Key Histologic Features Distinguish Cytomegalovirus Hepatitis from Acute T-cell Mediated Rejection in Liver Allografts

Cytomegalovirus (CMV) is a major opportunistic infection after liver transplantation and often mimics acute T cell-mediated rejection (TCMR), creating management uncertainty. We conducted a retrospective study to identify practical histologic features that distinguish CMV hepatitis from TCMR in routine practice. We included 10 recipients with CMV hepatitis and 5 with moderate to severe TCMR. Portal inflammation, bile duct injury, venous endotheliitis, lobular microgranulomas, neutrophilic microabscesses, and CMV inclusions were assessed. Clinical data were abstracted from the medical record. CMV hepatitis was diagnosed earlier after transplantation than TCMR (272 {+/-} 211 vs 549 {+/-} 522 days). Slides were available for 7 CMV and all 5 TCMR biopsies. Histologic findings and their diagnostic performance estimates were as follows: microgranulomas present in 7/7 CMV and 0/5 TCMR biopsies, sensitivity 100% and specificity 100%; bile duct injury minimal to absent in 6/7 CMV and 0/5 TCMR biopsies, sensitivity 86% and specificity 100%; neutrophilic microabscesses in 3/7 CMV and 0/5 TCMR biopsies, sensitivity 42.9% and specificity 100%. Antiviral therapy was administered in 9/10 CMV patients (90%); recurrent CMV viremia occurred in 4/10 (40%) and late chronic rejection in 2/10 (20%), while no CMV viremia occurred in the TCMR group. In routine practice, a pattern of portal lymphohistiocytic inflammation with lobular microgranulomas and minimal to absent bile duct injury supports CMV hepatitis over TCMR and can guide targeted search for inclusions and CMV PCR, which may help avoid unnecessary intensification of immunosuppression and enable timely antiviral therapy.