Hepatocellular carcinoma is the most common primary liver cancer and a leading cause of cancer death worldwide. It typically arises in the setting of chronic liver disease, especially cirrhosis caused by chronic hepatitis B or C infection, heavy alcohol use, or nonalcoholic fatty liver disease linked to obesity and diabetes. Aflatoxin exposure and certain inherited metabolic disorders are additional risk factors.

Research shows that hepatocellular carcinoma develops through a multistep process in which chronic inflammation, oxidative stress, and repeated cycles of cell death and regeneration drive genetic and epigenetic alterations. Frequent changes include mutations in TERT promoter, TP53, CTNNB1, and genes controlling cell cycle, chromatin remodeling, and Wnt and MAPK signaling. Distinct molecular subtypes have been described, some characterized by proliferation and poor prognosis, others more indolent.

Surveillance of high risk patients with ultrasound, with or without alpha fetoprotein measurement, improves early detection, though sensitivity is limited. Curative options include surgical resection, local ablation, and liver transplantation, but many patients present at intermediate or advanced stages.

Locoregional therapies such as transarterial chemoembolization and radioembolization can control intrahepatic disease. Systemic therapy has evolved rapidly, moving from sorafenib monotherapy to multiple targeted agents and immunotherapies. Combinations of immune checkpoint inhibitors with antiangiogenic drugs have improved overall survival and response rates compared with earlier standards. Ongoing studies are testing new combinations, neoadjuvant and adjuvant use, and biomarkers to better match therapies to tumor biology.

Current research emphasizes integrating molecular classification, immune profiling, and liver function assessment to personalize treatment and improve outcomes.