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

被引:15
作者
Gaweco, AS
Wiesner, RH
Porayko, M
Rustgi, VK
Yong, S
Hamdani, R
Harig, J
Chejfec, G
McClatchey, KD
Van Thiel, DH
机构
[1] Loyola Univ, Med Ctr, Dept Med, Liver Transplant Program,Div Gastroenterol Hepato, Maywood, IL 60153 USA
[2] Loyola Univ, Med Ctr, Dept Pathol, Liver Transplant Program, Maywood, IL 60153 USA
[3] Loyola Univ, Med Ctr, Dept Surg, Liver Transplant Program, Maywood, IL 60153 USA
[4] Mayo Clin & Mayo Fdn, Dept Med, Liver Transplant Ctr, Rochester, MN 55905 USA
[5] Thomas Jefferson Univ Hosp, Liver Transplantat Ctr, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA
[6] Georgetown Univ, Med Ctr, Dept Surg, Div Transplant Surg,Liver Transplant Program, Washington, DC 20007 USA
关键词
D O I
10.1053/he.2000.6983
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Nuclear factor kappa B (NF-kappa B) is activated during viral infection and is central to the regulation of host immune responses. The NF-kappa B 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-kappa B immunostaining was detected in HCV cases compared with controls (nontransplant: P < .001; transplant: P = .006), which correlated with the number of NF-kappa B positive hepatocytes (P = .007) and contrasted to the absent to weak staining of controls (nontransplant: P = .001; transplant: P = .009). Enhanced NF-kappa B staining of cytokeratin 19-positive bile ducts and proliferating ductules in the HCV group was in contrast to controls. Intense NF-kappa B 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-kappa B-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-kappa B 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-kappa B-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-kappa B-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-kappa B activation in the pathogenesis and progression of posttransplantation HCV disease recurrence.
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页码:1183 / 1191
页数:9
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