Role of complement component C4 in treatment response and disease progression in chronic hepatitis C patients

The basis of hepatitis C virus (HCV) evasion of immune system and its response to treatment is still elusive. There have been studies where the level of C4 has been found to be associated with HCV persistence and disease progression. This study aims to find out relationship between levels of C4 in serum, and its functional SNPs with response to treatment. The study included 84 patients with CHC who received treatment and 75 healthy controls. C4 expression, both at mRNA and protein level, was estimated by Real time and ELISA respectively. Its functional SNP's genotyped by AS-PCR. The mean +/- SD baseline C4 levels between the disease and healthy cases was significantly different (1075.74 +/- 65.25 vs 1593 +/- 24.55ng/mL, P<0.001). The mean +/- SD baseline C4 levels of CC, GC and GG genotype of rs2857009 in the healthy group were 1540.97 +/- 7.87, 1599.53 +/- 11.75 and 1604.86 +/- 10.79ng/mL, respectively (P<0.001), whereas the levels in the CHC group were 1022.81 +/- 32.95, 1058.19 +/- 55.02 and 1150.26 +/- 14.64ng/mL, respectively (P<0.001). CC genotype resulted in decreased C4 mRNA levels compared to GG genotype in healthy group (3.81-fold) and CHC group (1.4-fold). The CC genotype of rs2857009 is associated with reduced expression of C4, both at mRNA and protein level. The C4 serum level at baseline and total protein were found to be independent predictors for treatment response. New predictive score using the above factors, a value of 0.542 was found to predict positive response to treatment. Increased age, rs2857009 SNP and HCV genotype were associated with disease progression.