Cytomegalovirus and chronic rejection of liver grafts

Evans, Paul Charles (1997). Cytomegalovirus and chronic rejection of liver grafts. PhD thesis The Open University.

Abstract

This thesis tested the hypothesis that cytomegalovirus (CMV) may initiate or enhance chronic rejection of liver grafts. A polymerase chain reaction(PGR) test was developed and used to monitor 33 liver transplant patients for active CMV infection (Chapters 2 and 3). The incidence of urine PCR positivity and prolonged active CMV infection were risk factors for chronic rejection (Chapter 4).

Matching and mismatching of HLA alleles between donor and recipient was not shown to be a risk factor for chronic rejection. However, HLA class I matching was associated with (clearance of active CMV (Chapter 4).

Recipients with the TNF-2 promoter allele (associated with enhanced expression of TNF) were at increased risk of chronic rejection. Furthermore, active CMV infection and the TNF-2 promoter allele were shown to act synergistically as risk factors for chronic rejection (Chapter 4).

In addition, two or more episodes of acute rejection or a pre transplant diagnosis of primary biliary cirrhosis (PEG) were shown tu be risk factors for chronic rejection (Chapter 4).

CMV was also studied in the context of humoral immunity and chronic rejection (Chapter 5). Western blotting of hepatic artery and bile duct tissue (sites of rejection mediated damage) showed that post transplant IgA antibody to a 44 kD bile duct protein was associated with development of active CMV infection but was not associated with chronic rejection. However, pre transplant IgA antibodies to 94 and 39 kD bile duct proteins or IgG antibodies to 160 and 85 kD hepatic artery proteins were associated with an increased risk of chronic rejection.

CMV was identified in bile duct epithelial cells, vascular endothelial cells, hepatocytes and mononuclear cells of liver grafts by in situ hybridisation (Chapter 6). Active CMV infection of the graft, especially epithelial cells, was associated with chronic rejection.

Finally, human herpesvirus 6 (HHV-6) was not detected in serum, whole blood or liver graft tissue by PCR and was not an important pathogen after liver transplantation.

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