Serum hepatocyte growth factor levels in primary biliary cirrhosis.

Background: Recent studies have shown that serum levels of hepatocyte growth factor, a potent mitogen for hepatocytes, are increased in patients with fulminant liver failure and with advanced stages of liver cirrhosis. Design: Retrospective study. Methods: Serum levels of hepatocyte growth factor (HGF) were determined in 26 patients with advanced stages of liver cirrhosis by means of an enzyme-linked immunosorbent assay. In 23 of these patients, liver biopsies were obtained before treatment with ursodeoxycholic acid and investigated for hepatocyte expression of the proliferating cell nuclear antigen (PCNA) and the Ki-67 antigen by immunocytochemical methods. Results: In 25 of the 26 patients, serum HGF levels did not differ from those of patients with histologically normal livers. Levels did not vary between the different stages of primary biliary cirrhosis but increased moderately when re-evaluted after a period of 24+/-4.9 months or 54+/-0.7 months. An abnormally increased serum HGF level was observed in only one patient, who had end-stage liver cirrhosis before liver transplantation. Both PCNA and Ki-67 antigen labelling indices were significantly higher at all stages of primary biliary cirrhosis than in normal liver, indicating increased hepatocyte proliferation, but the labelling indices did not correlate with the HGF concentrations in serum. Conclusion: Serum HGF levels in almost all patients with primary biliary cirrhosis were within normal limits despite increased hepatocyte proliferation. The results support the hypothesis that HGF serum levels may reflect liver dysfunction rather than active hepatocyte proliferation.