Clinical Value of Surveillance Biopsies in Pediatric Liver Transplantation

Abstract

Although pediatric liver transplantation (LT) results in excellent long-term outcomes, a high incidence of early acute cellular rejection and late graft fibrosis persists. Routine measurement of allograft enzymes may not reliably detect rejection episodes, identify candidates for immunosuppression minimization, or indicate allograft fibrosis. Surveillance biopsies (SBs) can provide valuable information in this regard, but their role in pediatric LT is not fully established. A retrospective cohort of 236 pediatric LT recipients from a high-volume center was studied to characterize the risks and benefits of SB versus for-cause biopsies (FCBs). The study population was 47.1% male and 54.7% Hispanic, and 31% received living donor grafts. Our data suggest that patients in the SB group had better transplant outcomes (rejection-free, graft, and patient survival) compared with patients who had FCBs or who never underwent biopsy. Among 817 biopsies obtained from 236 patients, 150 (18.4%) were SBs. Only 6 patients had a biopsy-related complication, and none were observed in the SB subset. Graft biochemical blood tests did not accurately predict rejection severity on biopsy, with aspartate aminotransferase area under the receiver operating characteristic curve (AUROC) 0.66, alanine aminotransferase AUROC 0.65 (very poor predictions), and gammaglutamyltransferase AUROC 0.58 (no prediction). SBs identified subclinical rejection in 18.6% of biopsies, whereas 63.3% of SBs had evidence of fibrosis. SBs prompted changes in immunosuppression including dose reduction. Our experience suggests that SB in pediatric LT is safe, offers valuable information about subclinical rejection episodes, and can guide management of immunosuppression, including minimization. Improved outcomes with SB were likely multifactorial, potentially relating to a more favorable early posttransplant course and possible effect of management optimization through SB. Further multicenter studies are needed to examine the role of SBs on long-term outcomes in pediatric LT.

Surveillance Biopsies in Pediatric Liver Transplantation: Is the Juice Worth the Squeeze?

“…Ultimately, the report by Rocque et al (5) adds to the crescendo of data continuing to shed light on the occurrence and management of late graft changes. A livEr transplantation, vol.…”

“…Ultimately, the report by Rocque et al ( 5 ) adds to the crescendo of data continuing to shed light on the occurrence and management of late graft changes. A current literature review, however, shows the important contributions of HLA matching and the production of donor‐specific antibodies, neither of which were reported in this study.…”

“…Notably, these histological changes can be clinically silent, ( 4 ) so their detection often requires a commitment of the transplant team to perform surveillance biopsies (SBs), which must be weighed against the cost and potential risks of the procedure without knowing whether SBs ultimately benefit long‐term outcomes. In this issue of Liver Transplantation , Rocque et al ( 5 ) attempt to bring some clarity to this historically ambiguous subject.…”

Adaptation of Imaging Mass Cytometry to Explore the Single Cell Alloimmune Landscape of Liver Transplant Rejection

“…Despite a long-standing recognition that there is poor correlation between elevation of liver blood tests and active rejection, monitoring these values continues to be the main strategy a clinician can use to suspect a rejection episode after ruling out other causes ( 6 , 7 ). Indeed, our own recent review of >800 post-LT biopsies, including >150 surveillance biopsies, showed weak correlation between liver biochemistries and rejection ( 8 ). Prior studies have attempted to identify new biomarkers of rejection in clinical LT, but these have not been able to deeply examine alloimmunity at the single cell level within the liver, due to technical limitations in working with tiny core biopsy samples [reviewed in ( 9 )].…”

Are protocol graft biopsies after pediatric liver transplantation useful? Experience in a single center over 20 years

“…[5][6][7] The incidence of graft fibrosis varied considerably, from 30% to more than 90% of patients in some reports. [5][6][7][8][9][10][11][12][13][14] Inflammation and signs of rejection were also frequently reported features. 5,7,[9][10][11][12][13][14] Most of the patients included in these studies were clinically well and had normal liver biochemistry, which could be an argument in favor of performing PLB to detect occult graft injury.…”