Abstract
Background
Alpha-fetoprotein (AFP) levels for the diagnosis of hepatocellular carcinoma (HCC) may vary by geographical region and racial background. No data exists for this test in the Middle Eastern population. In addition, there is limited data on the impact of virological status on AFP levels.
Methods
In a multicenter, case-control study involving 206 cases, 199 cirrhotic and 197 chronic hepatitis controls, we assessed the utility of AFP in the diagnosis of HCC (sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and positive likelihood ratios (LR). PPV and NPV were evaluated for three additional HCC prevalence rates (5, 10, and 20%).
Results
The best discriminating AFP value was 11.7 ng/ml. The sensitivity ranged from 32 to 79.5% at different AFP levels with the specificity increasing sequentially from 47.7 to 98.5%. Sensitivity of AFP at the best cut-off level for hepatitis C virus (HCV), hepatitis B virus (HBV) and non-viral etiology for HCC was 73.7, 65.6, and 59.5%, respectively. Specificity at this level for HCV, HBV, and non-viral etiology was 36.6, 30.1, and 29.4%, respectively. AFP cut-off levels of 102, 200, and 400 ng/ml showed similar sensitivity (39.8, 35.9, and 32%, respectively) and specificity (96, 98.5, and 98.5% respectively). Positive LR for AFP at >11.7, >20, >102, >200, >400 ng/ml were 2.8, 3.3, 9.9, 23.8, and 21.2, respectively.
Conclusions
In cirrhotic patients, AFP has a poor screening and diagnostic value for HCC. Underlying viral etiology fails to influence the diagnostic accuracy of this test. An AFP level greater than 100 ng/ml has a high degree of specificity and may be used as a confirmatory test.
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References
Velazquez RE, Rodriguez M, Navascues CA, et al. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology. 2003;37:520–527.
Szilagyi A, Alpert L. Clinical and histopathological variation in hepatocellular carcinoma. Am J Gastroenterol. 1995;90:15–23.
Yuen MF, Cheng CC, Lauder IJ, Lam SK, Ooi CG, Lai CL. Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology. 2000;31:330–335.
McMahon BJ, Bulkow L, Harpster A, et al. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology. 2000;32:842–846.
Wong LL, Whitney ML, Severino P, Wong LM. Improved survival with screening for hepatocellular carcinoma. Liver Transpl. 2000;6:320–325.
Colombo M. Early diagnosis of hepatocellular carcinoma in Italy. A summary of a Consensus Development Conference held in Milan, 16 November 1990, by the Italian Association for the Study of the Liver (AISF). J Hepatol. 1992;14:401–403.
Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference. J Hepatol. 2001;35:421–430.
Bergstrand CG, Czar B. Demonstration of a new protein fraction in serum from the human fetus. Scand J Clin Lab Invest. 1956;8:174.
Masopust J, Kithier K, Radl J, Koutecky J, Kotal L. Occurrence of fetoprotein in patients with neoplasms and nonneoplastic diseases. Int J Cancer. 1968;3:364–373.
Javadpour N. The role of biologic tumour markers in testicular cancer. Cancer. 1980;45:1755–1761.
Liaw YF, Tai DI, Chen TJ, Chu CM, Huang MJ. Alpha-fetoprotein changes in the course of chronic hepatitis: relation to bridging hepatic necrosis and hepatocellular carcinoma. Liver. 1986;6:133–137.
Bloomer JR, Waldmann TA, McIntire KR, Klatskin G. Alpha-fetoprotein in non-neoplastic hepatic disorders. JAMA. 1975;233:38–41.
Silver HKB, Deneault J, Gold P, Thompson WG, Shuster J, Freedman SO. The detection of α-fetoprotein in patients with viral hepatitis. Cancer Res. 1974;34:244–247.
Bayati N, Silverman AL, Gordon S. Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C. Am J Gastroenterol. 1998;93:2452–2456.
Tsai JF, Chang WY, Jeng JE, Ho MS, Lin ZY, Tsai JH. Frequency of raised a-fetoprotein level among Chinese patients with hepatocellular carcinoma related to hepatitis B and C. Br J Cancer. 1994;69:1157–1159.
Stroffolini T, Andreone P, Andriulli A, et al. Characteristics of hepatocellular carcinoma in Italy. J Hepatol. 1998;29:944–952.
Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–1236.
Abdo AA, Karim HA, Al Fuhaid T, et al. Saudi Gastroenterology Association guidelines for the diagnosis and management of hepatocellular carcinoma: summary of recommendations. Ann Saudi Med. 2006;26(4):261–265.
Abdo AA, Al-Jarallah BM, Sanai FM, et al. Hepatitis B genotypes: relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia. World J Gastroenterol. 2006;12(43):7019–7024.
Child CG III, Turcotte JG. Surgery in portal hypertension. In: Child CG III, ed. The liver and portal hypertension. Philadelphia: W.B. Saunders; 1964:50.
Komaroff AL, Berwick DM. Decision theory and medical practice. In: Isselbacher KJ, Adams RD, Braunwald E, Pedersdorf RG, Wilson JD, eds. Principles of internal medicine. Update IV. New York: McGraw-Hill; 1983:243–254.
Colombo M, De Franchis R, Del Ninno E, et al. Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med. 1991;325:675–680.
Zoli M, Malagotti D, Bianchi G, Gueli C, Marchesini G, Pisi E. Efficacy of surveillance program for early detection of hepatocellular carcinoma. Cancer. 1996;78:977–985.
Imberti D, Fornari F, Sbolli G, Buscarini E, Squassante L, Buscarini L. Hepatocellular carcinoma in liver cirrhosis. A prospective study. Scand J Gastroenterol. 1993;28:540–544.
Curley SA, Izzo F, Gallipoli A, de Bellis M, Cremona F, Parisi V. Identification and screening of 416 patients with chronic hepatitis at high risk to develop hepatocellular carcinoma. Ann Surg. 1995;222:375–383.
Trevisani F, D’Intino PE, Morselli-Labate AM, et al. Serum α-fetoprotein for diagnosis of hepatocellular in patients with chronic liver disease: Influence of HBsAg and anti-HCV status. J Hepatol. 2001;34:570–575.
Nguyen MH, Garcia RT, Simpson PW, Wright TL, Keeffe EB. Racial differences in effectiveness of α-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis. Hepatology. 2002;36:410–417.
Soresi M, Magliarisi C, Campagna P, et al. Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res. 2003;23:1747–1753.
Taketa K, Okada S, Win N, Hlaing NK, Wind KM. Evaluation of tumor markers for the detection of hepatocellular carcinoma in Yangon General Hospital, Myanmar. Acta Med Okayama. 2002;56:317–320.
Kim KA, Lee JS, Jung ES, et al. Usefulness of serum alpha-fetoprotein (AFP) as a marker for hepatocellular carcinoma (HCC) in hepatitis C virus related cirrhosis: analysis of the factors influencing AFP elevation without HCC development. Korean J Gastroenterol. 2006;48(5):321–326.
Gupta S, Bent S, Kohlwes J. Test characteristics of alphafetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med. 2003;139:46–50.
Farinati F, Marino D, De Giorgio M, et al. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? Am J Gastroenterol. 2006;101(3):524–532.
Sherman M. Alphafetoprotein: an obituary. J Hepatol. 2001;34:603–605.
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Sanai, F.M., Sobki, S., Bzeizi, K.I. et al. Assessment of Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma in Middle Eastern Patients. Dig Dis Sci 55, 3568–3575 (2010). https://doi.org/10.1007/s10620-010-1201-x
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DOI: https://doi.org/10.1007/s10620-010-1201-x