Post-treatment levels of -fetoprotein predict long-term hepatocellular carcinoma development after sustained virological response in patients with hepatitis C

被引:22
作者
Tada, Toshifumi [1 ]
Kumada, Takashi [1 ]
Toyoda, Hidenori [1 ]
Kiriyama, Seiki [1 ]
Tanikawa, Makoto [1 ]
Hisanaga, Yasuhiro [1 ]
Kanamori, Akira [1 ]
Kitabatake, Shusuke [1 ]
Yama, Tsuyoki [1 ]
Tanaka, Junko [2 ]
机构
[1] Ogaki Municipal Hosp, Dept Gastroenterol & Hepatol, 4-86 Minaminokawa, Ogaki, Gifu 5038502, Japan
[2] Hiroshima Univ, Inst Biomed & Hlth Sci, Dept Epidemiol Infect Dis Control & Prevent, Hiroshima, Japan
关键词
-fetoprotein; hepatitis C; hepatocellular carcinoma; sustained virological response; time-dependent receiver operating characteristic; INTERFERON THERAPY; VIRUS-INFECTION; HISTOLOGIC IMPROVEMENT; RIBAVIRIN THERAPY; RISK-FACTORS; FOLLOW-UP; HCV RNA; FIBROSIS; HEPATOCARCINOGENESIS; ERADICATION;
D O I
10.1111/hepr.12839
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AimThe rate of hepatocellular carcinoma (HCC) development is reportedly lower in patients with chronic hepatitis C virus (HCV) who have achieved a sustained virological response (SVR) than in patients who were unresponsive to therapy. However, the development of HCC is sometimes observed in patients with SVR. Therefore, we clarified the predictive power of clinical factors for HCC incidence in patients with SVR using receiver operating characteristic (ROC) curve analysis that takes time dependence into account. MethodsA total of 571 patients with HCV who achieved SVR with interferon-based therapy were enrolled. Univariate and multivariate Cox proportional hazards models and time-dependent ROC curves were used to analyze clinical factors associated with the development of HCC. ResultsTwenty-four patients developed HCC during the follow-up period (median duration, 9.0years). The 5-, 10-, 15-, and 20-year cumulative incidence rates for HCC were 1.7%, 4.8%, 5.8%, and 6.6%, respectively. Multivariate Cox proportional hazards models showed that older age (hazard ratio [HR], 3.648), male sex (HR, 7.560), lower platelet count at 24weeks after the end of treatment (SVR24) (HR, 3.939), and higher -fetoprotein (AFP) at SVR24 (HR, 3.630) were independently associated with HCC development. In addition, time-dependent ROC analysis showed that, compared to platelet count at SVR24, AFP at SVR24 had higher predictive power for HCC incidence approximately 7years after SVR. ConclusionsElevated AFP at SVR24 is a risk factor for HCC in patients with HCV, even those who achieve SVR. -Fetoprotein is a good predictor of HCC development.
引用
收藏
页码:1021 / 1031
页数:11
相关论文
共 36 条
[1]   Amino Acid Substitutions in Hepatitis C Virus Core Region Predict Hepatocarcinogenesis Following Eradication of HCV RNA by Antiviral Therapy [J].
Akuta, Norio ;
Suzuki, Fumitaka ;
Hirakawa, Miharu ;
Kawamura, Yusuke ;
Sezaki, Hitomi ;
Suzuki, Yoshiyuki ;
Hosaka, Tetsuya ;
Kobayashi, Masahiro ;
Kobayashi, Mariko ;
Saitoh, Satoshi ;
Arase, Yasuji ;
Ikeda, Kenji ;
Kumada, Hiromitsu .
JOURNAL OF MEDICAL VIROLOGY, 2011, 83 (06) :1016-1022
[2]   A Risk for Hepatocellular Carcinoma Persists Long-term After Sustained Virologic Response in Patients With Hepatitis C-Associated Liver Cirrhosis [J].
Aleman, Soo ;
Rahbin, Nogol ;
Weiland, Ola ;
Davidsdottir, Loa ;
Hedenstierna, Magnus ;
Rose, Nina ;
Verbaan, Hans ;
Stal, Per ;
Carlsson, Tony ;
Norrgren, Hans ;
Ekbom, Anders ;
Granath, Fredrik ;
Hultcrantz, Rolf .
