Z Gastroenterol 2009; 47 - P277
DOI: 10.1055/s-0029-1241525

Bile acid levels as a host factor affecting antiviral treatment response but not viral replication in hepatitis C patients

R Iwata 1, B Stieger 2, J Mertens 1, O Goetze 1, K Sabrane 1, A Vergopoulos 3, J Braun 4, B Müllhaupt 1 A Geier 1, Swiss Hepatitis C Cohort Study Group (SCCS)
  • 1University Hospital Zurich, Clinic for Gastroenterology & Hepatology, Zurich, Switzerland
  • 2University Hospital Zurich, Division of Clinical Pharmacology, Zurich, Switzerland
  • 3University Hospital Zurich, Institute for Clinical Chemistry, Zurich, Switzerland
  • 4University of Zurich, Institute for Biostatistics, Zurich, Switzerland

Aims: The outcome of HCV infection varies among individuals and the likelihood of achieving a SVR to antiviral therapy depends on both viral and host characteristics. Recently, in vitro studies demonstrated that bile acids (BA) upregulate genotype 1 HCV (HCV-1) replication and interfere with IFN effects. Aim of this study was to investigate the influence of BA concentrations and an ABCB11 transporter polymorphism (V444A associated with lower BSEP expression) on viral load and SVR in HCV pts.

Methods: N=198 Caucasian HCV pts treated with PEG-IFN/ribavirin were included. 110 Caucasian individuals undergoing liver resection served as controls. The common ABCB11 variant 1331T>C was genotyped and serum BA levels were determined. Data were correlated with HCV RNA levels and SVR.

Results: The 1331C allele was slightly overrepresented in HCV pts compared to controls (63 vs. 55%; p=0.04). The CC genotype was encountered in 40% of HCV pts vs. 26% of controls (p=0.017; OR 0.54). For HCV pts median BA levels were increased in trend in the CC vs. TT genotype (7 vs. 4µmol/L; p=0.25). While differences of median BA levels within HCV-1 pts were not different (p=0.23), a highly significant difference for SVR vs. non-SVR was observed for HCV-2/3 (3µmol/L vs. 13µmol/L; p=0.0001). SVR rates for HCV-2/3 with normal vs. elevated BA levels differed 1.6-fold (89 vs. 55%; p=0.002). ROC analysis in HCV-2/3 shows 64% sensitivity and 77% specificity for BA levels of 8µmol/L to predict SVR (AUC=0.80). Accordingly, IFN response was not different within ABCB11 genotypes for HCV-1, but for HCV-2/3 SVR was increased in the TT vs. CC genotype with a clear trend (100 vs. 67.9%; p=0.15). No correlation between BA levels and HCV RNA was detected for any HCV genotype.

Conclusions: The difference in the allelic frequency of ABCB11 1331C in HCV pts compared to healthy subjects may be a hint towards a causal role of increased BA for HCV chronicity. Our data support a role for BA as a host factor affecting response to therapy in HCV-2/3, whereas no such association was found for HCV-1. In contrast to in vitro studies no effect of BA levels on viral load could be observed. The results highlight the complexity of host virus interaction and obvious differences between HCV-1 and HCV-2/3 biology.