Hepatocellular carcinoma: Epidemiology, diagnosis and treatment
Ezequiel Mauro, Tiago de Castro, Marcus Zeitlhoefler, Max W. Sung, Augusto Villanueva, Vincenzo Mazzaferro, Josep M. Llovet
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide and primarily affects individuals with cirrhosis. While viral hepatitis has historically been the predominant cause, the burden of HCC is increasingly shifting toward non-viral aetiologies, such as ALD (alcohol-related liver disease) and MASLD (metabolic dysfunction-associated steatotic liver disease). Preventive strategies, including HBV vaccination and antiviral therapies, have reduced the incidence of virus-related HCC, while emerging antifibrotic and metabolic agents may limit MASLD progression. Surveillance with biannual ultrasound and alpha-fetoprotein testing facilitates early detection and curative treatment, although underuse remains a critical limitation. Advances in surgical resection, liver transplantation, and locoregional therapies have improved outcomes in early and intermediate stages. In advanced HCC, immune checkpoint inhibitor-based combinations have shifted the treatment landscape, with median overall survival now exceeding two years and long-term responses observed in a subset of patients. Despite these advances, substantial unmet needs remain in prevention, early detection, and therapeutic access. Ongoing research into biomarkers and novel treatments offers the potential to further transform the HCC care continuum.