Liver cancer is the third leading cause of cancer mortality worldwide, and global incidence is rising. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for more than 90% of cases. Hepatitis B virus (HBV) infection is one of the most common causes of HCC development, accounting for approximately 50% of cases worldwide. The risk of developing HCC from hepatitis C virus (HCV) infection has significantly decreased, due to patients achieving a sustained virological response with available antiviral medications. In recent years, metabolic dysfunction associated steatohepatitis (MASH) has emerged as a rapidly growing cause of liver cancer, particularly in Western countries. MASH is linked to issues like obesity and diabetes, highlighting the importance of maintaining a healthy lifestyle to reduce the risk of liver-related diseases. Development and application of precision medicine has been challenging in HCC for several reasons, including infrequent tissue sampling, inter-patient variation, and intratumoural heterogeneity.

HCC is diagnosed through non-invasive imaging, and tumours are not frequently biopsied, presenting a barrier to both biomarker discovery and informing clinical practice. Ablation, surgical resection, or liver transplant is recommended for the minority of tumours diagnosed at an early stage, while intermediate and advanced tumours are treated with chemoembolization, systemic drugs, and more recently, immunotherapies. Due to a lack of symptoms, HCC is usually diagnosed late, and despite progress with approved therapeutics over the past 15 years, treatment for intermediate and advanced HCC is not curative. Even with early intervention, recurrence rates are high, and the five-year survival rate for liver cancer patients in Canada remains stubbornly low at 22%.