Role of CCR5Δ32 mutation in protecting patients with Schistosoma mansoni infection against hepatitis C viral infection or progression.

Abstract

Schistosomiasis has been incriminated in the significant increase in hepatitis C virus (HCV) infections, although the association has not been adequately explained. We hypothesized that the CCR5Δ32 mutation may be involved in the high prevalence of HCV with schistosomiasis. The aim was to explore the association between the CCR5Δ32 mutation in schistosomiasis patients and protection against HCV infection or progression. We compared 220 schistosomiasis patients (S group) and 190 patients with HCV and schistosomiasis (HCV/S group) for the presence of the CCR5Δ32 mutation. Clinical, biochemical, and radiological assessments were done. HCV infection was diagnosed with anti-HCV antibodies and a recombinant HCV antigen-based rapid immunochromatographic test, and confirmed by HCV reverse transcriptase PCR. HCV genotyping was done by reverse hybridization line probe assay. Schistosomiasis was diagnosed by FAST-ELISA and indirect hemagglutination for Schistosoma mansoni antibodies, and stool analysis for ova. Polymorphisms of the CCR5 receptor gene were assessed by PCR-based genotyping of the 32-bp deletion at the CCR5 locus in whole blood. Of HCV/S patients, 91.6 vs. 91.8 % of S patients had CCR5 WT/WT homozygosity (nonmutants). Heterozygous and homozygous CCR5Δ32 mutation patterns (CCR5Δ32/WT and CCR5Δ32/Δ32) were distributed similarly in the HCV/S and S groups (6.8 vs. 7.2 % and 0.53 vs. 0.90 %, respectively; p > 0.05, OR = 0.97). Genotype 4 was the predominant viral genotype (93 % of cases). No differences were observed in CCR5 gene patterns according to viral genotype, viral RNA count, or ALT level. However, CCR5Δ32 mutants (homozygous and heterozygous) had a lower rate of severe hepatic fibrosis vs. nonmutants (27 vs. 42 %, p = 0.101, OR = 0.51). Moreover, 53.4 % of CCR5Δ32/WT mutants showed spontaneous viral clearance vs. 26.2 % of nonmutants (p = 0.000, OR = 4.1). In conclusion, no association was detected between the CCR5Δ32 mutation and HCV disease susceptibility in schistosomiasis patients. However, patients with the CCR5Δ32 mutation and HCV infection were less prone to severe hepatic fibrosis and more likely to have spontaneous viral clearance than patients with the nonmutant genotype.