CHRONIC LEUKOCYTOCLASTIC VASCULITIS COMPLICATING HBV INFECTION - POSSIBLE ROLE OF MUTANT FORMS OF HBV IN PATHOGENESIS AND PERSISTENCE OF DISEASE

A young woman developed arthritis and leukocytoclastic vasculitis, fol lowed by hepatitis due to a precore mutant strain of hepatitis B virus (HBV) incapable of synthesizing HBe antigen. Tests for antibodies to HCV were persistently negative. Treatment of the patient with alpha in terferon initially led to a severe exacerbation of hepatitis. Later, h igher doses of interferon were tolerated and were associated with redu ction of HBV replication and improvement in liver histopathology and s erum aminotransferases. After interferon therapy, sequencing of HBV DN A from a repeat liver biopsy showed a cluster of new mutations, which may have led to alterations in immunodominant epitopes of viral protei ns. The findings suggest that a ''naturally occurring'' mutant form of HBV was associated with chronic hepatitis and vasculitis in the patie nt, and that the immunological pressure on HBV produced by therapy wit h interferon may have led to other mutations in the viral genome with persistence of low-level HBV infection.