Am J Transplant. 2018;18:1029. amjtransplant.com © 2017 The American Society of Transplantation | 1029
and the American Society of Transplant Surgeons DOI: 10.1111/ajt.14545
L E T T E R T O T H E E D I T O R
Use of thrombolytic therapy in DCD liver transplantation does not seem to improve outcome
To the Editor:
With great interest we read the article by Bohorquez et al “Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy.”1 The authors compared 100 consecutive donation after circulatory death (DCD) liver transplantations (LT) using a protocol that includes thrombolytic therapy (late DCD group) to a historical DCD group (early DCD group) and a cohort of donation after brain death (DBD) LT. The primary objective of the study was to “present the experience with 100 consecutive DCD LT using a protocol that includes tissue plasminogen activator (tPA) administration.”
While the team at Ochsner Clinic Foundation, New Orleans, de- serves to be congratulated for their excellent results, we do have re- marks about the added value of tPA, and we believe its advantages may have been overstated.
Bohorquez et al justly recalls that Ischemic-type biliary lesions (ITBL) is the most feared and frequent cause of DCD allograft failure. However, they report a low ITBL rate in the late DCD LT. Noticeable is that the fre- quency of ITBL in the early versus late DCD LT does not statistically differ (5% vs. 3%, P = .63), and was extremely low in both groups. This makes it likely a result of other improvements, such as the reported short cold isch- emia times, also explaining the low peak AST and thus less ITBL,2 rather than a result of the usage of tPA.
Interestingly, a significantly decreased number of retransplanta- tions was shown (1% vs. 18.4%, P = .001). However, only one patient in the early DCD group received a retransplantation for ITBL. Other causes for retransplantation were recurrent hepatitis C and hepatic artery thrombosis. These risks may have been managed by improved expertise in the late DCD group with endoscopic procedures, recip- ient selection (more HCC recipients with lower labMELD- scores), new hepatitis C virus (HCV) therapy or two surgeons performing the transplantation.
Furthermore, Bohorquez et al describe their hypothesis, that tPA prevents microthrombi formation in the peribiliary plexus, is sup- ported by Op den Dries et al3 Instead, in their study they showed that no microthrombi were found in bile ducts of the DCD and DBD livers that developed ITBL. This finding is also supported by Verhoeven et al4 who did not find a relation between the formation of microthrombi and the development of ITBL.
Lastly, although the clinical safety of using thrombolytic agents in DCD liver transplantation has been supported earlier by our study, in which urokinase (uPA) was used, we could not detect any benefit from the use of uPA, with an unchanged high rate of ITBL in our series (18%
in control group vs. 17.5% in urokinase group; P = .68), accompanied
by a longer cold ischemia time (572 minutes in control group vs. 535 minutes in study group; P = .09).5
In summary, we remain critical regarding the suggested effect of thrombolytic agents in reducing ITBL, and think that other factors, like the reported short ischemia times, may be the main explanation for the observed extremely low ITBL rates.
DISCLOSURE
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
Keywords
clinical research/practice, donors and donation: donation after brain death (DBD), donors and donation: donation after circulatory death (DCD), liver transplantation/hepatology, surgical technique, thrombosis and thromboembolism
Lars Pietersen1 Bart van Hoek2 Andries Erik Braat1
1Leiden University Medical Center–Surgery, Leiden, the Netherlands
2Leiden University Medical Center–Gastroenterology and Hepatology, Leiden, the Netherlands
Correspondence Lars Pietersen Email: larspietersen@gmail.com
REFERENCES
1. Bohorquez H, Seal JB, Cohen AJ, et al. Safety and outcomes in 100 consecutive donation after circulatory death liver transplants using a protocol that includes thrombolytic therapy. Am J Transplant.
2017;17(8):2155-2164.
2. den Dulk AC, Sebib Korkmaz K, de Rooij BJ, et al. High peak alanine aminotransferase determines extra risk for nonanastomotic biliary strictures after liver transplantation with circulatory death. Transpl Int.
2015;28:492-501.
3. op den Dries S, Westerkamp AC, Karimian N, et al. Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non- anastomotic biliary strictures. J Hepatol. 2014;60(6):1172-1179 4. Verhoeven CJ, Simon TC, de Jonge J, et al. Liver grafts procured from
donors after circulatory death have no increased risk of microthrombi formation. Liver Transpl. 2016;22(12):1676-1687.
5. Pietersen LC, den Dulk AC, Braat AE, et al. Flushing the liver with uro- kinase before transplantation does not prevent nonanastomotic biliary strictures. Liver Transpl. 2016;22(4):420-426.
