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

TitreImpact of common risk factors of fibrosis progression in chronic hepatitis C.
Publication TypeJournal Article
Year of Publication2015
AuthorsRüeger, S, Bochud, P-Y, Dufour, J-F, Müllhaupt, B, Semela, D, Heim, MH, Moradpour, D, Cerny, A, Malinverni, R, Booth, DR, Suppiah, V, George, J, Argiro, L, Halfon, P, Bourlière, M, Talal, AH, Jacobson, IM, Patin, E, Nalpas, B, Poynard, T, Pol, S, Abel, L, Kutalik, Z, Negro, F
Date Published10/2015
ISSN1468-3288 (Electronic)
Mots-clésBiopsy, Disease Progression, Female, Genome-Wide Association Study, Hepacivirus, Hepatitis C, Chronic, Humans, Incidence, Liver Cirrhosis, Male, Polymorphism, Single Nucleotide, Retrospective Studies, Risk Assessment, Risk Factors, RNA, Viral, Switzerland, Time Factors

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.


Publication types: Journal ArticlePublication Status: ppublish

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Alternate JournalGut
Citation Key / SERVAL ID3613
Peer reviewRefereed
PubMed ID25214320
Thème IUMSP et mots clés: 


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