Early Detection of Cytomegalovirus in the Allograft Liver Biopsy

Abstract

Cytomegalovirus (CMV) hepatitis can be distinguished from allograft rejection only by biopsy. It is important to document CMV hepatitis early, before inclusions become visible, since antirejection therapy can aggravate the hepatitis. CMV was isolated from 50 patients, 9 of whom had a biopsy-proven CMV hepatitis that was preceded by an apparently uninfected biopsy within 3-33 days (mean = 18 days). A monoclonal antibody to an intermediate early CMV antigen (Chemicon) was compared with a commercially available CMV DNA-hybridization kit (ENZO) for their ability to demonstrate virus in the earlier, apparently uninfected biopsies. All of the biopsies with CMV hepatitis and 3 of the 9 preceding biopsies revealed CMV nuclear antigen in both transformed and nontransformed cells in paraffin-embedded tissues. DNA hybridization revealed viral DNA in the hepatitis biopsies but not in the preceding ones. Thus, in this study CMV was detectable by means of antibody before there was overt histologic evidence of CMV effect. The monoclonal antibody stain was more sensitive, less expensive, and easier to perform and interpret in this study than the DNA hybridization. Demonstration of early CMV antigen is more rapid and sensitive than culture of the liver specimen (which grew CMV in only 3 of 5 attempts) and should be considered in all allograft liver biopsies in which rejection is suspected.