Liver transplantation (LT) was initially dedicated to the treatment of cirrhosis. Nowadays, it is playing an increasingly important role in the treatment of hepatocellular carcinoma (HCC). Surgery, in the form of partial or total (i.e., transplantation) liver resection, represents the only curative treatment of HCC. It is important to keep in mind that a patient affected by HCC has in fact two diseases: the cancer itself and the underlying cirrhosis. LT thus represents a very interesting approach that treats both of them, but is really challenging. Due to liver allograft shortage, graft allocations must be cautiously selected. HCC recurrence must indeed be considered as a failure of the selection process. In the 1980’s, LT for HCC was not popular due to poor long-term results, but the situation changed in 1996, when Mazzaferro introduced the Milan criteria. When following these criteria, LT for HCC was associated to an almost similar overall and disease-free survival compared to LT for benign diseases. However, these morphologic criteria rapidly appeared to be too restrictive, which led to the development of numerous prediction scores in order to widen the eligibility criteria for LT in HCC. These scores currently include morphological as well as biological parameters, both of static and dynamic nature. Notwithstanding, the role of immunosuppression (IS) remains unclear and has not been thoroughly investigated. This is surprising, since it is well known that the immune system plays a key role in the defense against cancer.
MATERIAL AND METHODS
This retrospective observational study sought to fill this gap of knowledge by analyzing the impact of acute cellular rejection (ACR) treatment on HCC recurrence in a large cohort of 781 European patients transplanted for HCC between February 1985 and June 2016. After propensity score matching (PSM), 116 patients treated with corticosteroid boluses for ACR were compared to 115 patients who were not treated for (histologically proven) ACR or did not present ACR at all.
The treated group presented an 18-fold higher risk of HCC recurrence (16.4% vs. 0.9%; p<0.0001), all recurrences having occurred after treatment. Following multivariate Cox regression analysis, corticosteroid use as ACR treatment appeared to be an independent risk factor for HCC recurrence (HR = 14.2; p = 0.01). Continuation of corticosteroid therapy for more than 12 months after rejection as well as high IS load were also associated with a higher recurrence rate (57.6% vs. 32.0% [p = 0.04] and 68.4% vs. 37.1% [p = 0.02], respectively).
ACR treatment using corticosteroids appears to be a risk factor for HCC recurrence. The intensification of immunosuppressive treatment after ACR also tends to be associated with at higher risk of cancer recurrence. More studies – especially prospective ones – are however needed to confirm these results and analyze the phenomenon more deeply.