title: Rapidity and Severity of Hemoglobin Decreasing Associated with Erythrocyte Inosine Triphosphatase Activity and ATP Concentration during Chronic Hepatitis C Treatment.
abstract: The purpose of this study was to evaluate the association between therapy-induced hemoglobin (Hb) decreasing rapidity and severity with erythrocyte inosine triphosphatase (ITPase) activity and ATP concentration in chronic hepatitis C patients receiving chronic hepatitis C (HCV) treatment. Forty-three Japanese patients were included in the study. Erythrocyte ITPase activity before therapy was determined by HPLC-UV. Erythrocyte ATP concentrations before and during therapy were determined by luciferase assay. Genotyping for ITPA 94C>A (rs1127354) and IVS2+21 A>C (rs7270101) was conducted using TaqMan probes. The median ITPase activity (µmol/h/g hemoglobin) of ITPA 94 CC, CA, and AA genotypes was 136.8 (range, 80.4-289.6), 41.1 (24.3-93.1), and 11.8, respectively. ITPase activity and Hb decreasing showed a significantly inverse relationship at therapeutic weeks 2, 4, and 6 (p<0.01). Erythrocyte ATP concentration was decreased by therapy, and Hb decreasing was significantly and inversely correlated with erythrocyte ATP concentration at week 4 and after week 8 (p<0.001 and 0.05, respectively). ATP concentration for patients with ITPA 94CA was significantly lower than ITPA 94CC at week 4 (p=0.045). We concluded that ITPase activity plays an important function and that ATP concentration changes due to therapy are related to the Hb decreasing mechanism in the early period of therapy with HCV treatment.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Kitasato University.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yokomori
authors.forename: Takako
authors.initials: T
authors.lastname: Komiyama
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D000069616:Simeprevir / Q000494:pharmacology / Q000627:therapeutic use; D000097630:Inosine Triphosphatase
chemical_list: D000255:Adenosine Triphosphate; D000998:Antiviral Agents; D006454:Hemoglobins; D011480:Protease Inhibitors; D011755:Pyrophosphatases; D012254:Ribavirin; D000069616:Simeprevir; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase