Intrahepatic mononuclear cell populations and major histocompatibility complex antigen expression in patients with chronic hepatitis B

Abstract

Objective. To evaluate whether the immune response to virally infected liver cell activity via T lymphocytes determines the natural history and response to alpha-interferon (alpha-IFN) in patients with hepatitis B virus (HBV) associated liver disease. Patients. Nine patients with chronic HBV liver disease were treated for 6 months with alpha-IFN (5χ106 million units three times weekly). Interventions. Liver biopsy specimens were obtained before, after 6 months of treatment and again 6 weeks after discontinuing therapy. Antibodies directed against CD3, CD4, CD8, 3G8 and class I and II major histocompatibility complex (MHC) antigens. The number of mononuclear, liver and bile ductular cells staining positively with each antibody in five high-power fields was determined. Results. Of the nine patients, three responded to alpha-IFN therapy. The number of 3G8+ natural killer cells in the liver increased significantly (P≤0.02) following treatment. Six weeks after treatment, the number of mononuclear cells staining positively with antibodies directed against CD3, CD4 and CD8 antigens differed significantly when liver specimens from responders and non-responders were compared (P≤0.05). Expression of class I and II MHC antigens on mononuclear, liver and bile duct cells was reduced (P≤0.03). By contrast, the difference in natural killer cell numbers noted after 6 months of therapy was no longer evident. Conclusions. Based upon these data, we conclude that: (1) natural killer cells are recruited as a result of alpha-IFN therapy and accumulate in the liver; (2) the presence of an active HBV infection is associated with increased numbers of CD3+, CD4+ and CD8+ mononuclear cells as well as the expression of MHC class I and II antigens by mononuclear, liver and bile duct cells, and (3) a response to alpha-IFN after discontinuing therapy is followed by a reduction in the number of CD3+, CD4+ and CD8+ mononuclear cells present and in the frequency of mononuclear and bile duct cells expressing class I antigens. These results suggest that the number of natural killer cells recruited as a result of alpha-IFN therapy, rather than the number of T lymphocytes within the liver, determines whether or not a clinical response of alpha-IFN therapy will occur