Global, regional, and national burden of hepatocellular carcinoma and contribution of nine modifiable risk factors across 185 countries/territories in 2022.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. However, no previous studies systematically provided global HCC burden and population attributable fractions (PAFs) of major risk factors for HCC at the global, regional, subregional, and national levels. We conducted a population-based study to assess the global burden of HCC and the contribution of nine modifiable risk factors. We used data from GLOBOCAN 2022, CI5, GBD 2021, and other large-scale data sources. We categorized nine major modifiable risk factors as infections (hepatitis B or C virus [HBV, HCV], or C. sinensis), metabolic factors (obesity, type 2 diabetes mellitus, and metabolic dysfunction-associated steatotic liver disease [MASLD]), and behavioral/toxic factors (high alcohol use, smoking, and aflatoxin B1). In 2022, globally, there were 684,659 new HCC cases and 597,434 deaths, with the highest age-standardized rates observed in Eastern Asia and Northern Africa. An estimated 78.4% (536,571/684,659) of global HCC cases were attributable to the evaluated risk factors, with 82.5% in Asia and 60.4% in America. Infections contributed most worldwide (65.9%), followed by behavioral/toxic risk factors (22.4%) and metabolic factors (19.7%). Region-specific predominant risk factors included HBV in Eastern Asia (72.5%), HCV in Northern Africa (43.9%), smoking in Northern America (24.5%), and high alcohol use in Western Europe (24.9%). Between 1990 and 2022, infection and behavioral/toxic factors declined globally, whereas metabolic factors steadily increased. The substantial variations in HCC burden and PAF across regions highlight the importance of tailored, region-specific preventive interventions to address the varying modifiable risk factors.