title: Impact of common risk factors of fibrosis progression in chronic hepatitis C.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland Institute of Social and Preventive Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Rüeger
authors.affiliation: Infectious Diseases Service, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Bochud
authors.affiliation: Department of Hepatology, University of Berne, Berne, Switzerland.
authors.forename: J-F
authors.initials: JF
authors.lastname: Dufour
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Müllhaupt
authors.affiliation: Department of Gastroenterology, Canton Hospital St Gallen, St Gallen, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Semela
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital of Basel, Basel, Switzerland.
authors.forename: M H
authors.initials: MH
authors.lastname: Heim
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Moradpour
authors.affiliation: Epatologia, Clinica Moncucco, Lugano, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Cerny
authors.affiliation: Pourtalès Hospital, Neuchatel, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Malinverni
authors.affiliation: Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Booth
authors.affiliation: Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney and University of Sydney Medical Foundation, Sydney, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Suppiah
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney and University of Sydney Medical Foundation, Sydney, Australia.
authors.forename: J
authors.initials: J
authors.lastname: George
authors.affiliation: Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires, INSERM-UMR 906/Université de la Méditerranée, Marseilles, France.
authors.forename: L
authors.initials: L
authors.lastname: Argiro
authors.affiliation: Laboratoire Alphabio, Hôpital Ambroise Paré, Marseilles, France.
authors.forename: P
authors.initials: P
authors.lastname: Halfon
authors.affiliation: Service d'Hépato-gastroentérologie, Hôpital Saint-Joseph, Marseilles, France.
authors.forename: M
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Talal
authors.affiliation: Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, USA.
authors.forename: I M
authors.initials: IM
authors.lastname: Jacobson
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, U980, Imagine Institute, Paris, France University Paris Descartes, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Patin
authors.affiliation: University Paris Descartes, Paris, France Département d'Hépatologie, INSERM Unité 1016, Groupe Hospitalier Cochin-Hôtel Dieu-Broca, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Nalpas
authors.affiliation: Université Pierre et Marie Curie, Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Poynard
authors.affiliation: University Paris Descartes, Paris, France Département d'Hépatologie, INSERM Unité 1016, Groupe Hospitalier Cochin-Hôtel Dieu-Broca, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Pol
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, U980, Imagine Institute, Paris, France University Paris Descartes, Paris, France St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Abel
authors.affiliation: Institute of Social and Preventive Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Z
authors.initials: Z
authors.lastname: Kutalik
authors.affiliation: Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland Department of Gastroenterology and Hepatology, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Negro
mesh_terms: D001706:Biopsy; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000032:analysis*; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology; D013997:Time Factors
chemical_list: D012367:RNA, Viral
keywords: CIRRHOSIS; FIBROSIS; HEPATITIS C