Hepatitis B virus quasispecies evolution after liver transplantation in patients under long-term lamivudine prophylaxis with or without hepatitis B immune globulin

Transpl Infect Dis. 2015 Apr;17(2):208-20. doi: 10.1111/tid.12360.

Abstract

Aims: To investigate an optimal long-term prophylactic strategy for prevention of hepatitis B virus (HBV) recurrence after liver transplantation, we conducted a randomized study of 29 transplant recipients receiving a short course of hepatitis B immune globulin (HBIg) + lamivudine (LAM), followed by randomization to long-term prophylaxis with LAM with or without HBIg.

Methods: The efficacy and safety, and impact on survival and HBV recurrence of these 2 prophylactic regimens were compared over a mean period of 10 years. In patients with viral recurrence, the HBV quasispecies in the surface/polymerase region were studied by ultra-deep pyrosequencing (UDPS).

Results: The 10-year survival rate was 76% and was not affected by the type of prophylaxis. Four patients had hepatitis B surface antigen (HBsAg) recurrence within the first 48 months after orthotopic liver transplantation (OLT). HBsAg-positive and -negative patients showed similar mean survival times, with no differences between the 2 regimens. Low HBV DNA levels were transiently detected in 32% of HBsAg-negative patients. UDPS showed major changes after OLT in the HBV quasispecies of patients with viral recurrence, which may be explained by a "bottleneck" effect of OLT together with prophylactic therapy.

Conclusion: Long-term survival after OLT in end-stage chronic hepatitis B patients was good with both prophylactic strategies. However, low, transient HBV DNA levels were detected even in the absence of HBsAg, showing the importance of continuing HBV prophylaxis.

Keywords: HBV DNA; HBV quasispecies; chronic hepatitis B; hepatitis B surface antigen (HBsAg); orthotopic liver transplantation; ultra-deep pyrosequencing (UDPS).

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Viral / blood*
  • End Stage Liver Disease / surgery*
  • End Stage Liver Disease / virology
  • Evolution, Molecular
  • Female
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / prevention & control*
  • Hepatitis B, Chronic / surgery
  • Humans
  • Immunoglobulins / therapeutic use*
  • Lamivudine / therapeutic use*
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Secondary Prevention
  • Sequence Analysis, DNA
  • Treatment Outcome

Substances

  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Immunoglobulins
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • hepatitis B hyperimmune globulin