Tissue biopsy monitoring of operational tolerance in liver allograft recipients

Abstract

Operationally tolerant liver allograft recipients can be successfully managed with very low, and sometimes no immunosuppression, but challenges exist. Newer approaches to tissue pathology and tissue, serum, and cross-platform analytics are needed to predict successful weaning and to monitor for subclinical events.

Is Minimal, [Almost] Steroid-Free Immunosuppression a Safe Approach in Adult Liver Transplantation? Long-term Outcome of a Prospective, Double Blind, Placebo-Controlled, Randomized, Investigator-Driven Study

“…It is indeed well known that normal liver function tests do not necessarily correlate with normal biopsy and viceversa. [9][10][11]32,33 These observations are also valid for other transplanted organs. 34,35 The relationship between CNI or steroids and posttransplant renal insufficiency (in 20%), 16 metabolic syndrome (in 40%) with its components diabetes, hypertension, dyslipidemia, obesity, and cardiovascular disease has been clearly identified.…”

“…Moreover, plasma cell hepatitis, de novo "auto-immune" hepatitis, and fibrosis, all possibly related to immune allograft "dysfunction," are more frequently diagnosed. 10,33 Their real meaning can only been determined by pathologic monitoring. These elements point toward the necessity to set up "biopsy clinics" to progress in induction, maintenance, and tolerance induction projects.…”

“…29 Our study underlines the importance of routine liver biopsies as part of long-term follow-up of liver recipients. 11,12,32,33,47 Integration of clinical, biochemical, and pathologic information is necessary to fine-tune long-term IS treatment. Such an approach may be valuable to reduce the number of liver recipients going toward renal replacement therapy; to reduce the loss of functioning grafts due to lethal cardiovascular, infectious, and oncologic events; and to facilitate IS withdrawal in tolerance induction protocols.…”

Impact of IgG3 Subclass and C1q-Fixing Donor-Specific HLA Alloantibodies on Rejection and Survival in Liver Transplantation

“…Moreover, antibody-mediated rejection (AMR) is now recognized as a cause of allograft loss in all solid organ transplants despite significant differences in incidence and outcome (6)(7)(8)(9)(10)(11). Historically, it has been recognized that the liver is relatively resistant to the pathologic effects of DSA compared to other solid organs (12)(13)(14)(15). However, with improved shortand long-term outcome in liver transplant recipients there has been a resurgence of interest in understanding the role of DSA in liver transplantation (16)(17)(18)(19)(20)(21)(22)(23)(24).…”

Tolerancia operacional en un receptor pediátrico de trasplante hepático. Caso clínico

“…Si bien la infección por VEB puede modular la respuesta inmune y permitir una transitoria disminución de la inmunosupresión, la persistente normalidad clínico-humoral con histología alejada sin hallazgos patológicos luego de la negativización de cargas virales orienta a fenómenos de tolerancia complejos. 14 Desafortunadamente, no disponemos de análisis de citoquinas, células dendríticas, T reguladoras ni polimorfismo de genes.…”