Emergence of an S Gene Mutant during Thymosin α1Therapy in a Patient with Chronic Hepatitis B

The presence of a hepatitis B virus S gene mutant was investigated in a patient being treated with thymosin alpha1. He was seropositive for hepatitis B e antigen throughout therapy but was intermittently seronegative for hepatitis B surface antigen (HBsAg) by an RIA. Sequence analysis revealed an S gene mutant in HBsAg-seronegative serum with two consecutive amino acid substitutions: threonine115-to-isoleucine and threonine116-to-asparagine, whereas no amino acid substitution or deletion was found in the pre-S region. A site-directed mutagenesis experiment confirmed that these mutations were responsible for the failure to detect HBsAg. In summary, an S gene mutant was identified in an HBsAg-seronegative patient. The mutations were located outside the putative "a" determinant. The emergence of an S gene mutant during thymosin alpha1 treatment suggests that enhanced host immunity against HBsAg may play a role in its antiviral activity.