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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
Author(s) -
Kurosaki Masayuki,
Tanaka Yasuhito,
Nishida Nao,
Sakamoto Naoya,
Enomoto Nobuyuki,
Matsuura Kentaro,
Asahina Yasuhiro,
Nakagawa Mina,
Watanabe Mamoru,
Sakamoto Minoru,
Maekawa Shinya,
Tokunaga Katsushi,
Mizokami Masashi,
Izumi Namiki
Publication year - 2013
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.23497
Subject(s) - itpa , ribavirin , gastroenterology , medicine , anemia , pegylated interferon , odds ratio , incidence (geometry) , hepatitis c virus , hepatitis c , confidence interval , genotype , immunology , biology , virus , physics , optics , biochemistry , gene
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. J. Med. Virol. 85:449–458, 2013. © 2013 Wiley Periodicals, Inc.