Theise N D, Conn M, Thung S N
Lillian and Henry N. Stratton-Hans Popper Department of Pathology, Mount Sinai Medical Center, New York, NY 10029.
Hum Pathol. 1993 Jan;24(1):103-8. doi: 10.1016/0046-8177(93)90069-s.
Cytomegalovirus (CMV) hepatitis is a common and serious complication of orthotopic liver transplantation. Immunohistochemical studies are the most sensitive methods of diagnosis. We compared immunoperoxidase staining with monoclonal antibodies to CMV immediate early and early antigens with routine hematoxylin-eosin stain. Eleven of 140 liver allograft recipients at our institution had CMV hepatitis identified by hematoxylin-eosin stain on biopsy specimens. We stained serial sections of all previous biopsy specimens and one post-ganciclovir biopsy specimen (when available) from each of these patients. One or both monoclonal antibodies confirmed the original hematoxylin-eosin stain diagnoses. Cytomegalovirus was detected in earlier, hematoxylin-eosin stain-negative biopsy specimens in seven of 11 patients. Detection of immediate early antigen often preceded that of early antigen. Earlier biopsy specimens demonstrated less positive staining, which become more extensive closer in time to the hematoxylin-eosin stain-positive biopsy specimens. Sinusoidal cells became positive earlier than hepatocytes. In one patient occult CMV antigens persisted in biopsy specimens following ganciclovir treatment. We conclude that (1) immunohistochemical staining for CMV antigens can result in earlier detection of viral infection, which may lead to earlier, more effective treatment; (2) CMV infection and antigen expression is focal, requiring extensive examination for diagnosis; (3) extent of occult infection may indicate the extent of active infection in the organ as a whole; (4) most CMV hepatitis begins with infection of sinusoidal lining cells as a result of hematogenous spread from within the allograft or from systemic viremia; and (5) posttreatment biopsy specimens may be more sensitive than resolution of serum liver enzyme abnormalities in evaluating the success of ganciclovir therapy.
巨细胞病毒（CMV）肝炎是原位肝移植常见且严重的并发症。免疫组织化学研究是最敏感的诊断方法。我们将针对CMV即刻早期和早期抗原的单克隆抗体免疫过氧化物酶染色与常规苏木精-伊红染色进行了比较。在我们机构的140例肝移植受者中，有11例经活检标本苏木精-伊红染色确诊为CMV肝炎。我们对这些患者之前所有活检标本以及一份更昔洛韦治疗后的活检标本（如有）的连续切片进行了染色。一种或两种单克隆抗体均证实了最初苏木精-伊红染色的诊断结果。11例患者中有7例在早期苏木精-伊红染色阴性的活检标本中检测到了巨细胞病毒。即刻早期抗原的检测通常早于早期抗原。早期活检标本显示阳性染色较少，而在时间上更接近苏木精-伊红染色阳性活检标本时，阳性染色范围变得更广泛。窦状隙细胞比肝细胞更早出现阳性。在1例患者中，更昔洛韦治疗后活检标本中仍存在隐匿性CMV抗原。我们得出结论：（1）CMV抗原的免疫组织化学染色可更早检测到病毒感染，这可能导致更早、更有效的治疗；（2）CMV感染和抗原表达是局灶性的，需要广泛检查以进行诊断；（3）隐匿感染的程度可能表明整个器官中活跃感染的程度；（4）大多数CMV肝炎始于窦状隙衬里细胞的感染，这是由于同种异体移植物内或全身病毒血症的血行播散所致；（5）在评估更昔洛韦治疗的成功与否时，治疗后活检标本可能比血清肝酶异常的缓解更敏感。
