Digestive Diseases and Sciences

, Volume 51, Issue 2, pp 338–345 | Cite as

The Combined Elevation of Tumor Markers CA 19-9 and CA 125 in Liver Disease Patients Is Highly Specific for Severe Liver Fibrosis

Liver

Abstract

Increased tumor markers in patients with liver cirrhosis are often considered to be unspecific. The use of this unspecific elevation to discriminate minimal fibrosis from severe fibrosis has never been explored. We aimed to answer the question, Do tumor markers predict severe liver fibrosis? The study group consisted of 125 patients with alcoholic liver disease, hepatitis B, or hepatitis C with available liver biopsy. Tumor markers CA 19-9, CA 15-3, and CA 125 were determined using routine laboratory methods and correlated with the extent of liver fibrosis. Fibrosis stages 1 and 2 were classified as minimal fibrosis; stages 3 and 4, as severe fibrosis.

Tumor markers CA 19-9, CA 125, and CA 15-3 increased with stage of fibrosis. For separating patients with mild fibrosis (F1+F2) from patients with severe fibrosis (F3+F4), CA 19-9 had a sensitivity of 70.5% and a specificity of 88.6, CA 125 had 38.1% and 89.7%, and CA 15-3 had 19.0% and 93.0%, respectively. Logistic regression of a combined score of CA19-9 and CA 125 values revealed that an increase of 1 point of the CA 19-9/CA125 score resulted in a 1.6 times increase in likelihood of the presence of severe fibrosis. The CA 19-9/CA 125 score achieved a similar specificity (97.1% vs. 100%) but a higher sensitivity (42.9% vs. 33.3%) than the widely used cirrhosis discriminant score of Bonacini. A specificity (98.5%) similar to that of the CA 19-9/CA 125 score was reached by the easier determination of the combined elevation of CA 19-9 and CA 125, which had the best positive predictive value, 92.9%. The excellent predictive ability of the combined elevation of CA 19-9 and CA 125 for severe liver fibrosis (F3+F4) was confirmed in an independent group of patients with liver disease. The combined elevation of CA 19-9 and CA 125 is useful for identifying patients with advanced fibrosis or cirrhosis with high specificity. Patients without a combined elevation of CA 19-9 and CA 125 still require histological examination to identify severe fibrosis or cirrhosis.

