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
Kurosaki, M.; Tanaka, Y.; Nishida, N.; Sakamoto, N.; Enomoto, N.; Matsuura, K.; Asahina, Y.; Nakagawa, M.; Watanabe, M.; Sakamoto, M.; Maekawa, S.; Tokunaga, K.; Mizokami, M.; Izumi, N.
Journal of Medical Virology 85(3): 449-458
ISSN/ISBN: 1096-9071 PMID: 23297176 DOI: 10.1002/jmv.23497
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.