Hepatocellular Carcinoma/update

Oncology - Hepatocellular Carcinoma

Authors: Ghassan K. Abou-Alfa, MD, Eileen O'Reilly, MD

Table of Contents

Introduction

Managing hepatocellular carcinoma (HCC) is a daunting and challenging task due to the ever-changing epidemiology, the complexities contributed by the underlying cirrhosis, and the evolving therapeutic algorithms. Integral to conquering this challenge is demystifying these complexities through a better understanding of the basics of this disease. This chapter provides an overview of the epidemiology, staging, and multidisciplinary management of the disease.
The incidence of HCC is governed by the epidemiology of the risk factors that contribute to the development of the disease. Globally, chronic hepatitis B virus (HBV) infection is the most prevalent risk factor for the development of HCC due to its endemic presence in the heavily populated regions such as Southeast Asia and Sub-Saharan Africa.[Parkin 2005] In the United States, HBV-related HCC predominantly occurs in cosmopolitan areas with high numbers of immigrants from endemic countries. In addition, the incidence of HCC is increasing at an alarming rate, according to a 1999 report by El-Serag and colleagues.[El-Serag 1999] From the data presented, one can deduce that a 3-fold increase in the age-adjusted rates for HCC, up to 7 cases per 100,000 people, is possibly correlated to the increasing incidence of hepatitis C virus (HCV) that was readily discernable in the last 3 decades. Moving forward, the reduction of the incidence of HCV, which has currently plateaued,[Daniels 2009] would ultimately contribute to a reduced incidence of HCC due to HCV. This could be accomplished through preventive and educational strategies. However, a liver injury and repair model characterized by HCV-damaged liver cells developing dysplasia and ultimately HCC, is estimated to occur over 10-30 years. Therefore, it will take that long to appreciate the impact of HCV reduction on the incidence of HCC.[El-Serag 1999]

Contrary to the anticipated reduction of the HCV risk factor for HCC, a continued rise in the incidence of HCC is expected secondary to the increased prevalence of nonalcoholic steatohepatitis (NASH). NASH occurs mainly in morbidly obese individuals with body mass indexes ≥ 35. The morbidly obese population has an increased relative risk of death from HCC, which is 4.52 times higher among men and 1.68 times higher among women when compared with men and women with body mass indexes within the normal range of 19-25.[Calle 1999] NASH has also been associated with patients with diabetes, another group of individuals who have been reported to have an increased risk of developing HCC.[El-Serag 2001] Alcohol-induced cirrhosis is a major contributor to the development of HCC in the United States and is responsible for almost one third of cases.[Morgan 2004] These 4 risk factors—HBV, HCV, NASH, and alcohol-induced cirrhosis—make up the majority of HCC cases in a typical practice in the United States. Other risk factors that contribute to HCC include a wide array of metabolic disorders, the most common of which is hemochromatosis.[Fracanzani 2001] Of all environmental factors, the one established as a causative risk for HCC is aflatoxins.[Jackson 1999]

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Clinical Presentation
Surgical Resection, Adjuvant Therapy, and Treatment of Locally Advanced HCC
Curative Treatments
Adjuvant Therapy for Hepatocellular Carcinoma
Therapy for Locally Advanced Disease
Systemic Therapy
Chemotherapy
Molecular Targets in Hepatocellular Carcinoma
Epidermal Growth Factor Receptor Inhibitors
Inhibitors of the Proangiogenic Pathway
Combination Therapy
Conclusion
Tables and Figures
References

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