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.

Figure 1

Study design and overview of patient population.

Figure 2

Protocol for treatment of steroid-resistant rejection in liver recipients. ATG, anti-thymocyte globulin; TAC, tacrolimus; MMF, mycophenolate mofetil; PL, prednisolone; MP, methylprednisolone; CXR; chest x-ray; CBC, complete blood count; f/u, follow-up; GVHD, graft-versus-host disease; QOD, every other day; q2 h, every 2 hours; PCR, polymerase chain reaction.

Figure 3

Surrogate laboratory markers pre- and post-ATG treatment for SRAR. (A) Total bilirubin, (B) AST, (C) ALT. ^†P-values were calculated by the Wilcoxon signed-rank test to compare changes in laboratory values pre- and post-rATG. ATG, anti-thymocyte globulin; SRAR, steroid-resistant acute rejection; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

Figure 4

Graft survival according to rejection type. SSAR, steroid-sensitive acute rejection; SRAR, steroid-resistant acute rejection.