Hepatitis C in healthcare personnel: follow-up analysis of treatments with direct-acting antiviral agents.
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ABSTRACT: Background
Hepatitis C infections (HCV) are associated with an increase in morbidity and mortality. The aim of this study is to update the results of treatment with direct-acting antiviral agents (DAAs) using a larger population of healthcare personnel (HP) and a longer observation period.Methods
Secondary data analysis of DAA treatment administered to HP (with confirmed occupational acquired HCV infection) between 1 January 2014 and 30 December 2018, is based on statutory accident insurance data from Germany. The end points of the study were results of a monitoring carried out 12 and 24 weeks after the end of treatment (sustained virological response, SVR), as well as side effects and the assessment of reduced work ability after treatment. Multivariate logistic regression models were constructed to investigate predictors of SVR.Results
The study population (n = 305) mainly comprised HP with a genotype 1 infection. The average age was 63 (SD 10) and 77% were female. Two thirds of the HP suffered from fibrosis or cirrhosis, and had experience of treatment. Statistically, men were significantly more likely to suffer from cirrhosis than women (60% compared to 21%, p < 0.001). The end-of-treatment response (ETR) rate was 99% and the SVR12 and SVR24 rates were 98%. Liver cirrhosis proved to be a predictor of a statistically significant reduction in success rates.Conclusion
DAA treatment leads to high SVR. Early HCV treatment is associated with higher SVR.
SUBMITTER: Westermann C
PROVIDER: S-EPMC8383415 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Hepatitis C Virus (HCV) infections are blood-borne, generally chronic and are associated with increased morbidity and mortality. The aim of this study is to describe the results of therapies with direct-acting antiviral agents (DAAs) in healthcare personnel. Methods:Secondary data analysis using data from the Statutory Accident Insurance of the Health and Welfare Service. The study surveyed DAA therapies administered to insured parties (healthcare personnel with an HCV infection recognised as an occupational disease) in Germany between 01/01/2014 and 30/11/2016. The end points were results of monitorings carried out twelve weeks after the end of treatment (SVR12), side effects and the results of the assessment of reduced work ability after treatment. Multivariate logistic regression models were constructed to model SVR12. Results:The study population (n =?180) comprised 74% women, 90% of the participants had an HCV genotype 1 infection. Two-thirds had fibrosis or cirrhosis and were treatment experienced. The most common combined therapy was ledipasvir and sofosbuvir (49%). A DAA therapy with ribavirin was administered in 20% of cases, with (pegylated) interferon and ribavirin used in 2% of cases. The majority of therapies were completed without any side effects. The overall SVR12 rate was 94%. Significant independent predictor of decrease odds of SVR12 was liver cirrhosis. Positive effects on the healthcare personnel's work ability were observed after successful therapy. Conclusion:High SVR12 rates were achieved in the sample population, with positive effects on their work ability. Early HCV therapy seems reasonable due to the increased chance of successful treatment of the infection.
| S-EPMC5970510 | biostudies-literature
Project description:ImportanceRecent reports based on the US Food and Drug Administration's voluntary Adverse Events Reporting System raised questions about the safety of direct-acting antivirals (DAAs) for treatment of the hepatitis C virus (HCV).ObjectiveTo assess the rates of adverse events in patients with HCV infection exposed to DAAs compared with those not exposed.Design, setting, and participantsA retrospective cohort study calculated unadjusted adverse event rates for exposed vs unexposed time, using claims and clinical data from 3 health systems between January 1, 2012, and December 31, 2017. Of 82 419 eligible adults, a total of 33 808 who met eligibility criteria (age, 18-88 years; HCV quantitative result or genotype from 2012 or later; continuously enrolled; naive to DAA treatment at baseline) were included. Marginal structural modeling methods were used to adjust time-to-event analyses for characteristics that are associated with both outcomes and probability of treatment.Interventions or exposuresExposure to DAAs compared with no DAA exposure.Main outcomes and measuresDeath, multiple organ failure, liver cancer, hepatic decompensation, acute-on-chronic liver event, acute myocardial infarction, ischemic or hemorrhagic stroke, arrhythmia, acute kidney failure, nonliver cancer, hepatitis B reactivation, hospitalizations, and emergency department visits.ResultsOf the 33 808 patients who met all inclusion criteria, 20 899 (61.8%) were men; mean (SD) age was 57.2 (10.6) years. In unadjusted analyses, DAA exposure was associated with significantly lower rates of death (10.7 vs 33.7 events per 1000 person-years; rate ratio [RR], 0.32, 95% CI, 0.25-0.40). Seven other unadjusted adverse clinical events ratios were below 70% and statistically significant favoring the DAA group: multiple organ failure (RR, 0.56; 95% CI, 0.44-0.72), liver cancer (RR, 0.62; 95% CI, 0.48-0.80), hepatic decompensation (RR, 0.62; 95% CI, 0.52-0.73), acute-on-chronic liver event (RR, 0.68; 95% CI, 0.56-0.84), acute myocardial infarction (RR, 0.64; 95% CI, 0.42-0.97), ischemic stroke (RR, 0.63; 95% CI, 0.42-0.95), and hemorrhagic stroke (RR, 0.47; 95% CI, 0.25-0.89); none favored the non-DAA group. In the marginal structural modeling-adjusted analysis, DAA exposure was associated with statistically significant lower odds of adverse events than non-DAA exposure for death (adjusted odds ratio [aOR], 0.42; 95% CI, 0.30-0.59), multiple organ failure (aOR, 0.67; 95% CI, 0.49-0.90), hepatic decompensation (aOR, 0.61; 95% CI, 0.49-0.76), acute-on-chronic liver event (aOR, 0.71; 95% CI, 0.56-0.91), and arrhythmia (aOR, 0.47; 95% CI, 0.25-0.88).Conclusions and relevanceDirect-acting antiviral exposure may not be associated with higher rates of any serious adverse events, including those related to liver, kidney, and cardiovascular systems. Safety concerns based on previous reports did not appear to be supported in this study with more comprehensive data and rigorous statistical methods.
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Project description:UnlabelledHepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events.ConclusionSVR12 rates for sofosbuvir-based DAA regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression.
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Project description:Hepatitis C virus (HCV) exists as six major genotypes that differ in geographical distribution, pathogenesis, and response to antiviral therapy. In vitro replication systems for all HCV genotypes except genotype 5 have been reported. In this study, we recovered genotype 5a full-length genomes from four infected voluntary blood donors in South Africa and established a G418-selectable subgenomic replicon system using one of these strains. The replicon derived from the wild-type sequence failed to replicate in Huh-7.5 cells. However, the inclusion of the S2205I amino acid substitution, a cell culture-adaptive change originally described for a genotype 1b replicon, resulted in a small number of G418-resistant cell colonies. HCV RNA replication in these cells was confirmed by quantification of viral RNA and detection of the nonstructural protein NS5A. Sequence analysis of the viral RNAs isolated from multiple independent cell clones revealed the presence of several nonsynonymous mutations, which were localized mainly in the NS3 protein. These mutations, when introduced back into the parental backbone, significantly increased colony formation. To facilitate convenient monitoring of HCV RNA replication levels, the mutant with the highest replication level was further modified to express a fusion protein of firefly luciferase and neomycin phosphotransferase. Using such replicons from genotypes 1a, 1b, 2a, 3a, 4a, and 5a, we compared the effects of various HCV inhibitors on their replication. In conclusion, we have established an in vitro replication system for HCV genotype 5a, which will be useful for the development of pan-genotype anti-HCV compounds.
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