Hepatocellular Carcinoma in 2021: An Exhaustive Update

Primary liver cancer is a challenging global health concern with an estimated more than a million persons to be affected annually by the year 2025. The commonest type is hepatocellular carcinoma (HCC), which has been increasing in incidence the world over, mostly due to chronic viral hepatitis B infection. In the last decade, paradigm changes in the etiology, understanding of molecular biology, and pathogenesis, including the role of gut microbiota; medical and surgical treatments, and outcome trends are notable. The application of omics-based technology has helped us unlock the molecular and immune landscape of HCC, through which novel targets for drug treatment such as immune-checkpoint inhibitors have been identified. Novel tools for the surveillance and diagnosis of HCC include protein-, genomics-, and composite algorithm-based clinical/biomarker panels. Magnetic resonance imaging-based novel techniques have improved HCC diagnosis through ancillary features that enhance classical criteria while positron emission tomography has shown value in prognostication. Identification of the role of gut microbiota in the causation and progression of HCC has opened areas for novel therapeutic research. A select group of patients still benefit from modified surgical and early interventional radiology treatments. Improvements in radiotherapy protocols, identification of parameters of futility among radiological interventions, and the emergence of novel first-line systemic therapies that include a combination of antiangiogenic and immune-checkpoint inhibitors have seen a paradigm change in progression-free and overall survival. The current review is aimed at providing exhaustive updates on the etiology, molecular biology, biomarker diagnosis, imaging, and recommended treatment options in patients with HCC.