The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and its absence could be associated with protection against HCV infection. Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients. Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. There was also no association of polymorphisms with variations in liver enzyme levels.
The course and outcome of HCV infection are determined by its virological characteristics and the immune responses triggered by the virus . HCV is a hepatotropic virus that induces the development of acute and chronic necroinflammatory disease, escaping the immune system in up to 85% of cases . Several cytokines play dual roles in viral infection and are responsible for viral clearance and tissue damage .
TNF-α is an important cytokine in the immune response, mediating the inflammatory process through innate immunity pathways and activation of the cellular response, which induces apoptosis or necrosis . Thus, genetic variations in the TNFA gene that alter cytokine production levels may contribute to the progression of HCV infection.
In the present study, the polymorphic genotype for the TNFA -308G>A variant, correlated with increased expression of the cytokine , was not present in the group of patients with chronic HCV. We speculate that the presence of the homozygous variant allele (AA) could contribute to better immune control, preventing the progression of HCV infection. Furthermore, high levels of TNF-α increase the expression of vascular endothelial adhesion molecules and increase the stimulation of endothelial cells and macrophages, which may lead to better infection resolution .
The high frequency of the wild-type allele (G) in the group of patients with chronic HCV infection could be a suggestion that in addition to having a higher risk of developing the infection, these patients could have a greater chance of developing the chronic form of the disease, this due to the inadequate production of TNF-α by dendritic cells favors the differentiation of CD4+ T cells into IL-10- and non-IFN-γ-producing cells . As the IL-10 cytokine is not effective in resolving the infection it progressed to the chronic form.
Studies on the TNFA -308G>A polymorphism performed in other ethnic groups also observed different frequencies of the polymorphic genotype in patients with HCV than without, showing that although the presence of the homozygous polymorphism was not observed in patients from France  and in India the prevalence of the polymorphism was higher in the group of patients with chronic HCV . As the population evaluated in this study is trihybrid, formed from the genetic contributions of whites, blacks, and indigenous people , the association of the polymorphism with the prevention or risk of HCV infection needs to be better investigated in other ethnic groups. Furthermore, the differences in the results might be due to the methodology used for genotyping the polymorphisms, which were also differents (the present study performed the genotyping by RT-PCR, while the other two used PCR–RFLP and gene sequencing).
IL-10 is an anti-inflammatory cytokine produced by Th2 cells that inhibits the activity of Th1, NK, and macrophage cells, the main cells responsible for pathogen elimination. The cytokine acts by limiting the marked pro-inflammatory response and damage caused by inflammation . In infectious processes, there is a direct correlation between lower IL-10 production and greater disease severity .
The IL10 -1082A>G polymorphism is associated with changes in IL-10 level, the wild-type genotype being associated with lower levels . In the present study, no differences in genotype frequencies were found between the groups with and without HCV infection. The evaluation of this polymorphism in HCV infection by other studies has shown different results. Although the present results were similar to those of another study, which also did not find an association between the frequency of the IL10 -1082A>G polymorphism and susceptibility to HCV infection , Ramos et al.  observed that the GG (polymorphic) genotype was associated with increased chances of viral infection resolution. The combined analysis of these results shows that the polymorphism does not influence the protection from or susceptibility to HCV infection but can influence the disease resolution, reducing the chances of progression to the chronic form among those who develop hepatitis C. These differences seem to be associated with differences between ethnic groups, and methodologies used for genotyping the polymorphisms.
The polymorphic genotype (GG) of the IL10 -1082A>G variant was associated with higher HCV viral load than the wild-type genotype. Most studies that investigated this polymorphism in HCV infection did not assess viral load levels. In the study by Abbas et al. , no difference in viral load was observed between genotypes in patients from Pakistan. Viral load has been associated with the frequency of the homozygous genotype (AA) and that of the wild-type (A) allele . The divergence between the results of that study and the present study may be related to the type of analysis performed, Gao et al.  evaluated the frequencies of genotypes in relation to the presence or absence of HCV RNA, while the present study evaluated the absolute plasma levels, which were converted to their base-10 logarithm. In addition, the differences may also be related to the ethnicity of the populations assessed between the different studies. The population evaluated in this work is originally from the Brazilian Amazon and has a genetic contribution from Europeans, native Indians and Africans , which could contribute to the result found. Some studies have shown that the genetic influence of ethnicity is associated with variations in genes related to the individual’s response to diseases [31, 32].
The polymorphic genotype (GG) for IL10 -1082A>G is associated with higher IL-10 expression. This cytokine inhibits the activation of Th1, NK, and macrophage cells, which are the main cells responsible for the elimination of HCV; higher levels of IL-10 reduce inflammatory activity at the infection site, favoring the persistence of the virus in the tissue, the main characteristic of chronic infection . Our findings raise the hypothesis that the polymorphic genotype could favor an increase in viral load in the liver tissue; but follow-up studies, as well as mechanistic studies, are needed to confirm this hypothesis.
The TNFA -308G>A and IL10 -1082A>G polymorphisms were not associated with different levels of necroinflammatory activity or with fibrosis score. Several studies have also found no relationship between these polymorphisms in the TNF and IL10 genes and different stages of the disease [15, 16, 24, 28, 33]; probably because the disease progression is due to other factors and not only to the host genetic profile.
Although the TNFA -308G>A and IL10 -1082A>G polymorphisms are associated with variations in the levels of the TNF-α and IL-10 cytokines, it was not possible to directly assess this relationship in the present study. Due to financial limitations, plasma cytokine dosage was not performed, which was the limitation of the study.
In conclusion, the polymorphic genotype at TNFA -308G>A was not present in the group of patients with chronic hepatitis C, and even though it could represent a protective action of this SNP against HCV infection, we understand that further studies must be performed in order to confirm it. In the same way, considering that this was a cross-sectional study, the polymorphic genotype for variant IL10 -1082A>G need to be better analyzed in a follow-up study in order to confirm its association with viral persistence.