Evaluation of a non-invasive screening approach to determine hepatitis E virus status of pig farms.

BACKGROUND: Identifying pig farms infected with hepatitis E virus (HEV) is a key aspect to implement surveillance programmes for this emerging zoonotic agent. Detection of HEV in blood has several drawbacks, including animal handling, economic costs and animal stress. The objective of this study was to evaluate the effectiveness of a non-invasive screening approach for determining the HEV status of pig farms under different management systems. METHODS: Forty stool samples randomly collected from the pen floor of 17 intensive pig farms and the yard of nine extensive ones were tested for HEV RNA. The invasive method used to confirm the HEV status of the farm was HEV RNA analysis of serum samples randomly collected from 40 animals on each farm. RESULTS: Twenty-one HEV-positive farms were detected by invasive and non-invasive methods. No positive serum or stool samples were detected on five intensive farms. A high intertest agreement (K=1; P<0.00001) was observed between both methodologies, showing the stool screening approach a 100 per cent of sensitivity and specificity with respect to the invasive method. Likewise, a significant negative relationship was observed between the HEV within-farm prevalence and the number of the first HEV-positive stool sample found (Spearman's rho=-0.64; P=0.0004). This negative relationship was higher in intensively managed farms. CONCLUSION: This non-invasive screening approach could be reliably applied in a large-scale surveillance programme for determining the HEV status of pig farms under different management systems.

Risk factors associated with hepatitis E virus in pigs from different production systems.

Pigs are considered important reservoirs of HEV and so constitute a major risk of transmission to humans, either via direct contact or by consuming raw or undercooked contaminated pork products. Once the scale of this disease on European pig farms has been estimated, the identification of risk factors associated with HEV infection in these species could help determine contingency strategies to minimize the risk of transmission to humans. Our objective was to evaluate risk factors associated with HEV in pigs under different production systems. We included 1040 pigs from 26 farms. The prevalence of HEV infection in the study population, evaluated by RT-qPCR, was calculated, then studied according to animal and farm characteristics. Factors associated with HEV infection were analyzed by multivariate analysis. One hundred and seventy-two pigs were infected by HEV, which gave an individual prevalence of 16.5% (95% CI: 14.4%-18.9%). Factors associated with higher prevalence of HEV infection were: extensive farming [23.9%; OR = 2.239 (1.036-4.837)], absence of sanitary ford [33.8%; OR = 3.597 (1.649-7.850)], no quarantine period [20.8%; OR = 2.723 (1.450-5.112)], and contact with domestic species [24.5%; OR = 3.893 (1.453-10.431)]. Our evidence showed that pigs reared on extensive farms are at a higher risk of HEV infection than those reared intensively. The use of control measures could reduce the risk of HEV infection in pigs and minimize the risk of zoonotic transmission.

Pharmacodynamic and pharmacokinetic evaluation of the combination of daclatasvir/sofosbuvir/ribavirin in the treatment of chronic hepatitis C.

INTRODUCTION: The combination of daclatasvir (DCV), sofosbuvir (SOF), and ribavirin (RBV) is a direct-acting antiviral (DAA) regimen for the treatment of hepatitis C virus (HCV) infection. The inclusion of newer effective DAAs such as SOF and DCV with high efficacy and excellent tolerance introduced a new scenario in HCV infection therapy: high rates of sustained virological response (SVR), shorter therapies, less toxicity, and interferon-free treatments. This combination was approved for the treatment of HCV in treatment-naive or treatment-experienced patients with chronic HCV genotype 1 or 3 infection. Areas covered: This review summarizes the pharmacokinetics, pharmacodynamics, efficacy, and safety of DCV plus SOF and RBV therapy in the treatment of HCV infection. The topics include data regarding drug absorption, distribution, metabolism, excretion, and antiviral activity strategies, such as clinical dose selection and treatment duration. Expert opinion: This combination, taken orally with or without food, has an excellent pharmacokinetic and pharmacodynamic profile. DAC/SOF/RBV achieves very high rates of SVR in treatment-naive and treatment-experienced patients with chronic HCV infection, including difficult-to-treat patients such as those with compensated cirrhosis, post-transplant recurrence, or HIV-1 co-infection.

Brief Report: Differential Timing of Cholesterol Increase During Successful HCV Therapy: Impact of Type of Drug Combination.

OBJECTIVE: To evaluate factors associated with increased serum cholesterol levels during interferon-free hepatitis C virus (HCV) therapy. DESIGN: Prospective longitudinal study. METHODS: HIV-infected patients who started and successfully completed interferon-free therapy for chronic HCV infection were included. Patients were treated using 2 different regimens, based on the clinician's opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir coadministered with ombitasvir and dasabuvir (PrOD). Both total cholesterol and low-density lipoprotein cholesterol were evaluated at baseline, weeks 1, 2, 4, 8, end of treatment (EOT), weeks SVR4, SVR12, and SVR24. RESULTS: The study population therefore comprised 85 patients reaching sustained virological response, 42 (49.4%) of whom were treated with SOF/LDV, and 43 (50.6%) with PrOD. Patients using SOF/LDV was showed a higher increase on both total cholesterol and low-density lipoprotein cholesterol during treatment period than those receiving PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8, and EOT, choice of HCV regimen was associated with differential increases in total cholesterol during therapy. After EOT, no differences were found between SOF/LDV and PrOD with respect to total cholesterol. CONCLUSIONS: Our study suggests that the differential timing of the restoration of cholesterol metabolism in HIV/HCV genotype 1 coinfected patients achieving sustained virological response is not mediated by HCV clearance but depends on the drug combination used.

