. Author manuscript; available in PMC: 2013 Aug 1.

Published in final edited form as: Nat Rev Gastroenterol Hepatol. 2012 Dec 11;10(2):79–89. doi: 10.1038/nrgastro.2012.225

Table 1.

Randomized clinical trials on pharmacological strategies to minimize hepatic IRI in deceased donor liver transplantation

Study	Pharmacological intervention	Mechanism	Patients (placebo/study drug)	Findings for intervention group
Klein et al. (1999)¹⁰⁵	Epoprostenol (iv bolus of 500 μg) before cross clamp	Improvement of sinusoidal perfusion	53/53	Decreased levels of AST and ALT after surgery
Bogetti et al. (2005)¹¹⁰	Thymoglobulin (1.5 mg/kg) during anhepatic phase and 2 doses after surgery	Suppression of inflammatory immune response	11/11	Decreased levels of AST and bilirubin after surgery, improved initial allograft function
Khan et al. (2005)¹²⁴	NAC iv and portal flush of donor liver	Antioxidant hepatoprotection	9/9	No protective effects on liver IRI or on acute cellular rejection
HEGPOL trial¹²⁶	HEGPOL (glycin) in multiple iv doses in liver transplant recipients	Decreased Kupffer cell activation	65/65	Trial completed but not yet published
Baskin-Bey et al. (2007)¹¹¹	IDN-6556 in organ storage solution and recipient	Inhibition of pan-caspase (apoptosis)	23 (placebo)/23/27/26^*	Decreased apoptosis and decreased liver injury for the group with study drug in preservation and flush solution
Lang et al. (2007)¹¹⁸	Inhaled NO (80 ppm) during liver transplantation	Downregulation of endogenous NO production	10/10	Decreased levels of AST after surgery, decreased hepatocyte apoptosis, improved rate of liver function
Kotsch et al. (2008)¹⁰⁶	Donor treatment with iv methylprednisolone before recovery	Suppression of inflammatory immune response	50/50	Decreased levels of AST, decreased serum levels of cytokine, improved levels of biomarkers after surgery and decreased incidence of acute rejection
Hilmi et al. (2010)¹²⁵	NAC (12 doses) in liver transplant patients	Antioxidant/GSH-mediated hepatoprotection	50/50	No effects on liver/renal injury, no increase in GSH levels in some patients (possibly because of inadequate dose/duration of NAC)
Kristo et al. (2011)¹²³	Intraoperative intraportal organ perfusion with tacrolimus	Suppression of inflammatory immune response	13/13	No effects on early graft function despite decreased immune response and inflammation on a genome-wide basis
Busuttil et al. (2011)¹¹³	Preimplantation allograft and recipient treatment with rPSGL-Ig	Blockade of leukocyte adhesion cascade	24/23	Decreased levels of AST after surgery in recipients with high DRI, and improved biomarkers (IL-10, CXCL10)

The first group received placebo through the process, the second group received IDN-6556 during cold storage and flush and placebo was given to the recipient, the third group received a solution of 5 μg/ml IDN-6556 during cold storage and flush and then 0.5 mg/kg of IDN-6556 every 6 h for 24 h after the surgery, the fourth group received a solution of 15 μg/ml IDN-6556 during cold storage and flush and then 0.5 mg/kg of IDN-6556 every 6 h for 48 h after the surgery.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; DRI, donor risk index; GSH, glutathione; IP-10, inducible protein 10; IRI, ischaemia–reperfusion injury; iv, intravenous; NAC, N-acetyl cysteine; NO, nitric oxide; rPSGL-Ig, recombinant P-selectin glycoprotein ligand IgG.