Impact of common risk factors of fibrosis progression in chronic hepatitis C

S Rüeger; P-Y Bochud; J-F Dufour; B Müllhaupt; D Semela; M H Heim; D Moradpour; A Cerny; R Malinverni; D R Booth; V Suppiah; J George; L Argiro; P Halfon; M Bourlière; A H Talal; I M Jacobson; E Patin; B Nalpas; T Poynard; S Pol; L Abel; Z Kutalik; F Negro

doi:10.1136/gutjnl-2014-306997

Impact of common risk factors of fibrosis progression in chronic hepatitis C

Gut. 2015 Oct;64(10):1605-15. doi: 10.1136/gutjnl-2014-306997. Epub 2014 Sep 11.

Authors

S Rüeger¹, P-Y Bochud², J-F Dufour³, B Müllhaupt⁴, D Semela⁵, M H Heim⁶, D Moradpour⁷, A Cerny⁸, R Malinverni⁹, D R Booth¹⁰, V Suppiah¹¹, J George¹², L Argiro¹³, P Halfon¹⁴, M Bourlière¹⁵, A H Talal¹⁶, I M Jacobson¹⁶, E Patin¹⁷, B Nalpas¹⁸, T Poynard¹⁹, S Pol¹⁸, L Abel²⁰, Z Kutalik²¹, F Negro²²

Affiliations

¹ 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.
² Infectious Diseases Service, University Hospital and University of Lausanne, Lausanne, Switzerland.
³ Department of Hepatology, University of Berne, Berne, Switzerland.
⁴ Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland.
⁵ Department of Gastroenterology, Canton Hospital St Gallen, St Gallen, Switzerland.
⁶ Department of Gastroenterology and Hepatology, University Hospital of Basel, Basel, Switzerland.
⁷ Department of Gastroenterology and Hepatology, University Hospital and University of Lausanne, Lausanne, Switzerland.
⁸ Epatologia, Clinica Moncucco, Lugano, Switzerland.
⁹ Pourtalès Hospital, Neuchatel, Switzerland.
¹⁰ Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia.
¹¹ 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.
¹² Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney and University of Sydney Medical Foundation, Sydney, Australia.
¹³ Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires, INSERM-UMR 906/Université de la Méditerranée, Marseilles, France.
¹⁴ Laboratoire Alphabio, Hôpital Ambroise Paré, Marseilles, France.
¹⁵ Service d'Hépato-gastroentérologie, Hôpital Saint-Joseph, Marseilles, France.
¹⁶ Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, USA.
¹⁷ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, U980, Imagine Institute, Paris, France University Paris Descartes, Paris, France.
¹⁸ University Paris Descartes, Paris, France Département d'Hépatologie, INSERM Unité 1016, Groupe Hospitalier Cochin-Hôtel Dieu-Broca, Paris, France.
¹⁹ Université Pierre et Marie Curie, Service d'Hépato-gastroentérologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
²⁰ 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.
²¹ Institute of Social and Preventive Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
²² Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland Department of Gastroenterology and Hepatology, University Hospitals of Geneva, Geneva, Switzerland.

PMID: 25214320
DOI: 10.1136/gutjnl-2014-306997

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.

Keywords: CIRRHOSIS; FIBROSIS; HEPATITIS C.

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Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biopsy
Disease Progression
Female
Genome-Wide Association Study
Hepacivirus / genetics*
Hepatitis C, Chronic / complications*
Hepatitis C, Chronic / virology
Humans
Incidence
Liver Cirrhosis / diagnosis
Liver Cirrhosis / epidemiology
Liver Cirrhosis / etiology*
Male
Polymorphism, Single Nucleotide*
RNA, Viral / analysis*
Retrospective Studies
Risk Assessment / methods*
Risk Factors
Switzerland / epidemiology
Time Factors

Substances

RNA, Viral