IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0072600.html
   My bibliography  Save this article

Relevance of Baseline Viral Genetic Heterogeneity and Host Factors for Treatment Outcome Prediction in Hepatitis C Virus 1b-Infected Patients

Author

Listed:
  • Verónica Saludes
  • Elisabet Bascuñana
  • Elena Jordana-Lluch
  • Sònia Casanovas
  • Mercè Ardèvol
  • Esther Soler
  • Ramón Planas
  • Vicente Ausina
  • Elisa Martró

Abstract

Background: Only about 50% of patients chronically infected with HCV genotype 1 (HCV-1) respond to treatment with pegylated interferon-alfa and ribavirin (dual therapy), and protease inhibitors have to be administered together with these drugs increasing costs and side-effects. We aimed to develop a predictive model of treatment response based on a combination of baseline clinical and viral parameters. Methodology: Seventy-four patients chronically infected with HCV-1b and treated with dual therapy were studied (53 retrospectively −training group−, and 21 prospectively −validation group−). Host and viral-related factors (viral load, and genetic variability in the E1–E2, core and Interferon Sensitivity Determining Region) were assessed. Multivariate discriminant analysis and decision tree analysis were used to develop predictive models on the training group, which were then validated in the validation group. Principal Findings: A multivariate discriminant predictive model was generated including the following variables in decreasing order of significance: the number of viral variants in the E1–E2 region, an amino acid substitution pattern in the viral core region, the IL28B polymorphism, serum GGT and ALT levels, and viral load. Using this model treatment outcome was accurately predicted in the training group (AUROC = 0.9444; 96.3% specificity, 94.7% PPV, 75% sensitivity, 81% NPV), and the accuracy remained high in the validation group (AUROC = 0.8148, 88.9% specificity, 90.0% PPV, 75.0% sensitivity, 72.7% NPV). A second model was obtained by a decision tree analysis and showed a similarly high accuracy in the training group but a worse reproducibility in the validation group (AUROC = 0.9072 vs. 0.7361, respectively). Conclusions and Significance: The baseline predictive models obtained including both host and viral variables had a high positive predictive value in our population of Spanish HCV-1b treatment naïve patients. Accurately identifying those patients that would respond to the dual therapy could help reducing implementation costs and additional side effects of new treatment regimens.

Suggested Citation

  • 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.
  • Handle: RePEc:plo:pone00:0072600
    DOI: 10.1371/journal.pone.0072600
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072600
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0072600&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0072600?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jacques Fellay & Alexander J. Thompson & Dongliang Ge & Curtis E. Gumbs & Thomas J. Urban & Kevin V. Shianna & Latasha D. Little & Ping Qiu & Arthur H. Bertelsen & Mark Watson & Amelia Warner & Andrew, 2010. "ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C," Nature, Nature, vol. 464(7287), pages 405-408, March.
    2. 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.
    3. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Tarik Asselah & Stefan Zeuzem & Vicente Soriano & Jean-Pierre Bronowicki & Ansgar W Lohse & Beat Müllhaupt & Marcus Schuchmann & Marc Bourlière & Maria Buti & Stuart K Roberts & Edward J Gane & Jerry , 2015. "ITPA Genotypes Predict Anemia but Do Not Affect Virological Response with Interferon-Free Faldaprevir, Deleobuvir, and Ribavirin for HCV Infection," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-13, December.
    3. 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.
    4. 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.
    5. Thomas R O'Brien & James E Everhart & Timothy R Morgan & Anna S Lok & Raymond T Chung & Yongwu Shao & Mitchell L Shiffman & Myhanh Dotrang & John J Sninsky & Herbert L Bonkovsky & Ruth M Pfeiffer & an, 2011. "An IL28B Genotype-Based Clinical Prediction Model for Treatment of Chronic Hepatitis C," PLOS ONE, Public Library of Science, vol. 6(7), pages 1-9, July.
    6. 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.
    7. 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.
    8. 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.
    9. Eric R Londin & Margaret A Keller & Cathleen Maista & Gretchen Smith & Laura A Mamounas & Ran Zhang & Steven J Madore & Katrina Gwinn & Roderick A Corriveau, 2010. "CoAIMs: A Cost-Effective Panel of Ancestry Informative Markers for Determining Continental Origins," PLOS ONE, Public Library of Science, vol. 5(10), pages 1-12, October.
    10. Nanye Long & Samuel P Dickson & Jessica M Maia & Hee Shin Kim & Qianqian Zhu & Andrew S Allen, 2013. "Leveraging Prior Information to Detect Causal Variants via Multi-Variant Regression," PLOS Computational Biology, Public Library of Science, vol. 9(6), pages 1-11, June.
    11. 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.
    12. 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.
    13. 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.
    14. 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.
    15. 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.
    16. 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.
    17. 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.
    18. 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.
    19. 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.
    20. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0072600. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.