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J Infect Dis. 1998 Sep;178(3):866-9.

Emergence of an S gene mutant during thymosin alpha1 therapy in a patient with chronic hepatitis B.

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Department of Pathology, Chang Gung Memorial Hospital and University, Taipei, Taiwan.


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.

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