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Published in: Digestive Diseases and Sciences 11/2009

01-11-2009 | Original Article

Serum Alpha-Fetoprotein Levels During and After Interferon Therapy and the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C

Authors: Yasushi Tamura, Satoshi Yamagiwa, Yohei Aoki, So Kurita, Takeshi Suda, Shogo Ohkoshi, Minoru Nomoto, Yutaka Aoyagi, The Niigata Liver Disease Study Group

Published in: Digestive Diseases and Sciences | Issue 11/2009

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Abstract

The association between serum alpha-fetoprotein (AFP) levels during and after interferon (IFN) therapy and the development of hepatocellular carcinoma (HCC) was evaluated in patients with chronic hepatitis C (CHC). A total of 263 patients treated by IFN with or without ribavirin were enrolled in the study. Serum AFP levels during and after IFN therapy were investigated retrospectively, and statistical analysis was performed to identify the factors associated with HCC development. During IFN therapy, serum AFP levels significantly decreased, regardless of virologic response to treatment. Increased serum AFP levels (≥10 ng/ml) at the end of IFN therapy (EOT) was a close-to-significant variable affecting the development of HCC (P = 0.057), and a significantly higher cumulative incidence of HCC was seen in patients with increased serum AFP levels at EOT (P = 0.021). Serum AFP level at EOT is a possible predictor of HCC in CHC patients after IFN therapy.
Literature
4.
go back to reference Ikeda K, Saitoh S, Koida I, 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.CrossRefPubMed Ikeda K, Saitoh S, Koida I, 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.CrossRefPubMed
6.
go back to reference Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989;321:1501–1506.PubMed Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989;321:1501–1506.PubMed
7.
go back to reference Di Bisceglie AM, Martin P, Kassianides C, et al. Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med. 1989;321:1506–1510.PubMed Di Bisceglie AM, Martin P, Kassianides C, et al. Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med. 1989;321:1506–1510.PubMed
8.
go back to reference Causse X, Godinot H, Chevallier M, et al. Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Gastroenterology. 1991;101:497–502.PubMed Causse X, Godinot H, Chevallier M, et al. Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Gastroenterology. 1991;101:497–502.PubMed
9.
go back to reference Chayama K, Saitoh S, Arase Y, et al. Effect of interferon administration on serum hepatitis C virus RNA in patients with chronic hepatitis C. Hepatology. 1991;13:1040–1043.CrossRefPubMed Chayama K, Saitoh S, Arase Y, et al. Effect of interferon administration on serum hepatitis C virus RNA in patients with chronic hepatitis C. Hepatology. 1991;13:1040–1043.CrossRefPubMed
11.
go back to reference Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1, 643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124–1130. doi:10.1002/hep.510290439.CrossRefPubMed Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1, 643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124–1130. doi:10.​1002/​hep.​510290439.CrossRefPubMed
12.
go back to reference Makiyama A, Itoh Y, Kasahara A, et al. Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy. Cancer. 2004;101:1616–1622. doi:10.1002/cncr.20537.CrossRefPubMed Makiyama A, Itoh Y, Kasahara A, et al. Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy. Cancer. 2004;101:1616–1622. doi:10.​1002/​cncr.​20537.CrossRefPubMed
13.
go back to reference Ikeda M, Fujiyama S, Tanaka M, et al. Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon. J Gastroenterol. 2005;40:148–156. doi:10.1007/s00535-004-1519-2.CrossRefPubMed Ikeda M, Fujiyama S, Tanaka M, et al. Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon. J Gastroenterol. 2005;40:148–156. doi:10.​1007/​s00535-004-1519-2.CrossRefPubMed
14.
go back to reference Abelev GI. Production of embryonal serum alpha-globulin by hepatoma: review of experimental and clinical data. Cancer Res. 1968;28:1344–1350.PubMed Abelev GI. Production of embryonal serum alpha-globulin by hepatoma: review of experimental and clinical data. Cancer Res. 1968;28:1344–1350.PubMed
15.
