Global gene expression of NASH patients

Background & Aims: Little is known about the molecular pathophysiology of non-alcoholic steatohepatitis (NASH). Methods: Total RNA from NASH livers and normal healthy livers were analyzed on a whole genome DNA oligo microarray. The microarray data were validated by real-time quantitative PCR analysis for many of the genes of interest. Results: Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Transcription of genes TLR4, LBP, CD14 and MD-2 were not significantly elevated in NASH livers. Conclusions: The augmented activity of all the available genes of the pathways for alcohol catabolism suggest that 1) there is a significant increase of alcohol in the circulation of NASH patients; 2) there is a high priority for the NASH livers to scavenge alcohol from the circulation. It was reported that gastrointestinal bacteria are the major cause of elevated alcohol in the circulation of obese animals. Mechanisms for alcohol to induce steatosis and oxidative stress were established decades ago. Our data is the first human evidence to support Diehl et al’s hypothesis that alcohol is an important factor in the development of non-alcoholic fatty liver diseases. Six NASH patients exhibiting significant insulin resistence were included in this study. For control groups, total RNA from 4 different subjects were purchased from ADMET. These subjects are free from liver disease.