ABSTRACT
This article discusses the infeasibility of adhering to the Brazil-Milan Criteria for determining whether patients with hepatocellular carcinoma (HCC) should be offered liver transplantation. The Criteria are currently used widely in Brazil. However, since they expand the net of the transplant-eligible population, and that transplantation is shown to improve clinical outcomes in HCC patients relative to other treatments, they are inherently attractive and may be adopted by other countries in determining whether HCC patients should receive liver transplantation. I argue that the Criteria unjustifiably disregard the number of tumour nodules found in the patient. This number may be indicative of the recurrence potential of the disease, since these nodules can originate from different clonal populations. The greater the number, the higher the risk these nodules are associated with clones which contain genetic mutations conferring even greater potential for proliferation and dissemination. Clusters of tumour cells may be micro-disseminated to vascular structures surrounding the liver, as well as extrahepatic systems. This increases recurrence potential and reduces the benefit of liver transplantation in these patients. Thus, HCC patients harbouring fewer but larger tumour nodules may present with a more favourable genomic and epigenomic profile than those with more, albeit smaller, tumour nodules. Patients with more tumour nodules may reap greater clinical benefit if initiated on systemic therapy early, rather than wait for a suitable donor liver. Although the Criteria are reached by consensus, with reference to findings from recent studies, as well as scientific theory, it is ripe for review.