Intrahepatic MxA expression is correlated with interferon-alpha expressionin chronic and fulminant hepatitis

Interferon-alpha (IFN-a) has potent pro-inflammatory and anti-viral functio ns. It exerts its effects by inducing intracellular proteins such as MxA. T o analyse the role of intrahepatic interferon activation, IFN-alpha and MxA expression was studied by immunohistochemistry in explant livers of 20 pat ients with fullminant hepatic failure (FHF), 41 patients with chronic liver disease (CLD), and ten normal controls (NCs). In NCs only small numbers of Kupffer cells. but no hepatocytes, showed IFN-alpha and MxA expression. In contrast, significantly enhanced numbers of IFN-alpha- and MxA-positive Ku pffer cells, along with small numbers of MxA-positive and larger numbers of IFN-a-positive lymphocytes, were found in CLD and in FHF. MxA protein was also expressed on hepatocytes and bile ducts in the vicinity of IFN-cc-posi tive inflammatory infiltrates (hepatocytes: NCs: 0%, CLD: 8%, FHF: 68%, bil e ducts: NCs: 19%, CLD: 46%,, FHF: 83%). A significant correlation was foun d between the numbers of IFN-alpha- and MxA-positive cells (r = 0.67, p < 0 .001). Thus, large amounts of IFN-alpha are released in the livers of patie nts with FHF, which is likely to contribute to immune-mediated liver cell d amage. Intrahepatic MxA expression corresponds to IFN-alpha produced partic ularly by infiltrating inflammatory cells, rather than by hepatocytes thems elves. Copyright (C) 2001 John Wiley & Sons, Ltd.