Review article: liver transplantation for hepatocellular carcinoma – a critical appraisal of the current worldwide listing criteria

Abstract

SUMMARY BackgroundLiver transplantation (LT) plays an important role in the management of patients with hepatocellular carcinoma (HCC). Although early results following LT for HCC were poor, since the introduction of the Milan criteria in 1996 morphological criteria have since been well established. Thereafter, various expansions of the Milan criteria were introduced worldwide. Listing criteria for LT for HCC in the United Kingdom (UK) initially conformed to the Milan criteria but were re-defined in 2009 by expansion of the Milan criteria. AimsTo look at the evidence in literature on listing criteria and management of HCC worldwide in comparison with the UK. Secondly, we aim to review worldwide vs. UK literature on prioritisation models, loco-regional therapy protocols and role of alpha-fetoprotein (AFP) in LT for HCC. MethodsAn electronic literature search with Medline was carried out to identify articles related to LT for HCC. ResultsAlthough various expansions of the Milan criteria have been described, they remain the gold standard against which other criteria are measured. The UK criteria are an expansion of the Milan criteria that go beyond Milan and University of California, San Francisco (UCSF) criteria. The current UK listing criteria for LT for HCC when compared to the worldwide criteria have a worse survival benefit (projected 5-year survival between 35-50%) when plotted on the metroticket calculator. ConclusionsIn keeping with most transplant centres worldwide, the UK have adopted expansions to Milan to allow more patients to benefit from LT. However, currently, as it stands the UK criteria when plotted in the modification of the Metroticket model project worse survival that would seem unjustified.

Hepatocellular carcinoma: A comprehensive review

“…These findings illustrated that this novel incorporation criterion improved in increasing rates of the incidence of Deceased Donor Liver Transplant (DDLT) for HCC individuals. Also, fivemonth rates to fall off the list greatly diminished, with increased survival rates in this time span, while noted to be waiting during the postMELD period [76] . These findings indicated these novel MELD allocation criterion showed definite benefit to candidates with HCC for transplantation.…”

Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future

“…Recently, it was shown once again that an AFP level > 1000 ng/mL is a reason for exclusion from the WL [24,25] , confirming data reported in 2001 [16] . However these data have not been taken into account by programs using expanded criteria that only consider an AFP level greater than 10000 ng/mL as a reason for exclusion [26] . This matter will be further examined when discussing the indications for downstaging of HCC prior to LT (Table 1).…”

“…It should be mentioned that until very recently, the criteria used in the United Kingdom for LT for HCC considered a maximum tumor diameter up to 15 cm (up to 5 tumors all ≤ 3 cm), which is well beyond the limit of the MC and UCSF criteria [26] .…”

“…Other authors have made similar suggestions [45] ; however, others have placed this limit at 10 cm, which results in a decrease in DFS [46] . This value should be universally accepted as the upper limit [26] . The expanded criteria require further validation because recurrence could be less often reported, increasing the risk of vascular invasion, microsatellites and poorly differentiated tumors [35,47,48] .…”

A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in the treatment of hepatocellular carcinoma

“…1,2 Previous study revealed that HCC was genetically complex, multifactorial, and heterogeneous tumor. 3,4 Therefore, several opinions about oncolytic treatments by targeting different signal pathways have been characterized.…”