title: ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type.
abstract: 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.
authors.affiliation: Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsuura
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: E
authors.initials: E
authors.lastname: Orito
authors.forename: M
authors.initials: M
authors.lastname: Kurosaki
authors.forename: N
authors.initials: N
authors.lastname: Izumi
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.forename: N
authors.initials: N
authors.lastname: Enomoto
authors.forename: H
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: A
authors.initials: A
authors.lastname: Kusakabe
authors.forename: N
authors.initials: N
authors.lastname: Shinkai
authors.forename: S
authors.initials: S
authors.lastname: Nojiri
authors.forename: T
authors.initials: T
authors.lastname: Joh
authors.forename: M
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011755:Pyrophosphatases; D012367:RNA, Viral; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase
keywords: IL28B; ITPA; anaemia; interferon; ribavirin