Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Feb 20, 2016; 6(1): 21-36
Published online Feb 20, 2016. doi: 10.5493/wjem.v6.i1.21
Hepatocellular carcinoma: Where are we?
Roberto Mazzanti, Umberto Arena, Renato Tassi
Roberto Mazzanti, Umberto Arena, Renato Tassi, Department of Experimental and Clinical Medicine, School of Sciences of Human Health, University of Florence, 50134 Firenze, Italy
Author contributions: Mazzanti R wrote the general part of the article, epidemiology, treatment and a general review of the subject; Tassi R wrote most of the biology of HCC, while Arena U wrote the diagnostic aspects.
Supported by Fondazione Italiana per lo Studio del Fegato - Italian Liver Foundation, Firenze, via Banchi 6, 50123, Italy.
Conflict-of-interest statement: The authors declare no any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Roberto Mazzanti, MD, Professor, Department of Experimental and Clinical Medicine, School of Sciences of Human Health, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
Telephone: +39-055-416635 Fax: +39-055-417123
Received: July 30, 2015
Peer-review started: July 31, 2015
First decision: September 16, 2015
Revised: December 14, 2015
Accepted: January 5, 2016
Article in press: January 7, 2016
Published online: February 20, 2016

Hepatocellular carcinoma (HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type II diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called “up to seven criteria” to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients.

Keywords: Hepatocellular carcinoma, Treatment, Liver cancer, Epidemiology, Liver transplantation, Percutaneous ethanol injection, Chemoembolization, Chemotherapy, Radiofrequency ablation

Core tip: This review summarizes on the current state of the art of treatment of hepatocellular carcinoma (HCC). After a brief chapter on epidemiology, risk factors and biology of HCC, the review presents all possible therapeutic approaches for HCC, from the most effective such as liver transplantation to important but palliative treatments which can prolong patient survival such as different types of trans-artery-chemo-embolization and chemotherapy.