Effects of the CCR5-Δ32 mutation on antiviral treatment in chronic hepatitis C

Ahlenstiel, Golo; Berg, Thomas; Woitas, Rainer P; Grünhage, Frank; Iwan, Agathe; Heß, Lothar; Brackmann, Hans H; Kupfer, Bernd; Schernick, Andrea; Sauerbruch, Tilman; Spengler, Ulrich

doi:10.1016/S0168-8278(03)00193-4

« Previous Next »Journal of Hepatology
Volume 39, Issue 2 , Pages 245-252, August 2003

Effects of the CCR5-Δ32 mutation on antiviral treatment in chronic hepatitis C

Golo Ahlenstiel
- Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
Thomas Berg
- Department of Internal Medicine, Center of Hepatology and Gastroenterology, Charité Campus, Virchow Klinikum, Berlin, Germany
Rainer P Woitas
- Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
Frank Grünhage
- Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
Agathe Iwan
- Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
Lothar Heß
- Institute of Experimental Hematology, University of Bonn, Bonn, Germany
Hans H Brackmann
- Institute of Experimental Hematology, University of Bonn, Bonn, Germany
Bernd Kupfer
- Institute of Medical Microbiology and Immunology, , University of Bonn, Bonn, Germany
Andrea Schernick
- Department of Internal Medicine, Center of Hepatology and Gastroenterology, Charité Campus, Virchow Klinikum, Berlin, Germany
Tilman Sauerbruch
- Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
Ulrich Spengler
- Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
- Corresponding author. Tel.: +49-228-287-6789; fax: +49-228-287-9822

Received 26 September 2002; received in revised form 11 April 2003; accepted 11 April 2003.

Abstract

Background/Aims: The CC-chemokine receptor (CCR) 5-Δ32 mutation may predispose to chronic liver disease and high level viremia in hepatitis C. However, it is unclear whether CCR5-Δ32 also affects the response to antiviral treatment.

Methods: We determined CCR5 genotypes in patients with hepatitis C treated with either interferon-α (N=78) or interferon and ribavirin (N=78). In each group, rates of end of treatment responses (ETRs) and sustained virological responses (SVRs) were compared between CCR5-Δ32 carriers and homozygous CCR5 wildtype patients.

Results: ETR and SVR were achieved in 25 and 12 patients with interferon-α and in 52 and 45 patients with interferon/ribavirin treatment, respectively. CCR5-Δ32 carriers had significantly lower ETR rates than homozygous CCR5 wildtype patients (10.5 vs. 39.0%; P=0.02), whereas SVR rates only showed a non-significant trend (5.3 vs. 18.6%). Multivariate analysis confirmed CCR5-Δ32 carriage as an independent negative predictor for ETR in interferon-α monotherapy (odds ratio: 0.16; 95% confidence limits: 0.032–0.82; P=0.03). In interferon/ribavirin treated patients CCR-Δ32 carriers and CCR5 wildtype patients had similar ETR rates [19.2% vs. 23.1%] and SVR rates [20.0% vs. 21.2%].

Conclusions: Response rates to interferon-α monotherapy are reduced in hepatitis C virus (HCV)-infected patients carrying the CCR5-Δ32 mutation. However, interferon/ribavirin combination treatment may overcome this negative effect of CCR5-Δ32.

Keywords: CCR5, Hepatitis C virus, Interferon, Ribavirin, Treatment response