Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection

Area of Science:

• Transplantation immunology
• Graft rejection mechanisms
• Graft survival and patient outcomes

Background:

• T cell-mediated rejection (TCMR) is a common complication following liver transplantation (LT).
• The impact of TCMR on long-term patient and allograft survival is often underestimated.
• Alloimmune responses evolve post-transplantation, necessitating an understanding of temporal rejection patterns.

Purpose of the Study:

• To investigate the influence of TCMR timing on patient and allograft survival after LT.
• To identify risk factors associated with early (≤6 weeks) and late (>6 weeks) TCMR.
• To correlate TCMR timing and severity with clinical outcomes.

Main Methods:

• Retrospective review of protocol liver biopsies from 787 consecutive LT recipients.
• Analysis of patient and allograft survival data over an 8.6-year follow-up period.
• Statistical analysis to determine risk factors and hazard ratios for early and late TCMR.

Main Results:

• Early TCMR (33.5% incidence) was associated with younger recipient age, more HLA mismatches, and deceased donor allografts, but did not impact survival.
• Late TCMR (17.7% incidence) was linked to antecedent moderate-to-severe early TCMR and steroid resistance.
• Late TCMR significantly increased the risk of mortality (HR, 1.89) and graft loss (HR, 1.71).

Conclusions:

• The timing and histologic grade of TCMR are critical determinants of post-liver transplant outcomes.
• Early, mild TCMR, when adequately treated, does not adversely affect survival.
• Late TCMR poses a significant long-term threat to graft survival and patient mortality, requiring vigilant monitoring.