Acute liver graft failure due to emergence of lamivudine resistant hepatitis B

liver411

Gut 2001;49:860-863 ( December)

Case report



Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir



D Mutimera d, B H Feraz-Netof, R Harrisonb, K O'Donnella, J Shawa, P Canec e, D Pillayc e

a Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK, b Pathology Unit, Queen Elizabeth Hospital, Birmingham, UK, c Public Health Laboratory Service Antiviral Susceptibility Reference Unit, Birmingham, UK, d Division of Medical Sciences, University of Birmingham Medical School, Birmingham, UK, e Division of Immunity and Infection, University of Birmingham Medical School, Birmingham, UK, f Liver Unit, Unifigado, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brasil





Correspondence to: Dr D Mutimer, Liver and Hepatobiliary Unit, Queen

Elizabeth Hospital, Birmingham B15 2TH, UK.





BACKGROUND Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated

with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure.



CASE REPORT A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the devlopment

of graft failure.



OUTCOME A rapid exponential decline in serum HBV titre was observed. Liver  function tests normalised and signs of liver failure resolved.



CONCLUSION The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent

inhibitor of lamivudine resistant HBV, should be used when failure of

prophylaxis is associated with graft hepatitis.



_______________________________________________________________