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Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance

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  • Dongliang Ge

    (Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA)

  • Jacques Fellay

    (Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA)

  • Alexander J. Thompson

    (School of Medicine, Duke University, Durham, North Carolina 27705, USA)

  • Jason S. Simon

    (Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA)

  • Kevin V. Shianna

    (Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA)

  • Thomas J. Urban

    (Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA)

  • Erin L. Heinzen

    (Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA)

  • Ping Qiu

    (Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA)

  • Arthur H. Bertelsen

    (Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA)

  • Andrew J. Muir

    (School of Medicine, Duke University, Durham, North Carolina 27705, USA)

  • Mark Sulkowski

    (Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA)

  • John G. McHutchison

    (School of Medicine, Duke University, Durham, North Carolina 27705, USA)

  • David B. Goldstein

    (Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA)

Abstract

Individual responses to hepatitis C virus Hepatitis C is one of the most common infections in the world. Many of its estimated 170 million sufferers live with the disease for years with no serious symptoms, but in about one in four patients it leads to cirrhosis of the liver. The discovery of a biomarker that predicts an individual's response to hepatitis C treatment raises the possibility that clinical outcomes could be improved by raising patient compliance to the often demanding interferon treatment regime. The new marker is a 'single letter' genetic variant — a C (cytosine) replacing a T (thymidine) in a segment of DNA near the IL28B gene that encodes interleukin 28B (interferon-γ-3). This finding goes some way towards explaining the different treatment outcomes between individuals of European (high IL28B frequency), African and Asian ancestry. And importantly, it is of immediate clinical utility.

