HCC management from 2020 to 2025: the revolution in epidemiology

The incidence of hepatocellular carcinoma (HCC) varies significantly across regions, driven by differences in risk factors, liver disease management protocols, and screening accessibility. Asia and Africa experience the highest rates, while the Americas, Europe, and the Middle East report a comparatively lower incidence (1–3).

Asia accounts for over 70% of global HCC cases, with China, Japan, India, Thailand, and Vietnam comprising the majority. Mongolia has the highest incidence globally, with 85.6 cases per 100,000 people. Hepatitis B virus (HBV) is the leading cause of HCC in the region, responsible for 60–80% of cases in endemic areas. Japan is an exception, where hepatitis C virus (HCV) dominates, accounting for over 70% of cases. China’s HBV vaccination programme and reduced aflatoxin exposure have led to declining HCC rates since the 1990s. Conversely, countries like Japan have reported increases in HCC incidence. Non-viral causes, such as metabolic-associated steatotic liver disease (MASLD), are rising due to growing obesity rates. In China, obesity prevalence increased from 3.7% in 1982 to 19.0% in 2002, with MASLD prevalence climbing from 25.4% in 2008–2010 to 32.3% in 2015–2018 (1–3).

Africa accounts for 7.8% of global liver cancer cases, with HCC constituting 77% of these cases. It is a leading cause of cancer deaths in sub-Saharan and northern Africa. In northern Africa, HCV is the leading risk factor, particularly in Egypt. HBV infection is the primary driver, contributing to 40% of cases in sub-Saharan regions. Aflatoxin exposure further exacerbates the risk, particularly in younger populations, with a median age of diagnosis around 45 years compared to 52–69 years in other regions. While HBV vaccination is widely adopted, access to treatment remains limited in many African nations. Emerging risk factors such as obesity and diabetes are expected to increase MASLD-related HCC cases (1–3).

Europe contributes 9.7% of global HCC cases, with notable regional disparities. Southern Europe reports higher incidence rates (6.7 cases per 100,000), while Central and Eastern Europe have the lowest (4.3 per 100,000). HCV is the leading cause of HCC in Western Europe (37%), while ALD dominates in Central and Eastern regions, accounting for nearly 50% of cases. HBV contributes to 16% of cases continent-wide. The rising prevalence of ALD and MASLD is shifting HCC risk profiles. Western Europe has experienced the largest global increase in MASLD prevalence from 1990 to 2017. Studies in the UK, Germany, and Italy have shown significant growth in MASLD-related HCC cases (1–3).

North America accounts for 5.1% and South America 4.4% of global HCC cases. In the United States, HCV accounts for 38% of cases, followed by ALD (29%), HBV (14%), and MASLD (10%). Recent trends indicate a stabilization in HCC incidence and mortality, with the U.S. reporting annual declines of 2.3% in incidence and 3.2% in mortality since 2010. The introduction of direct-acting antivirals (DAAs) for HCV in 2013 has significantly reduced HCV-related mortality. However, deaths linked to ALD- and MASLD-related HCC have continued to rise, with annual increases of 7.8% and 21.1%, respectively. Globally, MASLD-related liver cancer deaths grew fastest between 2009 and 2018, particularly in the Americas (1–4).

These epidemiological shifts significantly impact HCC patient care. HCC treatments show comparable efficacy regardless of aetiology, but the increased prevalence of ALD and MASLD is associated with a greater likelihood of severe cirrhosis and portal hypertension. MASLD carries a higher risk of post-operative decompensation, and an accurate evaluation of patients should be performed to avoid liver decompensation (5,6). The presence of portal hypertension is linked to higher HCC-related mortality, particularly after surgery, and increases the risk of decompensation following all HCC treatment modalities (7–11). Therefore, comprehensive assessment of underlying liver disease, including portal hypertension, is crucial for all HCC patients, potentially including prophylactic beta-blockers for portal hypertension management when indicated (12), to minimize post-treatment complications.