Background: Based on pre-2000 data, acute rejection (AR) has long been considered clinically less significant in liver transplant (LT) vs. other organ recipients (Charlton et al, Liver Transpl Surg 1999). However, prospective data from the more recent era may improve understanding of the impact of AR in different LT populations.

Aim: We explored the relationship between AR and patient and graft survival in prospective observational cohorts of living donor (LDLT) and deceased donor (DDLT) recipients.

Methods: We analyzed data from 136 DDLT recipients transplanted between 2005 and 2009 and 503 LDLT recipients transplanted between 2004 and 2014 from 12 North American centers in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Cox regression was used to examine the relationship between occurrence of first biopsy-proven AR episode and both patient survival and graft survival (defined as recipient death or retransplant). Patient characteristics (e.g. gender, race/ethnicity, liver disease diagnosis, donor/recipient age, BMI), baseline transplant variables (e.g. cold ischemia time, related vs. unrelated LDLT vs. DDLT, MELD, recipient on ventilator/dialysis) and AR as a time-dependent variable were tested as potential survival predictors.

Results: 259 AR episodes occurred a median of 49 days post-LT in 169 (26%) recipients. The probability of AR was significantly lower in biologically related LDLT compared to DDLT (hazard ratio (HR) = 0.52, p=0.001) and unrelated LDLT (HR=0.60, p=0.009). Factors significantly associated with mortality and graft failure were biopsy-proven AR, older recipient and donor age at LT, and recipient on ventilator at LT. Following a first biopsy-proven rejection episode, the risk of patient death and graft failure increased two-fold (HR=2.14, p=0.002; and HR=2.06, p=0.0004, respectively); results were similar in related and unrelated LDLT and DDLT.

Conclusion: Contrary to historical data, our results show that AR in both DDLT and LDLT is clinically significant in the recent era and independently associated with a two-fold increased risk of death and graft failure. Prospective studies investigating novel strategies to minimize the impact of AR and associated complications are warranted.

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