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

Autores de IIS La Fe

• Aymara Mas Perucho

  Autor

• Martín Prieto Castillo

  Autor

• Jose Ignacio Herrero Sanchez

  Autor

• Rafael Esteban Baño

  Autor

Participantes ajenos a IIS La Fe

• Buti M
• Tabernero D
• Homs M
• Rodríguez-Frías F
• Casafont F
• Casillas R
• González A
• Miras M
• Castells L

Grupos

• Hepatología experimental y Trasplante hepático

Abstract

AimsTo 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. MethodsThe efficacy and safety, and impact on survival and HBV recurrence of these 2 prophylactic regimens were compared over a mean period of 10years. In patients with viral recurrence, the HBV quasispecies in the surface/polymerase region were studied by ultra-deep pyrosequencing (UDPS). ResultsThe 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 48months 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. ConclusionLong-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

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