Mixed cryoglobulinemia type II in chronic hepatitis B associated with HBe-minus HBV mutant: cellular immune reactions and response to interferon treatment.
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 transaminases 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-alpha 2b3 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 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 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-alpha was found to be effective in mixed cryoglobulinemia even in the presence of HBe-minus HBV mutants.(ABSTRACT TRUNCATED AT 250 WORDS)
Löhr
H
H
I.Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universität, Mainz, Germany.
Goergen
B
B
Weber
W
W
Gödderz
W
W
Meyer zum Büschenfelde
K H
KH
Gerken
G
G
D000293:Adolescent; D003449:Cryoglobulinemia / Q000150:complications / Q000276:immunology* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications / Q000276:immunology* / Q000628:therapy / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006521:Hepatitis, Chronic / Q000150:complications / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007111:Immunity, Cellular; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology
D006513:Hepatitis B e Antigens; D016898:Interferon-alpha