OJGas  Vol.2 No.2 , May 2012
Serum SCCA-IgM as a predictor of hepatocellular carcinoma in patients with liver cirrhosis
ABSTRACT
Aberrant Squamous Cell Carcinoma Antigen (SCCA) expression is an early hepatocarcinogenetic event and circulating SCCA-IgM complexes are elevated in most HCC patients. We evaluated whether serum SCCA-IgM levels can identify HCV +ve cirrhotic patients at low HCC risk. In this retrospective study we enrolled 29 cirrhotic patients in whom serum SCCA-IgM was measured 8 - 69 months (median 31) before HCC diagnosis, and 28 cirrhotic patients who remained HCC- free, with SCCA-IgM measured 15 - 68 months (median 48) before the study end. The best discriminating value of SCCA-IgM was calculated and tested in predicting HCC diagnosis within 12, 24 and 36 months. Sensitivity analysis, considering different HCC incidence, was conducted to identify the patient subgroup with an annual cancer risk below the threshold of a cost-effective semiannual surveillance with ultrasound. Cumulative HCC incidence at 12, 24 and 36 months was 7.0%, 15.7% and 26.3%, respectively. SCCA-IgM levels were higher in HCC than in cirrhotic patients [median: 381 (95% C.I.: 50 - 5289) vs. 100 (70 - 493) AU/mL, P = 0.005]. The SCCA-IgM value ≤ 200 AU/mL accurately identified patients at low risk of HCC development in the subsequent year (sensitivity 75%, specificity 62%, positive predictive value 13% and negative predictive value 97%). Considering an annual HCC incidence ≤ 3%, patients with SCCA-IgM ≤ 200 AU/mL (60% of the whole patients) had an HCC risk below the accepted threshold of a cost-effective surveillance (1.5%). In conclusion, provided that our provocative results are confirmed in larger studies, SCCA-IgM serum measurement could permit implementation of a two step (with different costs) surveillance: an initial serological surveillance, based on the annual monitoring of this biomarker, and the conventional surveillance by semiannual US when SCCA-IgM becomes >200 AU/mL. This could improve the cost/effectiveness of surveillance of HCV infected patients at risk of HCC.

Cite this paper
Buccione, D. , Fatti, G. , Gallotta, A. , Loggi, E. , Donato, R. , Testa, L. , Saitta, C. , Santi, V. , Micoli, A. , Erroi, V. , Frigerio, M. , Fazio, V. , Picciotto, A. , Biasiolo, A. , Degos, F. , Pontisso, P. , Raimondo, G. and Trevisani, F. (2012) Serum SCCA-IgM as a predictor of hepatocellular carcinoma in patients with liver cirrhosis. Open Journal of Gastroenterology, 2, 56-61. doi: 10.4236/ojgas.2012.22012.
References
[1]   Parkin, D.M., Bray, F., Ferlay, J., et al. (2000) Estimating the world cancer burden: Globocan. International Journal of Cancer, 94, 153-156. doi:10.1002/ijc.1440

[2]   Bosch, F.X., Ribes, J., Cléries, R., et al. (2005) Epidemiology of hepatocellular carcinoma. Clinics in Liver Disease, 9, 191-211. doi:10.1016/j.cld.2004.12.009

[3]   Fassio, E. (2010) Hepatitis C and hepatocellular carcinoma. Annals of Hepatology, 9, 119-122.

[4]   Capocaccia, R., Sant, M., et al. (2007) Hepatocellular carcinoma: trends of incidence and survival in Europe and the United States at the end of the 20th century. American Journal of Gastroenterology, 102, 1661-1670. doi:10.1111/j.1572-0241.2007.01337.x

[5]   El-Serag, H.B. (2007) Epidemiology of hepatocellular carcinoma in USA. Hepatology Research, 37, 88-94. doi:10.1111/j.1872-034X.2007.00168.x

[6]   Zhang, B.H., Yang, B.H. and Tang, Z.Y. (2004) Randomized controlled trial of screening for hepatocellular carcinoma. Journal of Cancer Research and Clinical Oncology, 130, 417-422. doi:10.1007/s00432-004-0552-0

[7]   Bolondi, L., Sofia, S., Siringo, S., et al. (2001) Surveillance pro-gramme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: A cost effectiveness analysis. Gut, 48, 251-259. doi:10.1136/gut.48.2.251

[8]   Trevisani, F., De Notariis, S., Rapaccini, G., et al. (2002) Semiannual and annual surveillance of cirrhotic patients for hepatocellular carci-noma: Effects on cancer stage and patient survival (Italian experience). American Journal of Gastroenterology, 97, 734-744. doi:10.1111/j.1572-0241.2002.05557.x

[9]   Yuen, M.F., Cheng, C.C., Lauder, I.J., et al. (2000) Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology, 31, 330-335. doi:10.1002/hep.510310211

