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In schistosomiasis mansoni (SM), periportal fibrosis (PPF) arises due to an inflammatory response exacerbated by parasite eggs in the intrahepatic portal space, culminating in the deposition of collagen and extracellular matrix proteins. This fibrosis results from a remodeling process of the extracellular matrix, in which metalloproteinases play a significant role. The study evaluated the association between MMP-3 polymorphism (-1171 5A>6A) (rs 3025058) and sociodemographic factors with PPF in individuals with SM. This is an analytical cross-sectional study involving 242 individuals infected with S. mansoni, of these 122 were diagnosed with hepatosplenic form (HS) and 119 hepatointestinal form (HI), all from the state of Pernambuco, Brazil. Polymerase chain reaction with restriction enzyme digestion (Psyl) was used to determine the MMP-3 polymorphism (-1171 5A>6A). There was a significant association between the male gender and the HS form (OR = 1.7623 95% CI [1.0481-2.9631]; p-value = 0.0439) as well as individuals aged over 41, also had a greater chance of developing this clinical form of the disease (OR = 2.8299; 95% CI [1.5211-5.2650]; p-value = 0.0014), with greater emphasis on individuals over 61 years old (OR= 8.5541; 95% CI [3.6895-19.8326], p-value= 0.0000). There was no statistically significant association between the MMP-3 polymorphism (-1171 5A>6A) between the clinical groups (5A6A CI [0.7144-1.9879] p-value 0.5882 5A5A CI [0.0912-2.9231] p-value 0.7331 5A6A / 5A5A CI [0.6904-1.8937] p-value 0.6949). In conclusion, the results showed no association between the MMP-3 polymorphism (-1171 5A>6A) and the development of PPF. In addition, males, and age over 41 were predictive factors for the HS form of the disease in this Brazilian population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aims: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is an essential component in the host immune response to infection, and it has been reported to be an important mediator in severe periportal fibrosis (PPF). We hypothesized that the (-G308A) polymorphism of the TNF-α gene is associated with the severity of PPF and that these polymorphisms influence TNF-α expression., Methods: In this cross-sectional study, we genotyped these polymorphisms within the TNF-α gene in 256 Brazilian subjects infected with Schistosoma mansoni, with different patterns of PPF., Results: The genotype (-308) AA was associated with a significant increase in the risk to advanced PPF (OR = 4.60; p = 0.009). In addition, median levels of TNF-α were higher in patients with moderate to advanced PPF, compared with mild fibrosis (20 and 17.3 pg/mL, respectively; p = 0.040). There was no association between average serum levels of TNF-α and (-G308A) TNF-α polymorphism., Conclusions: Our results suggest the (-308) AA genotype may be a risk factor for severity in advanced PPF, in this Brazilian population, and could potentially be used to predict the severity of advanced PPF in schistosomiasis.

Introduction:: We evaluated the associations between interleukin-10 (IL-10) gene polymorphisms -G1082A/-C819T/-C592A and periportal fibrosis regression after specific treatment for schistosomiasis., Methods:: This retrospective cohort study involved 125 Brazilian patients infected with Schistosomiasis mansoni, who were followed up for 2 years after specific treatment to estimate the probability of periportal fibrosis regression., Results:: There was no evidence of associations between IL-10 polymorphisms and periportal fibrosis regression after treatment., Conclusions:: There was no evidence of associations between gene promoter polymorphisms of IL-10 and the regression of periportal fibrosis in this Brazilian population.

Introduction: We hypothesized higher mannose-binding lectin level and classic factors (i.e., age, sex, alcohol consumption, exposure, and specific treatment) are associated with the severity of periportal fibrosis in schistosomiasis., Methods: This cross-sectional study involved 79 patients infected with Schistosoma mansoni with severe or mild/moderate periportal fibrosis. Serum concentrations of mannose-binding lectin were obtained by enzyme-linked immunosorbent assay (ELISA)., Results: Higher serum level of mannose-binding lectin was significantly associated with advanced periportal fibrosis., Conclusions: Mannose-binding lectin may contribute to liver pathology in schistosomiasis and may represent a risk factor for advanced periportal fibrosis in the Brazilian population studied.

Interleukin 10 (IL-10) is an important anti-inflammatory cytokine that modulates severe periportal fibrosis (PPF). We hypothesized that genetic polymorphisms (-G1082A/-C819T/-C592A) of the IL-10 gene and classic factors (age, sex, alcohol, exposure, and specific treatment) are associated with the severity of PPF and that these polymorphisms influence IL-10 expression. In this cross-sectional study, we genotyped these polymorphisms within the IL-10 gene in 203 Brazilian subjects infected with Schistosoma mansoni, with different patterns of PPF. There was an association of protection between the ages of 41 and 60 years and advanced standard PPF. The -1082AA genotype was significantly associated with severity in PPF when compared with the -1082GG genotype. Similarly, when analyzed together, both the -1082GA+AA genotypes were significantly associated. The ACC and GTA haplotypes indicated a protective effect against PPF, while the ATA haplotype was significantly associated with PPF severity when compared with the GCC haplotype. There was no significant difference between average levels of IL-10 between clinical groups, and there was no association between average serum levels of IL-10 and (-G1082A) IL-10 polymorphism. Our results suggest that (-G1082A) IL-10 polymorphism and putative haplotypes are associated with PPF severity in the Brazilian population.