Hepatitis C-induced hepatic allograft injury is associated with a pretransplantation elevated viral replication rate

Citation
Sj. Pelletier et al., Hepatitis C-induced hepatic allograft injury is associated with a pretransplantation elevated viral replication rate, HEPATOLOGY, 32(2), 2000, pp. 418-426
Citations number
47
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
HEPATOLOGY
ISSN journal
02709139 → ACNP
Volume
32
Issue
2
Year of publication
2000
Pages
418 - 426
Database
ISI
SICI code
0270-9139(200008)32:2<418:HCHAII>2.0.ZU;2-2
Abstract
Hepatitis C virus (HCV) allograft infection after liver transplantation fol lows a variable but accelerated course compared with the nontransplantation population. Predictors of outcome and mechanisms of reinfection remain elu sive. The accelerated HCV-induced allograft injury associated with a 10- to 20-fold increase in serum viral quantity posttransplantation was hypothesi zed to be the result of elevated intrahepatic viral replication rates. Pati ents (N = 23) with HCV-induced end-stage liver disease who underwent liver transplantation between October 1995 and December 1998 were prospectively s tudied. HCV-induced allograft injury was defined by posttransplantation per sistent biochemical hepatitis or allograft fibrosis not explained by other diagnoses. Liver biopsies (N = 92) were obtained by protocol and when clini cally indicated. Negative-strand HCV RNA (putative intermediate for replica tion) was detected by a strand-specific reverse-transcription polymerase ch ain reaction (RT-PCR) assay and semiquantatively compared with constitutive ly expressed 18S rRNA. Recipients with increased pretransplantation replica tion were at increased risk for the development of posttransplantation bioc hemical hepatitis (P = .03), an increased rate of allograft fibrosis (P = . 006), and increased mortality rate (40.0% vs. 0.0%; P = .02). There was no correlation with quantities of genomic HCV RNA in the serum with relative i ntrahepatic viral replication either before or after liver transplantation. The relative rate of HCV replication within the allograft was not elevated in the posttransplantation period compared with that seen within the expla nted liver. Accelerated allograft injury caused by HCV may be predicted by viral replication rates within the explanted liver. The stable intrahepatic replication rate after transplantation suggests that elevated serum viral loads are the result of decreased viral clearance, possibly secondary to im munosuppressive therapy.