Hepatitis B virus mutations in the pre-S genome before and after liver transplantation.
Mutational changes in the pre-S region of hepatitis B virus (HBV) were analyzed in 20 patients who experienced HBV reinfection after orthotopic liver transplantation (OLT). HBV DNA was extracted from patient sera before and after OLT. The pre-S sequence was amplified via polymerase chain reaction, subcloned, sequenced, and analyzed. In 18 of 20 patients, mutational changes were found in the pre-S region pre- or post- OLT; 11 showed point mutations (1-10) and 7 cases major changes (insertions/deletions). For the point mutations, there was no trend in the selection of wild-type (wt) HBV before or after OLT in the pre-S region. Additional HBV reinfection during hepatitis B surface antigen antibody (anti-HBS) administration had no influence on selection pressure in the pre-S region. In contrast, insertions/deletions were more frequently found before OLT. In the 7 patients with deletions/insertions, changes in the hepatocyte attachment site were not seen after OLT. Interestingly, the only patient with changes in a major virus population after OLT had changes in the CCAAT-box of the S-promoter. As shown by gel shift analysis, this mutation was associated with loss of specific binding to this element and thus probably led to dysregulation of S-gene transcription. Major changes in the pre-S genome are mainly seen before OLT, and HBV reinfection does occur with the intact hepatocyte attachment sites after OLT. Anti-HBs (hepatitis B immune globulin [HBIg]) creates no selection pressure on the pre-S region. The mutation in the CCAAT-box of the S-promoter potentially leads to its dysregulation and may be associated with the occurrence of fibrosing cholestatic hepatitis after OLT.
Trautwein
C
C
Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany.
Schrem
H
H
Tillmann
H L
HL
Kubicka
S
S
Walker
D
D
Böker
K H
KH
Maschek
H J
HJ
Pichlmayr
R
R
Manns
M P
MP
D000328:Adult; D001483:Base Sequence; D005260:Female; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D011184:Postoperative Period; D012008:Recurrence; D014158:Transcription, Genetic
D015335:Molecular Probes