Cytomegalovirus infection of bile duct epithelial cells, hepatic artery and portal venous endothelium in relation to chronic rejection of liver grafts

Background/Aim: Chronic rejection is an important cause of graft loss follo wing liver transplantation. A number of risk factors for chronic rejection have been identified previously, albeit inconsistently. These include cytom egalovirus infection detected by a number of different techniques, includin g immunohistochemical staining and in situ hybridisation of liver grafts. H owever, tissue-based techniques for the detection of CMV have not been appl ied to grafts lost to conditions other than chronic rejection. The purpose of this study was to investigate the relationship between the presence of c ytomegalovirus infection detected by in situ hybridisation and immunohistoc hemistry with respect to graft outcome, the presence of cytomegalovirus inf ection detected by other techniques and in addition, the type of infected c ell. Methods: The 29 patients studied included 15 patients who lost their primar y liver graft to chronic rejection in 8 cases, to hepatic artery thrombosis in 4 cases and to causes other than chronic rejection or hepatic artery th rombosis in 3 further cases. In each case, sections containing septal or la rge ducts and vessels were selected (usually blocks) since these may be mor e representative. Needle biopsies from 14 further patients who ultimately a chieved satisfactory graft function served as control tissue. Of these, ten had evidence of cytomegalovirus infection at the time of study by serum/ur ine PCR, DEAFF testing or seroconversion, while 4 patients had no evidence of cytomegalovirus infection according to these techniques. Results: Cytomegalovirus infection was detected in the liver of 12 of the 2 9 patients. These included 8/15 grafts lost, which comprised 3/8 with chron ic rejection, 2/3 with hepatic artery thrombosis and 3/4 with grafts lost t o other causes, as well as 4/14 who retained grafts. CMV was detected most commonly in association with symptomatic infection and notably was detected only by in situ hybridisation in two cases. Predominant cell types that co ntained cytomegalovirus were hepatocytes and mononuclear cells. However, bi le duct epithelial cells, hepatic artery endothelial cells and portal venou s endothelial cells also contained cytomegalovirus in some cases. Conclusions: These data support previous studies that cytomegalovirus infec tion is detectable in patients with chronic rejection and are consistent wi th the theory that CMV is involved in chronic rejection. However, cytomegal ovirus infection was detected in explanted grafts lost to conditions other than chronic rejection, and the association may not be causal but a consequ ence of graft injury.