Intrahepatic gene expression profiles in chronic hepatitis B and autoimmune liver disease.

BACKGROUND: DNA microarray technology has enabled genomewide analysis of gene transcript levels, yielding insight into the molecular nature of liver disease.

METHODS: We compared gene expression of liver biopsy specimens in 16 patients with different stages of chronic hepatitis B, five with autoimmune hepatitis (AIH), five with primary biliary cirrhosis (PBC), and six with druginduced hepatitis.

RESULTS: Of 21 073 genes, 424 showed different expression in a particular disease group on analysis of variance. Genes associated with extracellular matrix, cell growth, and DNA repair were noted in the advanced fibrotic stage of chronic hepatitis B (B-3), while gene expression regarding complement activation and the innate immune response decreased. When we compared gene expression at the relatively early stage in each disease group with pathway analysis, pathways relating to chemotaxis and cell homeostasis were selected in chronic hepatitis B. In PBC, gene expression relating to structural constituents and contractions of muscle such as actin and myosin were enhanced, in contrast to the downregulation of genes relating to protein binding in AIH. A hierarchical clustering analysis of hepatitis B genes defined five clusters. Generally, the transcripts upregulated according to disease progression were associated with signaling pathway/transcription, including tumor-associated calcium signal transducer 1 and chemokine ligand 19, and with cell communication, such as collagen. In two groups, all transcripts were downregulated; transcripts related to chemokine ligands and metallothionein were further depressed in B-3.

CONCLUSIONS: Analysis of gene expression in liver may be useful for understanding features of distinct liver diseases and for guiding disease progression, particularly in chronic hepatitis B.