Relevance of Hepatitis B Virus Genome Variability in Organ Transplantation

Hepatitis B virus (HBV) can cause acute and chronic hepatitis in humans, with the latter possibly leading to liver cirrhosis and hepatocellular carcinoma. The clinical course of HBV infection is critically dependent on genetic and immune features of the host as well as on virological factors. In situations of immune suppression, e.g. in patients after organ transplantation with chronic HBV infection, severe progression of liver disease can occur, due to direct effects of immunosuppressive regimens on HBV's hepatotoxicity or replication and due to the selection of HBV mutants. HBV variants are commonly found in chronically infected patients because of the lack of proofreading capacity of the HBV reverse transcriptase. Examples of relevant HBV mutations include precore or basal core promoter mutants with increased replication capacity, escape mutants with alterations in the 'a-determinant' immune epitope, core gene deletions after renal transplantation, antiviral drug resistant strains and accumulation of complex HBV variants after long-term immune suppression. In this review, we present the virological background of HBV genetic variability, discuss frequent mutations observed in transplanted patients and address the effects of HBV genetic variability on the clinical