title: Model incorporating the ITPA genotype identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C.
abstract: This study aimed to develop a model for predicting anemia using the inosine triphosphatase (ITPA) genotype and to evaluate its relationship with treatment outcome. Patients with genotype 1b chronic hepatitis C (n = 446) treated with peg-interferon alpha and ribavirin (RBV) for 48 weeks were genotyped for the ITPA (rs1127354) and IL28B (rs8099917) genes. Data mining analysis generated a predictive model for anemia (hemoglobin (Hb) concentration <10 g/dl); the CC genotype of ITPA, baseline Hb <14.0 g/dl, and low creatinine clearance (CLcr) were predictors of anemia. The incidence of anemia was highest in patients with Hb <14.0 g/dl and CLcr <90 ml/min (76%), followed by Hb <14.0 g/dl and ITPA CC (57%). Patients with Hb ≥ 14.0 g/dl and ITPA AA/CA had the lowest incidence of anemia (17%). Patients with two predictors (high-risk) had a higher incidence of anemia than the others (64% vs. 28%, P < 0.0001). At baseline, the IL28B genotype was a predictor of a sustained virological response [adjusted odds ratio 9.88 (95% confidence interval 5.01-19.48), P < 0.0001]. In patients who achieved an early virological response, the IL28B genotype was not associated with a sustained virological response, while a high risk of anemia was a significant negative predictor of a sustained virological response [0.47 (0.24-0.91), P = 0.026]. For high-risk patients with an early virological response, giving >80% of the planned RBV dose increased sustained virological responses by 24%. In conclusion, a predictive model incorporating the ITPA genotype could identify patients with a high risk of anemia and reduced probability of sustained virological response.
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Asahina
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Maekawa
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced* / Q000235:genetics*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D011755:Pyrophosphatases; D012254:Ribavirin; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase