The present study evaluated the IL8-251 A/T polymorphism in samples from 74 patients with chronic hepatitis B (HBV), 100 patients with chronic hepatitis C (HCV), and 300 healthy donors (CG). The correlations of this polymorphism with plasma IL-8 and disease stage were calculated. Polymorphisms were identified by real-time PCR. IL-8 was measured by enzyme-linked immunosorbent assay. The IL8-251 A/T genotype was not associated with susceptibility to infection by HBV or HCV. The wild-type allele (A) was associated with higher levels of inflammation (p = 0.0464) and fibrosis scores (p = 0.0016) in the HBV group, representing an increased risk for increased inflammatory activity (OR = 1.84; p = 0.0464) and for high fibrosis scores (OR = 2.63; p = 0.0016). Viral load was higher in HBV patients with polymorphic genotypes (TA and TT) at the IL8-251 A/T polymorphism than in those with the wild-type genotype (p = 0.0272 and p = 0.0464, respectively). Plasma IL-8 was higher among patients infected with HBV or HCV than in the control group (p = 0.0445 and p = 0.0001, respectively). The polymorphic genotype was associated with lower IL-8 than the wild-type genotype in the HBV group (p = 0.0239) and the HCV group (p = 0.0372). The wild-type genotype for IL8-251 A/T and high IL-8 were associated with a worse prognosis for infections; therefore, they may contribute to viral persistence and the development of more severe forms of chronic viral liver diseases.

The dysregulation of cytokine production can lead to an inefficient immune response, promoting viral persistence that induces the progression of chronic viral hepatitis. The study investigated the association of the IL6-174G/C polymorphism with changes in cytokine levels and its influence on the persistence and progression of chronic hepatitis caused by HBV and HCV in 72 patients with chronic hepatitis B (HBV), 100 patients with hepatitis C (HCV), and a control group of 300 individuals. The genotyping of the IL6-174G/C polymorphism was performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). HCV patients with the wild-type genotype (GG) had a higher viral load (p = 0.0230). The plasma levels of IL-6 were higher among patients infected with HBV and HCV than among the control group (p < 0.0001). Patients with HCV were associated with increased inflammatory activity (A2–A3; p < 0.0001). In hepatitis C, carriers of the GG genotype had higher levels of IL-6 (p = 0.0286), which were associated with A2–A3 inflammatory activity (p = 0.0097). Patients with A2–A3 inflammatory activity and GG genotype had higher levels of IL-6 than those with the GC/CC genotype (p = 0.0127). In conclusion, the wild-type genotype for the IL6-174G/C polymorphism was associated with high levels of IL-6 and HCV viral load and inflammatory activity, suggesting that this genotype may be a contributing factor to virus-induced chronic infection.

An inefficient immune response against the hepatitis C virus (HCV), combined with viral evasion mechanisms, is responsible for the chronicity of infection. The need to evaluate the innate mechanisms of the immune response, such as TLR3 and IFN-λ3, and their relationship with the virus–host interaction is important for understanding the pathogenesis of chronic hepatitis C. The present study aimed to investigate the gene expressions of TRL3 and IFNL3 in liver tissue, seeking to evaluate whether these could be potential biomarkers of HCV infection. A total of 23 liver biopsy samples were collected from patients with chronic HCV, and 8 biopsies were collected from healthy control patients. RNA extraction, reverse transcription and qPCR were performed to quantify the relative gene expressions of TLR3 and IFNL3. Data on the viral load; AST, ALT, GGT and AFP levels; and the viral genotype were collected from the patients′ medical records. The intrahepatic expression of TLR3 (p = 0.0326) was higher in chronic HCV carriers than in the control group, and the expression of IFNL3 (p = 0.0037) was lower in chronic HCV carriers than in the healthy control group. The expression levels of TLR3 (p = 0.0030) and IFNL3 (p = 0.0036) were higher in the early stages of fibrosis and of necroinflammatory activity in the liver; in contrast, TLR3 and IFNL3 expressions were lower in the more advanced stages of fibrosis and inflammation. There was no correlation between the gene expression and the serum viral load. Regarding the initial METAVIR scale scores, liver transaminase levels were lower in patients with advanced fibrosis when correlated with TLR3 and IFNL3 gene expressions. The results suggest that in the early stages of the development of hepatic fibrosis, TLR3 and IFN-λ3 play important roles in the antiviral response and in the modulation of the tolerogenic liver environment because there is a decrease in the intrahepatic expressions of TLR3 and IFNL3 in the advanced stages of fibrosis, probably due to viral evasion mechanisms.

Backgrounds: Neural growth factor (NGF) is a neurotrophin that can interact with the p75^NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75^NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. Methods: The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. Results: The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75^NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. Conclusion: Mutations in the NGF (−198C > T, Ala35Val) and p75^NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

Introdução: O cuidado ampliado à saúde deve incluir o bem-estar espiritual. No Brasil, estudos prévios demonstram pouca inserção da espiritualidade nos currículos das áreas de saúde. Objetivo: Este estudo investigou a presença desta temática nos currículos das escolas médicas da região Norte do país e analisou a visão do interno de medicina sobre a importância do tema e seu próprio bem-estar espiritual. Método: Desenvolvida pesquisa do tipo transversal e descritivo, explorando projetos pedagógicos de dezessete escolas médicas; acrescido da aplicação de duas escalas tipo likert a 92 graduandos do último semestre de medicina, oriundos duas escolas médicas da região. A primeira escala versou sobre três dimensões (Espiritualidade e Saúde, Espiritualidade e Doença, Espiritualidade e Formação Médica), com pontuações de 1 a 4. As médias das assertivas foram divididas em três intervalos de pontuação: de 1 a 1,99 – zona de perigo; de 2 a 2,99 – zona de alerta; e de 3 a 4 – zona de conforto, conforme o comportamento atitudinal do grupo. Após a aplicação do questionário houve o processo de validação e de confiabilidade da mesma. A segunda escala se referiu ao bem-estar espiritual com o uso do escore FACIT-Sp‑Non‑Illnes – Version4, entre 0 a 48 pontos. Resultados: Dezesseis instituições responderam ao questionário e em 12,5% se identificou a presença da temática espiritualidade, em seus currículos. As médias dos escores das dimensões espiritualidade e saúde, espiritualidade e doença e espiritualidade e formação foram 3,29; 3,47 e 2,61, respectivamente, revelando fragilidade no aspecto de formação. O escore final do bem-estar espiritual dos graduandos dos cursos foi de 37 pontos. Conclusão: Concluiu-se que há baixa inserção da espiritualidade nos currículos, e, apesar dos graduandos estarem em bem-estar espiritual e reconhecerem sua importância, há grandes lacunas em sua formação.