Antibody Drug Treatment for Steroid-Resistant Rejection After Pediatric Living Donor Liver Transplantation: A Single-Center Experience

摘要

Abstract Background Antibody drugs have been used to treat steroid-resistant rejection (SRR) after liver transplantation. Although anti-thymocyte globulin has been used for SRR after liver transplantation in place of muromonab-CD3 since 2011 in Japan, the effectiveness of anti-thymocyte globulin after pediatric living-donor liver transplantation (LDLT) has not yet been reported. The aim of this study was to evaluate the effectiveness of antibody drug treatment for SRR after pediatric LDLT in our single center. Methods Between May 2001 and December 2013, 220 pediatric LDLTs were performed. Initial immunosuppression after LDLT included tacrolimus and methylprednisolone therapy. Acute rejection was diagnosed by use of a liver biopsy and the administration of steroid pulse treatment, and SRR was defined as acute rejection refractory to the steroid pulse treatment. Results Acute rejection and SRR occurred in 74 (33.6%) and 16 patients (7.3%), respectively. The graft survival rates of non-SRR and SRR were 92.4% and 87.5%, respectively ( P ?= .464). The median concentration of alanine aminotransferase before and after the administration of antibody drug was 193.5 mU/mL (range, 8–508) and 78 mU/mL (range, 9–655), respectively ( P ?= .012). The median rejection activity index before and after the administration of antibody drugs was 5 (range, 2–9) and 1 (range, 0–9), respectively ( P ?= .004). After antibody drug treatment, 12 patients had cytomegalovirus infections, 2 patients had Epstein-Barr virus infections, 3 patients had respiratory infections, and 1 patient had encephalitis. The cause of death in 1 patient with SRR was recurrence of infant fulminant hepatic failure. Conclusions Antibody drug treatment for SRR after pediatric LDLT is safe and effective. Highlights ? The effectiveness of ATG after pediatric LDLT has not yet been reported. ? The median concentration of ALT significantly declined from 193.5 (range, 8–508) to 78 (range, 9–655) mU/mL in the antibody drug group after treatment ( P ?= .012), and the median RAI significantly declined from 5 (range, 2–9) to 1 (range, 0–9) ( P ?= .004). ? After antibody drug treatment, 12 patients had CMV infections, 2 patients had EBV infections, 3 patients had respiratory infections, and 1 patient had encephalitis. The cause of death in 1 patient with SRR was recurrence of infant fulminant hepatic failure. ? Antibody drug treatment for SRR after pediatric LDLT is safe and effective.