Sorafenib before liver transplantation for hepatocellular carcinoma: risk or give up

Dear Sirs,\udWe read with interest the article by Truesdale et al. [1]\udregarding their experience in the use of sorafenib before\udliver transplantation (LT) in patients with hepatocellular\udcarcinoma (HCC). The authors compare ten patients who\udwere administered sorafenib during waiting time for LT\udwith twenty-three patients to whom the drug was not given.\udNo difference in terms of overall and HCC recurrence-free\udsurvival was seen between the two groups. Indeed a higher\udincidence of biliary complications (67% vs. 17%) and acute\udcellular rejections (67% vs. 22%) was observed in the first\udgroup. The authors assume that the higher amount of complications\udis secondary to the use of sorafenib because of its\udmain effect in inhibiting the vascular endothelial growth\udfactor (VEGFR), reducing the resistance to apoptosis of\udcholangiocytes and thus both hindering the integrity of biliary\udvascularization and altering the immune pathway leading\udto cellular rejection. However, some major issues arise\udreading this paper: the authors do not specify the inclusion\udcriteria for the use of sorafenib, the extension of the tumour\udburden before LT, the number of locoregional treatments\udbefore the drug was given and in general the efficacy of\uddown-sizing procedures in this group of patients.\udAn interesting matter of debate is the time to stop the\udadministration of sorafenib. Infact the authors assert that\udthe drug was stopped on the day of LT. In our experience\ud[2], it seems not to be safe to continue with the administration\udof the drug until the day of LT: although there is no\udinternational agreement about this point [2–5], we usually\udinterrupt the drug at least 3 weeks before a surgical procedure\udsuch as LT, because of the increased risk of bleeding\udof impaired wound healing and of liver dysfunction in the\udperioperative period in this setting of patients.\udAnother intriguing issue is that doubtlessly sorafenib\udcannot still be considered nowadays in the group of the\udstandard down-staging procedures of HCC in terms of\udsafety and cost–effectiveness, but it should be reserved to\udthe patients with advanced HCC traditionally treated with\udlocoregional therapies/hepatic resection in whom sorafenib\udplays as important role in bringing them within the\udaccepted criteria for LT with HCC. So as to exploit as much\udas possible the potential of the drug, we believe that sorafenib\udshould not be reserved to patients with advanced HCC to whom any other curative treatment is not possible, but\udit should be offered also to a different setting of patients\udsuch as young patients outside standard criteria to LT.\udIn the future, the challenge will be to break the Damocles\udsword of medical therapies for HCC, until now no\udeffective therapy exists. The integration of sorafenib in\udthe medical practice and its fully comprehension may\udpermit the best management of these patients as possibl