Hepatitis C Virus Treatment-Related Anemia Is Associated With Higher Sustained Virologic Response Rate

被引:92
作者
Sulkowski, Mark S. [1 ]
Shiffman, Mitchell L. [2 ]
Afdhal, Nezam H. [3 ]
Reddy, K. Rajender [4 ]
McCone, Jonathan [5 ]
Lee, William M. [6 ]
Herrine, Steven K. [7 ]
Harrison, Stephen A. [8 ]
Poordad, F. Fred [9 ]
Koury, Kenneth [10 ]
Deng, Weiping [10 ]
Noviello, Stephanie [10 ]
Pedicone, Lisa D. [10 ]
Brass, Clifford A. [10 ]
Albrecht, Janice K. [10 ]
McHutchison, John G. [11 ]
机构
[1] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA
[2] Liver Inst Virginia, Bon Secours Hlth Syst, Newport News, VA USA
[3] Beth Israel Liver Ctr, Boston, MA USA
[4] Univ Penn Hlth Syst, Philadelphia, PA USA
[5] Mt Vernon Endoscopy Ctr, Alexandria, VA USA
[6] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA
[7] Thomas Jefferson Univ, Philadelphia, PA 19107 USA
[8] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA
[9] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
[10] Merck & Co Inc, Whitehouse Stn, NJ USA
[11] Duke Clin Res Inst, Durham, NC USA
关键词
Adverse Effects of Hepatitis Therapy; Clinical Trial; Liver Disease; Blood Disorders; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; HCV-INFECTED PATIENTS; RED-CELL APLASIA; EPOETIN-ALPHA; COMBINATION THERAPY; PEGYLATED INTERFERON-ALPHA-2B; PEGINTERFERON ALPHA-2A; GENOTYPE-1; PATIENTS; GROWTH-FACTORS; MANAGEMENT;
D O I
10.1053/j.gastro.2010.07.059
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment is frequently complicated by anemia from ribavirin (RBV)-related hemolysis and peginterferon-alfa (PEG-IFN)-related bone marrow suppression. We investigated the relationships among treatment outcomes, anemia, and their management with RBV dose reduction and/or erythropoiesis-stimulating agents (ESAs). METHODS: We analyzed data from a trial conducted at 118 United States academic and community centers in treatment-naive patients with HCV genotype 1. Patients were treated for as many as 48 weeks with 1 of 3 PEG-IFN/RBV regimens. ESAs were permitted for anemic patients (hemoglobin [Hb] < 10 g/dL) after RBV dose reduction. Sustained virologic responses (SVR) were assessed based on decreases in Hb, anemia, and ESA use. RESULTS: While patients received treatment, 3023 had their Hb levels measured at least once. An SVR was associated with the magnitude of Hb decrease: >3 g/dL, 43.7%; <= 3 g/dL, 29.9% (P < .001). Anemia occurred in 865 patients (28.6%); 449 of these (51.9%) used ESAs. In patients with early-onset anemia (<= 8 weeks of treatment), ESAs were associated with higher SVR rate (45.0% vs 25.9%; P < .001) and reduced discontinuation of treatment because of adverse events (12.6% vs 30.1%, P < .001). ESAs did not affect SVR or discontinuation rates among patients with late-stage anemia. CONCLUSIONS: Among HCV genotype 1-infected patients treated with PEG-IFN/RBV, anemia was associated with higher rates of SVR. The effect of ESAs varied by time to anemia; patients with early-onset anemia had higher rates of SVR with ESA use, whereas no effect was observed in those with late-onset anemia. Prospective trials are needed to assess the role of ESAs in HCV treatment.
引用
收藏
页码:1602 / +
页数:11
相关论文
共 36 条
[11]   Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. [J].
Fried, MW ;
Shiffman, ML ;
Reddy, KR ;
Smith, C ;
Marinos, G ;
Goncales, FL ;
Haussinger, D ;
Diago, M ;
Carosi, G ;
Dhumeaux, D ;
Craxi, A ;
Lin, A ;
Hoffman, J ;
Yu, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (13) :975-982
[12]   Side effects of therapy of hepatitis C and their management [J].
Fried, MW .
HEPATOLOGY, 2002, 36 (05) :S237-S244
[13]   Diagnosis, Management, and Treatment of Hepatitis C: An Update [J].
Ghany, Marc G. ;
Strader, Doris B. ;
Thomas, David L. ;
Seeff, Leonard B. .
HEPATOLOGY, 2009, 49 (04) :1335-1374
[14]   Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin [J].
Hiramatsu, N. ;
Oze, T. ;
Yakushijin, T. ;
Inoue, Y. ;
Igura, T. ;
Mochizuki, K. ;
Imanaka, K. ;
Kaneko, A. ;
Oshita, M. ;
Hagiwara, H. ;
Mita, E. ;
Nagase, T. ;
Ito, T. ;
Inui, Y. ;
Hijioka, T. ;
Katayama, K. ;
Tamura, S. ;
Yoshihara, H. ;
Imai, Y. ;
Kato, M. ;
Yoshida, Y. ;
Tatsumi, T. ;
Ohkawa, K. ;
Kiso, S. ;
Kanto, T. ;
Kasahara, A. ;
Takehara, T. ;
Hayashi, N. .
JOURNAL OF VIRAL HEPATITIS, 2009, 16 (08) :586-594
[15]   Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C [J].
Jen, JF ;
Glue, P ;
Gupta, S ;
Zambas, D ;
Hajian, G .
THERAPEUTIC DRUG MONITORING, 2000, 22 (05) :555-565
[16]   Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C [J].
Loustaud-Ratti, Veronique ;
Alain, Sophie ;
Rousseau, Annick ;
Hubert, Isabelle Fouchard ;
Sauvage, Francois Ludovic ;
Marquet, Pierre ;
Denis, Francois ;
Lunel, Francoise ;
Cales, Paul ;
Lefebvre, Annie ;
Fauchais, Anne-Laure ;
Liozon, Eric ;
Vidal, Elisabeth .
HEPATOLOGY, 2008, 47 (05) :1453-1461
[17]   Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial [J].
Manns, MP ;
McHutchison, JG ;
Gordon, SC ;
Rustgi, VK ;
Shiffman, M ;
Reindollar, R ;
Goodman, ZD ;
Koury, K ;
Ling, MH ;
Albrecht, JK .
LANCET, 2001, 358 (9286) :958-965
[18]  
Maynard M, 2008, ANTIVIR THER, V13, P607
[19]   Telaprevir with Peginterferon and Ribavirin for Chronic HCV Genotype 1 Infection [J].
McHutchison, John G. ;
Everson, Gregory T. ;
Gordon, Stuart C. ;
Jacobson, Ira M. ;
Sulkowski, Mark ;
Kauffman, Robert ;
McNair, Lindsay ;
Alam, John ;
Muir, Andrew J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (18) :1827-1838
[20]   Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection [J].
McHutchison, John G. ;
Lawitz, Eric J. ;
Shiffman, Mitchell L. ;
Muir, Andrew J. ;
Galler, Greg W. ;
McCone, Jonathan ;
Nyberg, Lisa M. ;
Lee, William M. ;
Ghalib, Reem H. ;
Schiff, Eugene R. ;
Galati, Joseph S. ;
Bacon, Bruce R. ;
Davis, Mitchell N. ;
Mukhopadhyay, Pabak ;
Koury, Kenneth ;
Noviello, Stephanie ;
Pedicone, Lisa D. ;
Brass, Clifford A. ;
Albrecht, Janice K. ;
Sulkowski, Mark S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (06) :580-593