go back to reference Conor GI, Tatarinov YS, Abelev GI, Uriel J. A collaborative study for the evaluation of a serologic test for primary liver cancer. Cancer. 1970;25:1091–1098. doi:10.1002/1097-0142(197005)25:5<1091::AID-CNCR2820250514>3.0.CO;2-P.CrossRef Conor GI, Tatarinov YS, Abelev GI, Uriel J. A collaborative study for the evaluation of a serologic test for primary liver cancer. Cancer. 1970;25:1091–1098. doi:10.1002/1097-0142(197005)25:5<1091::AID-CNCR2820250514>3.0.CO;2-P.CrossRef
17.
go back to reference Goldstein NS, Blue DE, Hankin R, et al. Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores. Am J Clin Pathol. 1999;111:811–816.PubMed Goldstein NS, Blue DE, Hankin R, et al. Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores. Am J Clin Pathol. 1999;111:811–816.PubMed
21.
22.
go back to reference Chen TM, Huang PT, Tsai MH, et al. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a-ribavirin combination therapy. J Gastroenterol Hepatol. 2007;22:669–675.PubMed Chen TM, Huang PT, Tsai MH, et al. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a-ribavirin combination therapy. J Gastroenterol Hepatol. 2007;22:669–675.PubMed
24.
28.
go back to reference Niwa Y, Matsumura M, Shiratori Y, et al. Quantitation of alpha-fetoprotein and albumin messenger RNA in human hepatocellular carcinoma. Hepatology. 1996;23:1384–1392.PubMed Niwa Y, Matsumura M, Shiratori Y, et al. Quantitation of alpha-fetoprotein and albumin messenger RNA in human hepatocellular carcinoma. Hepatology. 1996;23:1384–1392.PubMed
29.
go back to reference Panduro A, Shalaby F, Weiner FR, Biempica L, Zern MA, Shafritz DA. Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration. Biochemistry. 1986;25:1414–1420. doi:10.1021/bi00354a034.CrossRefPubMed Panduro A, Shalaby F, Weiner FR, Biempica L, Zern MA, Shafritz DA. Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration. Biochemistry. 1986;25:1414–1420. doi:10.​1021/​bi00354a034.CrossRefPubMed
30.
go back to reference Wang XW, Xu B. Stimulation of tumor-cell growth by alpha-fetoprotein. Int J Cancer. 1998;75:596–599. doi:10.1002/(SICI)1097-0215(19980209)75:4<596::AID-IJC17>3.0.CO;2-7.CrossRefPubMed Wang XW, Xu B. Stimulation of tumor-cell growth by alpha-fetoprotein. Int J Cancer. 1998;75:596–599. doi:10.1002/(SICI)1097-0215(19980209)75:4<596::AID-IJC17>3.0.CO;2-7.CrossRefPubMed
32.
go back to reference Li MS, Li PF, Chen Q, Du GG, Li G. Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells. World J Gastroenterol. 2004;10:819–824.PubMed Li MS, Li PF, Chen Q, Du GG, Li G. Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells. World J Gastroenterol. 2004;10:819–824.PubMed
33.
go back to reference Li MS, Ma QL, Chen Q, et al. Alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance through altering the expression of Fas/FasL and tumor necrosis factor related apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells. World J Gastroenterol. 2005;11:2564–2569.PubMed Li MS, Ma QL, Chen Q, et al. Alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance through altering the expression of Fas/FasL and tumor necrosis factor related apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells. World J Gastroenterol. 2005;11:2564–2569.PubMed
36.
go back to reference Yuan JM, Govindarajan S, Arakawa K, Yu MC. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the US. Cancer. 2004;101:1009–1017. doi:10.1002/cncr.20427.CrossRefPubMed Yuan JM, Govindarajan S, Arakawa K, Yu MC. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the US. Cancer. 2004;101:1009–1017. doi:10.​1002/​cncr.​20427.CrossRefPubMed
37.
go back to reference Chiba T, Matsuzaki Y, Abei M, et al. The role of previous hepatitis B virus infection and heavy smoking in hepatitis C virus-related hepatocellular carcinoma. Am J Gastroenterol. 1996;91:1195–1203.PubMed Chiba T, Matsuzaki Y, Abei M, et al. The role of previous hepatitis B virus infection and heavy smoking in hepatitis C virus-related hepatocellular carcinoma. Am J Gastroenterol. 1996;91:1195–1203.PubMed
Metadata
Title
Serum Alpha-Fetoprotein Levels During and After Interferon Therapy and the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C
Authors
Yasushi Tamura
Satoshi Yamagiwa
Yohei Aoki
So Kurita
Takeshi Suda
Shogo Ohkoshi
Minoru Nomoto
Yutaka Aoyagi
The Niigata Liver Disease Study Group
Publication date
01-11-2009
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 11/2009
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-008-0642-y

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