Preserved liver function, portal thrombosis and absence of oesophageal varices are risk factors for metastasis of hepatocellular carcinoma.

Background: Extrahepatic metastases represent a major obstacle for further improving prognosis of hepatocellular carcinoma.

Aim: To assess clinical predictors of extrahepatic metastases in a large cohort followed in a single centre.

Methods: We evaluated clinical files of 520 consecutive patients with hepatocellular carcinoma admitted from 1994 to 2002 to our Liver Unit. The following risk factors were assessed: age, gender, hepatitis viruses, alcohol, diabetes, size, number and differentiation of hepatocellular carcinoma, percutaneous biopsy, portal thrombosis, alpha-fetoprotein, Child-Pugh, Cancer Liver Italian Program and Model for End-stage Liver Disease scores, Barcelona Clinic Liver Cancer classification, varices, hepatocellular carcinoma treatment.

Results: Extrahepatic metastases were detected in 55/520 patients (10.5%) after 0-72 months (median 15, CI 3-20) from initial evaluation. Lower bilirubin, INR, Child-Pugh and Model for End-stage Liver Disease scores, higher alpha-feto protein levels, portal thrombosis and absence of oesophageal varices were all associated with distant metastases at univariate analysis. Absence of oesophageal varices and portal thrombosis resulted as independent predictors (P = 0.0003 and P = 0.004, respectively) on multivariate logistic regression. Patients with metastases showed poorer survival (3 months) than total hepatocellular carcinoma population (26 months).

Conclusions: Extrahepatic metastases of hepatocellular carcinoma are rare but significantly impair prognosis. Extrahepatic metastases were more frequent in patients with well preserved liver function. Absence of oesophageal varices and presence of portal thrombosis were the strongest risk factors.