Intragraft localization of activated nuclear factor kappaB in recurrent hepatitis C virus disease following liver transplantation.
Nuclear factor kappaB (NF-kappaB) is activated during viral infection and is central to the regulation of host immune responses. The NF-kappaB activation status and its morphological sources were assessed by immunohistochemistry in allograft biopsy specimens of orthotopic liver transplantation patients with recurrent hepatitis C virus (HCV). Hepatocellular NF-kappaB immunostaining was detected in HCV cases compared with controls (nontransplant: P <.001; transplant: P =.006), which correlated with the number of NF-kappaB positive hepatocytes (P =.007) and contrasted to the absent to weak staining of controls (nontransplant: P =.001; transplant: P =.009). Enhanced NF-kappaB staining of cytokeratin 19-positive bile ducts and proliferating ductules in the HCV group was in contrast to controls. Intense NF-kappaB immunoreactivity was detected in CD68-positive Kupffer cells and macrophages of all HCV specimens compared with a few controls (nontransplant: P <.001; transplant: P =.001) and contrasted to the weak staining of controls (nontransplant: P <.001; transplant: P =.001). NF-kappaB-positive immunoreactivity correlated with the number of T cell receptor (TCR) alpha/beta-positive lymphocytes (P <.001), which was not observed in controls. In those HCV cases showing evidence of necroinflammatory activity (grade) and individual features of portal inflammation, periportal inflammation/piecemeal necrosis, lobular inflammation, and fibrosis (stage), higher NF-kappaB staining intensity scores within bile ducts, proliferating ductules, hepatocytes (piecemeal necrosis: P =.016; stage: P =.030), and lymphocytes (stage: P =.044) and increased number of NF-kappaB-positive cells within bile ducts, proliferating ductules (grade, lobular inflammation, piecemeal necrosis, stage: P =.022), hepatocytes, and lymphocytes were observed. Increased staining intensity and frequency of NF-kappaB-positive cells were similarly observed in HCV-positive allografts obtained from patients under tacrolimus- compared with cyclosporine-based immunosuppression. These data implicate an immunoregulatory role of intragraft NF-kappaB activation in the pathogenesis and progression of posttransplantation HCV disease recurrence.
Gaweco
A S
AS
Liver Transplant Program, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA. agaweco@luc.edu
Wiesner
R H
RH
Porayko
M
M
Rustgi
V K
VK
Yong
S
S
Hamdani
R
R
Harig
J
J
Chejfec
G
G
McClatchey
K D
KD
Van Thiel
D H
DH
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000494:pharmacology; D019281:Dimerization; D005260:Female; D006526:Hepatitis C / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D016559:Tacrolimus / Q000494:pharmacology
D016328:NF-kappa B; D012367:RNA, Viral; D016572:Cyclosporine; D016559:Tacrolimus