Hepatocellular cancer selection systems and liver transplantation: from the tower of babel to an ideal comprehensive score

Abstract

The Milan criteria (MC) remain the cornerstone for the selection of patients with hepatocellular cancer (HCC) to be listed for liver transplantation (LT). Recently, several expanded criteria have been proposed to increase the transplantability of HCC patients without compromising their (oncologic) outcome. This paper aims to systematically review the different reported HCC-LT selection systems looking thereby at their ability to increase the number of transplantable patients and the overall survival and oncological outcome. A systematic review of the literature covering the period 1993 (date of the first reported HCC-LT selection system)-2021 identified 59 different inclusion criteria of HCC for LT. Among the 59 studies reporting HCC-LT selection systems, 15 (28.3%) were exclusively based on morphological aspects of the tumor; 29 (54.7%) included biologic, seven (13.2%) radiological, and two (3.8%) only included pathological tumor features. Overall, 31% more patients could be transplanted when adhering to the new HCC-LT selection systems. Despite the increased number of LT, 5-year patient and disease-free survival rates were similar between MC-IN and MC-OUT/new HCC-LT-IN criteria. A careful extension of the inclusion criteria should allow many more patients to access a potentially curative LT without compromising their outcome. The development of a widely accepted "comprehensive" HCC-LT Score able to offer a fair chance of justified transplantation to more patients should become a priority within the liver transplant community. Further studies are needed to develop internationally accepted, expanded selection criteria for liver transplantation of HCC patients.

Keywords: Hepatocellular cancer; Liver transplantation; Recurrent tumor; Score; Selection criteria.

Fig. 1

PRISMA flow diagram showing the article selection process

Fig. 2

ROBINS-I qualitative assessment of the included studies

Fig. 3

Percentage of supplementary liver transplantations compared to the Milan criteria when using new expanded criteria

Fig. 4

5-year overall survival rates in the different reported HCC criteria

Fig. 5

5-year disease-free survival rates in patients within the Milan criteria, without the Milan criteria but within the new expanded criteria or exceeding the new criteria

Fig. 6

Forest plot and meta-analysis on the post-transplant recurrence: Milan criteria vs. enlarged selection criteria