Detecting Donor-Derived DNA by Real-Time PCR in Recipients Suspected of Graft-Versus-Host-Diseases After Liver Transplantation: A Case Series and Literature Review

BACKGROUND: Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but fatal complication. GVHD diagnosis is usually based on clinical symptoms and pathologic confirmation. However, it is often misdiagnosed due to its non-specific symptoms. Here, we report the detection of donor-cell chimerism using peripheral blood (PB) donor-derived deoxyribonucleic acid (ddDNA) for 3 cases with suspected GVHD after LT (GVHD-LT) through real-time quantitative polymerase chain reaction (qPCR) assay targeting 39 insertions and/or deletions of chromosomes. MATERIAL/METHODS: The qPCR assay for detecting donor-cell chimerism was performed for 3 post-LT patients with suspected GVHD using KMRtype(®) and KMRtrack(®) assays (GenDx, Netherlands). The mean recipient/donor-cell fraction of informative markers unique to each recipient or donor was calculated. RESULTS: In Case 1, who received living donor LT (LDLT) from his daughter, initial sign was diarrhea at post-operative day (POD) #23. Case 2 received unrelated deceased donor LT and initial sign was cytopenia at POD #29. Case 3 received LDLT from her son and GVHD associated cytopenia was developed at POD #80. Average PB ddDNA fractions in post-transplant samples of cases 1, 2, and 3 were 39.68%, 78.38%, and 4.76%, respectively. Despite an active treatment including steroid and tumor necrosis factor-α inhibitor, 2 patients (cases 1 and 2) died due to multiple organ failures. CONCLUSIONS: Early detection of donor-cell chimerism may help halt fatal progression of GVHD-LT. A qPCR test targeting INDEL of chromosomes would be a helpful procedure for timely diagnosis of GVHD.