New Insights into Liver Transplantation for Hepatocellular Carcinoma

The Milan criteria are commonly used to determine the suitability of Child B/C hepatocellular carcinoma (HCC) patients for undergoing liver transplantation, but the accuracy is controversial. Today，Professor Sheung-Tat Fan， from the Department of Surgery, The University of Hong Kong, presented a report on liver transplantation for hepatocellular carcinoma. He said that in order to improve the current liver allocation system, it is important to study the biological behavior of HCC. Among the different possible ways to predict the tumor biological behavior, studies have shown that the response of a tumor to non-surgical treatments, such as transarterial chemoembolization, and tumor differentiation grade are not totally predictive of the biological behavior of HCC.

Professor Fan pointed out that numerous studies have been carried out on the prognostic values of genes/markers in relation to various aspects of hepatocarcinogenesis. AA454543 and extracellular matrix metalloproteinase inducer, CD147, for example, have been shown to function as cell invasion and are predictive of tumor recurrence after liver transplantation. Because not more than 70% of the tumors express the same gene, more than one gene is needed to accurately predict the outcome of treatment. However, no such study has been proved clinically applicable.
In obtaining tumor tissues for genetic tests, tumor biopsy inevitably poses a risk of cancer cell dissemination into the circulation or cancer cell spillage into the peritoneal cavity. An alternative way is to examine the circulating cancer cells. To detect the circulating cancer cells, we may employ immunocytochemistry to identify the surface marker of the cancer cell, identify the protein secreted by the cells using EPISPOT assay, or measure the quantity of free nucleic acid released from mRNA of the cancer cells. Alpha-fetoprotein and plasma albumin mRNA are possible markers of tumor cells, but large scale clinical studies have not been performed to validate their usefulness.

He continued that the cancer stem cell is a more recent concept. It is hypothesized that it has the ability to deposit and grow in the distant organs and liver graft to produce recurrence. The cancer stem cell of HCC, identified by CD45-, CD90+ and CD44+, have recently been found not only in tumor tissues, but also in the blood in 90% of HCC patients, whereas in the blood of normal persons and cirrhotic patients, they are totally absent. It was found that the number of circulating cancer stem cells can predict both intrahepatic and extrahepatic tumor recurrence. The prediction ability appears to be higher than that of plasma albumin mRNA. CD44 antibody has also been shown to be useful for prevention of HCC recurrence after liver transplantation in animal models.

Finally, Professor Fan concluded that blood is the preferred or clinically applicable sample source of study of HCC biological behavior. The focus of research is on the circulating cancer cell marker. On this aspect, the cancer stem cell may be the focus of future research because eradication of the circulating cancer stem cell may render a patient tumor-free after transplantation. In the future, molecular screening may play an important role of selecting the appropriate patients to receive liver transplantation. Studies on such biomarkers will also provide opportunities of designing target agents to regress the tumor before transplant or prevent it from recurring after transplantation.