CLINICAL INFECTIOUS DISEASES, 2013, 57 (02) :230-236
[3]   α-Fetoprotein Levels After Interferon Therapy and Risk of Hepatocarcinogenesis in Chronic Hepatitis C [J].
Asahina, Yasuhiro ;
Tsuchiya, Kaoru ;
Nishimura, Takashi ;
Muraoka, Masaru ;
Suzuki, Yuichiro ;
Tamaki, Nobuharu ;
Yasui, Yutaka ;
Hosokawa, Takanori ;
Ueda, Ken ;
Nakanishi, Hiroyuki ;
Itakura, Jun ;
Takahashi, Yuka ;
Kurosaki, Masayuki ;
Enomoto, Nobuyuki ;
Nakagawa, Mina ;
Kakinuma, Sei ;
Watanabe, Mamoru ;
Izumi, Namiki .
HEPATOLOGY, 2013, 58 (04) :1253-1262
[4]   An algorithm for the grading of activity in chronic hepatitis C [J].
Bedossa, P ;
Poynard, T .
HEPATOLOGY, 1996, 24 (02) :289-293
[5]   Management of hepatoceullular carcinoma [J].
Bruix, J ;
Sherman, M .
HEPATOLOGY, 2005, 42 (05) :1208-1236
[6]   Management of Hepatocellular Carcinoma: An Update [J].
Bruix, Jordi ;
Sherman, Morris .
HEPATOLOGY, 2011, 53 (03) :1020-1022
[7]   Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: Incidence and survival in hepatitis C patients with advanced fibrosis [J].
Cardoso, Ana-Carolina ;
Moucari, Rami ;
Figueiredo-Mendes, Claudio ;
Ripault, Marie-Pierre ;
Giuily, Nathalie ;
Castelnau, Corinne ;
Boyer, Nathalie ;
Asselah, Tarik ;
Martinot-Peignoux, Michelle ;
Maylin, Sarah ;
Carvalho-Filho, Roberto J. ;
Valla, Dominique ;
Bedossa, Pierre ;
Marcellin, Patrick .
JOURNAL OF HEPATOLOGY, 2010, 52 (05) :652-657
[8]   A Polymorphism in Interferon L3 Is an Independent Risk Factor for Development of Hepatocellular Carcinoma After Treatment of Hepatitis C Virus Infection [J].
Chang, Kuo-Chin ;
Tseng, Po-Lin ;
Wu, Yi-Ying ;
Hung, Hung-Chao ;
Huang, Chao-Min ;
Lu, Sheng-Nan ;
Wang, Jing-Houng ;
Lee, Chuan-Mo ;
Chen, Chien-Hung ;
Tsai, Ming-Chao ;
Yen, Yi-Hao ;
Lin, Ming-Tsung ;
Wu, Cheng-Kun ;
Huang, Chao-Cheng ;
Chen, Hsiu-Hsi ;
Hu, Tsung-Hui .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2015, 13 (05) :1017-1024
[9]   Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus [J].
Chung, Raymond T. ;
Davis, Gary L. ;
Jensen, Donald M. ;
Masur, Henry ;
Saag, Michael S. ;
Thomas, David L. ;
Aronsohn, Andrew I. ;
Charlton, Michael R. ;
Feld, Jordan J. ;
Fontana, Robert J. ;
Ghany, Marc G. ;
Godofsky, Eliot W. ;
Graham, Camilla S. ;
Kim, Arthur Y. ;
Kiser, Jennifer J. ;
Kottilil, Shyam ;
Marks, Kristen M. ;
Martin, Paul ;
Mitruka, Kiren ;
Morgan, Timothy R. ;
Naggie, Susanna ;
Raymond, Daniel ;
Reau, Nancy S. ;
Schooley, Robert T. ;
Sherman, Kenneth E. ;
Sulkowski, Mark S. ;
Vargas, Hugo E. ;
Ward, John W. ;
Wyles, David L. .
HEPATOLOGY, 2015, 62 (03) :932-954
[10]   Survival model predictive accuracy and ROC curves [J].
Heagerty, PJ ;
Zheng, YY .
BIOMETRICS, 2005, 61 (01) :92-105