Malignant Liver Tumours: Basic Concepts and Clinical Management

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), both increasing in incidence, have become a major topic of basic and clinical research as well as clinical practice in hepatology. Experts in the field update the current concepts on the carcinogenesis of HCC and CC such as genetic alterations in the pathways of cell cylce and apoptosis regulation, the hypothesis of dedifferentiation of hepatocytes to the malignant phenotype vs that of activation of hepatic progenitor cells incapable of maturation (maturation arrest hypothesis). In spite of an increasing number of genetic alterations described in human HCC as well as cell regulatory pathways tested in experimental HCC models, the key hits causing progression of the cell cycle in imbalance with apoptosis, tissue invasive growth and metastatic potential of cell clones still remain elusive. Very powerful genomic and proteomic techniques are promising insights into the carcinogenesis of liver malignancies that will allow more efficient therapeutic strategies. The current concepts on risk profiling, surveillance of risk groups and therapeutic strategies are evidence-based for HCC and less detailed for CC. Surveillance of risk groups improves detection of liver tumours in curable stages. Best strategies for curative treatment of HCC use neoadjuvant antitumour therapies before liver transplantation and a role is emerging for living donor-related liver transplantation. New palliative therapies for HCC are in the experimental stage with biological response modifiers, including angiogenesis inhibitors, and entering phase II clinical trials with the alpha-fetoprotein derived vaccines.