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Original Paper

A Combination of α-Fetoprotein and Des-γ-Carboxy Prothrombin Is Superior in Detection of Hepatocellular Carcinoma

Ertle J.M.a · Heider D.c · Wichert M.b · Keller B.a · Kueper R.d · Hilgard P.e · Gerken G.a · Schlaak J.F.a

Author affiliations

aDepartment of Gastroenterology and Hepatology, and bCentral Laboratory, University Hospital Essen, cDepartment of Bioinformatics, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, dWAKO Chemicals GmbH, Neuss, and eDepartment of Internal Medicine and Gastroenterology, Evangelisches Krankenhaus Mülheim an der Ruhr, Mülheim an der Ruhr, Germany

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Digestion 2013;87:121–131

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 30, 2012
Accepted: November 20, 2012
Published online: February 08, 2013
Issue release date: April 2013

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 2

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: https://www.karger.com/DIG

Abstract

Background and Aim: The incidence of hepatocellular carcinoma (HCC) is increasing in western countries. Despite its low sensitivity, the diagnosis of HCC still depends on detection of α-fetoprotein (AFP). Therefore, the aim of this study was to evaluate the combined analysis of AFP and des-γ-carboxy prothrombin (DCP) in a European cohort. Methods: We performed a single-center study (164 HCC/422 controls), in which the serum concentrations of AFP and DCP were determined. Results: AFP and DCP were elevated in HCC patients compared to controls (p < 0.0001). By combination of AFP and DCP, the sensitivity was improved from 28.7% for AFP (cutoff 400 ng/ml; AFP at cutoff 10 ng/ml: 54.9%) to 78.0% using cutoffs of 10 ng/ml for AFP and 5 ng/ml for DCP (DCP alone, cutoff 5 ng/ml: 63.4%). Among early-stage patients, the sensitivity increased from 20% for AFP (cutoff 400 ng/ml; AFP at cutoff 10 ng/ml: 38%) to 55% in combination (DCP alone, cutoff 5 ng/ml: 47%). The area under the curve (AUC) for AFP and DCP was similar (AFP: 0.88; DCP: 0.87; combined: 0.91). Among non-cirrhotic patients, DCP (AUC: 0.93) showed a better performance than AFP (AUC: 0.84). Especially patients with non-alcoholic steatohepatitis had a high percentage of DCP-positive tumors. Conclusion: The data suggest that AFP alone is not sufficient for the serological diagnosis of HCC in European patients, while a combination of AFP and DCP can increase the sensitivity even in early-stage patients.

