6533b820fe1ef96bd127913f

RESEARCH PRODUCT

Mixed cryoglobulinemia type II in chronic hepatitis B associated with HBe-minus HBV mutant: Cellular immune reactions and response to interferon treatment

subject

description

The case of a young female patient with chronic active hepatitis B, vasculitic purpura, edema, and circulating immune complexes due to mixed Cryoglobulinemia is described. Serum transami-nases were elevated. Serological assays showed hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti-HBe), and antibody to hepatitis B core antigen (anti-HBc) antibodies but no antibody to hepatitis C virus (anti-HCV) or antibody to hepatitis delta virus (anti-HDV) antibodies. Using hepatitis B virus-polymerase chain reaction (HBV-PCR) and direct sequencing a precore/core (preC/C) mutant unable to synthesize HBeAg was detected in serum. HBV antigens were demonstrated in the circulating immune complexes. Following 1 month of treatment with interferon-a 2b 3 miu three times weekly, alanine aminotransferases returned to normal levels while cryoglobulins and immune complexes disappeared from serum. In addition, 2 months after the onset of treatment serum HBV-DNA was no longer detectable by PCR. Prior to treatment the analysis of cellular immune reactions of peripheral blood mononu-clear cells showed a major proliferative response to HBcAg, preS1Ag and HBxAg and a minor response to HBeAg and HBsAg. One month after conclusion of treatment a decline in T-cell reactivity against all HBV antigens was observed. During clinical response to the therapy, however, a strong proliferative response of T cells to HBcAg and HBeAg was demonstrated. In conclusion, immune complex disease may complicate chronic hepatitis B in patients expressing HBe-minus HBV mutants. Treatment with interferon-a was found to be effective in mixed Cryoglobulinemia even in the presence of HBe-minus HBV mutants. Antiviral effects of interferon-a induce a decrease in specific T-cell recognition of HBV antigens. Clinical response and virus elimination were, however, accompanied by a reconstitution of cellular immune responses to HBV core antigens, i.e., HBcAg and HBeAg. The response to certain T cell epitopes on these antigens may be of pathogenetic relevance for virus elimination. © 1994 Wiley-Liss, Inc.