Evolving thresholds for liver transplantation in hepatocellular carcinoma: A Western experience

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Once considered an experimental treatment with dismal survival rates, liver transplantation for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. In the modern post-Milan-criteria era, 5-year survival outcomes are now upwards of 70% in select patients. Liver transplantation (LT) is now considered the optimal treatment for patients with moderate to severe cirrhosis and HCC, and the rates of transplantation in the United States are continuing to rise. Several expanded selection criteria have been proposed for determining which patients with HCC should be candidates for undergoing LT with similar overall and recurrence-free survival rates to patients within the Milan criteria. There is also a growing experience with downstaging of patients who fall outside conventional LT criteria at the time of HCC diagnosis with the goal of tumor shrinkage via locoregional therapies to become a candidate for transplantation. The aim of this review article is to characterize the various patient selection criteria for LT, discuss balancing organ stewardship with outcome measures in HCC patients, present evidence on the role of downstaging for large tumors, and explore future directions of LT for HCC.

Keywords: hepatocellular carcinoma; liver transplant selection; organ stewardship; transplant criteria; transplantation.

Figure 1

Survival probabilities according to the UCSF criteria based on pathology of liver explants. Meeting criteria: (solid line), yes; (dashed line), no. Reprinted from Yao et al29 with permission from John Wiley and Sons

Figure 2

Survival for patients within Milan, beyond Milan but within up‐to‐seven, and exceeding both sets of criteria. Reprinted from Mazzaferro et al,31 Copyright 2009, with permission from Elsevier

Figure 3

A, Overall survival of validation cohort from Sapisochin et al 2016; B, cumulative risk of recurrence of validation cohort. Reprinted from Sapisochin et al,33 with permission from John Wiley and Sons

Figure 4

Survival analysis of HCC patients treated with LT stratified by Milan and UCSF criteria. Reproduced without changes from Patel et al40 under the Creative Commons Attribution License

Figure 5

Kaplan‐Meier's post‐transplant survival probabilities of downstaging group vs T2 group from Yao et al 2015. Reprinted from Yao et al,43 with permission from John Wiley and Sons

Figure 6

Mazzaferro et al proposed paradigm shift in management of LT in patients with HCC who are (A) within and (B) beyond criteria. Reprinted from Mazzaferro et al,46 with permission from John Wiley and Sons