Mutations in the HBsAg loop of a reactivated HBV variant. The complicated folded loop forms the surface of HBV and HBsAg particles. The exact topology and three-dimensional shape of the loop are unknown. One circle corresponds to one amino acid in the single letter code of the normal (wildtype) HBV, each square to a mutation. The boxed-in part is named a-determinant and is believed to be immunodominant, but immune escape induced mutations occurred in the entire HBsAg loop. Yellow (shaded) squares cause the loss of an immunodominant HBsAg subtype determinant. This variant replicated in a patient receiving lymphoma therapy. The patient was anti-HBc and anti-HBs positive before the immunosuppressive lymphoma therapy and developed severe acute hepatitis B after end of the therapy due to immunopathogenesis against the variant which had become abundant under immunosuppression. The serum from the acute reactivated hepatitis B phase had a high virus load, but was HBsAg negative in all assays.