Is Liver Cancer Rare?
Liver cancer is not rare globally—it is the sixth most common cancer worldwide and the second leading cause of cancer death, though its incidence varies dramatically by geography and risk factor exposure. 1
Global Burden and Geographic Variation
Liver cancer represents a major global health burden with substantial geographic heterogeneity:
Worldwide, liver cancer accounted for approximately 841,080 new cases and 781,631 deaths in 2018, representing 4.8% of all new cancer cases and 8.2% of all cancer deaths. 1
In men, liver cancer is the fifth most common cancer globally and the second most common cause of cancer death. 1
The incidence varies dramatically from 3 per 100,000 in Western countries to 78.1 per 100,000 in Mongolia, with the highest rates in Eastern Asia, Middle Africa, and Western Africa. 1
Approximately 71% of all liver cancers occur in Asia, particularly in Eastern (55.6%), South-Eastern (10.6%), and South-Central (5.2%) regions. 1
In Europe, the estimated incidence rate is 10.0 per 100,000 in men and 3.3 per 100,000 in women. 1
Risk Factor-Dependent Incidence
The rarity of liver cancer depends entirely on the presence or absence of specific risk factors:
High-Risk Populations (Not Rare)
Chronic hepatitis B infection increases HCC risk 100-fold in the presence of cirrhosis, with an annual incidence of 3-5% in cirrhotic patients. 1, 2
Chronic hepatitis C cirrhosis carries a 3-5% annual risk of HCC development, with some studies reporting up to 12% per year in certain populations. 1
Genetic hemochromatosis with iron overload carries a 7-9% annual risk of HCC in cirrhotic patients. 1
In South Korea, 59.1% of HCC patients had HBV infection and 10.7% had HCV, demonstrating that liver cancer is common in populations with endemic viral hepatitis. 1
Emerging Risk: NAFLD/NASH
The rising prevalence of obesity and type 2 diabetes has led to increasing incidence of NAFLD/NASH-related HCC, which is expected to potentially overtake other etiologies in some regions. 1
A significant proportion of NAFLD/NASH-associated HCC occurs without histological evidence of cirrhosis, expanding the at-risk population beyond traditional cirrhotic patients. 1
Low-Risk Populations (Relatively Rare)
In populations without viral hepatitis, cirrhosis, or metabolic risk factors, liver cancer remains relatively rare, with incidence rates below 5 per 100,000 in Northern Europe, Australia, New Zealand, and Caucasian populations in North and Latin America. 3
Less than 10% of HCC cases occur in otherwise normal livers without underlying chronic liver disease. 1
Temporal Trends
The incidence of HCC has been rising worldwide over the last 20 years and is expected to continue increasing until 2030 in countries like the United States, though some countries like Japan have seen declining rates. 1
Clinical Implications
Given the strong association with identifiable risk factors, liver cancer should not be considered rare in patients with:
- Chronic HBV or HCV infection (especially with cirrhosis)
- Alcoholic cirrhosis
- NAFLD/NASH with advanced fibrosis or cirrhosis
- Genetic hemochromatosis
- Any cirrhosis regardless of etiology
These high-risk populations warrant systematic HCC surveillance with abdominal ultrasound every 6 months. 1
Common Pitfall
Do not dismiss liver cancer risk in non-cirrhotic patients with NAFLD/NASH or in younger patients from endemic areas, as HCC can develop without cirrhosis in metabolic liver disease and occurs at younger ages (20s-40s) in high-risk geographic regions with early-life viral exposures. 1, 3