A longitudinal analysis of hepatitis C virus replication following liver transplantation.
OBJECTIVE
The pathogenesis of graft injury in liver transplant recipients with recurrent hepatitis C virus (HCV) infection remains poorly understood. In this study, the relationship between HCV replication, genotype, and the evolution of graft damage was investigated.


METHODS
HCV RNA was quantified in 184 protocol sera from 25 patients transplanted for HCV cirrhosis. HCV isolates were genotyped, and hepatic expression of core and NS4 antigens was sought in protocol allograft biopsy specimens.


RESULTS
Acute lobular hepatitis was accompanied by a steep increase in HCV RNA levels and the appearance of core and NS4 antigens in the graft. Methylprednisolone treatment for acute rejection led to a 4-100-fold increase in serum HCV RNA. At the end of follow-up, HCV RNA levels were 3-112 times pretransplant levels and were higher in patients with more severe hepatitis. Progressive liver damage developed in 7 of 14 patients with HCV genotype 1b and in 1 of 11 patients infected with other genotypes (P = 0.03).


CONCLUSIONS
Peak viremia levels and the initial detection of HCV antigens in hepatocytes suggests increased viral replication at the time of acute HCV hepatitis in the graft. Genotype 1b and higher viremia levels were associated with more severe chronic graft damage.
Gane
E J
EJ
Institute of Liver Studies, King's College School of Medicine and Dentistry, Denmark Hill, London, England.
Naoumov
N V
NV
Qian
K P
KP
Mondelli
M U
MU
Maertens
G
G
Portmann
B C
BC
Lau
J Y
JY
Williams
R
R
D000328:Adult; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000188:drug therapy; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy; D018936:Hepatitis C Antigens / Q000032:analysis; D006801:Humans; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D014766:Viremia; D014779:Virus Replication
D018936:Hepatitis C Antigens; D012367:RNA, Viral; D004317:Doxorubicin; D008775:Methylprednisolone