Recently in 2020, the combination of atezolizumab and bevacizumab also received FDA approval and showed significant improvement in the overall and progression-free survival outcomes compared to sorafenib in unresectable or metastatic HCC. After a decade of negative trials, the approvals of lenvatinib as first-line along with regorafenib, carbozantinib, and recombinant immunoglobulin G1 (IgG1) monoclonal antibody ramucirumab as second-line post-sorafenib in early 2019 paved the way to sequential systemic therapy in HCC. Among the targeted therapies, sorafenib was the first systemic drug that showed efficacy in advanced HCC and had remained the standard of care as first-line therapy for over 10 years. Systemic therapies and transarterial radioembolization (TACE) are the only available treatment options for advanced-stage disease. Current treatment options reserved for early-stage HCC include local ablative therapies, resection, and liver transplantation.

The treatment of HCC depends on various factors, including the tumor stage, patient performance status, and liver functional reserve, thereby requiring a multidisciplinary approach. Other medications such as statins and aspirin have been shown to reduce the risk of HCC incidence. Furthermore, anti-diabetic agents such as sulfonylureas and insulin are associated with an increased risk of HCC in contrast to metformin and thiazolidinediones, which are associated with a reduced risk of HCC development. Additionally, aflatoxin B1, a secondary metabolite of a few Aspergillus fungi species, is a known potent mycotoxin ingested through staple food contamination and a major cause of HCC in high-risk geographical regions of Africa and Asia. HCC does also arise in the setting of hepatitis B virus (HBV) infection even without cirrhosis, given the ability of HBV to stimulate oncogenesis through integration into the liver cell DNA.

Cirrhosis arises in the setting of chronic liver diseases such as hepatitis C (HCV) infection, alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), and hemochromatosis (resulting in liver iron overload).

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