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

Rüeger, S; Bochud, P-Y; Dufour, Jean-François; Müllhaupt, B; Semela, D; Heim, M H; Moradpour, D; Cerny, A; Malinverni, R; Booth, D R; Suppiah, V; George, J; Argiro, L; Halfon, P; Bourlière, M; Talal, A H; Jacobson, I M; Patin, E; Nalpas, B; Poynard, T; ... (2014). Impact of common risk factors of fibrosis progression in chronic hepatitis C. Gut, 64(10), pp. 1605-1615. BMJ Publishing Group 10.1136/gutjnl-2014-306997

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Dufour, Jean-François

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0017-5749

Publisher:

BMJ Publishing Group

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

20 Apr 2015 10:54

Last Modified:

06 Nov 2015 09:39

Publisher DOI:

10.1136/gutjnl-2014-306997

PubMed ID:

25214320

Uncontrolled Keywords:

CIRRHOSIS; FIBROSIS; HEPATITIS C

BORIS DOI:

10.7892/boris.67147

URI:

https://boris.unibe.ch/id/eprint/67147

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