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A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease

Lookup NU author(s): Professor Ann Daly, Professor Chris Day

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Abstract

Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member 11) 1331 T > C and NR1H4 (nuclear receptor) -1G > T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol > 40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012-1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1-110) mu mol/l compared with 3.5 (1-61) mu mol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P = 0.047) was observed in the chi(2) test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F >= 2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.


Publication metadata

Author(s): Iwata R, Baur K, Stieger B, Mertens JC, Daly AK, Frei P, Braun J, Vergopoulos A, Stickel F, Sabrane K, Martin IV, Schmitt J, Goetze O, Day CP, Mullhaupt B, Geier A, Swiss Hepatitis C Cohort Study Group

Publication type: Article

Publication status: Published

Journal: Clinical Science

Year: 2011

Volume: 120

Issue: 7-8

Pages: 287-296

Print publication date: 01/04/2011

ISSN (print): 0143-5221

ISSN (electronic): 1470-8736

Publisher: Portland Press Ltd

URL: http://dx.doi.org/10.1042/CS20100246

DOI: 10.1042/CS20100246


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