Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major cause of cancer deaths worldwide. It typically arises in the setting of chronic liver disease, especially cirrhosis caused by chronic hepatitis B or C infection, alcohol abuse, or non alcoholic fatty liver disease. Aflatoxin exposure and metabolic disorders also contribute to risk.

Molecularly, HCC is highly heterogeneous. Frequent alterations affect telomere maintenance, cell cycle control, Wnt β catenin signaling, oxidative stress pathways, and chromatin remodeling. Mutations in TERT promoter, CTNNB1, TP53 and genes regulating epigenetics are common. Distinct molecular subclasses correlate with proliferation, inflammation, metabolic changes and prognosis. The tumor microenvironment, including immune and stromal cells, plays a key role in tumor growth and treatment response.

Diagnosis relies on imaging characteristics in high risk patients, supported by blood markers such as alpha fetoprotein, and increasingly by other serum and imaging biomarkers. Early detection is critical because curative options such as surgical resection, liver transplantation and local ablation are mainly effective in early stage disease.

For advanced HCC, systemic therapy has expanded beyond multi kinase inhibitors targeting angiogenesis and growth signals. Immune checkpoint inhibitors that block PD 1, PD L1 or CTLA 4 have improved survival, particularly in combination with antiangiogenic agents. However, responses are variable and resistance is common, driving efforts to identify predictive biomarkers and optimize combination regimens. Ongoing research focuses on integrating genomics, immunology, and metabolism to refine risk stratification, personalize therapy, and develop new targeted and immunotherapy approaches that improve outcomes while limiting toxicity.