Iwata, R; Stieger, B; Mertens, J C; Müller, T; Baur, K; Frei, P; Braun, J; Vergopoulos, A; Martin, I V; Schmitt, J; Goetze, O; Bibert, S; Bochud, P Y; Müllhaupt, B; Berg, T; Geier, A (2011). The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C. Journal of Viral Hepatitis, 18(11):768-778.
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Summary. The outcome of hepatitis C virus (HCV) infection and the likelihood of a sustained virological response (SVR) to antiviral therapy depends on both viral and host characteristics. In vitro studies demonstrated that bile acids (BA) interfere with antiviral interferon effects. We investigate the influence of plasma BA concentrations and an ABCB11 polymorphism associated with lower transporter expression on viral load and SVR. Four hundred and fifty-one Caucasian HCV-patients treated with PEG-interferon and ribavirin were included in the study. ABCB11 1331T>C was genotyped, and plasma BA levels were determined. The 1331C allele was slightly overrepresented in HCV-patients compared to controls. In HCV-patients, a significant difference between patients achieving SVR vs non-SVR was observed for HCV-2/3 (5 vs 9 mum; P = 0.0001), while median BA levels in HCV-1 were marginally elevated. Elevated BA levels >8 mum were significantly associated with SVR (58.3%vs 36.3%; OR 2.48; P = 0.0001). This difference was significant for HCV-2/3 (90.7%vs 67.6%; P = 0.002) but marginal in HCV-1 (38.7%vs 27.8%; P = 0.058). SVR rates were equivalent between ABCB11 genotypes for HCV-1, but increased for HCV-2/3 (TT 100%vs CC 78%; OR 2.01; P = 0.043). IL28B genotype had no influence on these associations. No correlation between BA levels and HCV RNA was detected for any HCV genotype. The higher allelic frequency of ABCB11 1331C in HCV-patients compared to controls may indirectly link increased BA to HCV chronicity. Our data support a role for BA as host factor affecting therapy response in HCV-2/3 patients, whereas a weaker association was found for HCV-1.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry|
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
|DDC:||610 Medicine & health|
|Deposited On:||22 Feb 2011 10:29|
|Last Modified:||27 Nov 2013 20:22|
|Citations:||Web of Science®. Times Cited: 5|
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