Hepatitis B Virus is the Most Common Etiological Factor for Hepatocellular Carcinoma Worldwide
Hepatitis B virus (HBV) is the most common etiological factor for hepatocellular carcinoma (HCC) worldwide, accounting for approximately 54% of all cases globally. 1
Epidemiological Evidence
The global distribution of HCC etiological factors shows clear geographical patterns:
Worldwide distribution: According to the most recent EASL guidelines (2018), approximately 54% of HCC cases can be attributed to HBV infection (which affects 400 million people globally), while 31% can be attributed to HCV infection (affecting 170 million people), leaving approximately 15% associated with other causes 1
Regional variations:
Risk Factors by Region
The EASL guidelines provide a detailed breakdown of HCC etiology by geographical region 1:
| Region | HBV (%) | HCV (%) | Alcohol (%) | Others (%) |
|---|---|---|---|---|
| East Asia | 41 | 9 | 32 | 18 |
| Africa (Sub-Saharan) | 29-45 | 11-20 | 29-40 | 11-15 |
| Western Europe | 13 | 44 | 32 | 10 |
| North America | 9 | 31 | 37 | 23 |
Pathogenesis of HBV-Related HCC
HBV contributes to hepatocarcinogenesis through several mechanisms:
- Integration of viral DNA into host cellular DNA, which can disrupt or promote expression of genes important for cell growth and differentiation 2
- HBx protein acts as a transactivating protein that promotes cell growth, survival, and development of HCC 2
- Chronic inflammation leading to repeated cycles of hepatocyte injury, regeneration, and accumulation of genetic alterations 1
Risk Modifiers in HBV-Related HCC
Several factors increase the risk of HCC development in patients with chronic HBV infection:
- Viral factors: HBeAg seropositivity, high viral load, and genotype C are independent predictors of HCC development 1
- Demographic factors: Male sex, older age (particularly males ≥40 years and females ≥50 years) 1
- Environmental factors: Alcohol consumption, aflatoxin B1 exposure (particularly in Africa and Asia) 1
- Presence of cirrhosis: The strongest predictor, with an annual HCC incidence of 1-8% in cirrhotic patients 1
Emerging Trends
While HBV remains the dominant global cause of HCC, the epidemiological landscape is changing:
- NAFLD/NASH-related HCC is increasing in Western countries due to rising obesity and diabetes rates 1
- HCV-related HCC remains significant in Western countries and Japan 3
- Universal HBV vaccination programs have shown success in reducing HCC incidence in some regions 1
Clinical Implications
Understanding that HBV is the primary etiological factor for HCC worldwide has important implications:
- Prevention strategies should focus on universal HBV vaccination at birth 1
- Surveillance programs should target high-risk populations, particularly those with chronic HBV infection 1
- Antiviral therapy for chronic HBV can reduce the risk of HCC development 1
In conclusion, while there are regional variations in the etiology of HCC, hepatitis B virus infection represents the most significant risk factor globally, responsible for more than half of all HCC cases worldwide.