Cytokine and apoptosis gene polymorphisms influence the outcome of hepatitis C virus infection

BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis.METHODS:Polymorphisms of the genes IL-1 (-889 IL-1α,-511 and +3954 IL-1β,IL-1Ra),IL-18 (-137 and-607),IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP,PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis.The patients were classified into two groups:G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA).RESULTS:The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008;OR=0.26;95% CI,0.10-0.73).We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026;OR=3.49;95% CI,1.13-10.69).Adjustment for known covariate factors (age,gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and-607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017,respectively).CONCLUSION:The two genotypes GC-CA of the (-137 and-607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.

The Monitoring Interest of BK Virus Load in Renal Allograft Tunisian Recipients: Prospective Study

BK virus (BKV) may cause nephropathy in renal transplant recipients receiving immunosuppressive therapy, resulting in renal dysfunction and, possibly graft loss. However, the positive and negative predictive values of BK viral load are still controversial. In this prospective, single-center study, BKV DNA was measured 1, 3 and 6 months after transplantation. The viral load in urine and plasma was quantified with the real-time Q-PCR (Argen kit) in 73 renal allograft recipients Three of them showed acute rejection. To determine the cutoff value of viral load, 60 sera samples of healthy blood donors, matched for age and sex, were tested. The mean plasmatic viral load one month post-transplantation was statistically higher in renal transplant recipients (17.23 copies/ml) compared to that in controls (2 copies/ml) (p: 0.06). This difference of the distribution of viremia values is more evident in the third and sixth month (p: 0.002 and 0.010 respectively). Furthermore, analysis of the kinetic of viral load revealed an average rise of viremia at 3 months (1589.14 copies/ml) followed by its decrease at 6 months (249.75 copies/ml). However, the difference was not statistically significant. The same is true for the distribution of values of viruria and in all cases the average viral load was statistically higher in urine than in plasma. In addition, this study did not shown significant relationsheep between viremia/viruria and the occurrence of acute rejection, the renal function deterioration, the source of allograft or immunosuppressive therapy protocol. If the results of this study demonstrate the importance of the replication of BKV in renal transplant patients from the first month compared to that in immunocompetent subjects, the screening of the DNA of this virus does not appear to have a prognostic value in the occurrence of acute rejection. However, the plasma and urine monitoring of BKV load beyond 6 months , not appear to exclude the relationsheep between these two biomarkers and the occurrence of chronic graft dysfunction.