Z Gastroenterol 2010; 48 - P4_18
DOI: 10.1055/s-0029-1246512

Increased bile acid levels reduce antiviral treatment response in genotype 2/3 hepatitis C patients whereas gamma-GT selectively predicts SVR in genotype 1

R Iwata 1, B Stieger 2, JC Mertens 1, O Goetze 1, IV Martin 3, K Sabrane 1, A Vergopoulos 4, J Braun 5, B Müllhaupt 1, A Geier 1
  • 1Abteilung Gastroenterologie und Hepatologie, Universität Zürich, Schweiz, Zürich
  • 2Klinische Pharmakologie, Universitätsspital Zürich, Zürich, Schweiz
  • 3Department of Internal Medicine III, RWTH Aachen, Aachen
  • 4Institut für Klinische Chemie, Universitätsspital Zürich, Zürich, Schweiz
  • 5Institut für Sozial- und Präventivmedizin, Universität Zürich, Zürich, Schweiz

Aims: 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 HCV replication and interfere with IFN effects.

Aims: To investigate the influence of BA concentrations and a frequent ABCB11 transporter SNP (associated with lower BSEP expression) on viral load and SVR in HCV pts.

Methods: N=198 pts with chronic HCV infection from the Swiss HCV Cohort study 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.

Results: The 1331C allele was slightly overrepresented in HCV pts (63 vs. 55% in controls; p=0.04). 1331CC encountered in 40% of HCV pts vs. 26% of controls (p=0.017). For HCV pts median BA levels were increased in trend in 1331CC vs. TT (7 vs. 4µmol/L). HCV genotypes 2 (n=24) and 3 (n=70) were combined to increase statistical power. While differences of median BA levels within HCV-1 pts (n=104) were not different, 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). 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 infection 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.