ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type
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...
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| Published in | Journal of viral hepatitis Vol. 21; no. 7; pp. 466 - 474 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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England
Blackwell Publishing Ltd
01.07.2014
Wiley Subscription Services, Inc |
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| Abstract | 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. |
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| AbstractList | 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, greater than or equal to 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 greater than or equal to 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 greater than or equal to 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. 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. 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. [PUBLICATION 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. 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 ( H b) 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. |
| Author | Sakamoto, N. Enomoto, N. Watanabe, T. Shinkai, N. Mizokami, M. Kusakabe, A. Matsuura, K. Orito, E. Yatsuhashi, H. Kurosaki, M. Fujiwara, K. Joh, T. Tanaka, Y. Nojiri, S. Izumi, N. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24750345$$D View this record in MEDLINE/PubMed |
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| Copyright | 2013 John Wiley & Sons Ltd 2013 John Wiley & Sons Ltd. Copyright © 2014 John Wiley & Sons Ltd |
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| Keywords | IL28B anaemia ribavirin interferon ITPA |
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| Notes | Ministry of Health, Labour and Welfare of Japan ark:/67375/WNG-TH20CKPR-7 The Uehara Memorial Foundation istex:62C180ED145189FB03368403B21B309AEA5BFBE8 Ministry of Education, Culture, Sports, Science and Technology Fig. S1. Reduction in haemoglobin levels up to the initial 12 weeks of treatment according to ITPA genetic variants.Fig. S2. Proportion of haemoglobin <10 g/dL up to the initial 12 weeks of treatment according to baseline haemoglobin level, age and ITPA genetic variants. ArticleID:JVH12171 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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| PublicationDate | July 2014 |
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| PublicationTitle | Journal of viral hepatitis |
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Inosine triphosphatase (ITPA) genetic variants are strongly associated with ribavirin (RBV)‐induced anaemia during pegylated interferon (PEG‐IFN) plus... Inosine triphosphatase (ITPA) genetic variants are strongly associated with ribavirin (RBV)-induced anaemia during pegylated interferon (PEG-IFN) plus RBV... Summary Inosine triphosphatase ( ITPA ) genetic variants are strongly associated with ribavirin ( RBV )‐induced anaemia during pegylated interferon ( PEG ‐ IFN... Summary Inosine triphosphatase (ITPA) genetic variants are strongly associated with ribavirin (RBV)-induced anaemia during pegylated interferon (PEG-IFN) plus... |
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| SubjectTerms | 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 |
| Title | ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type |
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