Predictors and Outcomes of Acute Graft-Versus-Host Disease After Liver Transplant

Purpose: Graft-versus-Host Disease (GVHD) is a rare complication of liver transplant (LT) that has an estimated incidence of 0.1%-2% per year and is associated with a short-term mortality of up to 90%. There is limited data on GVHD after LT, and prior reported risk factors include: older age of recipient, close HLA A and B matching, \u3e20-year donor to recipient age diference, hepatocellular carcinoma (HCC), and alcoholic liver disease. Due to the high mortality associated with this diagnosis we aimed to study the predictors and outcomes of acute GVHD. Methods: This is a retrospective review of patients who underwent LT between 2014-2018 at a high volume LT center. Patients diagnosed with acute GVHD were identifed from this cohort. GVHD was diagnosed both on clinical characteristics and biopsies of the skin, GI tract and bone marrow. Short tandem repeats (STR) were tested in the serum and tissue biopsies. Descriptive statistics were utilized to analyze risk factors and outcomes. Results: 480 patients underwent LT during the study period of which 13 (2.7%) were diagnosed with acute GVHD after LT. 69% were male and 77% were Caucasian. The mean donor-recipient age diference was 27.5 years, and 85% had an age gap \u3e20 years between donor and recipient. Median time from transplant to diagnosis of GVHD was 41 days. The most common etiologies of cirrhosis were NASH (54%), alcohol (31%), hepatitis C (23%), and a combination of HCV and alcohol (15%). HCC was present in 31% of the cohort pre-LT. The most common clinical manifestation at presentation of GVHD was rash (77%), and fevers (62 %). Additionally, 23% had diarrhea, 54% had leukopenia, 92% were anemic and 46% had thrombocytopenia at presentation. All patients showed an absolute lymphocyte count of 0.5 or less at the time of diagnosis. 54% and 69% patients shared at least 1 MHC class I and class II allele with the donor, respectively. Median STR rates at diagnosis were 42% bone marrow, 14% skin, 11% gastrointestinal and 2% blood. 7 patients received Thymoglobulin for induction, 5 Simulect and 1 patient received steroid only induction. All patients received IV steroids for treatment for GVHD. 69% were also treated with Etanercept and 39% with photophoresis. Mortality was 62% with median follow-up of 115 days. Median time from diagnosis to death was 33 days. Survival was associated with only skin involvement on presentation and negative donor STR in the blood. Conclusions: This study aids in our understanding of a dismal complication after LT. In this cohort, the majority of patients presented with rash and fevers, the most common etiology of liver disease was NASH, and a donor-recipient age gap \u3e20 years was commonly seen. Despite the high mortality with GVHD, limited skin involvement portends a favorable prognosis compared to all other presentations. Further research is planned to compare this cohort with non-GVHD control group in order to better understand risks factors and predictors for disease