Suggested Citation

  • Dongliang Ge & Jacques Fellay & Alexander J. Thompson & Jason S. Simon & Kevin V. Shianna & Thomas J. Urban & Erin L. Heinzen & Ping Qiu & Arthur H. Bertelsen & Andrew J. Muir & Mark Sulkowski & John , 2009. "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance," Nature, Nature, vol. 461(7262), pages 399-401, September.
    • Handle: RePEc:nat:nature:v:461:y:2009:i:7262:d:10.1038_nature08309
    DOI: 10.1038/nature08309
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    1. Georgios Grammatikos & Christian Lange & Simone Susser & Susanne Schwendy & Nektarios Dikopoulos & Peter Buggisch & Jens Encke & Gerlinde Teuber & Tobias Goeser & Robert Thimme & Hartwig Klinker & Wul, 2014. "Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients," PLOS ONE, Public Library of Science, vol. 9(2), pages 1-9, February.
    2. John M Murray & Rémy Moenne-Loccoz & Aurélie Velay & François Habersetzer & Michel Doffoël & Jean-Pierre Gut & Isabel Fofana & Mirjam B Zeisel & Françoise Stoll-Keller & Thomas F Baumert & Evelyne Sch, 2013. "Genotype 1 Hepatitis C Virus Envelope Features That Determine Antiviral Response Assessed through Optimal Covariance Networks," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-9, June.
    3. Tonggang Liu & Kaihui Sha & Luhua Yang & Yun Wang & Liguo Zhang & Xianxian Liu & Fang Yang, 2014. "IL-28B Polymorphisms Correlated with Treatment Response in HCV-4 Mono-Infected Patients: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-10, March.
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    5. Ming-Lung Yu & Chen-Hua Liu & Chung-Feng Huang & Tai-Chung Tseng & Jee-Fu Huang & Chia-Yen Dai & Zu-Yau Lin & Shinn-Cherng Chen & Liang-Yen Wang & Suh-Hang Hank Juo & Wan-Long Chuang & Jia-Horng Kao, 2012. "Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-8, December.
    6. I-Cheng Lee & Yi-Hsiang Huang & Chien-Wei Su & Yuan-Jen Wang & Teh-Ia Huo & Kuei-Chuan Lee & Han-Chieh Lin, 2013. "CXCL9 Associated with Sustained Virological Response in Chronic Hepatitis B Patients Receiving Peginterferon Alfa-2a Therapy: A Pilot Study," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-1, October.
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    9. Helen Kovari & Stefan Russmann & Bruno Ledergerber & Daniel Müller & Margalida Rotger & Pablo Velli & Matthias Cavassini & Juan Ambrosioni & Andrea Bregenzer & Marcel Stöckle & Enos Bernasconi & Andri, 2015. "Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-11, July.
    10. Thanthima Suwanthawornkul & Thunyarat Anothaisintawee & Abhasnee Sobhonslidsuk & Ammarin Thakkinstian & Yot Teerawattananon, 2015. "Efficacy of Second Generation Direct-Acting Antiviral Agents for Treatment Naïve Hepatitis C Genotype 1: A Systematic Review and Network Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-17, December.
    11. Verónica Saludes & Elisabet Bascuñana & Elena Jordana-Lluch & Sònia Casanovas & Mercè Ardèvol & Esther Soler & Ramón Planas & Vicente Ausina & Elisa Martró, 2013. "Relevance of Baseline Viral Genetic Heterogeneity and Host Factors for Treatment Outcome Prediction in Hepatitis C Virus 1b-Infected Patients," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-8, August.
    12. Logan Dumitrescu & Cara L Carty & Kira Taylor & Fredrick R Schumacher & Lucia A Hindorff & José L Ambite & Garnet Anderson & Lyle G Best & Kristin Brown-Gentry & Petra Bůžková & Christopher S Carlson , 2011. "Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study," PLOS Genetics, Public Library of Science, vol. 7(6), pages 1-15, June.
    13. Tarik Asselah & Alex J Thompson & Robert Flisiak & Manuel Romero-Gomez & Diethelm Messinger & Georgios Bakalos & Mitchell L Shiffman, 2016. "A Predictive Model for Selecting Patients with HCV Genotype 3 Chronic Infection with a High Probability of Sustained Virological Response to Peginterferon Alfa-2a/Ribavirin," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-20, March.
    14. Emilie Estrabaud & Kevin Appourchaux & Ivan Bièche & Fabrice Carrat & Martine Lapalus & Olivier Lada & Michelle Martinot-Peignoux & Nathalie Boyer & Patrick Marcellin & Michel Vidaud & Tarik Asselah, 2015. "IFI35, mir-99a and HCV Genotype to Predict Sustained Virological Response to Pegylated-Interferon Plus Ribavirin in Chronic Hepatitis C," PLOS ONE, Public Library of Science, vol. 10(4), pages 1-19, April.
    15. Frédégonde About & Tiphaine Oudot-Mellakh & Jonathan Niay & Pascaline Rabiéga & Vincent Pedergnana & Darragh Duffy & Philippe Sultanik & Carole Cagnot & Fabrice Carrat & Patrick Marcellin & Fabien Zou, 2015. "Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Stud," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-13, December.
    16. Mei-Hsuan Lee & Sheng-Nan Lu & Yong Yuan & Hwai-I Yang & Chin-Lan Jen & San-Lin You & Li-Yu Wang & Gilbert L'Italien & Chien-Jen Chen & for the R.E.V.E.A.L.-HCV Study Group, 2014. "Development and Validation of a Clinical Scoring System for Predicting Risk of HCC in Asymptomatic Individuals Seropositive for Anti-HCV Antibodies," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-10, May.
    17. Sean A. P. Clouston & Marcie S. Rubin & Jo C. Phelan & Bruce G. Link, 2016. "A Social History of Disease: Contextualizing the Rise and Fall of Social Inequalities in Cause-Specific Mortality," Demography, Springer;Population Association of America (PAA), vol. 53(5), pages 1631-1656, October.
    18. Martin Probst & Christoph Hoeller & Peter Ferenci & Albert F Staettermayer & Sandra Beinhardt & Hubert Pehamberger & Harald Kittler & Katharina Grabmeier-Pfistershammer, 2014. "IL28B Polymorphism Cannot Predict Response to Interferon Alpha Treatment in Patients with Melanoma," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-7, November.
    19. Zhifang Jia & Yanhua Ding & Suyan Tian & Junqi Niu & Jing Jiang, 2012. "Test of IL28B Polymorphisms in Chronic Hepatitis C Patients Treated with PegIFN and Ribavirin Depends on HCV Genotypes: Results from a Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(9), pages 1-10, September.
    20. Ester Aparicio & Mariona Parera & Sandra Franco & Nuria Pérez-Alvarez & Cristina Tural & Bonaventura Clotet & Miguel Angel Martínez, 2010. "IL28B SNP rs8099917 Is Strongly Associated with Pegylated Interferon-α and Ribavirin Therapy Treatment Failure in HCV/HIV-1 Coinfected Patients," PLOS ONE, Public Library of Science, vol. 5(10), pages 1-5, October.
    21. Deanna M. Santer & Daniel Li & Yanal Ghosheh & Muhammad Atif Zahoor & Dhanvi Prajapati & Bettina E. Hansen & D. Lorne J. Tyrrell & Jordan J. Feld & Adam J. Gehring, 2022. "Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    22. Chun-Yen Lin & Ji-Yih Chen & Tsung-Nan Lin & Wen-Juei Jeng & Chien-Hao Huang & Chang-Wen Huang & Su-Wei Chang & I-Shyan Sheen, 2011. "IL28B SNP rs12979860 Is a Critical Predictor for On-Treatment and Sustained Virologic Response in Patients with Hepatitis C Virus Genotype-1 Infection," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-9, March.
    23. Verónica Saludes & Maria Alma Bracho & Oliver Valero & Mercè Ardèvol & Ramón Planas & Fernando González-Candelas & Vicente Ausina & Elisa Martró, 2010. "Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors," PLOS ONE, Public Library of Science, vol. 5(11), pages 1-8, November.

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