Cytomegalovirus Hepatitis in Allograft Livers May Show Histologic Features of Acute Cellular Rejection

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.

MeSH terms

  • Allografts
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus
  • Cytomegalovirus Infections* / diagnosis
  • Cytomegalovirus Infections* / drug therapy
  • Graft Rejection / diagnosis
  • Hepatitis* / complications
  • Hepatitis* / diagnosis
  • Hepatitis* / drug therapy
  • Humans
  • Liver Transplantation* / adverse effects
  • Middle Aged
  • Retrospective Studies


  • Antiviral Agents