Hepatocellular Carcinoma


Primary liver cancer is the third leading cause of cancer‐related deaths and fifth most common cancer in the world. Globally, estimated 877 000 people develop liver cancer and an almost equal number die of it in 2007. The worldwide prevalence, unique geographic distribution and well‐established aetiologic factors of hepatocellular carcinoma (HCC) have provided a strong impetus for elucidating mechanisms underlying the development of this aggressive malignancy. A better understanding of the specific molecular features of hepatocarcinogenesis has revealed clues for novel preventative and therapeutic strategies. Of particular note, the recent extraordinary progress in the genetic and genomic understanding of this disease may shed light on the molecular mechanisms of HCC progression and this knowledge may offer great opportunities for improving the treatment and prevention of HCC.

Key Concepts:

  • HBV, HCV, alcohol, aflatoxin, diabetes and obesity constitute the main risk factors for HCC.

  • Prediction of prognosis and response to therapy, screening of high‐risk cases and science‐based therapy are the challenging tasks to improve clinical medicine.

  • HCC is a highly heterogeneous disease, which exists between primary tumours from different individuals as well as within a single carcinoma, where subpopulation can range from primitive, stem‐like cells to foci of well‐differentiated malignant epithelium.

  • Both genetic and epigenetic changes contribute to HCC, the understanding of mechanisms behind those changes may lead to personalised HCC medicine.

Keywords: HBV; HCV; p53; genomics; miRNAs; DNA methylation; cancer stem cells

Figure 1.

Model of multistage hepatocellular carcinogenesis. HBx, HBV X protein; AFB1, aflatoxin B1.

Figure 2.

Clinical management of hepatocellular carcinoma (HCC). Currently only about 10–30% patients presenting with HCC are eligible for surgical invention [hepatic resection (HR) or liver transplantation (LT)]. For the majority of HCC patients, treatment options are limited to palliative care or the administration of local/regional therapies such as radio frequency ablation (RFA) or percutaneous ethanol injection (PEI) TACE, transcatheter arterial chemoembolisation.

Figure 3.

Model of the parallels between hepatocellular carcinoma (HCC) subtypes and normal human liver cell lineage. EpCAM+AFP+HCC, hepatic stem cell‐like HCC; HpSC‐HCC; EpCAM+AFP–HCC, bile duct epithelium‐like HCC; BDE‐HCC; EpCAMAFP+HCC, hepatocytic progenitor‐like HCC; HP‐HCC; EpCAMAFPHCC, mature hepatocyte‐like HCC; MH‐HCC.

Figure 4.

Signalling pathways altered in hepatic cancer cells. Multiple signal transduction pathways are operational in liver cancer cells (whether the tumour consists of stem‐like cells and/or more differentiated subpopulations), many of which converge influencing cellular proliferation, growth, survival and differentiation (Kumar et al., ).



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Zhao, Xuelian, Elmore, Lynne W, Harris, Curtis C, and Wang, Xin Wei(Jul 2011) Hepatocellular Carcinoma. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006112.pub2]