This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1β, IL-15, IFN-γ, IL-4, IL-10, TGF-β, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-β and suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.
Background Direct-acting antivirals (DAA) are currently used for the treatment of chronic hepatitis C (HCV). However, few studies describe the adverse effects (AE) associated with DAA therapy in "real-word" cohorts. Aim To evaluate AE in Brazilian chronic HCV patients after DAA-therapy. Setting A reference center for hepatitis treatment in Rio de Janeiro, Brazil. Methods An observational "real-world" study was conducted with 102 chronic HCV patients undergoing DAA therapy for 12 or 24 weeks. The self-reported AE were correlated with cirrhosis status, genotype, age, current therapeutic schemes and comorbidities. Serious AE were also investigated. Main outcome measure Frequency of AE during DAA therapy. Results Overall, mean ± SD age was 60.9 ± 9.4 years, 67% were females, HCV-genotype 1 was the most prevalent (81%) and 74% were cirrhotic. Moreover, all patients reached sustained virological response. About 90% of patients reported at least one AE associated with current treatment, with a mean of 2.7 symptoms per patient. The most frequently reported AE were fatigue (43%), headache (42%), neuropsychiatric symptoms (30%) and nausea (26%). Furthermore, hemoglobin < 12 mg/dL was the most frequent (38%) laboratory abnormality observed. Neuropsychiatric symptoms were the only AE significantly different in treatment-experienced group when compared to naïve patients (41.7 vs. 12.5, P = 0.002). The higher frequency of AE did not correlate with the presence of previous treatment, cirrhosis, genotype, age, current therapeutic schemes with DAA or comorbidities. Conclusion DAA-based therapeutic regimens demonstrated safety in a Brazilian "real-world" cohort of chronic hepatitis C patients.
BackgroundGunshot wounds require surgeons to decide whether to remove or leave bullet fragments in the body. Surgeons also decide how to follow up with patients who have lead fragments retained in their body. Current literature recommends to remove only intra-articular fragments without the need for a follow-up for patients with the metal retained. Therefore, this study investigates chronic lead toxicity for gunshot wounds.MethodsThe study was performed in the metropolitan area of Rio de Janeiro/Brazil, between 2013 and 2015. It was a case-control study that included 45 victims of gunshot lesions with metallic fragments retained for more than 6 months. The 45 controls were matched for gender, age, and race. We compared the lead blood levels and frequency of symptoms.ResultsThe control group had average blood lead levels of 2.17 μg/dL (95% Confidence Interval [CI]; 1.71–2.63) and median 2.1 μg/dL. The case group had average values of 9.01 μg/dL (CI; 6.07–11.96) and median values of 6.5 μg/dL with p-values < = 0.001. The case group reported the following more frequently: irritancy, bad mood, headache, memory losses, daylight drowsiness, myalgia, weakness, abdominal pain, joint pain, trembling, tingling limbs. There was statistical significance for the differences of symptoms frequencies and for odds ratio between groups.ConclusionsAlthough the mean lead levels found were lower than the current laboratory references, low levels have been associated with both rising morbidity and mortality. The WHO stated: “There is no known level of lead exposure that is considered safe”. In conclusion, this work showed that bullets retained in the body are not innocuous. There are impacts in the blood lead levels and symptoms related to it, even with few fragments, extra-articular located or existing with low blood lead levels.
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