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BackgroundIn this study, we have evaluated the immunological status of hepatitis C virus (HCV)-infected patients aiming at identifying putative biomarkers associated with distinct degrees of liver fibrosis. Peripheral blood and tissue T-cells as well as cytokine levels were quantified by flow cytometry.ResultsData analysis demonstrated higher frequency of circulating CD8+ T-cells and Tregs along with a mixed proinflammatory/IL-10-modulated cytokine pattern in HCV patients. Patients with severe liver fibrosis presented lower frequency of circulating CD8+ T-cells, higher levels of proinflammatory cytokines, but lower levels of IL-10, in addition to the higher viral load. Despite the lower frequency of intrahepatic T-cells and scarce frequency of Tregs, patients with severe liver fibrosis showed higher levels of proinflammatory cytokines (TNF and IFN-γ). The tissue proinflammatory cytokine pattern supported further studies of serum cytokines as relevant biomarkers associated with different liver fibrosis scores. Serum cytokine signature showed that mild liver fibrosis is associated with higher IL-10 serum levels as compared to severe liver disease. There was a clear positive connection of IL-10 with the TNF node in patients with mild liver fibrosis, whereas there is an evident inverse correlation between IL-10 with all other cytokine nodes.ConclusionsThese results suggest the absence of modulatory events in patients with severe liver damage as opposed to mild fibrosis. Machine-learning data mining pointed out TNF and IL-10 as major attributes to differentiate HCV patients from non-infected individuals with highest performance. In conclusion, our findings demonstrated that HCV infection triggers a local and systemic cytokine ensemble orchestrated by TNF and tuned by IL-10 in such a manner that mirrors the liver fibrosis score, which highly suggests the relevance of these set of biomarkers for clinical investigations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0610-6) contains supplementary material, which is available to authorized users.

We declare no confl ict of interest. ABSTRACTThe association of HIV infection and hepatitis C virus (HCV) infection often occurs because both viruses share the same transmission routes, increasing the possibility of HIV/HCV coinfection. World prevalence greater than 30% of coinfected cases is estimated, and it can reach 90% depending on the transmission route. With the aim of determining the frequency and profi le of HIV/HCV coinfected patients, a descriptive analysis was carried out with patients with HIV/AIDS whose serology was positive for hepatitis C virus (HCV), cared for at the Fundação de Medicina Tropical do Amazonas from 2000 to 2007. In the present study, of the 2,653 AIDS cases notifi ed in SINAN, 1,582 patients underwent serology test for hepatitis C, and a frequency of 4.42% (n = 70) of HIV/HCV coinfected patients was identifi ed in the period studied. The most frequent infection route was sexual transmission (84.3%), 68.6% among heterosexual individuals. Most patients were males (72.9%), aged between 25 and 40 years (60.1%), of low income (50% earning up to one minimum wage), and low educational level (80% had completed only middle school). A high percentage of deaths were observed during the study (34.3%). The results indicate a low seroprevalence of HIV/HCV coinfection in this population, in which sexual transmission, characterized by sexual promiscuity among heterosexual individuals, is the major transmission route of the virus rather than the use of injection drugs, as shown in world statistics.

The genotype of 69 HCV positive patients was determined. An in-house standardized nested-PCR was used to detect HCV RNA. Genotype assignment was based on type-specific motifs on the sequenced amplicons delimited by primers HC11/HC18 from the 5' untranslated region. Results: Of the 69 patients studied, 65.2% were male and 34.8% were female. Genotype 1 showed the greatest prevalence, followed by 3 and 2. Conclusions: These data suggesting that Manaus is the point of arrival of HCV in the State of Amazonas.