Hepatic interferon-alpha gene transcripts and products in liver specimens from acute and chronic hepatitis B virus...

In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus.