RESUMO
BACKGROUND: Recurrence of hepatocellular carcinoma after orthotopic liver transplantation not amenable to surgical approaches is associated with poor outcome. AIMS: Retrospective evaluation of the safety and efficacy of sorafenib in patients with post-transplant hepatocellular carcinoma recurrence. METHODS: Patients with post-transplant hepatocellular carcinoma recurrence were treated with sorafenib. Adverse events were assessed using National Cancer Institute Common Toxicity Criteria of AEs version 3.0, tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours. RESULTS: First-line therapy after recurrence was surgery (n=6), radiation therapy (n=1), chemotherapy (n=1), and sorafenib (n=3). Finally, 11 patients were treated with sorafenib. Nine patients (82%) received an additionally targeted therapy with sirolimus as part of their immunosuppressive regimen. Most common grade 3 adverse events included diarrhoea (46%), hand-foot skin reaction (27%), nausea, fatigue, and leucopoenia (all 18%). Sorafenib had to be discontinued in two patients due to adverse events and six additional patients required a dose adjustment. No deterioration of liver graft function occurred. Median time to progression was 4.1 months; however, patients were treated with ongoing sorafenib in case of clinical benefit (median 8.9 months). Median overall survival after initiation of sorafenib treatment was 20.1 months. CONCLUSION: Sorafenib in combination with immunosuppression including sirolimus may be administered to patients with post-transplant hepatocellular carcinoma recurrence with acceptable toxicity and without deterioration of liver graft function.
Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Recidiva Local de Neoplasia/terapia , Piridinas/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Estudos Retrospectivos , Sirolimo/uso terapêutico , Sorafenibe , Tacrolimo/uso terapêuticoRESUMO
In patients with hepatitis C, a loss-of-function mutation of chemokine receptor CCR5 (CCR5Delta32) has been shown to be associated with spontaneous viral clearance and lower levels of hepatic inflammation. In the present study, we show that CCR5 is coexpressed with the inhibitory NKG2A receptor on CD8(+) T cells. Consequently, CCR5(+) T cells were highly susceptible to NKG2A-mediated inhibition of cytotoxic activity and NKG2A(+) lymphocytes were preferentially attracted by CCR5 ligands induced by hepatitis C virus E2 antigen. Thus, CCR5 is likely to exert immunoregulatory effects in hepatitis C virus infection by preferentially recruiting CD8(+) T cells bearing the inhibitory NKG2A receptor to the liver.
