Risk factors for hepatocellular carcinoma recurrence after liver transplantation

Abstract

Liver transplantation (LT) provides an excellent option for the long-term survival of patients with unresectable hepatocellular carcinoma (HCC) based on the Milan criteria. Despite careful selection of patients, HCC may still recur after LT, which represents the most important negative predictor of post-transplant survival. The growing demand for LT in HCC has led to the expansion of patient selection criteria, with a resultant increase in the risk of post-transplant HCC recurrence. Numerous tumor and host factors predict HCC recurrence. The morphological, histological, and serological characteristics of tumors in predicting HCC recurrence have been extensively studied. Furthermore, the type and duration of anticancer response before LT has also been considered a surrogate marker of tumor aggressiveness and is associated with the risk of recurrence. The demographic and clinical characteristics of recipients, as well as the type and duration of exposure to immunosuppressive therapy, represent the main hostrelated risk factors. Many studies have attempted to describe predictive models for the risk of HCC recurrence, considering evaluable parameters both before and after LT. Although many models have been proposed, relatively few have been externally validated on different patient populations. This paper aims to comprehensively summarize the available data on the predictive factors of HCC recurrence after LT, and to examine and discuss those that have been externally validated.

Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review

“…The certainty of always being able to carry out an accurate and reproducible measurement of the size and number of nodules to capture millimeter differences with respect to the MC probably represents the greatest limitation of the new criteria based exclusively on the morphological characteristics of HCC. There is great heterogeneity and different accuracies of liver imaging techniques applied to detect liver nodules and to properly characterize them, such as contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) [19]. Several reports have indicated that as many as 20-25% of patients undergoing LT for HCC have been inaccurately staged when only imaging techniques were used [32,33].…”

“…For example, in deceased donor liver transplantation, the date of the transplant is never predictable. Thus, the optimal time interval between transplantation and AFP measurement that would make it a predictive marker of recurrence was unclear [19]. Instead of adopting cutoff values of AFP, an interesting approach is to consider multiple AFP measurements to calculate a trend in the increase or decrease in its serum levels.…”

“…A very innovative approach to select patients for LT presenting at baseline beyond the MC is to evaluate the characteristics of tumor response after LRT and consider it a surrogate marker of biological HCC aggressiveness and of the risk of recurrence [19]. When LRT is used to control tumor growth with the aim of reducing the risk of waiting list dropout, it may be considered a "bridge" treatment to LT.…”

“…The 5-year HCC recurrence rate was 5.3% in patients who achieved CR or PR after TACE compared with 17.6% in those who achieved SD or PD. It should be noted that although the mRECIST criteria are sufficiently detailed, they may not be systematically adopted among different transplant centers, such that the results obtained by LRT may not be comparable [19].…”

“…The reasons why the MC did not allow accurate prediction of the outcome after LT in all patients stem from the fact that they were based exclusively on tumor morphological characteristics, such as the size and number of nodules. To overcome this limitation, several selection criteria that sought to expand the MC were proposed [19]. Some of these criteria were constructed using morphological and biological variables of the tumor obtainable pretransplant (Tables 1 and 2), others on variables obtainable only after transplantation (for example, the full histology of the tumor), and others by combining variables obtainable in both the pre-and post-transplantation periods.…”