Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future

Abstract

The aim of liver transplantation (LT) for hepatocellular carcinoma (HCC) is to ensure a rate of disease-free survival similar to that of patients transplanted due to benign disease. Therefore, we are forced to adopt strict criteria when selecting candidates for LT and prioritizing patients on the waiting list (WL), to have clarified indications for bridging therapy for groups at risk for progression or recurrence, and to establish certain limits for downstaging therapies. Although the Milan criteria (MC) remain the standard and most employed criteria for indication of HCC patients for LT by far, in the coming years, criteria will be consolidated that take into account not only data regarding the size/ volume and number of tumors but also their biology. This criteria will mainly include the alpha fetoprotein (AFP) values and, in view of their wide variability, any of the published logarithmic models for the selection of candidates for LT. Bridging therapy is necessary for HCC patients on the WL who meet the MC and have the possibility of experiencing a delay for LT greater than 6 mo or any of the known risk factors for recurrence. It is difficult to define single AFP values that would indicate bridging therapy (200, 300 or 400 ng/mL); therefore, it is preferable to rely on the criteria of a French AFP model score > 2. Other single indications for bridging therapy include a tumor diameter greater than 3 cm, more than one tumor, and having an AFP slope greater than 15 ng/mL per month or > 50 ng/mL for three months during strict monitoring while on the WL. When considering the inclusion of patients on the WL who do not meet the MC, it is mandatory to determine their eligibility for downstaging therapy prior to inclusion. The upper limit for this therapy could be one lesion up to 8 cm, 2-3 lesions with a total tumor diameter up to 8 cm, or a total tumor volume of 115 cm 3 . Selection of patients with hepatocellular carcinoma for liver transplantation: Past and future the WL should take into account the recently described HCC model for end-stage liver disease, which considers hepatic function, HCC size and the number and the log of AFP values. This formula has been calibrated with the survival data of non-HCC patients and produces a dynamic and more accurate assessment model.

Living donor liver transplantation for hepatocellular carcinoma at the University of Tokyo Hospital

“…Another meta-analysis (23) of 1,198 patients indicated that the presence of vascular invasion, poor differentiation, tumor diameter over 5 cm, and tumor status beyond the Milan criteria were independent risk factors for HCC recurrence. Unfortunately, these large studies do not include biomarkers such as AFP and DCP, however, there have been numerous reports (21,22,24), as well as the present study that report the significance of these biomarkers in predicting HCC recurrence after LT. Two other major Japanese centers, Kyoto (25) and Kyushu (26), indeed, include DCP value as their expanded criteria for HCC patients. The inclusion of biomarkers to the existing criteria based on the number and the size of tumor will be a critical issue in the future debate regarding the indication of LT for HCC.…”

Brazilian Society of Hepatology Updated Recommendations for Diagnosis and Treatment of Hepatocellular Carcinoma

“…Evaluation of response to locoregional treatment, while on the waitlist, should be performed at three-month intervals by radiological evaluation using the mRECIST (Modified Response Evaluation Criteria in Solid Tumors) criteria (176) and biological markers dosage such as AFP (177) .…”

Transplante de fígado e alocação dos órgãos no Brasil: entre Rawls e o utilitarismo

“…Algumas situações clínicas foram consideradas especiais desde o início, pois, mesmo não afetando seriamente a função hepática, podem levar rapidamente ao óbito sem elevar o MELD. Essas condições são: alguns tumores raros, polineuropatia amiloidótica familiar, síndrome hepatopulmonar grave, algumas doenças metabólicas, hemangiomatose ou doença policística, deficiência de alfa-1 antitripsina e, principalmente, hepatocarcinoma 23,27 . Pacientes com essas condições clínicas recebem 20 pontos adicionais ao entrarem na lista de espera, que são, posteriormente, elevados para 24 e 29 pontos após três e seis meses na lista de espera, respectivamente 26 .…”