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Original article
Impact of common risk factors of fibrosis progression in chronic hepatitis C
  1. S Rüeger1,2,3,
  2. P-Y Bochud4,
  3. J-F Dufour5,
  4. B Müllhaupt6,
  5. D Semela7,
  6. M H Heim8,
  7. D Moradpour9,
  8. A Cerny10,
  9. R Malinverni11,
  10. D R Booth12,
  11. V Suppiah12,13,
  12. J George13,
  13. L Argiro14,
  14. P Halfon15,
  15. M Bourlière16,
  16. A H Talal17,
  17. I M Jacobson17,
  18. E Patin18,19,
  19. B Nalpas19,20,
  20. T Poynard21,
  21. S Pol19,20,
  22. L Abel18,19,22,
  23. Z Kutalik2,3,
  24. F Negro23,24
  1. 1Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
  2. 2Institute of Social and Preventive Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland
  3. 3Swiss Institute of Bioinformatics, Lausanne, Switzerland
  4. 4Infectious Diseases Service, University Hospital and University of Lausanne, Lausanne, Switzerland
  5. 5Department of Hepatology, University of Berne, Berne, Switzerland
  6. 6Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
  7. 7Department of Gastroenterology, Canton Hospital St Gallen, St Gallen, Switzerland
  8. 8Department of Gastroenterology and Hepatology, University Hospital of Basel, Basel, Switzerland
  9. 9Department of Gastroenterology and Hepatology, University Hospital and University of Lausanne, Lausanne, Switzerland
  10. 10Epatologia, Clinica Moncucco, Lugano, Switzerland
  11. 11Pourtalès Hospital, Neuchatel, Switzerland
  12. 12Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia
  13. 13Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney and University of Sydney Medical Foundation, Sydney, Australia
  14. 14Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires, INSERM-UMR 906/Université de la Méditerranée, Marseilles, France
  15. 15Laboratoire Alphabio, Hôpital Ambroise Paré, Marseilles, France
  16. 16Service d'Hépato-gastroentérologie, Hôpital Saint-Joseph, Marseilles, France
  17. 17Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, USA
  18. 18Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, U980, Imagine Institute, Paris, France
  19. 19University Paris Descartes, Paris, France
  20. 20Département d'Hépatologie, INSERM Unité 1016, Groupe Hospitalier Cochin-Hôtel Dieu-Broca, Paris, France
  21. 21Université Pierre et Marie Curie, Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
  22. 22St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA
  23. 23Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland
  24. 24Department of Gastroenterology and Hepatology, University Hospitals of Geneva, Geneva, Switzerland
  1. Correspondence to Professor Francesco Negro, Divisions of Clinical Pathology and of Gastroenterology and Hepatology, Geneva University Hospital, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 4, Switzerland; Francesco.Negro{at}hcuge.ch

Abstract

Objective The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C.

Design We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR.

Results Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR.

Conclusions Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.

  • HEPATITIS C
  • CIRRHOSIS
  • FIBROSIS

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