Lautenschlager I, Halme L, Höckerstedt K, Krogerus L, Taskinen E
Department of Virology, Helsinki University Hospital and Helsinki Univerity, Helsinki, Finland.
Transpl Infect Dis. 2006 Mar;8(1):21-30. doi: 10.1111/j.1399-3062.2006.00122.x.
The most common organ-specific manifestation of cytomegalovirus (CMV) infection after liver transplantation is hepatitis. Here we retrospectively describe the detailed virological, histological, immunological, and clinical findings associated with CMV infection in 229 consecutive adult liver transplantation patients. CMV infection was diagnosed by pp65 antigenemia. From 439 liver biopsies, CMV antigens were demonstrated by immunohistochemistry and CMV DNA by hybridization. The Banff criteria were used for histology. The expression of various adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], endothelial leukocyte adhesion molecule-1 [ELAM-1]), their ligands (leukocyte function antigen-1 [LFA-1], very late antigen-4 [VLA-4], Sialyl-LewisX-molecule [SLeX]), and lymphoid activation markers (major histocompatibility complex [MHC] Class II, interleukin-2-receptor [IL-2R]) was demonstrated by immunohistochemistry. CMV infection of the transplant occurred in 26 patients (11% of all 229 patients and 17% of the 151 patients with liver biopsy). The incidence was higher among seronegative (26%) than in seropositive recipients (9%), but most cases 18/26 (70%) were reactivations. The CMV pp65 antigenemia levels were usually high in primary infections (893+/-1069, range 50-3000 pp65+cells), but varied widely in reactivations (388+/-740, range 3-3000). The histological Banff score was slightly increased (2.3+/-0.9). Microabscesses, lymphocytic infiltration, Kupffer cell reaction, and parenchymal alterations were common but viral inclusions rare. CMV significantly (P<0.05) increased ICAM-1 and VCAM-1 expression and the number of LFA-1, VLA-4, and Class II-positive lymphocytes in the graft. All CMV infections were successfully treated with antivirals. Intragraft CMV infection had no influence on the long-term outcome, but biliary complications were common. In conclusion, CMV infection of the liver transplant occurred both in primary infection and in reactivation, and also in the cases with low pp65 antigenemia levels. Microabscesses and other histological alterations were common but viral inclusions rare. Increased adhesion molecule expression was associated with lymphocyte infiltration. Successfully treated CMV hepatitis had no influence on the long-term clinical outcome.
肝移植后巨细胞病毒（CMV）感染最常见的器官特异性表现是肝炎。在此，我们回顾性描述了229例连续成年肝移植患者中与CMV感染相关的详细病毒学、组织学、免疫学和临床发现。通过pp65抗原血症诊断CMV感染。在439次肝活检中，通过免疫组织化学检测CMV抗原，通过杂交检测CMV DNA。组织学采用班夫标准。通过免疫组织化学检测各种黏附分子（细胞间黏附分子-1[ICAM-1]、血管细胞黏附分子-1[VCAM-1]、内皮白细胞黏附分子-1[ELAM-1]）、它们的配体（白细胞功能抗原-1[LFA-1]、极迟抗原-4[VLA-4]、唾液酸化路易斯X分子[SLeX]）以及淋巴细胞活化标志物（主要组织相容性复合体[MHC]II类、白细胞介素-2受体[IL-2R]）的表达。26例患者发生移植肝的CMV感染（占所有229例患者的11%，151例行肝活检患者的17%）。血清阴性受者中的发生率（26%）高于血清阳性受者（9%），但大多数病例18/26（70%）为复发感染。原发性感染时CMV pp65抗原血症水平通常较高（893±1069，范围50 - 3000个pp65 +细胞），但复发感染时差异较大（388±740，范围3 - 3000）。组织学班夫评分略有升高（2.3±0.9）。微脓肿、淋巴细胞浸润、库普弗细胞反应和实质改变常见，但病毒包涵体少见。CMV显著（P<0.05）增加了移植物中ICAM-1和VCAM-1的表达以及LFA-1、VLA-4和II类阳性淋巴细胞的数量。所有CMV感染均用抗病毒药物成功治疗。移植物内CMV感染对长期预后无影响，但胆道并发症常见。总之，肝移植的CMV感染在原发性感染和复发感染中均有发生，在pp65抗原血症水平较低的病例中也有发生。微脓肿和其他组织学改变常见，但病毒包涵体少见。黏附分子表达增加与淋巴细胞浸润相关。成功治疗的CMV肝炎对长期临床预后无影响。
