Expanded criteria for hepatocellular carcinoma through down-staging prior to liver transplantation: not yet there

The accepted treatment strategy for hepatocellular carcinoma (HCC) is supported by randomized controlled trials (RCTs), meta-analysis, and large cohort studies. For instance, the Milan criteria applied for indicating liver transplantation have been validated by several cohort studies including more than 1000 patients. Regarding medical treatments, approximately 80 RCTs have been published so far in HCC. These studies provide the evidence to support chemoembolization as the treatment for patients at intermediate stage (meta-analysis of 6 RCTs) and show the lack of benefit of tamoxifen assessed in 12 RCTs including more than 1500 patients. In this scenario, what is the evidence to advocate for the expansion of HCC criteria through down-staging prior to liver transplantation? Such an approach has never been tested through RCTs or even well-designed cohort studies including enough patients and adequate follow-up. Only a few small studies with heterogeneous target populations and treatments applied are available. The results of these studies are inconsistent and do not provide compelling evidence to accept down-staging as a standard of care.