Leukocytes are the major target of hepatitis C virus infection: Possible mechanism of multiorgan involvement including the heart

Chronic hepatitis C virus infection has been associated with several extrahepatic manifestations, among these, renal and cardiac involvement. However, morphological evidence of hepatitis C virus localization in various organs remains to be clarified.

We used immunohistochemistry to analyze the hepatitis C virus core and nonstructural antigens. Peripheral blood mononuclear cells were obtained from four patients with hepatitis C virus infection. Liver, kidney, heart, and bone marrow were taken from autopsy specimens from nine patients with hepatocellular carcinoma and three patients with cardiomyopathies with positive hepatitis C virus infection.

Antibody against hepatitis C virus core antigen stained peripheral blood mononuclear cells, and the majority of positive staining was seen in CD68-positive macrophages. Hepatitis C virus core and NS4 antibodies stained mostly infiltrating cells in the liver, heart, kidney, and bone marrow, but not hepatocytes, myocytes, or globular cells. Serial sections stained by CD68, CD3, and CD20 antibodies showed that most of the hepatitis C virus-positive cells were CD68-positive macrophages.

We demonstrate for the first time clear distribution of hepatitis C virus antigen in mononuclear cells in various organs from patients with hepatitis C virus infection. This study suggests that macrophages are the major target of hepatitis C virus infection.