CONTRIBUTION OF PRIMARY CULTURES OF ADULT HUMAN HEPATOCYTES TO THE PATHOPHYSIOLOGY OF HEPATOCELLULAR-CARCINOMA

Background/Aims: The mechanisms of hepatocarcinogenesis are still poor ly understood. The development of hepatocellular carcinoma has recentl y been shown to be associated with increased DNA synthesis in cirrhosi s. The aim of this work was to determine whether the high rate of hepa tocyte regeneration observed in cirrhotic liver with hepatocellular ca rcinoma is associated with the presence of a growth factor that could be detectable in the serum. Methods: Adult human hepatocytes in primar y culture, allowing the evaluation of the release of circulating hepat otrophic factors, were used. These cultures were treated for 48 h with serum from patients with cirrhosis with and without hepatocellular ca rcinoma, from patients with liver metastasis, and from healthy subject s. The rate of DNA synthesis in these cultures was assessed by measuri ng the amount of [H-3]-thymidine incorporation into genomic DNA. Resul ts: On average, the synthesis of DNA was increased 2.5-, 2.2-, 2.1-, a nd 2.3-fold, respectively, in response to serum from patients with cir rhosis with hepatocellular carcinoma, from patients with cirrhosis wit hout hepatocellular carcinoma, from patients with liver metastasis, an d from healthy subjects. Conclusions: We conclude that the hepatotroph ic activity of the serum is not significantly different in patients wi th cirrhosis with or without hepatocellular carcinoma. These results s uggest that the increased DNA synthesis in hepatocytes of cirrhotic li ver with hepatocellular carcinoma might be due to proliferative factor (s) acting by paracrine or autocrine pathways.