Barkholt L M, Ehrnst A, Veress B
Dept. of Transplantation Surgery, Huddinge Hospital, Karolinska Institute, Sweden.
Scand J Gastroenterol. 1994 Jun;29(6):553-60. doi: 10.3109/00365529409092472.
Cytomegalovirus (CMV) infections are common in liver transplant recipients, and some of the patients develop CMV hepatitis. Clinically, this condition is difficult to distinguish from acute rejection. The histologic criteria for acute liver graft rejection are well accepted, but the criteria for the histomorphologic changes in CMV hepatitis vary considerably. We have recently applied immunohistologic examinations, in situ hybridization, and virus isolation for identification of CMV in liver biopsy specimens.
CMV hepatitis was studied with repeated liver biopsies during the first 3 post-transplant months in 57 transplanted liver grafts. The histopathologic changes due to CMV were compared with those of acute rejection in 99 biopsy specimens. CMV-specific monoclonal antibodies (mAbs) were used to detect the presence of CMV antigens by means of immunofluorescence and immunoperoxidase methods. In situ hybridization for the detection of CMV-DNA was performed on the same paraffin-embedded liver specimens. In most cases, fresh, post-transplant liver specimens were also subjected to virus isolation.
Although 60% of the liver graft donors were CMV-seropositive, CMV was rarely detected in the perioperatively obtained specimens: 1 of 36 by in situ hybridization only. None of the 21 specimens (21 patients) obtained from diseased liver grafts during the 1st post-transplant month showed evidence of CMV infection. In contrast, 8 of the 42 specimens (42 patients) obtained during the 2nd and 3rd months showed histopathologic signs of a predominant viral cholangitis (4 cases) or viral lobulitis (4 cases). The presence of CMV was ascertained in 7 of these 42 patients (17%).
In liver transplant patients with clinical and laboratory signs of liver involvement, the identification of CMV by immunomorphologic methods and/or by virus isolation permitted the diagnosis of CMV hepatitis with the positive and negative predictive values of 0.86 and 1.0, and 1.0 and 1.0 for the former and the latter methods, respectively, as compared with histologic changes. By using immunohistopathologic techniques, it is possible to initiate antiviral therapy early in patients with CMV hepatitis.
巨细胞病毒（CMV）感染在肝移植受者中很常见，部分患者会发生CMV肝炎。临床上，这种情况很难与急性排斥反应区分开来。急性肝移植排斥反应的组织学标准已被广泛接受，但CMV肝炎组织形态学改变的标准差异很大。我们最近应用免疫组织学检查、原位杂交和病毒分离技术来鉴定肝活检标本中的CMV。
对57例移植肝在移植后前3个月内进行多次肝活检，研究CMV肝炎。将99例活检标本中CMV引起的组织病理学改变与急性排斥反应的改变进行比较。使用CMV特异性单克隆抗体（mAb）通过免疫荧光和免疫过氧化物酶方法检测CMV抗原的存在。在相同的石蜡包埋肝标本上进行原位杂交检测CMV-DNA。在大多数情况下，还对新鲜的移植后肝标本进行病毒分离。
虽然60%的肝移植供体CMV血清学阳性，但在围手术期获得的标本中很少检测到CMV：仅通过原位杂交在36例中的1例检测到。在移植后第1个月从患病肝移植中获得的21份标本（21例患者）中，均未显示CMV感染的证据。相比之下，在第2个月和第3个月获得的42份标本（42例患者）中，有8例显示出以病毒性胆管炎（4例）或病毒性小叶炎（4例）为主的组织病理学迹象。在这42例患者中有7例（17%）确定存在CMV。
在有肝脏受累临床和实验室体征的肝移植患者中，通过免疫形态学方法和/或病毒分离鉴定CMV，与组织学改变相比，诊断CMV肝炎的阳性预测值和阴性预测值分别为0.86和1.0，以及1.0和1.0。通过使用免疫组织病理学技术，可以在CMV肝炎患者中早期启动抗病毒治疗。
