Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation

Abstract

Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child–Turcotte–Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients’ median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients. However, the occurrence of HCV reactivation and CMV infection in LT patients should be monitored after rATG treatment in these patients.

Significant association between FOXP3 gene polymorphism and steroid‐resistant acute rejection in living donor liver transplantation

“…The median dose of total intravenous MP used was 937.5 mg (range, 500‐3,525 mg), and the median duration of treatment was 5 days (range, 2‐8 days). Consistent with the incidence of SRAR in previous reports, 5 out of 16 (31.25%) patients suffering from ACR were diagnosed as having SRAR. One of these patients was treated with OKT3, 3 with rATG, and 1 without OKT3/rATG.…”

“…However, current methods to predict the risk of SRAR still display insufficient specificity and sensitivity, making implementation of targeted therapies difficult. Although treatment with rATG is an effective therapeutic option for SRAR with acceptable complications in LT recipients, emerging surrogate markers of SRAR would further improve the safety, efficacy, and outcomes of this specific remedy.…”

“…(41) However, current methods to predict the risk of SRAR still display insufficient specificity and sensitivity, making implementation of targeted therapies difficult. Although treatment with rATG is an effective therapeutic option for SRAR with acceptable complications in LT recipients, (36,42,43) emerging surrogate markers of SRAR would further improve the safety, efficacy, and outcomes of this specific remedy. The effects of steroids depend on their capacity to bind to the glucocorticoid receptor (GCR) and form a steroid-GCR complex, which acts as a transcription factor enhancing the expression of numerous genes.…”

Acute and Chronic Rejection After Liver Transplantation: What A Clinician Needs to Know

“…50,51 Various treatments used for steroid resistant rejection include conversion to Tacrolimus, Sirolimus, Mycophenolate, anti thymocyte globulin, anti-CD3 monoclonal antibody (OKT3) and anti interleukin 2 agents. [51][52][53][54][55][56][57][58][59]…”

Treatment of steroid-resistant acute rejection after living donor liver transplantation

“…Two patients died from sepsis/multi-organ failure. Lee et al [19] reported that 9 of 11 SRAR patients positive efficiency of ATG treatment. They reported one patient with HCV reactivation and one patient with fungemia.…”