title: 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.
authors.affiliation: Stijn Van Hees, Peter Michielsen, Thomas Vanwolleghem, Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Edegem, Belgium.
authors.forename: Stijn
authors.initials: S
authors.lastname: Van Hees
authors.affiliation: Stijn Van Hees, Peter Michielsen, Thomas Vanwolleghem, Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Edegem, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Michielsen
authors.affiliation: Stijn Van Hees, Peter Michielsen, Thomas Vanwolleghem, Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Edegem, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanwolleghem
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D053673:Glypicans / Q000378:metabolism; D006509:Hepatitis B / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D006515:Hepatitis B virus; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D014463:Ultrasonography; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; C410824:GOLM1 protein, human; C105937:GPC3 protein, human; D053673:Glypicans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; C506895:SPP1 protein, human; D015843:Serpins; D000509:alpha-Fetoproteins; C051072:squamous cell carcinoma-related antigen; D053495:Osteopontin; C008208:acarboxyprothrombin; D011516:Prothrombin
keywords: Alpha-fetoprotein; Biomarkers; Diagnostic; Hepatitis B virus infection; Hepatocellular carcinoma; Limitations; MicroRNA; Predictive; Validation