Impact of common risk factors of fibrosis progression in chronic hepatitis C
| Autor: | F. Negro, Darius Moradpour, Stanislas Pol, Beat Müllhaupt, David R. Booth, Pierre-Yves Bochud, David Semela, Philippe Halfon, Thierry Poynard, Jacob George, Vijayaprakash Suppiah, Andrew H. Talal, Sina Rüeger, Laurent Argiro, M. Bourlière, Ira M. Jacobson, Bertrand Nalpas, Jean-François Dufour, Raffaele Malinverni, Markus H. Heim, A. Cerny, Etienne Patin, Laurent Abel, Zoltán Kutalik |
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| Přispěvatelé: | Rueger, S, Bochud, PY, Dufour, JF, Mullhaupt, B, Negro, F, Suppiah, V |
| Rok vydání: | 2015 |
| Předmět: |
Liver Cirrhosis
Male medicine.medical_specialty Time Factors Cirrhosis Biopsy Hepacivirus Polymorphism Single Nucleotide Risk Assessment Gastroenterology 03 medical and health sciences Liver disease 0302 clinical medicine Risk Factors Fibrosis Internal medicine medicine Humans hepatitis c Retrospective Studies 030304 developmental biology Hepatitis 0303 health sciences medicine.diagnostic_test business.industry Incidence fibrosis Hepatitis C Hepatitis C Chronic medicine.disease 3. Good health Liver biopsy Attributable risk Immunology Disease Progression RNA Viral Female 030211 gastroenterology & hepatology progression business Body mass index Switzerland Genome-Wide Association Study |
| Zdroj: | Gut |
| DOI: | 10.1136/gutjnl-2014-306997 |
| Popis: | ObjectiveThe 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.ResultsAge 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. ConclusionsMost factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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