Key Words

CA 19-9 CA 125 tumor marker liver fibrosis 

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References

  1. 1.
    Perrillo RP: The role of liver biopsy in hepatitis C. Hepatology 26(Suppl 1):57S–61S, 1997PubMedGoogle Scholar
  2. 2.
    Piccinino F, Sagnelli E, Pasquale G, Guisti G: Complications following percutaneous liver biopsy: a multicentre retrospective study on 68,276 biopsies. J Hepatol 2:165–173, 1986CrossRefPubMedGoogle Scholar
  3. 3.
    3. Garcia-Tsao G, Boyer JL: Outpatient liver biopsy: how safe is it? Ann Intern Med 118:150–153, 1993PubMedGoogle Scholar
  4. 4.
    Piccinino F, Sagnelli E, Pasquale G, Giusti G: Complications following percutaneous liver biopsy: a multicenter retrospective study om 68,276 biopsies. J Hepatol 2:165–173,1986CrossRefPubMedGoogle Scholar
  5. 5.
    Nord JH: Biopsy diagnosis of cirrhosis: blind percutaneous versus guided direct vision techniques. A review. Gastrointest Endosc 28:102–104, 1982Google Scholar
  6. 6.
    Teran JC, Bashour FN, Sondhi SS, Mullen KD: Validation of a discriminant score for the diagnosis of cirrhosis in patients with chronic hepatitis. Gastroenterology 108:A1185, 1995 (abstract)CrossRefGoogle Scholar
  7. 7.
    Bonacini M. Hadi G, Govindarajan S, Lindsay KL: Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol 92:1302–1304, 1997PubMedGoogle Scholar
  8. 8.
    Knoddel RG, Ishak KG, Black WC, et al.: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435, 1981Google Scholar
  9. 9.
    Saadeh S, Cammell G, Carey WD, Younossi Z, Barnes D, Easley K: The role of liver biopsy in chronic hepatitis C. Hepatology 33:196–200, 2001CrossRefPubMedGoogle Scholar
  10. 10.
    Oberti F, Valsesia E, Pilette C, Rousselet MC, Bedossa P, Aubé C, Gallois Y, Rifflet H, Maïga MY, Penneau-Fontbonne D, Calès P: Noninvasive diagnosis of hepatic fibrosis or cirrhosis. Gastroenterology 113:1609–1616, 1997CrossRefPubMedGoogle Scholar
  11. 11.
    Naveau S, Poynard T, Benattar C, Bedossa P, Chaput J-C: Alpha-2-macroglobulin and hepatic fibrosis. Dig Dis Sci 39(11):2426–2432, 1994CrossRefPubMedGoogle Scholar
  12. 12.
    Molina R, Filella X, Bruix J, Mengual P, Bosch J, Calvet X, Jo J, Ballesta AM: Cancer antigen 125 in serum and ascitic fluid of patients with liver diseases. Clin Chem 37(8):1379–1383, 1991PubMedGoogle Scholar
  13. 13.
    Zuckerman E, Lanir A, Sabo E, Rosenvald-Zuckerman T, Matter I, Yeshurun D, Eldar S: Cancer Antigen 125: A sensitive marker of ascites in patients with liver cirrhosis. Am J Gastroenterol 94:1613–1618, 1999CrossRefPubMedGoogle Scholar
  14. 14.
    Collazos J: Clinical and laboratory evaluation of CA 19–9 in cirrhotic patients. Eur J Med 1(4):215–218, 1992PubMedGoogle Scholar
  15. 15.
    Canney PA, Moore M, Wilkinson PM, James RD: Ovarian cancer antigen CA125: a prospective clinical assessment of its role as a tumour marker. Br J Cancer 50(6):765–769, 1984PubMedGoogle Scholar
  16. 16.
    Touitou Y, Bogdan A: Tumor markers in non-malignant diseases. Eur J Cancer Clin Oncol 24(7):1083–1091, 1988 (review)CrossRefPubMedGoogle Scholar
  17. 17.
    Ludwig J: Histopathological diagnosis and terminology of chronic hepatitis. J Hepatol 1:49–53, 1995Google Scholar
  18. 18.
    Deschenes M, Michel RP, Alpert E, Barkun JS, Metrakos P, Tchervenkov J: Elevation of CA-125 level is due to abdominal distension in liver transplantation candidates. Transplantation 72(9):1519–1522, 2001PubMedGoogle Scholar
  19. 19.
    Guyader D, Jacquelinet C, Moirand R, Turlin B, Mendler MH, Chaperon J, David V, Brissot P, Adams P, Deugnier Y: Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. Gastroenterology 115(4):929–936, 1998CrossRefPubMedGoogle Scholar
  20. 20.
    Collazos J, Genolla J, Ruibal A: CA 19-9 in non-neoplastic liver diseases. A clinical and laboratory study. Clin Chim Acta 210(1–2):145–151, 1992Google Scholar
  21. 21.
    Osswald BR, Klee FE, Wysocki S: The reliability of highly elevated CA 19-9 levels. Dis Markers 11(5–6):275–278, 1993PubMedGoogle Scholar
  22. 22.
    Kadayifci A, Simsek H, Savas MC, Toppare M: Serum tumor markers in chronic liver disease. Neoplasma 43(1):17–21, 1996PubMedGoogle Scholar
  23. 23.
    Collazos J, Genolla J, Ruibal A: Breast cancer-associated antigen CA 15.3 in liver cirrhosis. Acta Oncol 31(7):741–744, 1992PubMedGoogle Scholar
  24. 24.
    Collazos J, Genolla J, Ruibal A: CA 15.3 in nonmalignant liver diseases. Int J Biol Markers 6(3):188–192, 1991PubMedGoogle Scholar
  25. 25.
    Giannini E, Borro P, Botta F, Chiarbonello B, Fasoli A, Malfatti F, Romagnoli P, Testa E, Risso D, Lantieri PB, Antonucci A, Boccato M, Milone S, Testa R: Cholestasis is the main determinant of abnormal CA 19-9 levels in patients with liver cirrhosis. Int J Biol Markers 15(3):226–230, 2000PubMedGoogle Scholar
  26. 26.
    Mann DV, Edwards R, Ho S, Lau WY, Glazer G: Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol 26(5):474–479, 2000CrossRefPubMedGoogle Scholar
  27. 27.
    Romagnuolo J, Jhangri GS, Jewell LD, Bain VG: Predicting the liver histology in chronic hepatitis C: how good is the clinician? Am J Gastroenterol 96(11):3165–3174, 2001CrossRefPubMedGoogle Scholar
  28. 28.
    Myers RP, Hilsden RJ, Lee SS: Historical features are poor predictors of liver fibrosis in Canadian patients with chronic hepatitis C. J Viral Hepat 8(4):249–255, 2001CrossRefPubMedGoogle Scholar
  29. 29.
    Poynard T, Aubert A, Bedossa P, Abella A, Naveau S, Paraf F, Chaput JC: A simple biological index for detection of alcoholic liver disease in drinkers. Gastroenterology 100:1397–402, 1991PubMedGoogle Scholar
  30. 30.
    Teare JP, Sherman D, Greenfield SM, Simpson J, Bray G, Catterall AP, Murray-Lyon IM, Peters TJ, Williams R, Thompson RP: Comparison of serum procollagen III peptide concentrations and PGA index for assessment of hepatic fibrosis. Lancet 342:895–898, 1993CrossRefPubMedGoogle Scholar
  31. 31.
    Kanzler S, Baumann M, Schirmacher P, Dries V, Bayer E, Gerken G, Dienes HP, Lohse AW: Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta. J Viral Hepat 8(6):430–437, 2001CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Maximilian Schöniger-Hekele
    • 1
  • Christian Müller
    • 1
    • 2
  1. 1.Universitätsklinik für Innere Medizin IV, Klinische Abteilung Gastroenterologie und HepatologieMedical University of ViennaAustria
  2. 2.Klinische Abteilung Gastroenterologie und HepatologieUniversitätsklinik für Innere Medizin IVWienAustria

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