Effects of the CCR5-Delta32 mutation on antiviral treatment in chronic hepatitis C

J Hepatol. 2003 Aug;39(2):245-52. doi: 10.1016/s0168-8278(03)00193-4.

Abstract

Background/aims: 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.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Interferons / administration & dosage
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Point Mutation
  • Receptors, CCR5 / genetics*
  • Ribavirin / administration & dosage*

Substances

  • Antiviral Agents
  • Receptors, CCR5
  • Ribavirin
  • Interferons