Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B

Am J Gastroenterol. 2013 Jun;108(6):942-8. doi: 10.1038/ajg.2013.111. Epub 2013 Apr 30.


Objectives: The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone.

Methods: A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up.

Results: Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients.

Conclusions: Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / prevention & control*
  • Hepatitis B, Chronic / surgery
  • Humans
  • Kaplan-Meier Estimate
  • Lamivudine / therapeutic use*
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • Postoperative Care
  • Proportional Hazards Models
  • Secondary Prevention
  • Survival Rate
  • Viral Load
  • Young Adult


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Organophosphonates
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Adenine