Introduction: Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the third largest cause of cancer-relateddeaths worldwide. Potentially curative treatments (surgical resection, radiofrequency or liver transplantation) are only available for few patients, while transarterial chemoembolization (TACE) or systemic agents are the best treatments for intermediate and advanced stage disease. The identification of markers that allow us to choose the best treatment for the patient is urgent.Areas covered: In this review we summarize the potential biological markers to predict the efficacy of all treatment available in patients with HCC and discuss anew biomarker with ahigher potential of success in the next future.Expert opinion: HCC is aheterogeneous disease. Tumors are heterogeneous in terms of genetic alteration,with spatial heterogeneity in cellular density, necrosis and angiogenesis.This heterogeneity may affect prognosis and treatment. Tumor heterogeneity can be difficult to quantify with traditional imaging due to subjective assessment of images; the same for sampling biopsy, which evaluates only asmall part of the tumor. We think that combining multi-OMICSwith radiomics represents apromising strategy for evaluating tumor heterogenicity and for identifying biomarkers of response and prognosis.
Keywords: Biomarkers; Hepatocellular Carcinoma; Immune checkpoints inhibitors; Liquid biopsy; Radiomics; Sorafenib; α-fetoprotein.