Anemia and thrombocytosis induced by ribavirin monotherapy in patients with chronic hepatitis C

被引:13
作者
Kobayashi, Tomoe [1 ]
Hige, Shuhei [1 ]
Terashita, Katsumi [1 ]
Nakai, Masato [1 ]
Horimoto, Hiromasa [1 ]
Sho, Takuya [1 ]
Nakanishi, Mitsuru [1 ]
Ogawa, Koji [2 ]
Chuma, Makoto [1 ]
Sakamoto, Naoya [3 ]
Asaka, Masahiro [4 ]
机构
[1] Hokkaido Univ Hosp, Dept Gastroenterol, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[2] Hakodate Municipal Hosp, Dept Gastroenterol, Hakodate, Hokkaido 0418680, Japan
[3] Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Bunkyo Ku, Tokyo 1138519, Japan
[4] Hokkaido Univ, Grad Sch Med, Dept Canc Prevent Med, Kita Ku, Sapporo, Hokkaido 0600812, Japan
关键词
Ribavirin; Anemia; Erythropoietin; Thrombocytosis; ITPA SNP; IRON-DEFICIENCY ANEMIA; GENOME-WIDE ASSOCIATION; VIRUS-INFECTION; COMBINATION THERAPY; PEGYLATED INTERFERON; PLUS RIBAVIRIN; ERYTHROPOIETIN; PEGINTERFERON; HEMOGLOBIN; ALPHA;
D O I
10.1007/s00535-012-0579-y
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
An inosine triphosphatase (ITPA) single-nucleotide polymorphism (SNP) is associated with anemia induced by pegylated interferon and ribavirin (RBV) combination therapy in patients with chronic hepatitis C (CHC). However, there are very few reports on the hematological effects of RBV monotherapy. Here, hematological changes were monitored in patients with CHC who received RBV monotherapy, and the mechanism of these changes was investigated. Patients with CHC (n = 30) received RBV monotherapy for 4 weeks. The RBV dose was determined on the basis of body weight. Complete blood count, and serum erythropoietin (EPO) and thrombopoietin (TPO) levels were assessed. The associations between these parameters and the ITPA SNP (rs1127354) were analyzed. Over the 4 weeks, the median hemoglobin level of all patients decreased significantly, from 13.6 (10.5-16.6) to 11.7 (9.4-14.9) g/dl (P < 0.001), and the platelet counts increased, from 14.0 x 10(4) (8.9-37.4 x 10(4)) to 15.8 x 10(4) (10.2-40.6 x 10(4)) /mm(3) (P = 0.003). At week 4, hemoglobin levels differed between patients with the ITPA CC genotype and those with the AA or AC genotypes [11.1 (9.4-13.5) vs. 12.9 (12.5-14.9) g/dl, P = 0.001]. The platelet change ratio (i.e., platelet count at week 4/platelet count at baseline) in the patients with developing anemia was correlated with the increase in the serum EPO level over 4 weeks (r = 0.88, P = 0.002), but not with the increase in the serum TPO level over 4 weeks. RBV monotherapy induced anemia and affected thrombocytosis in patients with CHC. Elevated endogenous EPO may stimulate platelet production.
引用
收藏
页码:1228 / 1237
页数:10
相关论文
共 26 条
[1]   Amino acid sequence homology of thrombopoietin and erythropoietin may explain thrombocytosis in children with iron deficiency anemia [J].
Bilic, E ;
Bilic, E .
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 2003, 25 (08) :675-676
[2]   HEMATOLOGICAL AND BONE-MARROW EFFECTS OF RIBAVIRIN IN RHESUS-MONKEYS [J].
CANONICO, PG ;
KASTELLO, MD ;
COSGRIFF, TM ;
DONOVAN, JC ;
ROSS, PE ;
SPEARS, CT ;
STEPHEN, EL .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1984, 74 (02) :163-172
[3]   Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: Role of membrane oxidative damage [J].
De Franceschi, L ;
Fattovich, G ;
Turrini, F ;
Ayi, K ;
Brugnara, C ;
Manzato, F ;
Noventa, F ;
Stanzial, AM ;
Solero, P ;
Corrocher, R .
HEPATOLOGY, 2000, 31 (04) :997-1004
[4]   EFFECT OF HUMAN RECOMBINANT ERYTHROPOIETIN ON HUMAN MARROW MEGAKARYOCYTE COLONY FORMATION INVITRO [J].
DESSYPRIS, EN ;
GLEATON, JH ;
ARMSTRONG, OL .
BRITISH JOURNAL OF HAEMATOLOGY, 1987, 65 (03) :265-269
[5]   Estimating the Net Contribution of Interleukin-28B Variation to Spontaneous Hepatitis C Virus Clearance [J].
di Iulio, Julia ;
Ciuffi, Angela ;
Fitzmaurice, Karen ;
Kelleher, Dermot ;
Rotger, Margalida ;
Fellay, Jacques ;
Martinez, Raquel ;
Pulit, Sara ;
Furrer, Hansjakob ;
Guenthard, Huldrych F. ;
Battegay, Manuel ;
Bernasconi, Enos ;
Schmid, Patrick ;
Hirschel, Bernard ;
Barnes, Eleanor ;
Klenerman, Paul ;
Telenti, Amalio ;
Rauch, Andri .
HEPATOLOGY, 2011, 53 (05) :1446-1454
[6]   ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C [J].
Fellay, Jacques ;
Thompson, Alexander J. ;
Ge, Dongliang ;
Gumbs, Curtis E. ;
Urban, Thomas J. ;
Shianna, Kevin V. ;
Little, Latasha D. ;
Qiu, Ping ;
Bertelsen, Arthur H. ;
Watson, Mark ;
Warner, Amelia ;
Muir, Andrew J. ;
Brass, Clifford ;
Albrecht, Janice ;
Sulkowski, Mark ;
McHutchison, John G. ;
Goldstein, David B. .
NATURE, 2010, 464 (7287) :405-408
[7]   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
[8]   Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C -: A randomized study of treatment duration and ribavirin dose [J].
Hadziyannis, SJ ;
Sette, H ;
Morgan, TR ;
Balan, V ;
Diago, M ;
Marcellin, P ;
Ramadori, G ;
Bodenheimer, H ;
Bernstein, D ;
Rizzetto, M ;
Zeuzem, S ;
Pockros, PJ ;
Lin, A ;
Ackrill, AM .
ANNALS OF INTERNAL MEDICINE, 2004, 140 (05) :346-355
[9]   Telaprevir and Peginterferon with or without Ribavirin for Chronic HCV Infection [J].
Hezode, Christophe ;
Forestier, Nicole ;
Dusheiko, Geoffrey ;
Ferenci, Peter ;
Pol, Stanislas ;
Goeser, Tobias ;
Bronowicki, Jean-Pierre ;
Bourliere, Marc ;
Gharakhanian, Shahin ;
Bengtsson, Leif ;
McNair, Lindsay ;
George, Shelley ;
Kieffer, Tara ;
Kwong, Ann ;
Kauffman, Robert S. ;
Alam, John ;
Pawlotsky, Jean-Michel ;
Zeuzem, Stefan .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (18) :1839-1850
[10]   High-performance liquid chromatographic determination of ribavirin in whole blood to assess disposition in erythrocytes [J].
Homma, M ;
Jayewardene, AL ;
Gambertoglio, J ;
Aweeka, F .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (11) :2716-2719