INTRODUCTION

Hepatocellular carcinoma (HCC) results in between 250,000 and one million deaths globally per annum [1-4]. HCC has unique geographic, sex, and age distributions that are likely determined by specific etiologic factors.

This topic will review the epidemiology and etiologic associations of HCC. Surveillance recommendations, clinical manifestations, diagnosis, and management of HCC are discussed separately. (See "Prevention of hepatocellular carcinoma and recommendations for surveillance in adults with chronic liver disease" and "Clinical features and diagnosis of primary hepatocellular carcinoma" and "Staging and prognostic factors in hepatocellular carcinoma" and "Overview of treatment approaches for hepatocellular carcinoma".)

EPIDEMIOLOGY

Liver cancer in men is the fifth most frequently diagnosed cancer worldwide, and is the second leading cause of cancer-related death in the world [5]. In women, it is the seventh most commonly diagnosed cancer and the sixth leading cause of cancer death. In the United States, liver cancer is the ninth leading cause of cancer death [6]. The number of deaths per year in HCC is virtually identical to the incidence throughout the world, underscoring the high case fatality rate of this aggressive disease [5]. Almost 80 percent of cases are due to underlying chronic hepatitis B and C virus infection [7].

Geographic variation — The incidence of HCC varies widely according to geographic location (table 1) [5]. The distribution of HCC also differs among racial and ethnic groups within the same country, and between regions within the same country [1]. These extreme differences in distribution of HCC are probably due to regional variations in exposure to hepatitis viruses and environmental pathogens. As an example, the frequency of hepatitis B virus carriers is relatively high in the high-incidence regions and low in the low-incidence regions. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection".)

• High-incidence regions (more than 15 cases per 100,000 population per year) include sub-Saharan Africa, the People's Republic of China, Hong Kong, and Taiwan [1]. The incidence is 24.2/100,000 in parts of Africa, and 35.5/100,000 in Eastern Asia [8]. Over 40 percent of all cases of HCC occur in the People's Republic of China, which has an annual incidence of 137,000 cases [9]. Japan has had one of the highest incidence rates of HCC associated with chronic HCV infection; however, the incidence appears to be decreasing in recent years [10].
• Intermediate-incidence areas include several countries in Eastern and Western Europe, Thailand, Indonesia, Jamaica, Haiti, New Zealand (Maoris), and Alaska (Eskimos) [1].
• North and South America, most of Europe, Australia and parts of the Middle East are low-incidence areas with fewer than three cases reported per 100,000 population per year. However, the incidence in the United States has increased during the past two decades, possibly due to a large pool of people with longstanding chronic hepatitis C [11,12]. The rate began to accelerate in the mid 1980s, most likely because of the increased incidence of cirrhosis due to chronic HCV infection and nonalcoholic fatty liver disease, combined with a large influx of immigrants from East Asia and other geographic areas with high endemic rates of hepatitis B viral infection [13].