Circulating predictive and diagnostic biomarkers for hepatitis B virus-associated hepatocellular carcinoma

Abstract

Chronic hepatitis B virus (HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma (HCC). HCC is the fifth most common and third most deadly cancer worldwide. Up to 50% of newly diagnosed HCC cases are attributed to HBV infection. Early detection improves survival and can be achieved through regular screening. Six-monthly abdominal ultrasound, either alone or in combination with alpha-fetoprotein serum levels, has been widely endorsed for this purpose. Both techniques however yield limited diagnostic accuracy, which is not improved when they are combined. Alternative circulating or histological markers to predict or diagnose HCC are therefore urgently needed. Recent advances in systems biology technologies have enabled the identification of several new putative circulating biomarkers. Although results from studies assessing combinations of these biomarkers are promising, evidence for their clinical utility remains low. In addition, most of the studies conducted so far show limitations in design. Attention must be paid for instance to different ethnicities and different etiologies when studying biomarkers for hepatocellular carcinoma. This review provides an overview on the current understandings and recent progress in the field of diagnostic and predictive circulating biomarkers for hepatocellular carcinoma in chronically infected HBV patients and discusses the future prospects.

Keywords: Alpha-fetoprotein; Biomarkers; Diagnostic; Hepatitis B virus infection; Hepatocellular carcinoma; Limitations; MicroRNA; Predictive; Validation.

Figure 1

Cellular origin of the discussed predictive and diagnostic biomarkers in a physiological and oncological setting. Predictive biomarkers are displayed in italics. PIVKA-II: Protein induced by vitamin K absence; AFP: Alpha-fetoprotein; GPC3: Glypican-3; SCCA: Squamous cell carcinoma antigen; DKK1: Dickkopf-1 protein; miRNA: MicroRNA; COMP: Cartilage oligomeric matrix protein; GP73: Glycoprotein-73; sPD-1: Soluble programmed death-1; Gamma-GT: Gamma-glutamyltransferase.