From the Department of Pathology and Laboratory Medicine, Massachusetts General Hospital, Boston (Shih, Masia, Misdraji).
The Department of Pathology, David Geffen School of Medicine at the University of California, Los Angeles (Naini).
Arch Pathol Lab Med. 2023 Jun 1;147(6):655-664. doi: 10.5858/arpa.2021-0551-OA.
CONTEXT.—: Cytomegalovirus (CMV) hepatitis in allograft livers is an important infectious complication, with histology that historically has been described to overlap with that of acute cellular rejection (ACR), a diagnosis that compels a different treatment regimen.
OBJECTIVE.—: To update the clinicopathologic features of CMV hepatitis and explore its clinical and histologic relationship with ACR.
DESIGN.—: A retrospective analysis of 26 patients with a diagnosis of CMV hepatitis across 4 institutions was performed, including clinical, histologic, and immunohistochemical features.
RESULTS.—: Patients were predominantly CMV donor positive/recipient negative (D+/R-; n = 9 of 15) and received a diagnosis of CMV hepatitis at a mean age of 52 years (SD, 17 years), at a mean interval of 184 days (SD, 165 days) from transplantation. Mean CMV viral load at diagnosis was 241 000 IU/mL (SD, 516 000 IU/mL), and liver biochemical enzymes were elevated (mean alanine aminotransferase, 212 U/L [SD, 180 U/L]; mean aspartate aminotransferase, 188 U/L [SD, 151 U/L]; mean alkaline phosphatase, 222 U/L [SD, 153 U/L]). Ten cases did not show histologic features of ACR, and 16 cases demonstrated features of ACR (including marked bile duct injury and endotheliitis). Viral cytopathic change was found in all cases. All patients were treated with a combination of antiviral therapy and CMV intravenous immunoglobulin, with near resolution of biochemical enzymes in all patients with undetectable serum CMV viral titers.
CONCLUSIONS.—: CMV hepatitis and ACR are complex processes with interlinking mechanisms that are important to distinguish. A subset of transplantation patients with CMV hepatitis show histologic changes that mimic ACR but were treated successfully with antiviral therapy alone.
移植肝中的巨细胞病毒(CMV)肝炎是一种重要的感染性并发症,其组织学特征在历史上与急性细胞排斥反应(ACR)重叠,后者的诊断需要不同的治疗方案。
更新 CMV 肝炎的临床病理特征,并探讨其与 ACR 的临床和组织学关系。
对 4 家机构的 26 例 CMV 肝炎患者进行回顾性分析,包括临床、组织学和免疫组织化学特征。
患者主要为 CMV 供体阳性/受体阴性(D+/R-;15 例中有 9 例),平均年龄为 52 岁(标准差,17 岁),平均在移植后 184 天(标准差,165 天)时被诊断为 CMV 肝炎。诊断时的平均 CMV 病毒载量为 241000 IU/mL(标准差,516000 IU/mL),肝生化酶升高(平均丙氨酸氨基转移酶,212 U/L[标准差,180 U/L];平均天冬氨酸氨基转移酶,188 U/L[标准差,151 U/L];平均碱性磷酸酶,222 U/L[标准差,153 U/L])。10 例未显示 ACR 的组织学特征,16 例显示 ACR 的特征(包括明显的胆管损伤和内皮炎)。所有病例均发现病毒细胞病变。所有患者均接受抗病毒治疗联合 CMV 静脉免疫球蛋白治疗,所有患者的生化酶均接近正常,血清 CMV 病毒滴度均无法检测。
CMV 肝炎和 ACR 是相互关联的复杂过程,需要加以区分。一组 CMV 肝炎移植患者的组织学变化类似于 ACR,但单独接受抗病毒治疗即可成功治疗。