Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus
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Increases in tumor markers are sometimes seen in patients with chronic liver disease without hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between the levels of three tumor markers [alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3%), and des-γ-carboxy prothrombin (DCP)] and hepatic carcinogenesis to identify hepatitis C virus (HCV) carriers at high risk for cancer development.
A total of 623 consecutive HCV carriers with follow-up periods of >3 years were included. The average integration values were calculated from biochemical tests, and tumor markers, including AFP, AFP-L3%, and DCP, and factors associated with the cumulative incidence of HCC were analyzed.
HCC developed in 120 (19.3%) of the 623 patients. Age >65 years [adjusted relative risk, 2.303 (95% confidence interval, 1.551–3.418), P < 0.001], low platelet count [3.086 (1.997–4.768), P < 0.001], high aspartate aminotransferase value [3.001 (1.373–6.562), P < 0.001], high AFP level [≥10, <20 ng/mL: 2.814 (1.686–4.697), P < 0.001; ≥20 ng/mL: 3.405 (2.087–5.557), P < 0.001] compared to <10 ng/mL, and high AFP-L3% level [≥5, <10%: 2.494 (1.291–4.816), P = 0.007; ≥10%: 3.555 (1.609–7.858), P < 0.001] compared to <5% were significantly associated with an increased incidence of HCC on multivariate analysis.
Increased AFP or AFP-L3% levels were significantly associated with an increased incidence of HCC. Among HCV carriers, patients with ≥10 ng/mL AFP or patients with ≥5% AFP-L3% are at very high risk for the development of HCC even if AFP is less than 20 ng/mL or AFP-L3% is less than 10%, which are the most commonly reported cutoff values.
- Colombo M, de Franchis R, Del Ninno E, Sangiovanni A, De Fazio C, Tommasini M, et al. Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med. 1991;325:675–80. CrossRef
- Kew MC, Purves LR, Bersohn I. Serum alpha-fetoprotein levels in acute viral hepatitis. Gut. 1973;14:939–42. CrossRef
- Alpert E, Feller ER. Alpha-fetoprotein (AFP) in benign liver disease. Evidence that normal liver regeneration does not induce AFP synthesis. Gastroenterology. 1978;74:856–8.
- Eleftheriou N, Heathcote J, Thomas HC, Sherlock S. Serum alpha-fetoprotein levels in patients with acute and chronic liver disease. Relation to hepatocellular regeneration and development of primary liver cell carcinoma. J Clin Pathol. 1977;30:704–8. CrossRef
- Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332:1463–6. CrossRef
- Bayati N, Silverman AL, Gordon SC. Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C. Am J Gastroenterol. 1998;93:2452–6. CrossRef
- Hu KQ, Kyulo NL, Lim N, Elhazin B, Hillebrand DJ, Bock T. Clinical significance of elevated alpha-fetoprotein (AFP) in patients with chronic hepatitis C, but not hepatocellular carcinoma. Am J Gastroenterol. 2004;99:860–5. CrossRef
- Chu CW, Hwang SJ, Luo JC, Lai CR, Tsay SH, Li CP, et al. Clinical, virologic, and pathologic significance of elevated serum alpha-fetoprotein levels in patients with chronic hepatitis C. J Clin Gastroenterol. 2001;32:240–4. CrossRef
- Taketa K. Alpha-fetoprotein: reevaluation in hepatology. Hepatology. 1990;12:1420–32. CrossRef
- Shimizu K, Katoh H, Yamashita F, Tanaka M, Tanikawa K, Taketa K, et al. Comparison of carbohydrate structures of serum α-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis. Clin Chim Acta. 1996;254:23–40. CrossRef
- Mita Y, Aoyagi Y, Yanagi M, Suda T, Suzuki Y, Asakura H. The usefulness of determining des-gamma-carboxy prothrombin by sensitive enzyme immunoassay in the early diagnosis of patients with hepatocellular carcinoma. Cancer. 1998;82:1643–8. CrossRef
- Sassa T, Kumada T, Nakano S, Uematsu T. Clinical utility of simultaneous measurement of serum high-sensitivity des-gamma-carboxy prothrombin and Lens culinaris agglutinin A-reactive alpha-fetoprotein in patients with small hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 1999;11:1387–92. CrossRef
- Kumada T, Toyoda H, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, et al. Relation between incidence of hepatic carcinogenesis and integration value of alanine aminotransferase in patients with hepatitis C virus infection. Gut. 2007;56:738–9. CrossRef
- Kumada T, Toyoda H, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, et al. Incidence of hepatocellular carcinoma in hepatitis C carriers with normal alanine aminotransferase levels. J Hepatol. 2009;50:729–35. CrossRef
- Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20. CrossRef
- Shen L, Li JQ, Zeng MD, Lu LG, Fan ST, Bao H. Correlation between ultrasonographic and pathologic diagnosis of liver fibrosis due to chronic virus hepatitis. World J Gastroenterol. 2006;28:1292–5.
