*Purpose: Graft-versus-Host Disease (GVHD) is a rare complication of liver transplant (LT) with an estimated incidence of 0.1-2% per year and a high mortality. There is limited data on GVHD after LT. Due to an increased incidence of GVHD at our center we aimed to examine the predictors and outcomes of acute GVHD, compare the incidence over time based on varying immunosuppression, and to compare to the unaffected post-transplant cohort.

*Methods: This is a retrospective review of patients who underwent LT between 2014-2018 at our center. Patients diagnosed with GVHD were identified and compared to a control population of patients who did not develop GVHD. GVHD was diagnosed by clinical characteristics, tissue biopsies as well as short tandem repeat (STR) testing. Due to the increased incidence of GVHD we adjusted our immunosuppression. From Jan 2014 to Dec 2016 (Era 1) all patients received rabbit antithymoglobulin (rATG). From Jan 2017 to Apr 2018 (Era 2), rATG was used in recipients under age 60 and Basiliximab was used in patients over age 60. From May 2018 to Dec 2018, no antibody-based induction was used.

*Results: 480 patients underwent LT during the study period of which 13 were diagnosed with GVHD after LT. 69% were male and 77% were Caucasian. The mean donor-recipient age difference was 27.5 years, 85% had an age gap> 20 years between donor and recipient. Median time from LT to diagnosis of GVHD was 41 days. The most common etiologies of cirrhosis were NASH (54%), alcohol (31%). HCC was present in 31% of the cohort pre-LT. The most common clinical presentation of GVHD was rash (77%) and fever (62%). 54% and 69% of patients shared at least 1 MHC class I and II allele with the donor, respectively. Median STR rates at diagnosis were 42% bone marrow, 14% skin, 11% gastrointestinal and 2% blood. Comparing the affected to non-affected cohort there were significant differences in recipient age (62.2 vs 57.0:P=0.050), donor-recipient age gap (27.5 vs. 16.6: P=0.020) and percent male donor (85% vs. 57% P=0.048). There were no differences in HLA mismatches (9.2 vs 8.7). There was no effect of change in induction therapy with an incidence of GVHD of 2.72% (Era 1), 3.57% (Era 2) and 1.61% (Era 3) (P=0.789). Mortality was 62%. Median time from diagnosis to death was 33 days. Improved survival was associated with only skin involvement on presentation and negative donor STR in the blood.

*Conclusions: The majority of GVHD patients presented with rash and fevers, had a history of NASH cirrhosis, and a greater donor-recipient age gap than the non-affected cohort. We found that the increased incidence at our center was significantly associated with increasing recipient age and increasing recipient-donor age difference, whereas the induction immunosuppression regimen did not appear to have a causal relationship. Limited skin involvement portends a favorable prognosis in GVHD compared to all other presentations.

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