The appropriate time point for starting immunosuppressive treatment with calcineurin inhibitors after orthotopic liver transplantation (OLT) has been a subject of debate. The aim of the study was to analyze the effects of anti-thymocyte globulin (ATG) induction therapy on rejection, renal function, infection, tumor rate, and survival. We retrospectively analyzed 391 patients after OLT who had either received calcineurin inhibitors immediately after OLT (n = 129) or after an initial short-term Thymoglobulin induction therapy (n = 262). The 1-year acute rejection rate was 14.5% vs. 31.8% in favor of ATG (P = 0.0008). Rejection grades and the need for treatment also differed significantly (7.3% vs. 23.3%; P = 0.001). Serum creatinine at transplantation was similar in both groups (1.14 mg/dL vs.1.18 mg/dL; P = NS). Postoperative hemofiltration was less frequently seen after induction therapy (P < 0.05). Reduced renal function at 1 year was commonly observed, but serum creatinine (1.26 mg/dL vs. 1.37mg/dL; P = 0.015) and glomerular filtration rate (81 mL/min vs. 75 mL/min; P = 0.02) were far better in the ATG group. Undesired side effects occurred at a similar rate in both groups. Five-year patient survival was also similar in the 2 groups (70.1% and 74.3%; P > 0.05). Short-term ATG induction therapy with delayed administration of calcineurin inhibitors led to a more favorable rejection rate and an improved clinical course in case of a rejection episode. It has beneficial effects on renal function immediately after OLT as well as later, and no additional harmful effects. Liver Transpl 13:1039–1044, 2007. © 2007 AASLD.

Hypothermic oxygenated machine perfusion (HOPE) preconditions liver grafts before transplantation. While beneficial effects on patient outcomes were demonstrated, biomarkers for viability assessment during HOPE are scarce and lack validation. This study aims to validate the predictive potential of perfusate flavin mononucleotide (FMN) during HOPE to enable the implementation of FMN-based assessment into clinical routine and to identify safe organ acceptance thresholds. FMN was measured in perfusate samples of 50 liver grafts at multiple time points. After transplantation, patients were followed up for development of early allograft dysfunction (EAD), transplantation, and 1-year survival. FMN concentrations were significantly higher for grafts that developed EAD at 5 and 60 minutes into HOPE (p = 0.008, p = 0.026). The strongest predictive potential of FMN for EAD was observed at 5 minutes of HOPE with an AUC of 0.744. Similarly, 5-minute FMN was predictive for 1-year mortality (p < 0.001), reaching a remarkable AUC of 0.890. Cutoffs for prediction of EAD (10.6 ng/mL) and early mortality (23.5 ng/mL) were determined and allowed risk stratification of grafts. Particularly, patients receiving low-risk grafts developed EAD in 9% of cases, while all patients survived the first postoperative year. In contrast, high-risk organs developed an incidence of EAD at 62%, accompanied by the necessity of retransplantation in 38% of cases. One-year mortality in the high-risk cohort was 62%. Evaluation of FMN as early as 5 minutes during HOPE allows for risk stratification of liver grafts. Low-risk grafts, according to FMN, display a negligible risk for patients. Yet, high-risk grafts are associated with increased risk for EAD, transplantation, and early mortality and should not be used for transplantation without further assessment.

T-cell depletion is an essential aspect of clinical immunosuppression. The aim of the present study was to compare the efficacy of two dosage regimens in this setting. We retrospectively compared 246 patients (group 1) who received a 10-day antithymocyte globulin (ATG) induction protocol with 226 patients (group 2) who received a 3-day protocol. The 6-month rejection rate was 22.3% in group 1 and 12.7% in group 2 (P = 0.03). The sub-analysis showed a higher rejection rate in patients with cholestatic disease (P = 0.01), who were more numerous in group 1. This resulted in an overall difference between the groups. Rates of de novo malignancies and recurrent hepatocellular carcinoma were identical. Viral infection rates were 16% and 18%, respectively (P > 0.5). The rates of bacterial and fungal infection were also similar (37% vs. 42%, P > 0.1). However, infection and ATG administration are independent risk factors for survival. A lower rate of fatal infection was observed in group 2 (P = 0.01), while the 10-day ATG regimen had a detrimental effect on patients who had infection (P < 0.0001). Our results strongly support the application of 3-day ATG induction therapy regimen after orthotopic liver transplantation, as it is associated with the same rejection rate as long-term ATG induction therapy, without the negative survival effect of the latter due to lethal infection.