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

Caroline C. Jadlowiec, Paige E. Morgan, Avinash K. Nehra, Matthew A. Hathcock, Walter K Kremers, Julie K. Heimbach, Russell H. Wiesner, Timucin Taner

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

T cell–mediated rejection (TCMR) is common after liver transplantation (LT), and it is often thought to have a minimum impact on outcomes. Because alloimmune response changes over time, we investigated the role of the timing of TCMR on patient and allograft survival and examined the risk factors for early and late TCMR. We reviewed protocol liver biopsies for 787 consecutive LT recipients with an 8.6-year follow-up. The incidence of early TCMR (≤6 weeks after LT) was 33.5% with nonalcoholic steatohepatitis patients having the lowest incidence. Younger recipient age (P < 0.01), number of human leukocyte antigen mismatches (P < 0.01), and use of deceased donor allografts (P = 0.01) were associated with increased risk of early TCMR, which had no impact on allograft (hazard ratio [HR], 1.02; 95% CI, 0.79-1.32; P = 0.89) or overall survival (HR, 1.03; 95% CI, 0.78-1.34; P = 0.86). Late TCMR (>6 weeks after LT) was less common (17.7%) and was associated with different risk factors. The majority of late TCMR (56.2%) episodes had no antecedent early TCMR, although moderate-to-severe early TCMR (HR, 2.85; 95% CI, 1.55-5.23; P < 0.01) and steroid resistance (HR, 3.62; 95% CI, 1.87-6.99; P < 0.01) were associated with late TCMR. Late TCMR increased risk of mortality (HR, 1.89; 95% CI, 1.35-2.65; P = 0.001) and graft loss (HR, 1.71; 95% CI, 1.23-2.37; P = 0.001). Thus, these data suggest that the timing and histologic grade of TCMR determine its impact on patient and allograft survival. Early mild TCMR episodes after LT do not adversely impact patient or allograft survival provided that they are adequately treated. The occurrence of late TCMR carries deleterious effects with increased longterm risk of graft loss and decreased survival. Patients with moderate-to-severe early TCMR are at an increased risk for late TCMR and warrant closer clinical follow-up.

Original languageEnglish (US)
Pages (from-to)425-435
Number of pages11
JournalLiver Transplantation
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2019

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Liver Transplantation
Allografts
Liver
Transplants
Incidence
Steroids
Biopsy
Survival
Mortality

ASJC Scopus subject areas

  • Surgery
  • Hepatology
  • Transplantation

Cite this

Not All Cellular Rejections Are the Same : Differences in Early and Late Hepatic Allograft Rejection. / Jadlowiec, Caroline C.; Morgan, Paige E.; Nehra, Avinash K.; Hathcock, Matthew A.; Kremers, Walter K; Heimbach, Julie K.; Wiesner, Russell H.; Taner, Timucin.

In: Liver Transplantation, Vol. 25, No. 3, 01.03.2019, p. 425-435.

Research output: Contribution to journalReview article

Jadlowiec, CC, Morgan, PE, Nehra, AK, Hathcock, MA, Kremers, WK, Heimbach, JK, Wiesner, RH & Taner, T 2019, 'Not All Cellular Rejections Are the Same: Differences in Early and Late Hepatic Allograft Rejection', Liver Transplantation, vol. 25, no. 3, pp. 425-435. https://doi.org/10.1002/lt.25411
Jadlowiec, Caroline C. ; Morgan, Paige E. ; Nehra, Avinash K. ; Hathcock, Matthew A. ; Kremers, Walter K ; Heimbach, Julie K. ; Wiesner, Russell H. ; Taner, Timucin. / Not All Cellular Rejections Are the Same : Differences in Early and Late Hepatic Allograft Rejection. In: Liver Transplantation. 2019 ; Vol. 25, No. 3. pp. 425-435.
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AU - Morgan, Paige E.

AU - Nehra, Avinash K.

AU - Hathcock, Matthew A.

AU - Kremers, Walter K

AU - Heimbach, Julie K.

AU - Wiesner, Russell H.

AU - Taner, Timucin

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N2 - T cell–mediated rejection (TCMR) is common after liver transplantation (LT), and it is often thought to have a minimum impact on outcomes. Because alloimmune response changes over time, we investigated the role of the timing of TCMR on patient and allograft survival and examined the risk factors for early and late TCMR. We reviewed protocol liver biopsies for 787 consecutive LT recipients with an 8.6-year follow-up. The incidence of early TCMR (≤6 weeks after LT) was 33.5% with nonalcoholic steatohepatitis patients having the lowest incidence. Younger recipient age (P < 0.01), number of human leukocyte antigen mismatches (P < 0.01), and use of deceased donor allografts (P = 0.01) were associated with increased risk of early TCMR, which had no impact on allograft (hazard ratio [HR], 1.02; 95% CI, 0.79-1.32; P = 0.89) or overall survival (HR, 1.03; 95% CI, 0.78-1.34; P = 0.86). Late TCMR (>6 weeks after LT) was less common (17.7%) and was associated with different risk factors. The majority of late TCMR (56.2%) episodes had no antecedent early TCMR, although moderate-to-severe early TCMR (HR, 2.85; 95% CI, 1.55-5.23; P < 0.01) and steroid resistance (HR, 3.62; 95% CI, 1.87-6.99; P < 0.01) were associated with late TCMR. Late TCMR increased risk of mortality (HR, 1.89; 95% CI, 1.35-2.65; P = 0.001) and graft loss (HR, 1.71; 95% CI, 1.23-2.37; P = 0.001). Thus, these data suggest that the timing and histologic grade of TCMR determine its impact on patient and allograft survival. Early mild TCMR episodes after LT do not adversely impact patient or allograft survival provided that they are adequately treated. The occurrence of late TCMR carries deleterious effects with increased longterm risk of graft loss and decreased survival. Patients with moderate-to-severe early TCMR are at an increased risk for late TCMR and warrant closer clinical follow-up.

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