Recurrent hepatocellular carcinoma after liver transplantation

Abstract

Recurrent hepatocellular carcinoma after liver transplant was regarded as a terminal disease. Recurrent tumour often progressed rapidly under suppressed host immunity. Recent advances in immunosuppression, systemic therapy and local therapy have led to a paradigm shift in management strategy. Patients with oligo-recurrence, i.e. recurrent tumours limited in number and location, have been treated with a radical intent, by a combination of systemic and loco-regional therapies. However, radical therapy in an immunocompromised host is a major undertaking and there is considerable criticism over an aggressive treatment approach. In this thesis, the outcomes of patients receiving various treatments for recurrent hepatocellular carcinoma after liver transplant were studied. The results came from the pioneering liver transplant centre in Asia. Patients with recurrence were staged with dual-tracer positron emission tomography-computed tomography. It was a more sensitive modality than conventional contrast computed tomography and it effectively differentiated oligo-recurrence from more advanced disease. In patients with oligo-recurrence, propensity-score analysis confirmed that radical therapy was associated with improved survival outcomes. In the radical approach, concomitant systemic control was essential. Targeted therapy will remain the mainstay of systemic therapy because immunotherapy was associated with fatal graft rejection. Mammalian target of rapamycin inhibitor-based immunosuppression conferred anti-tumour effect offering improved survival in established recurrence. Apart from disease volume, clinical surrogates of tumour biology also determined prognosis and they included timing of recurrence and level of alpha-fetoprotein upon recurrence. Survival benefits associated with radical therapy were superior in patients with favourable biological recurrence but were also observed in patients with poor tumour biology. Individual patients’ fitness, procedural morbidity and prognosis were important considerations when formulating a treatment plan for patients with post-transplant hepatocellular carcinoma recurrence.