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Background and aims: Chemokines are small polypeptides, a major function of which is lymphocyte recruitment and trafficking. The aim of this study was to assess the involvement of inherited variations in CCR2, CCR5, and the ligand RANTES in determining disease outcome in hepatitis C virus (HCV) infected individuals. Methods: A total of 283 women, all exposed to HCV genotype 1b from a single donor, and including those who had spontaneously cleared the virus and those chronically infected, were genotyped for CCR2, CCR5, and RANTES polymorphisms. The frequencies of these polymorphisms were then compared with disease activity and severity. Results: CCR5, CCR2, and RANTES genotypes were compared with HCV polymerase chain reaction (PCR) status, alanine aminotransferase levels, and liver histology. There was no significant relationship between CCR2 or RANTES polymorphisms and disease outcome or severity. However, CCR5D32 heterozygotes were more likely to have spontaneous clearance of the virus than those without the mutation (42% PCR negative v 28.3% negative; p = 0.044, odds ratio 1.83 (95% confidence interval 1.1-3.6)). Among the subgroup of DRB1*03011 negative individuals, previously found to be associated with more severe inflammation, the difference in histological inflammatory score (CCR5WT/WT = 4.9 v CCR5D32/ WT = 3.53; p = 0.043) was significant. Conclusion: Heterozygosity for CCR5D32 was shown to be significantly associated with spontaneous hepatitis C viral clearance and with significantly lower hepatic inflammatory scores in subgroups within this cohort. Both controls and the HCV population had similar heterozygosity frequencies.

This study reveals a moderate increase in prevalence of fibromyalgia in HCV patients. The number of tender points was related to mode of acquisition but not to PCR status. Anxiety and depression levels are also increased in HCV patients compared with controls. Prevalence of RF was higher in PCR-positive patients compared with controls and those who had cleared the virus.

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Intrahepatic thrombotic events have been postulated to play a key role in the pathogenesis of hepatic fibrosis. Genetic and acquired thrombotic risk factors may therefore contribute to the varying rates of fibrosis progression observed in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to assess the impact of inherited mutations in factor V and factor II (prothrombin) on hepatic fibrosis progression rates in individuals infected with HCV. Two hundred and ten Irish women infected with HCV genotype 1b, contracted from a single source (HCV-contaminated anti-D immunoglobulin) were genotyped for the factor V Leiden G1691A and prothrombin G20210A polymorphisms, and compared with Irish Caucasoid controls. Index and subsequent liver biopsies were scored (Ishak scoring system) by a single pathologist. Statistical analysis was performed using SPSS. Factor V Leiden and prothrombin G20210A heterozygosity were determined in 3.7% and 1.85%, respectively, of the study population. There was no association between these polymorphisms and fibrotic score on the index biopsy, or degree of change in fibrotic score on subsequent biopsies. The mean fibrotic score for factor V wild type was 1.06 vs 0.71 for the heterozygotes (P = 0.89). The mean change in fibrotic scores between subsequent biopsies was 0.72 for factor V wild type vs 0.50 for heterozygotes (P = 0.68). Similarly, there was no significant difference in fibrotic score for those with the prothrombin G20210A polymorphism (P = 0.936). Alanine aminotransferase levels for factor V wild type were significantly lower than those for the heterozygotes, 45.9 vs 57 (P = 0.032). Factor V Leiden and prothrombin G20210A heterozygosity rates were infrequently detected in this HCV cohort and were similar to rates seen in a Caucasian Irish control population. In this cohort, neither factor V Leiden nor prothrombin G20210A polymorphisms had a significant impact on fibrotic scores or degree of change between subsequent biopsies. These data do not support a key role for thrombotic risk factors in fibrogenesis in HCV-infected patients.