What is the most common etiologic factor for hepatocellular carcinoma (liver cancer) worldwide?

Hepatitis B Virus is the Most Common Etiologic Factor for Hepatocellular Carcinoma Worldwide

Hepatitis B virus (HBV) infection is the most common etiologic factor for hepatocellular carcinoma (HCC) worldwide, accounting for approximately 54% of all cases globally. 1

Epidemiology of HCC Etiologies

Viral Hepatitis

• Hepatitis B virus (HBV):

  • Responsible for 54% of HCC cases globally 1
  • Particularly dominant in Africa and East Asia, where it accounts for 60% of cases 1, 2
  • Affects approximately 400 million people worldwide 1
  • Risk factors for HBV-related HCC include HBeAg seropositivity, high viral load, and genotype C 1

• Hepatitis C virus (HCV):

  • Accounts for 31% of HCC cases globally 1
  • More prevalent in Western countries, Japan, and parts of Europe 1
  • Affects approximately 170 million people worldwide 1
  • Annual HCC development rate in HCV-infected cirrhotic patients is 3-8% 1

Other Etiologic Factors

• Alcoholic liver disease:

  • Significant cause of cirrhosis leading to HCC, especially in Western countries 2
  • Accounts for approximately 40% of cirrhosis deaths in the United States 2

• Aflatoxin B1 exposure:

  • Important co-factor for HCC development, especially in Africa and parts of Asia 1, 2
  • Often acts synergistically with HBV infection 2

• Non-alcoholic fatty liver disease (NAFLD):

  • Emerging as a significant cause of HCC 1, 3
  • Associated with obesity, diabetes, and metabolic syndrome 2
  • May lead to HCC even without cirrhosis in some cases 1

• Other causes:

  • Hemochromatosis, alpha-1-antitrypsin deficiency, and other inherited metabolic diseases 1, 2
  • Collectively account for a smaller percentage of global HCC cases

Geographic Distribution of HCC Etiologies

• Africa and East Asia:

  • HBV is the dominant cause (60% of cases) 1
  • Aflatoxin exposure is an important co-factor 2

• Western countries (Europe and North America):

  • HCV is more prevalent (only 20% of cases attributed to HBV) 1
  • Alcoholic liver disease and increasingly NAFLD are significant contributors 1, 2

• Japan:

  • HCV has historically been the predominant cause 1
  • Recent decline in HCV-related HCC incidence noted 1

Risk Factors and Disease Progression

• Cirrhosis:

  • Present in approximately 90% of HCC cases 1
  • Annual risk of HCC development in cirrhotic patients is 1-8% 1
  • Risk varies by etiology (higher in viral hepatitis-related cirrhosis) 1

• Other risk factors:

  • Male gender and older age 1, 2
  • Severity of liver disease (portal hypertension, liver stiffness) 1
  • Genetic factors and viral characteristics 1

Clinical Implications

• HBV vaccination programs have shown success in reducing HCC incidence in endemic regions 1
• Early antiviral treatment of HBV and HCV can reduce HCC risk 1
• Surveillance is recommended for high-risk populations, particularly those with cirrhosis 1
• The rising prevalence of NAFLD may change the epidemiological landscape of HCC in the future 1, 3

Conclusion

While regional variations exist in the predominant causes of HCC, hepatitis B virus remains the single most common etiologic factor worldwide, responsible for more than half of all cases globally. This underscores the importance of HBV prevention strategies, including universal vaccination and antiviral therapy, in reducing the global burden of HCC.