The changing epidemiology of primary liver cancer in the 21^st century

During the 21st century, the global burden of primary liver cancer has continued to rise, with the absolute numbers of incident cases and deaths increasing by 59.4% and 55.8%, respectively, between 2000 and 2023. Analysis of the GBD 2023 database shows that although age-standardised incidence and mortality rates declined from 2000, this favourable trend reversed around 2020, highlighting the need for continued surveillance. Viral hepatitis remains the leading cause of primary liver cancer worldwide, but its proportional contribution is decreasing. Notably, despite earlier gains from vaccination and antiviral therapies, hepatitis B- and hepatitis C-associated liver cancer incidence and mortality have rebounded globally since 2020. In contrast, metabolic dysfunction-associated steatotic liver disease has exhibited the fastest growth, with sustained increases in age-adjusted incidence and mortality across regions. Marked geographical variation persists in underlying aetiologies, with hepatitis B predominant in East Asia and Sub-Saharan Africa, hepatitis C in the Middle East, North Africa, the Americas, and alcohol-related disease in Europe and Australasia. Additionally, rising incidence and mortality of intrahepatic cholangiocarcinoma underscore the need for dedicated research beyond hepatocellular carcinoma. Collectively, these findings emphasise the urgency of sustained public health and clinical interventions targeting preventable and treatable liver diseases to curb future liver cancer burden.