Original Article/TransplantationHepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience
Introduction
Liver transplantation (LT) is the best curative treatment of hepatocellular carcinoma (HCC) developed in a cirrhotic liver [1]. Unfortunately, about 15%–20% of LT patients experience HCC recurrence [2]. During the last two decades, multiple pre- and post-LT risk factors for recurrence have been investigated [3], [4], [5]. Although HCC development and recurrence had already been linked to immunosuppression (IS) more than 30 years ago both in the experimental and clinical settings, the “tumor risk factor IS” has shown controversial results [6], [7], [8], [9], [10]. The inconsistency of the studies regarding IS with HCC recurrence is explained by the fact that most investigated cohorts were heterogeneous, receiving very different IS schemes. Moreover, almost all attention in this field of transplant oncology has been given to the morphologic (numbers and diameter of tumor) and biologic (tumor markers and PET-scan tumor uptake) behavior of cancer [11].
Clinical research on HCC recurrence has been primarily done in relation to the detrimental role of the IS load in form of continued steroid use or higher dosage of calcineurin inhibitors (CNI) and the protective role of mammalian target of rapamycin inhibitors (mTORi), with these latter drugs exhibiting both immunosuppressive and anti-angiogenic/proliferative properties [12], [13], [14], [15], [16], [17]. The impact of the treatment of acute cellular rejection (ACR) as a possible risk factor for HCC recurrence has never been reported.
The study aimed to investigate the effect of ACR treatment with steroids on HCC recurrence in a broader European population of LT patients using a rigorous statistical approach based on a propensity score matching (PSM).
Section snippets
Methods
A retrospective analysis was performed including 781 adult patients transplanted between February 1, 1985 and June 30, 2016, and having a pre-LT radiological/pathological diagnosis of HCC. Data were obtained from the prospectively collected databases of three collaborative centers: Brussels (n = 309), Innsbruck (n = 296), and Mainz (n = 176). In order to create two homogeneous and comparable groups, the following exclusion criteria were used: (a) follow-up shorter than two years after LT in
Results
Patient- and tumor-related characteristics before and after PSM are displayed in Tables 1 and 2. After PSM, 116 patients with one or more episodes of ACR treated with steroid boluses were identified and compared to 115 patients consisting of 75 (65.2%) patients who did not present ACR and 40 (34.8%) patients who presented a documented but clinically irrelevant rejection not deserving treatment. When comparing these two groups, no differences were observed concerning patient characteristics,
Discussion
The majority of studies dealing with HCC recurrence focus on the well-established tumor-related variables morphology (number and diameter), biology (evolution of tumor and inflammatory markers in the absence or presence of LRT and tumor uptake at PET-scan) [23], [24] and pathology (microvascular invasion, tumor differentiation, satellite lesions) of the hepatectomy specimen.
Conversely, the role of IS has been less extensively clarified, although several studies have been published on this
Contributors
LQ, IS, FA and LJ were responsible for the conception, design and analysis of the study and for writing the paper. LQ, IS, FA, HLM, FM, and LK were involved with the collection and interpretation of data. FA, HLM and OG participated in data management and manuscript review. All authors contributed to the design and interpretation of the study and to further drafts. LQ is the guarantor.
Funding
None.
Ethical approval
Not needed.
Competing interest
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
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