ITPA genetic variants influence efficacy of PEG‐IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type. Issue 7 (3rd September 2013)

• Record Type: Journal Article
• 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.
• Is Part Of: Journal of viral hepatitis. Volume 21:Issue 7(2014)
• Page Start: 466
• Page End: 474
• Publication Date: 2013-09-03
• Subjects: Hepatitis, Viral -- Periodicals; Hepatitis, Viral, Animal; Hepatitis, Viral, Human; 616.3623
• DOI: 10.1111/jvh.12171
• Languages: English
• ISSNs: 1352-0504

Abstract

<abstract abstract-type="main" id="jvh12171-abs-0001"> <title>Summary</title> <p>Inosine triphosphatase (<italic>ITPA</italic>) genetic variants are strongly associated with ribavirin (RBV)‐induced anaemia during pegylated interferon (PEG‐IFN) plus RBV therapy. However, the treatment efficacy of <italic>ITPA</italic> 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 <italic>ITPA</italic> SNP: rs1127354 and <italic>IL28B</italic> 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)] (<italic>P </italic><<italic> </italic>0.0001). <italic>ITPA</italic> genotype, pretreatment Hb level and age were independent predictive factors for severe anaemia: Hb < 10 g/dL. In <italic>IL28B</italic> 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) <italic>vs</italic> 40% (26/65), <italic>P </italic>=<italic> </italic>0.005], although there was no significant difference in treatment efficacy according to <italic>ITPA</italic> 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 (<italic>P </italic>=<italic> </italic>0.025), resulting in a lower relapse rate. In conclusion, <italic>ITPA</italic> genetic variants were associated with severe RBV‐induced anaemia and could influence the efficacy of PEG‐IFN plus RBV treatment among elderly patients with <italic>IL28B</italic> favourable type.</p> </abstract>