*Purpose: The mortality of Acute Graft vs. Host Disease (aGvHD) after Liver Transplantation (LT) can be greater than 85% due to delays in diagnosis and severity of complications. We retrospectively conducted a large cohort study to explore the risk factors of aGvHD and the role of Donor Lymphocyte Chimerism (D%) in supporting accurate diagnosis and effective control for this disease.

*Methods: This study included 1444 recipients (pts) with LT since 2007. A subgroup of 144 pts suspected to have aGvHD were tested for D% using peripheral blood (PB), CD3⁺T (T), CD8⁺T, and NK cells by short tandem repeat assay. Donor/recipient factors for age, gender, race, and HLA matching were evaluated in 362 LT pairs with HLA typing and D% data. D% at initial and peak stage testing, days of aGvHD resolution, and aGvHD related mortality were analyzed. Clinical suspicions with CD8⁺T D% >25% were initially treated with methylprednisolone and/or reduced immunosuppression. Thymoglobulin was added to cases with no improvement after initial therapy.

*Results: Of 144 pts, 29 with CD8⁺T D% >5 were grouped into C0 (n=10, D%≤10, data not shown) as possible, C1 (n=9) as mild/severe, and C2 (n=4)/3 (n=5) as severe aGvHD. Donor homozygosity at HLA-A and C loci, but not other donor/recipient factors (data not shown), was significantly higher in C0-3 compared to 333 healthy controls (Table 1a). Pts in C2/C3 had obvious increase of median CD8⁺T D% than those in C1 at initial (p<0.001) and peak (p<0.001) phases, which was concurrently associated with high D% of NK and/or T cells. Individuals with severe aGvHD were either associated with aGvHD related mortality (C3) or had concomitant longer duration of treatment (C2) compared to pts in C1 (p<0.05) (Table 1b). Five out of 18 (C1-3) pts expired given 28% aGvHD related mortality. D% in PB was uninformative for aGvHD diagnosis (data not shown).

*Conclusions: Donor homozygosity is a high risk factor for aGvHD. D% of CD8⁺T cell along with NK and/or T cells are key determinants of aGvHD severity. Our successful reduction of aGvHD related mortality demonstrates that accurate and timely diagnosis of this disease by D% before the donor immune system has fully engrafted is critical for recovering from the damages of aGvHD after LT.

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