[10]   Stravitz, R.T., Heuman, D.M., Chand, N., et al. (2008) Surveillance for hepato-cellular carcinoma in patients with cirrhosis improves outcome. American Journal of Medicine, 121, 119-126. doi:10.1016/j.amjmed.2007.09.020

[11]   Bruix, J. and Sherman, M. (2011) Management of heap-tocellular carcinoma: An update. Hepatology, 53, 1020- 1022. doi:10.1002/hep.24199

[12]   Arii, S., Sata, M., Sakamoto, M., et al. (2010) Management of hepatocellular carci-noma: Report of Consensus Meeting in the 45th Annual Meeting of the Japan Society of Hepatology (2009). Hepatology Research, 40, 667-685. doi:10.1111/j.1872-034X.2010.00673.x

[13]   Poon, D., Anderson, B.O., Chen, L.T., et al. (2009) Management of hepatocellular carcinoma in Asia: Consensus statement from the Asian Oncology Summit 2009. Lancet Oncology, 10, 1111-1118. doi:10.1016/S1470-2045(09)70241-4

[14]   Sarasin, F.P., Giostra, E., Hadengue, A. (1996) Cost- effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. American Journal of Medicine, 101, 422-434. doi:10.1016/S0002-9343(96)00197-0

[15]   Arguedas, M.R., Chen, V.K., Eloubeidi, M.A., et al. (2003) Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: A cost-utility analysis. American Journal of Gastroenterology, 98, 679-690. doi:10.1111/j.1572-0241.2003.07327.x

[16]   Ganne-Carrié, N., Chastang, C., Chapel, F., et al. (1996) Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis. Hepatology, 23, 1112-1118. doi:10.1002/hep.510230527

[17]   Degos, F., Christidis, C., Ganne-Carriè, N., et al. (2000) Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut, 47, 131-136. doi:10.1136/gut.47.1.131

[18]   Velázquez, R.F., Rodríguez, M., Navascués, C.A., et al. (2003) Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology, 37, 520-527. doi:10.1053/jhep.2003.50093

[19]   Yuen, M.F., Tanaka, Y., Fong, D.Y., et al. (2009) Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. Journal of Hepatology, 50, 80-88. doi:10.1016/j.jhep.2008.07.023

[20]   Kato, H. (1996) Expression and function of squamous cell carcinoma an-tigen. Anticancer Research, 16, 2149- 2153.

[21]   Pontisso, P., Calabrese, F., Benvegnù, L., et al. (2004) Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma. British Journal of Cancer, 90, 833-837. doi:10.1038/sj.bjc.6601543

[22]   Guido, M., Roskams, T., Pontisso, P., et al. (2008) Squamous cell carcinoma antigen in human liver carcinogenesis. Journal of Clinical Pathology, 61, 445-447. doi:10.1136/jcp.2007.051383

[23]   Benedice, L., Castaldi, F., Marino, M., et al. (2005) Squamous cell carcinoma antigen-immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma. Cancer, 103, 2558-2565. doi:10.1002/cncr.21106

[24]   Giannelli, G., Fransvea, E., Trerotoli, P., et al. (2007) Clinical validation of combined serological biomarkers for improved hepatocellular carcinoma diagnosis in 961 patients. Clinica Chimica Acta, 383, 147-152. doi:10.1016/j.cca.2007.05.014

[25]   Pontisso, P., Quarta, S., Caberlotto, C., et al. (2006) Pro- gressive increase of SCCA-IgM immune complexes in cirrhotic patients is associated with development of heap- tocellular carcinoma. International Journal of Cancer, 119, 735-740. doi:10.1002/ijc.21908

[26]   Mazzaferro, V., Regalia, E., Doci, R., et al. (1996) Liver transplantation for the treat-ment of small hepatocellular carcinomas in patients with cirrhosis. New England Jour- nal of Medicine, 334, 693-699. doi:10.1056/NEJM199603143341104

[27]   Sangiovanni, A., Del Ninno, E., Fasani, P., et al. (2004) Increased survival of cirrhotic patients with a hepato-cellular carcinoma detected during surveillance. Gastroenterology, 126, 1005-1014. doi:10.1053/j.gastro.2003.12.049

[28]   Lin, O.S., Keeffe, E.B., Sanders, G.D., et al. (2004) Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. Alimentary Pharma-cology and Therapeutics, 19, 1159- 1172. doi:10.1111/j.1365-2036.2004.01963.x

[29]   Moriyama, M., Matsumura, H., Aoki, H., et al. (2003) Long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C and liver cirrhosis after interferon therapy. Intervirology, 46, 296-307. doi:10.1159/000073209

[30]   Lok, A.S., Seeff, L.B., Morgan, T.R., et al. (2009) Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology, 136, 138-148. doi:10.1053/j.gastro.2008.09.014

 
 
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