Hepatocellular Carcinoma: Current Treatment Strategies Aaron Shields, BA K. Rajender Reddy, MD Address Gastroenterology Division, Hospital of the University of Pennsylvania, 3 Ravdin, 3400 Spruce Street, Philadelphia, PA 19104, USA. E-mail: rajender.reddy@uphs.upenn.edu Current Treatment Options in Gastroenterology 2005, 8:457–466 Current Science Inc. ISSN 1092–8472 Copyright © 2005 by Current Science Inc. Introduction The incidence of hepatocellular carcinoma (HCC) is on the rise, with the age-adjusted incidence rate doubling in the United States over the past two decades [1]. In contrast to the recent rapid increase in the United States and Europe, HCC has long been known to be a primary cause of cancer worldwide, reaching its greatest prevalence in Africa and Asia. Worldwide, HCC it is the fifth most com- mon malignancy [2]. Hepatitis B (HBV) was, and still is, the main cause of HCC in Africa and Asia (excluding Japan). The rapid increase of HCC in the United States and in European populations is due to an increased recogni- tion of progressive liver disease that is related to hepatitis C (HCV) [3]. All patients with cirrhosis, regardless of etiol- ogy, are at risk for developing HCC; reports are varied, placing the cause of death between 36% and 71% in patients with compensated cirrhosis [4,5]. The dual pre- sentation of cirrhosis and HCC in the majority of patients presents a clinical challenge in treating HCC. Both the function of the liver and the staging of the tumor must be considered in light of the treatment strategy. Treatment strategies differ among institutions, due to the lack of a globally accepted policy. Strategies pursued at the Hospital of The University of Pennsylvania (HUP) mirror some of the most widely accepted approaches. The best available staging system is the Barcelona-Clinic Liver-Cancer system, as it is the only system to correlate tumor stage and liver function with treatment viability [6••] (Fig. 1). This has been further validated by a North American experience [7]. The best treatment options are surgical methods of transplantation or resection. The available effective short- and intermediate-term treatments are ablative therapies. These are used to treat unresectable tumors or those that fall outside of ideal criteria for liver trans- plantation. Ablative therapies fall under two categories: thermal—tumor destruction by heat (radiofrequency Opinion statement Hepatocellular carcinoma (HCC) is an increasingly prevalent clinical problem. The presence of cirrhosis in the majority of patients makes treatment difficult because both the stage of the tumor and the stage of cirrhosis must be taken into account. This is compounded by the difficulty in diagnosing HCC in the early stages, where treatment is most effective, and the lack of a globally accepted treatment policy. Liver transplantation and liver resection are the optimal treatments, with resection being preferred in patients with small lesions, clinically well-preserved liver function, and absence of portal hypertension. Patients unsuit- able for these procedures, due to localized but large tumor bulk, are only treatable by abla- tive and palliative therapies. Ablation involves either thermal (preferably radiofrequency ablation) or chemical methods, with the choice of method being dependent on both the size and placement of the tumor and the operator. Ablation may also be used as a bridge to transplantation in centers where significant waiting times are anticipated. Tumors that are too large in size or number to ablate are treated with transarterial chemoembolization, involving the distribution of chemotherapeutic agents and the blocking of the blood supply to the tumor; this is not considered a curative therapy. Combination therapies may also be used. These treatment options need further evaluation for determination of the optimal course of therapy for individual patients.