- Iacobellis A, Fusilli S, Mangia A, Clemente R, Festa V, Giacobbe A, et al. Ultrasonographic and biochemical parameters in the non-invasive evaluation of liver fibrosis in hepatitis C virus chronic hepatitis. Aliment Pharmacol Ther. 2005;22:769–74. CrossRef
- Caturelli E, Castellano L, Fusilli S, Palmentieri B, Niro GA, del Vecchio-Blanco C, et al. Coarse nodular US pattern in hepatic cirrhosis: risk for hepatocellular carcinoma. Radiology. 2003;226:691–7. CrossRef
- Kudo M. Imaging diagnosis of hepatocellular carcinoma and premalignant/borderline lesions. Semin Liver Dis. 1999;19:297–309. CrossRef
- Torzilli G, Minagawa M, Takayama T, Inoue K, Hui AM, Kubota K, et al. Accurate preoperative evaluation of liver mass lesions without fine-needle biopsy. Hepatology. 1999;30:889–93. CrossRef
- Tanaka S, Kitamura T, Nakanishi K, Okuda S, Yamazaki H, Hiyama T, et al. Effectiveness of periodic checkup by ultrasonography for the early diagnosis of hepatocellular carcinoma. Cancer. 1990;66:210–4. CrossRef
- Takayasu K, Furukawa H, Wakao F, Muramatu Y, Abe H, Terauchi T, et al. CT diagnosis of early hepatocellular carcinoma: sensitivity, findings, and CT-pathologic correlation. AJR Am J Roentgenol. 1995;164:885–90.
- Ebara M, Ohto M, Watanabe Y, Kimura K, Saisho H, Tsuchiya Y, et al. Diagnosis of small hepatocellular carcinoma: correlation of MR imaging and tumor histologic studies. Radiology. 1986;159:371–7.
- Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, et al. Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006;4:111–7. CrossRef
- Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dienstag JL, Bonkovsky HL, et al. Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial. J Hepatol. 2005;43:434–41. CrossRef
- Ikeda K, Saitoh S, Koida I, Arase Y, Tsubota A, Chayama K, et al. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology. 1993;18:47–53. CrossRef
- Nakamura S, Nouso K, Sakaguchi K, et al. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006;101:2038–43. CrossRef
- Lu SN, Wang JH, Liu SL, Hung CH, Chen CH, Tung HD, et al. Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification of patients at high-risk for hepatocellular carcinoma. Cancer. 2006;107:2212–22. CrossRef
- Kaneko S, Unoura M, Takeuchi M, Terasaki S, Ogino H, Matsushita E, et al. The role of hepatitis C virus in hepatocellular carcinoma in Japan. Intervirology. 1994;37:108–13.
- Tarao K, Shimizu A, Ohkawa S, Harada M, Ito Y, Tamai S, et al. Development of hepatocellular carcinoma associated with increases in DNA synthesis in the surrounding cirrhosis. Gastroenterology. 1992;103:595–600.
- Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem. 2000;46:2050–68.
- Anisimov VN. Biology of aging and cancer. Cancer Control. 2007;14:23–31.
- Goukassian D, Gad F, Yaar M, Eller MS, Nehal US, Gilchrest BA. Mechanisms and implications of the age-associated decrease in DNA repair capacity. FASEB J. 2000;14:1325–34. CrossRef
- Murashima S, Tanaka M, Haramaki M, Yutani S, Nakashima Y, Harada K, et al. A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP. Dig Dis Sci. 2006;51:808–12. CrossRef
- Arase Y, Ikeda K, Suzuki F, Suzuki Y, Kobayashi M, Akuta N, et al. Interferon-induced prolonged biochemical response reduces hepatocarcinogenesis in hepatitis C virus infection. J Med Virol. 2007;79:1485–90. CrossRef
- Hisaka T, Yano H, Ogasawara S, Momosaki S, Nishida N, Takemoto Y, et al. Interferon-alphaCon1 suppresses proliferation of liver cancer cell lines in vitro and in vivo. J Hepatol. 2004;41:782–9. CrossRef
- Ikeda K, Arase Y, Saitoh S, Kobayashi M, Suzuki Y, Suzuki F, et al. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor––a prospective randomized study of hepatitis C virus-related liver cancer. Hepatology. 2000;32:228–32. CrossRef
- Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus
Journal of Gastroenterology
Volume 46, Issue 4 , pp 536-544
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Alpha-fetoprotein (AFP)
- Lens culinaris agglutinin-reactive fraction of AFP
- Hepatic regeneration
- Necroinflammatory activity
- Industry Sectors
- Author Affiliations
- 1. Department of Gastroenterology, Ogaki Municipal Hospital, 4-86, Minaminokawa-cho, Ogaki, Gifu, 503-8052, Japan
- 2. Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan