De novo tumours after liver transplantation in adults. What is the actual risk?

Abstract

Liver transplantation (LT) has become the best therapeutic option for end-stage liver diseases and, to date, more than 70 000 procedures have been performed worldwide. The mid-term results of LT are steadily improving with an overall 5 year-survival of 70% [1]. In part, such results have been made possible by the progress made in the prevention of liver graft rejection, so that deaths by graft loss have become a very rare event. However, these results require the use of life-long immunosuppression with its own adverse effects, which account for a speci®c morbidity and mortality [2,3]. In this issue of Journal of Hepatology, Haagsma et al. [4] focus on one of the major adverse reactions of the therapeutic immunosuppression, namely the occurrence of post-transplant de novo tumours. By reviewing the chart records of 174 adult liver transplant recipients surviving more than one year, they analyzed the incidence and risk factors of post-transplantation de novo tumours and compared the rates of cancers observed in this population with those expected in the Dutch population over the same period. They found a cumulative risk for de novo malignancies of 20 and 55% at 10 and 15 years post-transplant, with an overall relative risk of neoplasia, as compared with the general population of 4.3 (95% CI: 2.4± 7.1), rising from 2.0 at 5 years to 13.5 at 10 years. They also found a cancer-related risk to die of 15% at 15 years. In their series, the risk of de novo neoplasia was increased for skin tumours, which represented about one half of the whole cancers, but also for non-skin solid tumours such as colon and renal cancers; by contrast, they observed an unusually low incidence of post-transplant lymphoproliferative disorders (PTLD). The risk of de novo tumour has been established for years after renal transplantation [5]. In the kidney recipient population, the most frequent tumours are B cell lymphoproliferative disorders, which are most common in the ®rst year after transplantation, and skin, lips and perineal cancers, with an increasing incidence with duration of follow-up [6]. By contrast, the frequency of cancers which are common in the general population such as carcinomas of the lung, prostate, breast and colon is not increased among kidney recipients [5]. The increased rate of tumours after renal transplantation is usually considered the result of (a) the exposure to oncogenic viruses such as Epstein±Barr virus, Human Herpes Virus 8, or Human Papilloma Virus (b) a chronic, graft-related, antigen stimulation and (c) a reduction of the immune surveillance of virus-transformed cells, leading to virus-induced malignant disorders [7]. Several risk factors for de novo tumours have been identi®ed after renal transplantation, including the use of induction immunosuppression with antilymphocyte antibodies, which increases the risk of lymphoproliferative disorders [5], length of exposure to immunosuppressive drugs [8,9], maintenance immunosuppressive regimens based on high cyclosporin trough blood levels [9], age over 50 [9], and male sex. Contrasting with what has been observed after renal transplantation, the risk of de novo tumour after LT in adults has been little studied until recently [10±14]. This is probably related to the shorter duration of follow-up after LT than after renal transplantation. However, a better assessment of the risk of malignancy is essential after LT as long survival is now achieved in most patients; detection and treatment of any condition which might impair the long term survival of LT recipients must be then perfectly known by physicians who are in charge of LT recipients. Initial studies have shown that after LT, the most common tumours are PTLDs and skin cancers. Lymphoproliferative disorders account for 20±50% of de novo tumours after LT [10,11,13,15] and are more frequent in paediatric than in adult recipients [10] because of a high incidence of primary EBV infection in paediatrics. In adults, other factors may play a role, and we recently reported an unexpected high incidence of PTLDs in patients transplanted for HCV-related cirrhosis and treated with antilymphocyte antiJournal of Hepatology 34 (2001) 161±164