Introduction: Acute rejection (AR) remains a major determinant of morbidity and mortality after ITX. We studied patterns of AR and graft loss to understand potential loci for intervention.

Methods: We reviewed all ITX without concomitant liver graft between 2011 and 2018 at a single-center using a prospectively maintained database. AR, patient and graft survival were outcomes of interest.

Results: We analyzed 72 ITX without liver replacement. Twenty-eight grafts had at least one episode of AR (39%). Majority of AR occurred during first 6 months (57%) post- ITX and remainder occurred sporadically during the entire post-ITX period. Of 35 total episodes of AR among 28 grafts, 13 were mild (37%), 4 moderate, (11%), and 18 (51%) severe AR based on histological grades. Patient survival did not show a difference between ITX with and without AR (p=0.750), though, AR was the most common cause of mortality (n=6, 8%). Censoring death with functioning graft (n=12), AR was the most common cause of graft loss (n=11, 15%). Mild AR tended to develop early (< 12 months) post-ITX. Severe AR was observed evenly during the entire post-ITX period (Figure 1).

There was no graft loss or mortality related to mild or moderate AR. There were 11 graft losses out of 18 episodes of severe AR (graft salvage rate of 39%). Graft enterectomy was performed in 6 patients due to refractory severe AR. Among those, 5 survived and 3 went on to successful re-ITX. Five patients were not candidates for graft enterectomy due to profound sepsis and all died. Early severe AR, occurring < 6 months after ITX, had a poor treatment response (7 severe AR with 6 graft losses). High panel reactive antibody (PRA), positive donor specific anti-HLA antibody (DSA) and cross match appeared related to development of AR. However, there were also 23 episodes of AR in 18 grafts (33%), which occurred despite low PRA, negative DSA and negative cross match; of these 14 were severe AR with 7 graft losses (Figure 2).

Conclusion: Our analysis supports previous reports that severe AR is a major cause for graft loss and mortality in ITX. Presence of PRA, DSA and a positive cross match seem related to risk of developing AR. Of note, patients with no apparent heighted immunological risk factors also develop severe AR with a high frequency of graft loss. Mild to moderate AR has no apparent impact on outcome.