ALR, a hepatotrophic protein essential for liver regeneration is overexpressed in hepatocellular carcinoma and cirrhosis

ALR (Augmenter of Liver Regeneration) a member of the hepatotrophic growth factors was found to be essential cellular growth and to have specific liver regeneration enhancing effects. Further it was proposed that ALR might act through auto- and paracrine mechanism during liver cell proliferation, but little is known about its expression in normal and cirrhotic or cancerous human liver tissue. Expression analysis of ALR was performed by immunohistochemistry on paraffin sections of human normal liver tissue (n=43), cirrhotic livers (n=66) and hepatocellular carcinomas (HCC) (n=137) with various underlying diseases. Significantly enhanced ALR expression levels were observed in HCC and cirrhotic tissue compared to normal liver. Correlation study of ALR expression with grading or TNM classification revealed no statistically significant difference. Most interestingly, within the group of HCC tissue, samples from patients with an underlying hepatitis C virus infection had significantly elevated ALR levels compared to HCC samples of alcohol and hepatitis B virus aetiology. Furthermore ALR immunosignals were detected in the cytosol and in the perinuclear regions of hepatocytes and cholangiocytes. In non-parenchymal liver-cells no immunostaining were observed. These results were confirmed by analyzing mRNA levels of isolated liver cells (hepatocytes, bile duct-, Kupffer-, Ito-, endothelial cells) by quantitative RT-PCR. The expression pattern of increased hepatic ALR in cirrhotic livers and hepatocellular carcinomas indicates an important role of ALR in mitogenic altered cell proliferation. Further studies to elucidate a potential use of ALR for clinical diagnosis of liver cirrhosis and cancer, particularly of hepatitis aetiology, are currently under investigation.

cirrhosis - growth factors - hepatocelluar carcinoma - liver regeneration