MIXED CRYOGLOBULINEMIA TYPE-II IN CHRONIC HEPATITIS-B ASSOCIATED WITHHBE-MINUS HBV MUTANT - CELLULAR IMMUNE-REACTIONS AND RESPONSE TO INTERFERON TREATMENT

The case of a young female patient with chronic active hepatitis B, va sculitic purpura, edema, and circulating immune complexes due to mixed cryoglobulinemia is described. Serum transaminases were elevated. Ser ological assays showed hepatitis B surface antigen (HBsAg), antibody t o hepatitis B e antigen (anti-HBe), and antibody to hepatitis B core a ntigen (anti-HBc) antibodies but no antibody to hepatitis C virus (ant i-HCV) or antibody to hepatitis delta virus (anti-HDV) antibodies. Usi ng hepatitis B virus-polymerase chain reaction (HBV-PCR) and direct se quencing 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-alpha 2b 3 miu three times weekly, alanine aminotransferases returned to no rmal levels while cryoglobulins and immune complexes disappeared from serum. In addition, 2 months after the onset of treatment serum HBV-DN A was no longer detectable by PCR.Prior to treatment the analysis of c ellular immune reactions of peripheral blood mononuclear 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 proliferati ve response of T cells to HBcAg and HBeAg was demonstrated. In conclus ion, immune complex disease may complicate chronic hepatitis B in pati ents expressing HBe-minus HBV mutants. Treatment with interferon-alpha . was found to be effective in mixed cryoglobulinemia even in the pres ence of HBe-minus HBV mutants. Antiviral effects of interferon-alpha i nduce a decrease in specific T-cell recognition of HBV antigens. Clini cal response and virus elimination were, however, accompanied by a rec onstitution of cellular immune responses to HBV core antigens, i.e., H BcAg and HBeAg. The response to certain T cell epitopes on these antig ens may be of pathogenetic relevance for virus elimination. (C) 1994 W iley-Liss, Inc.