SELECTION OF MUTATIONS IN THE HEPATITIS-B VIRUS POLYMERASE DURING THERAPY OF TRANSPLANT RECIPIENTS WITH LAMIVUDINE

We describe mutations in the hepatitis B virus (HBV) polymerase gene i n viruses which reactivated in two patients during therapy with -2'-de oxy-3'-thiacytidine, or lamivudine (3TC), and following orthotopic Liv er transplantation for chronic hepatitis B. Virus resistance to 3TC is associated with mutations which lead to amino acid substitutions in t he highly conserved tyr-met-asp-asp (YMDD) motif, part of the active s ite of the polymerase, and which parallel those seen in resistant huma n immunodeficiency virus (HIV) Substitutions of valine and isoleucine for methionine were found in the two cases. The significance of single secondary mutations, which differ between viruses from the two patien ts, remains to be determined. Thus, viral resistance to lamivudine of hepatitis B virus mimics that of HIV and can occur in the setting of i mmunosuppression after liver transplantation.