Combination of genetic polymorphisms in TLR influence cytokine profile in HCV patients treated with DAAs in the State of Amazonas.

Hepatitis C is a public health problem and affects approximately 3% of the world's population. HCV infections have a wide spectrum of clinical manifestations, and several single nucleotide polymorphisms (SNPs) in the genes of the toll-like receptors are cited to influence the clinical outcomes. A cross-sectional study was conducted in the Amazonas State, Brazil in which SNPs in TLR4 and TLR9 genes were genotyped by PCR-RFLP in 151 HCV chronic liver disease patients and 206 healthy donors. The circulating cytokines IL-6, TNF, IL-10, IL-2, IFN-γ, IL-4 and IL-17A were measured by cytometric bead array (CBA) which revealed that the combined genotypes of TLR9 -1237T/T and -1486C/T seem to influence the cytokine profile under lipopolysaccharide (LPS) stimulation of the Th17 profile, especially among patients with advanced chronic liver disease when treated with DAAs.

Immunological Dynamics Associated with Direct-Acting Antiviral Therapies in Naive and Experimented HCV Chronic-Infected Patients.

The therapeutic strategies used in the treatment of hepatitis C are essentially based on the combination of direct-acting antiviral agents (DAAs). This therapy has been shown to be very effective in relation to patient adherence to treatment and has shown high rates of sustained virological response (SVR). However, the immunological dynamics of patients infected with HCV is poorly understood. This fact led us to investigate the immune system of naive and experienced patients, who we followed before the therapy and three months after the end of treatment. In this study, 35 naive and experienced Brazilian patients with chronic hepatitis C and 50 healthy donors (HD group) were studied. The analysis of the soluble immunological biomarkers was performed using the flow cytometry methodology. The SVR rate was >90% among the 35 patients. Before treatment, correlations in the naive HCV group demonstrated a mix of inflammatory response occurring with moderate correlations between chemokines, inflammatory cytokines, and Th2 profile, with a strong regulation between IL-10 and IL-17A. On the other hand, experienced patients demonstrated a poor interaction between cytokines, chemokines, and cells with a strong correlation between IL-10, IL-6, CXCL-10, and CD8+ besides the interactions between IFN-γ and IL-4. Furthermore, naive and experienced patients seem to have a distinct soluble biomarker profile; therefore, a long-term follow-up is needed to evaluate patients treated with DAAs.

Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil.

Hepatitis C is considered a major public health problem caused by the hepatitis C virus (HCV). Viral infections are known to induce production of IL1ß through the signaling pathway of inflammasomes. Emerging evidences suggest that Inflammasome genes may influence the immune response against HCV as the host genetic background may contribute to the balance between acute and chronic inflammation. We investigated in 151 patients with chronic hepatitis C and 206 healthy blood donors' individuals (HD). Polymorphisms in the IL1B and IL18 genes were genotyped by PCR-RFLP, while NLRP3, CARD8, CTSB and AIM2 by RT- PCR. Serum assay of IL-1ß cytokine was performed by ELISA. 84 patients presented mild fibrosis (

Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon.

Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.

Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon

Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.