Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection
OBJECTIVE: To identify genetic factors that predict sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin (RBV) in HIV/hepatitis C virus (HCV) genotype 1 or 4-coinfected patients and that enhance the predictive capacity of IL28B genotype in this population.
DESIGN: Prospective cohort study.
SETTING: Five tertiary care centers in Spain.
PATIENTS: Two hundred and five HIV/HCV genotype 1 or 4-coinfected patients who received a complete course of Peg-IFN/RBV for 48 weeks.
MAIN OUTCOME MEASURES: All individuals were genotyped for 144 single-nucleotide polymorphisms (SNPs).
RESULTS: One hundred and sixty-two (79%) patients bore HCV genotype 1. Overall SVR was achieved by 73 (36%) individuals. SNPs at the following genes were associated with SVR: IL28B, low-density lipoprotein receptor (LDLR), transforming growth factor β (TGF-β), aquaporine 2 (AQP-2), very-low-density lipoprotein receptor, Sp110 nuclear body protein, interferon alpha/beta receptor 1, 2'-5'-oligoadenylate synthase 1 and apolipoprotein B. There was a strong synergy between SNPs at IL28B, TGF-β and AQP-2 genes: the number of patients reaching SVR with all three favorable genotypes versus unfavorable genotypes were 22 (78.6%) versus 1 (7.1%) (P = 2.1 × 10). HCV baseline viral load, IL28B, TGF-β, AQP-2 and LDLR haplotypes were independently associated with SVR.
CONCLUSION: A number of genetic factors modify the predictive capacity of IL28B genotype. These can be used to identify HCV genotype 1 or 4-infected patients with a very high or a very low probability to respond to bitherapy with Peg-IFN/RBV. Predictive models based on these factors could be helpful to tailor direct acting antiviral-based therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
AIDS (London, England) - 27(2013), 17 vom: 13. Nov., Seite 2715-24 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Neukam, Karin [VerfasserIn] |
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| Links: |
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| Themen: |
49717AWG6K |
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| Anmerkungen: |
Date Completed 07.07.2014 Date Revised 13.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/01.aids.0000432459.36970.a9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM229050298 |
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| 100 | 1 | |a Neukam, Karin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 07.07.2014 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: To identify genetic factors that predict sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin (RBV) in HIV/hepatitis C virus (HCV) genotype 1 or 4-coinfected patients and that enhance the predictive capacity of IL28B genotype in this population | ||
| 520 | |a DESIGN: Prospective cohort study | ||
| 520 | |a SETTING: Five tertiary care centers in Spain | ||
| 520 | |a PATIENTS: Two hundred and five HIV/HCV genotype 1 or 4-coinfected patients who received a complete course of Peg-IFN/RBV for 48 weeks | ||
| 520 | |a MAIN OUTCOME MEASURES: All individuals were genotyped for 144 single-nucleotide polymorphisms (SNPs) | ||
| 520 | |a RESULTS: One hundred and sixty-two (79%) patients bore HCV genotype 1. Overall SVR was achieved by 73 (36%) individuals. SNPs at the following genes were associated with SVR: IL28B, low-density lipoprotein receptor (LDLR), transforming growth factor β (TGF-β), aquaporine 2 (AQP-2), very-low-density lipoprotein receptor, Sp110 nuclear body protein, interferon alpha/beta receptor 1, 2'-5'-oligoadenylate synthase 1 and apolipoprotein B. There was a strong synergy between SNPs at IL28B, TGF-β and AQP-2 genes: the number of patients reaching SVR with all three favorable genotypes versus unfavorable genotypes were 22 (78.6%) versus 1 (7.1%) (P = 2.1 × 10). HCV baseline viral load, IL28B, TGF-β, AQP-2 and LDLR haplotypes were independently associated with SVR | ||
| 520 | |a CONCLUSION: A number of genetic factors modify the predictive capacity of IL28B genotype. These can be used to identify HCV genotype 1 or 4-infected patients with a very high or a very low probability to respond to bitherapy with Peg-IFN/RBV. Predictive models based on these factors could be helpful to tailor direct acting antiviral-based therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
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| 700 | 1 | |a Merino, Dolores |e verfasserin |4 aut | |
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| 700 | 1 | |a Rivero, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Pineda, Juan A |e verfasserin |4 aut | |
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