ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type

• Published in: Journal of viral hepatitis Vol. 21; no. 7; pp. 466 - 474
• Main Authors: Matsuura, K., Tanaka, Y., Watanabe, T., Fujiwara, K., Orito, E., Kurosaki, M., Izumi, N., Sakamoto, N., Enomoto, N., Yatsuhashi, H., Kusakabe, A., Shinkai, N., Nojiri, S., Joh, T., Mizokami, M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-07-2014; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; anaemia; Anemia - chemically induced; Anemia - epidemiology; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Female; Genotype; Genotype & phenotype; Hepacivirus - classification; Hepacivirus - genetics; Hepacivirus - isolation & purification; Hepatitis; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; IL28B; interferon; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Interferons; Interleukins - genetics; ITPA; Male; Medical research; Middle Aged; Polymorphism, Single Nucleotide; Pyrophosphatases - genetics; Recurrence; ribavirin; Ribavirin - adverse effects; Ribavirin - therapeutic use; RNA, Viral - blood; Treatment Outcome; Viral Load; IL28B; anaemia; ribavirin; interferon; ITPA
• ISSN: 1352-0504; 1365-2893
• DOI: 10.1111/jvh.12171

Summary
Inosine triphosphatase (ITPA) genetic variants are strongly associated with ribavirin (RBV)‐induced anaemia during pegylated interferon (PEG‐IFN) plus RBV therapy. However, the treatment efficacy of ITPA genetic variants has not been fully explored. We enrolled 309 individuals infected with hepatitis C virus genotype 1, who were treated with PEG‐IFN plus RBV for 48 weeks. The ITPA SNP: rs1127354 and IL28B SNP: rs8099917 were genotyped. We examined the risk factors for severe anaemia up to week 12 after the start of treatment and treatment efficacy. The incidence of severe anaemia, ≥3 g/dL reduction or <10 g/dL of haemoglobin (Hb) up to week 12, was more frequent in patients with CC at rs1127354 [65% (145/224), 33% (73/224)] than in those with CA/AA [25% (21/85), 6% (8/85)] (P < 0.0001). ITPA genotype, pretreatment Hb level and age were independent predictive factors for severe anaemia: Hb < 10 g/dL. In IL28B favourable type, the sustained virologic response rate was higher in ≥60‐year‐old patients with CA/AA than in those with CC [71% (22/31) vs 40% (26/65), P = 0.005], although there was no significant difference in treatment efficacy according to ITPA genetic variants in the <60‐year‐old patients. The proportion of patients administered ≥80% of the dosage of RBV was significantly higher in the patients with CA/AA than in those with CC (P = 0.025), resulting in a lower relapse rate. In conclusion, ITPA genetic variants were associated with severe RBV‐induced anaemia and could influence the efficacy of PEG‐IFN plus RBV treatment among elderly patients with IL28B favourable type.