© 2013 S. Karger AG, Basel


References

  1. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395.
  2. Chen J-G, Zhu J, Parkin DM, Zhang Y-H, Lu J-H, Zhu Y-R, Chen T-Y: Trends in the incidence of cancer in Qidong, China, 1978–2002. Int J Cancer 2006;119:1447–1454.
  3. Parkin DM: The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006;118:3030–3044.
  4. Bruix J, Sherman M: Management of hepatocellular carcinoma. Hepatology 2005;42:1208–1236.
  5. Simonetti RG, Cammà C, Fiorello F, Politi F, D’Amico G, Pagliaro L: Hepatocellular carcinoma. A worldwide problem and the major risk factors. Dig Dis Sci 1991;36:962–972.
  6. Bruix J, Sherman M: Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020–1022.
  7. Gupta S, Bent S, Kohlwes J: Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med 2003;139:46–50.
    External Resources
  8. Chen J, Röcken C, Treiber G, Jentsch-Ulrich K, Malfertheiner P, Ebert MPA: Clinical implications of alpha-fetoprotein expression in gastric adenocarcinoma. Dig Dis 2003;21:357–362.
  9. Daniele B, Bencivenga A, Megna AS, Tinessa V: Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology 2004;127:108–112.
  10. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodés J: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421–430.
  11. Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, Coleman MS, Furie B: Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 1984;310:1427–1431.
  12. Bertino G, Ardiri AM, Boemi PM, Ierna D, Interlandi D, Caruso L, Minona E, Trovato MA, Vicari S, Li Destri G, Puleo S: A study about mechanisms of des-gamma-carboxy prothrombin’s production in hepatocellular carcinoma. Panminerva Med 2008;50:221–226.
    External Resources
  13. Okuda H, Nakanishi T, Takatsu K, Saito A, Hayashi N, Takasaki K, Takenami K, Yamamoto M, Nakano M: Serum levels of des-gamma-carboxy prothrombin measured using the revised enzyme immunoassay kit with increased sensitivity in relation to clinicopathologic features of solitary hepatocellular carcinoma. Cancer 2000;88:544–549.
  14. Bertino G, Ardiri AM, Calvagno GS, Bertino N, Boemi PM: Prognostic and diagnostic value of des-γ-carboxy prothrombin in liver cancer. Drug News Perspect 2010;23:498–508.
    External Resources
  15. Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ, Lok AS: Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients. Hepatology 2003;37:1114–1121.
  16. Bertino G, Neri S, Bruno CM, Ardiri AM, Calvagno GS, Malaguarnera M, Toro A, Malaguarnera M, Clementi S, Bertino N, Di Carlo I: Diagnostic and prognostic value of alpha-fetoprotein, des-γ-carboxy prothrombin and squamous cell carcinoma antigen immunoglobulin M complexes in hepatocellular carcinoma. Minerva Med 2011;102:363–371.
    External Resources
  17. Yamaguchi I, Nakamura K, Kitano H, Masuda Y, Kanke F, Kobatake S, Satomura S: Development of des-gamma-carboxy prothrombin (DCP) measuring reagent using the LiBASys clinical analyzer. Clin Chem Lab Med 2008;46:411–416.
  18. Yamagata Y, Shimizu K, Nakamura K, Henmi F, Satomura S, Matsuura S, Tanaka M: Simultaneous determination of percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein and alpha-fetoprotein concentration using the LiBASys clinical auto-analyzer. Clin Chim Acta 2003;327:59–67.
  19. Sing T, Sander O, Beerenwinkel N, Lengauer T: ROCR: visualizing classifier performance in R. Bioinformatics 2005;21:3940–3941.
  20. Marrero JA, Feng Z, Wang Y, Nguyen MH, Befeler AS, Roberts LR, Reddy KR, Harnois D, Llovet JM, Normolle D, Dalhgren J, Chia D, Lok AS, Wagner PD, Srivastava S, Schwartz M: Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009;137:110–118.
  21. Yamashiki N, Sugawara Y, Tamura S, Kaneko J, Yoshida H, Aoki T, Hasegawa K, Akahane M, Ohtomo K, Fukayama M, Koike K, Kokudo N: Diagnostic accuracy of α-fetoprotein and des-γ-carboxy prothrombin in screening for hepatocellular carcinoma in liver transplant candidates. Hepatol Res 2011;41:1199–1207.
  22. Sterling RK, Wright EC, Morgan TR, Seeff LB, Hoefs JC, Di Bisceglie AM, Dienstag JL, Lok AS: Frequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C. Am J Gastroenterol 2012;107:64–74.
  23. Lok AS, Lai CL: alpha-Fetoprotein monitoring in Chinese patients with chronic hepatitis B virus infection: role in the early detection of hepatocellular carcinoma. Hepatology 1989;9:110–115.
  24. Malaguarnera G, Giordano M, Paladina I, Berretta M, Cappellani A, Malaguarnera M: Serum markers of hepatocellular carcinoma. Dig Dis Sci 2010;55:2744–2755.
  25. Forner A, Reig M, Bruix J: Alpha-fetoprotein for hepatocellular carcinoma diagnosis: the demise of a brilliant star. Gastroenterology 2009;137:26–29.
  26. Toyoda H, Kumada T, Tada T: Highly sensitive lens culinaris agglutinin-reactive α-fetopro-tein: a new tool for the management of hepatocellular carcinoma. Oncology 2011;81:61–65.
  27. Bertino G, Ardiri A, Malaguarnera M, Malaguarnera G, Bertino N, Calvagno GS: Hepatocellualar carcinoma serum markers. Semin Oncol 2012;39:410–433.
  28. Alkofer B, Lepennec V, Chiche L: Hepatocellular cancer in the non-cirrhotic liver. J Visc Surg 2011;148:3–11.
  29. Ertle J, Dechêne A, Sowa J-P, Penndorf V, Herzer K, Kaiser G, Schlaak JF, Gerken G, Syn W-K, Canbay A: Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 2011;128:2436–2443.
  30. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, Srishord M: Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011;9:524–530.
  31. Cabibbo G, Craxì A: Epidemiology, risk factors and surveillance of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci 2010;14:352–355.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 30, 2012
Accepted: November 20, 2012
Published online: February 08, 2013
Issue release date: April 2013

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 2

ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)

For additional information: https://www.karger.com/DIG


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