HLA-B, HLA-C and KIR improve the predictive value of IFNL3 for Hepatitis C spontaneous clearance.

IFNL3 is the strongest predictor of spontaneous resolution (SR) of hepatitis C virus (HCV), however, consideration of IFNL3 genotype alone is of limited clinical value for the prediction of SR or chronic HCV infection. The objective of this study was to analyze the impact of HLA-B, HLA-C and KIRs on SR, as well as their additive effects on the predictive value of the IFNL3 genotype. We conducted a retrospective study of HIV patients that included both SR and chronic HCV patients. In our study, 61.6% of patients with IFNL3 CC achieved SR, and 81.5% with non-CC genotypes did not achieve SR. HLA-B*44, HLA-C*12, and KIR3DS1 were identified as predictive factors for SR, with percentages of 77.4%, 85.7% and 86.2%, respectively, for patients who did not experience SR. The presence of at least one of these three markers, defined as a genetically unfavorable profile (GUP), combined with the IFNL3 non-CC genotype showed a value of 100% for non-SR. The absence of the three markers, defined as a genetically favorable profile (GFP), in addition to the IFNL3 CC genotype showed a percentage of 74.1% for SR. The combination of these markers in addition to the IFNL3 genotype improves the predictive value of IFNL3 for SR of acute HCV infection in HIV patients, which would be clinically valuable.

Pharmacokinetic drug evaluation of velpatasvir plus sofosbuvir for the treatment of hepatitis C virus infection.

INTRODUCTION: The fixed-dose combination therapy of sofosbuvir (SOF) plus velpatasvir (VEL) is the first pangenotypic, direct-acting antiviral (DAA), single-treatment regimen (STR) for the treatment of hepatitis C virus (HCV) infection to be commercialized. It is approved for the treatment of HCV genotypes 1, 2, 3, 4, 5, and 6. Following approval in 2016, new pharmacokinetic and pharmacodynamic data were reported, which led to important clinical applications. Areas covered: This review provides a summary of the pharmacokinetics, pharmacodynamics, efficacy and safety of SOF/VEL therapy for treatment of HCV infection. The topics covered include data regarding the drug's absorption, distribution, metabolism, excretion and antiviral activity strategies, such as clinical dose selection and treatment duration. Expert opinion: This novel combination therapy containing 400 mg of SOF plus 100 mg of VEL, taken orally, once daily, with or without food, has an excellent pharmacokinetic and pharmacodynamic profile. SOF/VEL achieved very high rates of sustained virological response in treatment-naive and treatment-experienced patients with chronic HCV genotype 1-6 infection, including those with compensated cirrhosis or HIV-1 co-infection.

Hepatitis E Virus (HEV) Infection in Anti-HEV Immunoglobulin G-Carrying Patients After Successful Hepatitis C Virus Treatment: Reactivation or Reinfection?

Although hepatitis E virus (HEV) is regarded as a self-limiting infection and anti-HEV antibodies seem to protect against reinfection, its pathogenesis is not well established. We describe 2 cases of acute symptomatic HEV infection after hepatitis C therapy in patients carrying anti-HEV immunoglobulin G antibodies, raising 2 major questions: reactivation or reinfection?

Economic evaluation of botulinum toxin versus thoracic sympathectomy for palmar hyperhidrosis: data from a real-world scenario.

INTRODUCTION: Local botulinum toxin injections and endoscopic thoracic sympathectomy (ETS) have shown clinical effectiveness for the treatment of palmar hyperhidrosis in several studies. Although both strategies cause considerable costs for health-care systems, at the moment there are no studies examining directly their cost-effectiveness performance. The aim of the study was to assess the incremental cost-effectiveness of botulinum toxin when compared with ETS for palmar hyperhidrosis. MATERIALS AND METHODS: Costs, effectiveness, and incremental cost-effectiveness ratio (ICER) were calculated. Costs were assessed from a Spanish National Health System perspective in a historical cohort of patients with palmar hyperhidrosis attending a tertiary referral hospital. Effectiveness was evaluated by using the Hyperhidrosis Disease Severity Scale (HDSS). A responder was defined as a patient who reported at least a two-grade improvement on the HDSS scale with respect to the baseline value. The horizon of time was 1 year. RESULTS: Effectiveness was greater for ETS (n = 128) when compared with botulinum toxin (n = 100) for the treatment of palmar hyperhidrosis (92% vs. 68%; odds ratio (OR) = 6.22 [2.80, 13.80]; absolute risk ratio (ARR) = -0.24 [-0.45, -0.14]; number-needed-to-treat (NNT) = -4 [-2, -11]). Botulinum toxin had an ICER of 125 € when compared with ETS during the first year of treatment. CONCLUSIONS: In this retrospective real-world observational sample of patients with palmar hyperhidrosis, treatment with ETS appears to be more effective and less costly when compared with botulinum toxin during the first year of treatment. Analyses such as this give decision makers the tools to choose a better treatment option which is both highly effective and yet has a low cost.