Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma.

AIM

To define NGF (nerve growth factor) and its high-affinity receptor trkA(NGF) presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC.

METHODS

Intracellular distribution of NGF and trkA(NGF) were assessed by immunohistochemistry and immuno-electron microscopy in liver specimens from HCC, cirrhosis or both. ELISA was used to measure circulating NGF levels.

RESULTS

NGF and trkA(NGF) were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkA(NGF) were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls.

CONCLUSION

NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF.