflow obstruction , or inferior vena cava obstruction without Behcet's disease (BD) and 512 patients with Behcet's disease were examined at Hacettepe Universi ty Hospital. The presence of and the effect of hepatic venous obstruct ion on the subsequent development of HCC was assessed. In each case, h epatic vein thrombosis was assessed by hepatic venography and by digit al subtraction angiography (DSA), computed tomography (CT), ultrasonog raphy (US), and liver biopsy. Coagulation factors, including protein C , protein S, anti-thrombin III, and routine laboratory studies assessi ng the coagulability of blood were also investigated. The role of hepa tic venous outflow obstruction on the subsequent development of HCC wa s determined by periodic laboratory investigations that included alpha -fetoprotein (AFP), ultrasonography, and when indicated liver biopsy. During the same time period all patients diagnosed as having HCC were investigated to identify all potential etiologic factors responsible f or the HCC. Fifty-five (10.7%) of the 512 patients with ED were found to have one or more large vein thromboses. Sixteen of these 55 (29%) p atients had hepatic vein thrombosis. During the follow-up period HCC d eveloped in 2 of these 16 patients (12.5%), 34 and 21 months after a d iagnosis of hepatic vein thrombosis was established. Forty patients fr om a total of 1,748 patients with clinical evidence of portal hyperten sion and cirrhosis, but without ED, were found to have evidence of hep atic vein thrombosis. Twenty-one of these 40 patients had an identifia ble underlying disorder responsible for their hepatic vein thrombosis. Despite a full clinical and laboratory investigation in the other 19 patients, the etiologic factor responsible for the hepatic vein thromb osis remained obscure. Only one of these 19 patients, who also had por tal vein thrombosis, developed HCC during a 9-year follow-up. Thus, a total of three of the 56 (5.36%) of cases of hepatic vein thrombosis d eveloped an HCC. All of the hepatic tumors were of the multicentric, n odular, rapidly growing type. Despite the presence of hepatic vein thr ombosis, there was no clear-cut histologic evidence for cirrhosis. Our experience suggests that hepatic vein thrombosis may be a contributin g factor responsible for HCC development. Moreover, we advise that ind ividuals with hepatic Vein thrombosis should be assessed periodically for the development of HCC.