STUDIES ON HOST FACTORS RELATED TO FULMINANT HEPATITIS

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Fulminant hepatitis is a poor prognostic liver disease characterized with massive death of hepatocytes and poor liver regeneration, however, host factors related to the fulminant hepatitis is not well known. First, we comprehensively analyzed the changes in gene expression during mouse liver regeneration using an in-house microarray. Genes involved in protein synthesis and posttranslational processing were enriched in the cluster characterized by rapid gene activation. Genes for plasma, protein secretion and intermediate metabolism were enriched in clusters exhibiting the features of gradual gene activation. Thus, clustering analysis of expression patterns of functionally classified genes gave insights into mechanism and pathophysiology of liver regeneration. Then, the gene expression profiles in oval cell induction models, mimicking fulminant hepatitis, were also examined with DNA microarray. Four genes including osteopontin were up-regulated in these models suggesting that these genes might be related to the development of fulminant hepatitis. The serum osteopontin level was revealed to be significantly higher in patients with fulminant hepatitis compared to those with acute self limited hepatitis. Further studies is uncle way to reveal the role of osteopontine during the development of fulmimant hepatitis.