Protective effect of low-dose aspirin against acute cellular allograft rejection after primary liver transplantation.

Abstract

To the editor, We read with great interest the study by Oberkofler et al1 entitled “Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation.” The authors analyzed data from an international, multicenter cohort study of primary adult liver transplantation. They found that low-dose aspirin may reduce the risk of acute cellular rejection and hepatic artery thrombosis. Although inspiring, we would like to raise the following comments. First, many critical baseline characteristics of the 2 groups differed significantly, including the model for end-stage liver disease score, body mass index, prior transarterial chemoembolization, cold ischemia time, intraoperative transfusion, etc. These variables have been found to be independently associated with poor outcomes (higher risk of acute cellular rejection, hepatic artery thrombosis, and mortality).2,3 Therefore, we highly recommend that the authors use propensity score matching to partly eliminate the discrepancies between 2 groups of patients possessing distinct baseline characteristics. In a retrospective study design, propensity score matching analysis has been widely implemented to adjust confounders. Although the authors have taken an effort to perform multivariate analysis for bias reduction, propensity score matching would have probably been a better modality to adjust for potential confounders mentioned above, thus enabling balanced and unbiased comparison. Second, the authors did not specify whether the patients were simultaneously under other drugs during follow-up, including statins, which are often used in combination with aspirin. Recipients in the aspirin group had a higher cardiovascular risk, particularly for dyslipidemia and cardiovascular disease, thus being likely to be taking statins simultaneously. Becchetti et al demonstrated that statin use by liver transplantation recipients may confer a survival advantage and protection against biliary-vascular complications.4 It is reasonable to infer that the between-group differences might be partly attributed to stain exposure. Moreover, thromboprophylaxis protocol mainly focuses on aspirin, unfractionated heparin, low-molecular-weight heparin, and Vitamin K antagonists or a combination of these regimens. The authors should clarify whether recipients, especially those in the no-aspirin group, were using other anticoagulants. Potential confounders mentioned above should be adjusted for in the Cox regression multivariable analysis to eliminate selection bias. In summary, due to the limitations mentioned above, the conclusion that low-dose aspirin use after primary liver transplantation confers protection against acute cellular rejection and hepatic artery thrombosis still needs more robust evidence to confirm.