Hepatocellular Carcinoma in 2021: An Exhaustive Update

Abstract

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.

Keywords: ablation; bclc; chronic hepatitis; cirrhosis; liver cancer; liver transplantation; portal hypertension; tace.

Figure 1. Schematic representation of biomarkers

This diagram represents all the pertinent biomarkers that are currently in use and those with potential for future use in the surveillance and diagnosis of hepatocellular carcinoma. The biomarkers are divided into protein-, genome- and microbiota-based markers. AFP - alpha-fetoprotein, DCP - des-gamma-carboxy-prothrombin, PIVKA - protein induced by vitamin K absence or antagonist, SCC - squamous cell carcinoma, PPPD-L1 - pretreatment peripheral programmed cell death ligand-1, AKR1B - aldo-keto reductase 1B, HMBG - high-mobility-group-box, AFP-L3 - third electrophoretic form of lentil lectin-reactive AFP, SNP - single nucleotide polymorphism, miRNA- micro-RNA

Figure 2. Schematic representation of updated and recommended treatment for hepatocellular carcinoma (HCC)

The infographic represents the staging of HCC as per Barcelona Clinic Liver Cancer (BCLC) staging for decision-making. The overall survival (OS) associated with each treatment modality is showcased along with current updates on each of the treatment options. LT - liver transplantation, TACE - transarterial chemoembolization, TARE - transarterial radioembolization, MELD - model for end-stage liver disease, DEB-TACE - drug-eluting bead-TACE, PV - portal vein, HV - hepatic vein, ICG - indocyanine green, HAP - hepatic arterial prognostic score, MWA - microwave ablation, RFA - radiofrequency ablation, SBRT - stereotactic body radiation therapy, IRE - irreversible electroporation