Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation

Abstract

Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor's biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as (18)F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.

Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology

“…The presence of microinvasion (MI) defined as portal venous, hepatic vein, bile duct infiltration and/or intrahepatic metastasis (satellite nodules) is the best indicator of poor prognosis after HR and transplantation; in fact, in this study of Yamashita et al, the recurrence‐free survival of the MI‐positive group after HR was significantly worse than that of the MI‐negative group. Furthermore, the histological grade of HCC is a significant prognostic factor after surgery, and high‐grade HCC was found to be an independent predictor of vascular microinfiltration …”

3D MR Elastography of Hepatocellular Carcinomas as a Potential Biomarker for Predicting Tumor Recurrence

“…Currently, tumor characteristics mainly rely on imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Hepatobiliary contrast‐enhanced imaging and diffusion‐weighted imaging have shown promise in evaluating the aggressiveness of HCCs, but are limited in assessing the malignant phenotype of the tumor, and this may be one of the reasons why patients of the same stage may show a different prognosis . In MRI, hypointense hepatic nodules during the hepatobiliary phase were associated with recurrence .…”

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

“…One such example would be the introduction of 'Up-to-seven' criteria by Mazzaferro (who initially proposed the Milan criteria) and colleagues [41]. Similarly, the emphasis on tumor biology (such as tumor differentiation, tumor response to bridging/downstaging therapies and AFP) rather than tumor burden in selecting patients for LT is gaining momentum [11,24,40,42]. Therefore, it is not unreasonable to speculate that LT will emerge as an acceptable treatment choice for selected patients with advanced HCC in the near future.…”

“…Improvements in understanding HCC biology and its role in predicting outcomes has rekindled the interest in LT for advanced HCC [11]. Encouragement from the improved outcomes with LT for HCC and dissatisfaction with the poor outcomes of palliative therapy has led to reexamination of the role of LT in advanced HCC.…”