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, followed 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 interferon initially led to a severe exacerbation of hepatitis. Later, higher doses of interferon were tolerated and were associated with reduction of HBV replication and improvement in liver histopathology and serum aminotransferases. After interferon therapy, sequencing of HBV DNA from a repeat liver biopsy showed a cluster of new mutations, which may have led to alterations in immunodominant epitopes of viral proteins. The findings suggest that a "naturally occurring" mutant form of HBV was associated with chronic hepatitis and vasculitis in the patient, and that the immunological pressure on HBV produced by therapy with interferon may have led to other mutations in the viral genome with persistence of low-level HBV infection.