Definition of liver cancer

Primary liver cancer is a disease in which malignant (cancer) cells form within the tissues of the liver. Secondary or metastatic liver cancer occurs when malignant cells are initially formed in other parts of the body and spread to the liver (NCI 2022, Cancer Research UK 2021). Different types of cancer can occur in the liver. The most common is hepatocellular carcinoma, which starts in the main liver cells, the hepatocytes, and has various subtypes. Cholangiocarcinoma is another form of cancer that starts in the small bile ducts within the liver. Other liver cancers include hepatoblastoma and angiosarcoma; however, these are less common (WCRF 2018). As the early stages of liver cancer are usually asymptomatic, the disease is generally advanced by the time of diagnosis. 

Incidence of liver cancer in the European Union

Liver cancer was estimated to be the 13th most diagnosed cancer and and the 6th most common cause of cancer mortality, for both sexes in the EU in 2022. Age-adjusted incidence of liver cancer is higher in men than in women, with the largest difference seen in Portugal (3.7 fold higher incidence in men than in women), and the smallest difference in Ireland (1.7 fold difference). In addition, there are also large variations in incidence between countries; Romania has the highest incidence of liver cancer both in men and women, whereas Poland has the lowest incidence in men and Malta has the lowest incidence in women (ECIR 2022). Table 1 presents the liver cancer age-adjusted incidence estimates within European Union (EU) countries in 2022 (ECIS 2022). 

Table 1: Age-standardised incidence rate of liver cancer 

Factors related to liver cancer risk

Non-modifiable risk factors comprise age, sex, race, ethnicity and inherited metabolic diseases (ACS 2019a , WCRF/AICR 2018 ). Liver cancer risk increases with age and it is more common among males than females (WCRF, AICR 2018). Among females, there is moderate but statistically significant evidence that older age at first menstrual period (menarche) is associated with a reduced risk of liver cancer (ACS 2019b). Modifiable risk factors include diet, body weight, physical activity level, tobacco smoking, alcohol consumption, infections (viral hepatitis, mainly from hepatitis viruses B and C) and medication use (e.g. contraceptives or oral steroids) (WCRF, AICR 2018). 

Liver cancer is among the main infection-attributable cancers. In 2019, approximately 70% of liver cancers globally were attributed to viral infection with hepatitis B or C (WCRF, AICR 2018). Hepatitis B virus (HBV) is transmitted through exposure to infected blood, semen, and other body fluids. It can be sexually transmitted and transmitted vertically (from mother-to-children at the time of birth),  through transfusions, during medical procedures or by sharing injecting equipment among people who inject drugs. Hepatitis C virus (HCV) is mostly transmitted through exposure to blood, though sexual transmission is also possible. There are certain key populations disproportionately affected by infection by HBV, HCV, or both: men who have sex with men, sex workers, people in prisons, people who inject drugs, and trans and gender diverse people (WHO 2022). Furthermore, presence of some medical conditions is associated with an increased risk of liver cancer. People living with liver cirrhosis (scarring of the liver due to previous damage), for instance, have the highest risk of developing hepatocellular carcinoma (WCRF, AICR 2018). Metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, gallstones and diabetes are also associated with an increased risk of liver cancer (NIH 2023). Table 2 summarises evidence on the main modifiable risk factors for liver cancer. 

Table 2: Modifiable risk factors related to liver cancer 

Disease and economic burden related to liver cancer

Disease burden related to liver cancer

According to the European Cancer Information System, more than 50 000 deaths in the EU in 2022 were due to liver cancer, accounting for 11.1 deaths per 100 000 population in the EU in 2022 (age-standardised mortality rate) (Table 3) (ECIS 2022). The mortality rate is higher among males (17.2 deaths per 100 000) than females (6.3 deaths per 100 000).

Table 3: Estimated age-adjusted mortality rate from liver cancer in the EU in 2022 

According to the Global Burden of Disease (GBD) 2021 Study (GBD 2021), over 820 000 Disability Adjusted Life Years (DALYs) were dueto liver cancer in the EU in 2021. Table 4 shows the DALYs per 100 000 population attributed to liver cancer in EU Member States in 2021 (GBD Results Tool 2021).

Table 4: Disability Adjusted Life Years due to liver cancer in the EU in 2021 

View map: Disability-Adjusted Life Years (DALYs) due to liver cancer in males in EU Member States 

View map: Disability-Adjusted Life Years (DALYs) due to liver cancer in females in EU Member States 

View map: Age-standardised deaths due to liver cancer in males in EU Member States 

View map: Age-standardised deaths due to liver cancer in females in EU Member States 

Economic burden related to liver cancer

The economic burden of liver cancer in 31 European countries (EU-27, Iceland, Norway, Switzerland and the United Kingdom) in 2018 was estimated at €4 billion (IHE 2020), representing 2% of the total cost of cancer in those countries that year. This comprises €1.2 billion of direct healthcare costs (expenditures that are made within the healthcare system such as primary, emergency, outpatient and hospital inpatient care and drugs and treatments) and €2.8 billion of indirect costs including informal care costs (€0.6 billion) and productivity losses due to liver cancer morbidity (€0.3 billion) and mortality (€1.9 billion) (e.g., costs of inability to work, either due to premature mortality or due to sick leave, early retirement and disability) (Digestive Cancers Europe 2021).

Policies related to the prevention of liver cancer

EU countries have implemented initiatives to tackle cancer burden,with an emphasis on mitigating cancer modifiable risk factors (primary prevention) and establishing screening programmes to detect cancer at earlier stages (secondary prevention).

Primary prevention of liver cancer (modifiable risk factors)

Europe’s Beating Cancer Plan (EC 2021) prioritises cancer prevention by promoting healthy behaviours, reducing health inequalities and mitigating risk factors. One of its main pillars is prevention and includes actions and policies to promote health literacy, reduce tobacco and alcohol consumption and to improve access to healthier diets and physical activity. The Cancer Plan also highlights that the European Commission will help to ensure access to vaccination against hepatitis B and to treatments to prevent liver cancer associated with the hepatitis C virus. Hepatitits B immunisation is proposed as an effective measure to prevent and manage the burden of liver cancer (ACS 2019b , WHO 2017), and a new Council Recommendation, based on a proposal by the Commission, calls on EU Member States to strengthen their vaccination programmes to boost cancer prevention, and to tailor these to vulnerable populations (CEU 2024).

Policy recommendations addressing alcohol  and tobacco use, nutrition, physical activity and obesity prevention are listed in the dedicated pages of this Health Promotion and Disease Prevention Knowledge Gateway. 

European initiatives supporting the implementation of these and other policy recommendations to reduce the burden of NCDs include the ‘Healthier Together – EU non-communicable diseases’ initiative and the Joint Action PreventNCD.

Secondary prevention of liver cancer (screening)

Secondary prevention strategies for cancer include screening methods designed to detect the disease during its early stages, prior to the onset of symptoms. In the case of liver cancer, screening of people at elevated risk entails uncommon but serious harms, and might not result in decreased mortality (NCI 2024). 
Seeing the effect of hepatitis B and C infection on the risk of cancer, screening for these viral infections is a complementary measure to prevent liver cancer, especially among vulnerable groups for which the burden of these is highest.
 

References

Overview of the references to this brief