Hepatocellular Carcinoma Disease Background

Introduction

Hepatocellular carcinoma is a cancer originating from the liver.

Epidemiology

Hepatocellular carcinoma is the most common type of primary liver cancer accounting for 75-85% of cases and is the fourth leading cause of cancer mortality worldwide. It is the sixth most common cancer worldwide, the fifth most common in males, and the ninth most common in females. Hepatocellular carcinoma is more common in men and this may be due to a higher prevalence of hepatitis B and C viruses, hormonal differences, smoking and alcohol consumption. The incidence of hepatocellular carcinoma increases with age in both men and women. This may be due to longer exposure to predisposing factors such as hepatitis B virus, nonalcoholic steatohepatitis, and alcohol.  

In 2020, the majority of new hepatocellular carcinoma cases occurred in Asia and Africa. Northern Europe and South Central Asia have the lowest incidence of hepatocellular cancer. Asia has the highest incidence of hepatocellular carcinoma relative to blacks, Hispanics and whites. Seventy-one percent (71%) of reported hepatic cancers worldwide are from Eastern (55.6%), South-Eastern (10.6%) and South Central (5.2%) Asia. In Singapore, it is the fifth most common cancer in males and the third most common cause of cancer death in males and fourth in females. In Sub-Saharan Africa, hepatocellular carcinoma is the second leading cause of cancer deaths in males and fourth in women. There is a >2:1 ratio of male-to-female predominance.

Etiology

Approximately 80% of hepatocellular carcinoma cases are caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, especially in those with cirrhosis. Other causes that may lead to cirrhosis, include nonalcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease, excessive alcohol use, hemochromatosis, alpha1-antitrypsin deficiency and primary biliary cirrhosis. Hepatocellular carcinoma may be caused by diabetes, obesity, aflatoxin, anabolic steroid use, and cigarette smoking. 

Hepatocellular Carcinoma_Disease Background

Risk Factors

The presence of cirrhosis and chronic liver disease regardless of etiology, are the major risk factors for the development of hepatocellular carcinoma (HCC).

Hepatocellular Carcinoma_Disease Background 2

• Asian male ≥40 years old who are hepatitis B carriers
• Asian female ≥50 years old who are hepatitis B carriers
• Hepatitis B carriers with family history of hepatocellular carcinoma
• Africans and North Americans with hepatitis B
• Chronic hepatitis B infection
• Cirrhotic hepatitis B and C infected individuals
• Cirrhotic hepatitis B and C carriers
• Alcoholic cirrhosis
• Individuals with coinfection of hepatitis B and/or C, and human immunodeficiency virus
• Individuals with metabolic dysfunction-associated steatotic liver disease and cirrhosis
• Individuals with stage 4 primary biliary cirrhosis
• Individuals with genetic hemochromatosis and cirrhosis
• Individuals with alpha₁-antitrypsin deficiency and cirrhosis
• Individuals with cirrhosis from other etiologies
• Environmental exposure to aflatoxin which is a natural product of the Aspergillus fungus found in various grains

Classification

Types of Hepatocellular Carcinoma by Morphology  

The types of hepatocellular carcinoma by morphology are: Nodular, which is characterized by nodules that are well-circumscribed and often associated with cirrhosis; massive, which occupies a large area that may or may not have satellite nodules in the surrounding liver and is usually associated with non-cirrhotic liver; and diffuse, which is a less common type and is characterized by diffuse involvement of many small indistinct tumor nodules throughout the liver.