Effects of the CCR5-Delta32 mutation on antiviral treatment in chronic hepatitis C.
OBJECTIVE
The CC-chemokine receptor (CCR) 5-Delta32 mutation may predispose to chronic liver disease and high level viremia in hepatitis C. However, it is unclear whether CCR5-Delta32 also affects the response to antiviral treatment.


METHODS
We determined CCR5 genotypes in patients with hepatitis C treated with either interferon-alpha (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-Delta32 carriers and homozygous CCR5 wildtype patients.


RESULTS
ETR and SVR were achieved in 25 and 12 patients with interferon-alpha and in 52 and 45 patients with interferon/ribavirin treatment, respectively. CCR5-Delta32 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-Delta32 carriage as an independent negative predictor for ETR in interferon-alpha monotherapy (odds ratio: 0.16; 95% confidence limits: 0.032-0.82; P=0.03). In interferon/ribavirin treated patients CCR-Delta32 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-alpha monotherapy are reduced in hepatitis C virus (HCV)-infected patients carrying the CCR5-Delta32 mutation. However, interferon/ribavirin combination treatment may overcome this negative effect of CCR5-Delta32.
Ahlenstiel
Golo
G
Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Strasse 25, D-53105, Bonn, Germany.
Berg
Thomas
T
Woitas
Rainer P
RP
Grünhage
Frank
F
Iwan
Agathe
A
Hess
Lothar
L
Brackmann
Hans H
HH
Kupfer
Bernd
B
Schernick
Andrea
A
Sauerbruch
Tilman
T
Spengler
Ulrich
U
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017354:Point Mutation; D019713:Receptors, CCR5 / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage*
D000998:Antiviral Agents; D019713:Receptors, CCR5; D012254:Ribavirin; D007372:Interferons