Relevance of hepatitis B core gene deletions in patients after kidney transplantation.
OBJECTIVE
Hepatitis B virus (HBV) infection is a major cause of death in the long-term follow-up after organ transplantation and immunosuppressive therapy. The selection pressure on the HBV genome in these patients is reduced. The aim was to analyze and characterize variations in the HBV core gene after organ transplantation and their impact for prognosis.


METHODS
In patients with chronic HBV infection after organ transplantation (liver, n = 60; heart, n = 50; kidney, n = 30) the HBV core gene was amplified by polymerase chain reaction (PCR). Core gene deletions were cloned into replication competent and expression vectors. The impact of these mutations on HBV replication and capsid formation was analyzed and correlated with disease progression.


RESULTS
Central core gene deletions only were detected in patients after kidney transplantation. Two types of core gene deletions--small and large--were found. Large core gene deletions showed no capsid formation and HBV replication, which resulted in nuclear core expression. The occurrence of large core gene deletions was associated with a severe course of liver disease.


CONCLUSIONS
Core gene deletions occur specifically after kidney transplantation. Only large core gene deletions resulted in impaired capsid formation and nuclear localization of the core protein. The presence of large core gene deletions was associated with progressive disease.
Bock
C-Thomas
CT
Department of Gastroenterology, Hepatology and Oncology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Buerke
Boris
B
Tillmann
Hans L
HL
Tacke
Frank
F
Kliem
Volker
V
Manns
Michael P
MP
Trautwein
Christian
C
D002478:Cells, Cultured; D017353:Gene Deletion; D005816:Genetic Complementation Test; D016679:Genome, Viral; D006512:Hepatitis B Core Antigens / Q000032:analysis / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000209:etiology / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D014779:Virus Replication
D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens