Intrahepatic gene expression in human alcoholic hepatitis.

OBJECTIVE

Alcoholic hepatitis remains an important cause of morbidity and mortality. Treatment remains unsatisfactory, in part, due to limited understanding of the pathogenesis. The aim of this study is to define the global intrahepatic expression profile of human alcoholic hepatitis.

METHODS

Gene expression was analysed by DNA microarray on RNA isolated from liver of patients with alcoholic hepatitis (AH, n = 8), alcoholic steatosis (AS, n = 9) and explants from non-diseased donor liver controls (ND, n = 7). Differential expression of selected genes was confirmed by real-time RT-PCR and immunohistochemistry.

RESULTS

Cluster analysis allowed differentiation of alcoholic hepatitis from alcoholic steatosis. The gene expression profile of AH revealed 586 genes differentially expressed from AS and 211 genes differentially expressed from that of ND liver. In comparison, only 98 genes were differentially expressed in AS from ND. Novel differentially expressed genes in AH in comparison to ND and AS included claudins, osteopontin, CD209, selenoprotein and genes related to bile duct proliferation. Real-time RT-PCR confirmed up-regulation of IL-8, osteopontin, and TNFRSF14 and down-regulation of SAMeS and CD209.

CONCLUSIONS

This study has defined the intrahepatic gene expression profile of human alcoholic hepatitis and revealed a number of novel differentially expressed genes.