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AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

Lookup NU author(s): Dr Gary Beale, Dr Dipanker Chattopadhyay, Dr Joseph Gray, Dr Stephen Stewart, Dr Mark Hudson, Professor Chris Day, Professor Derek Manas, Professor Helen ReevesORCiD



Background: The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin - in patients with HCC arising on a background of ALD or NAFLD. Methods: Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP. Results: Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination. Conclusion: We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 - suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease. © 2008 Beale et al; licensee BioMed Central Ltd.

Publication metadata

Author(s): Beale GS, Chattopadhyay D, Gray J, Stewart SF, Hudson M, Day CP, Trerotoli P, Giannelli G, Manas DM, Reeves HL

Publication type: Article

Publication status: Published

Journal: BMC Cancer

Year: 2008

Volume: 8

Pages: 200

ISSN (electronic): 1471-2407

Publisher: BioMed Central Ltd.


DOI: 10.1186/1471-2407-8-200


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