Liver Transplantation for Hepatocellular Carcinoma: How Should We Improve the Thresholds?

Abstract

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor’s biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed.

Protective benefit of minimally invasive liver surgery for hepatocellular carcinoma prior to transplant

“…However, it is important to consider the small sample size of OLT as a second-line surgical treatment after MILS. This number is expected to grow due to the increased prevalence of MILS and the changes in Italy's organ allocation score since 2018 [4,[34][35][36] .…”

“…While LT is the definitive treatment of these curative treatment options, the possibility of recurrence, waiting list times, and limited organ supply require consideration of LR prior to LT. Italy's organ allocation system uses the ISO score, a blended model of urgency, utility, and transplant benefit [3,4] . Given the high likelihood of RHCC, post-transplant recurrence and outcomes must be considered [5,6] .…”

Current Approaches in the Allocation of Liver Transplantation

“…Most US centers require patients with a previous non-hepatic malignancy to have a recurrence-free survival period before transplantation or a very low recurrence rate (i.e., high expectations of cancer cure) based on tumor type and stage [ 51 , 52 ]. Active and uncontrolled infections, particularly with fungi or resistant bacteria, at the time of transplantation are associated with a low survival [ 53 ].…”

Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation

“…Various new selection criteria have been investigated for decades to extend the Milan criteria and optimize the candidate criteria to identify patients who can benefit greatly from liver transplantation, such as the University of California, San Francisco criteria [ 6 ], the model for end-stage liver disease (MELD) score [ 7 ], and Hangzhou criteria [ 8 ]. These criteria are equivalent to or better than the Milan criteria, which can achieve a 4-year OS of 75% [ 9 ].…”