Intragraft localization of activated nuclear factor κB in recurrent hepatitis C virus disease following liver transplantation

Anderson S. Gaweco, Russell H. Wiesner, Michael Porayko, Vinod K. Rustgi, Sherri Yong, Raza Hamdani, James Harig, Gregorio Chejfec, Kenneth D. Mcclatchey, David H. Van Thiel

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17 Scopus citations

Abstract

Nuclear factor κB (NF-κB) is activated during viral infection and is central to the regulation of host immune responses. The NF-κB 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-κB immunostaining was detected in HCV cases compared with controls (nontransplant: P < .001; transplant: P = .006), which correlated with the number of NF-κB positive hepatocytes (P = .007) and contrasted to the absent to weak staining of controls (nontransplant: P = .001; transplant: P = .009). Enhanced NF-κB staining of cytokeratin 19-positive bile ducts and proliferating ductules in the HCV group was in contrast to controls. Intense NF-κB 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-κB-positive immunoreactivity correlated with the number of T cell receptor (TCR) α/β-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-κB 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-κB-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-κB-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-κB activation in the pathogenesis and progression of posttransplantation HCV disease recurrence.

Original languageEnglish (US)
Pages (from-to)1183-1191
Number of pages9
JournalHepatology
Volume31
Issue number5
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Hepatology

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    Gaweco, A. S., Wiesner, R. H., Porayko, M., Rustgi, V. K., Yong, S., Hamdani, R., Harig, J., Chejfec, G., Mcclatchey, K. D., & Van Thiel, D. H. (2000). Intragraft localization of activated nuclear factor κB in recurrent hepatitis C virus disease following liver transplantation. Hepatology, 31(5), 1183-1191. https://doi.org/10.1053/he.2000.6983