Immune-mediated hepatitis-associated aplastic anemia caused by the emergence of a mutant hepatitis B virus undetectable by standard assays

Hepatitis-associated aplastic anemia (HAA) is characterized by marrow failure developing after acute seronegative hepatitis. A patient with agammaglobulinemia developed HAA in association with HBsAg-negative, hepatitis B virus (HBV) DNA-positive acute hepatitis. Sequence analysis showed several substitutions in the major antigenic determinant of HBsAg, potentially affecting the detection by diagnostic immunoassays. Viral mutants may therefore be implicated as etiologic agents of HBsAg-negative HAA. HBV DNA determination may be necessary to exclude mutant HBV as a cause of HAA, particularly in categories at high risk of mutant selection such as agammaglobulinemic and transplanted patients.