Hepatitis B virus variants with antiviral drug-resistant mutations and/or hepatitis B immune globulin-resistant mutations are the main cause of hepatitis B virus reinfections post-liver transplant. 2. Early diagnosis of antiviral drug resistance and prompt initiation of rescue therapy are important in preventing hepatitis flares and hepatic decompensation. 3. Virologic breakthrough is the first indication of antiviral drug resistance. 4. Genotypic resistance testing should be performed when possible to avoid unnecessary modification of treatment in patients who do not have confirmed antiviral drug resistance and to permit appropriate selection of rescue therapy in those who have confirmed antiviral drug resistance. 5. Choice of rescue therapy requires knowledge of the past history of hepatitis B virus treatments and virologic response to those treatments, patterns of mutations detected at the time of virologic breakthrough, and in vitro cross-resistance data. 6. Occurrence of antiviral drug resistance can be reduced by the use of the most potent nucleos(t)ide analogue(s) with the highest genetic barrier to resistance, emphasis of medication compliance, and close monitoring of virologic response.
