UNASSIGNED: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality.
UNASSIGNED: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders.
UNASSIGNED: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2-32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9-30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1-8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18-0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78-84%).
UNASSIGNED: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health.
UNASSIGNED: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3-12 years and the first in Europe for adolescents aged 12-17.

BACKGROUND: In Poland, active HCV infection affects between 0.4 and 0.5% of the population, i.e., about 150,000 people, while the number of patients with epilepsy is estimated to be 350,000-400,000. Currently available antiviral therapies show little interaction with neurological drugs. The aim of our study was to evaluate the effectiveness and safety of the treatment of chronic HCV infection in patients with coexisting epilepsy.
METHODS: A total of 184 epilepsy patients were selected from the group of 10,152 HCV-infected patients treated for HCV infection within the Epiter-2 database from 2015 to 2018. Comparing the effectiveness and safety of anti-HCV regimens between the patients with comorbid epilepsy and 3573 patients without comorbidities was our study\'s objective.
RESULTS: The effectiveness of anti-HCV treatment was high in both the sample and the control group. No statistically significant SVR difference was observed between the sample group, with ITT = 93.5% and mITT = 95.5%, and the control group, with ITT = 95.2% and mITT = 97.5%, regardless of the genotype and the stage of liver disease at the start of therapy. The treatment was safe in patients with epilepsy.
CONCLUSIONS: The effectiveness and safety of HCV treatment in patients with epilepsy are comparable to those of patients with no significant comorbidities.

HCV is a hepatotropic RNA virus recognized for its frequent virulence and fatality worldwide. Despite many vaccine development programs underway, researchers are on a quest for natural bioactive compounds due to their multivalent efficiencies against viral infections, considering which the current research aimed to figure out the target-specificity and therapeutic potentiality of α, β, and δ subunits of amyrin, as novel bioactive components against the HCV influx mechanism. Initially, the novelty of amyrin subunits was conducted from 203 pharmacophores, comparing their in-silico pharmacokinetic and pharmacodynamic profiles. Besides, the best active site of CD81 was determined following the quantum tunneling algorithm. The molecular dynamic simulation was conducted (100 ns) following the molecular docking steps to reveal the parameters- RMSD (Å); Cα; RMSF (Å); MolSA (Å2); Rg (nm); PSA (Å); SASA (Å2), and the MM-GBSA dG binding scores. Besides, molecular strings of CD81, along with the co-expressed genes, were classified, as responsible for encoding CD81-mediated protein clusters during HCV infection, resulting in the potentiality of amyrins as targeted prophylactics in HCV infection. Finally, in vivo profiling of the oxidative stress marker, liver-specific enzymes, and antioxidant markers was conducted in the DMN-induced mice model, where β-amyrin scored the most significant values in all aspects.

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Introduction. Lichen planus (LP) is a mucocutaneous T-cell mediated disorder of unknown etiology. There is growing evidence that oxidative stress is an important player in the pathogenesis of LP. Therefore, we have investigated oxidative stress markers in LP and the influence of hepatitis C virus (HCV) infection, a frequently associated condition, on oxidative stress in LP patients. Method. We have determined the serum levels of 4- hydroxynonenal (4-HNE) and symmetric dimethylarginine (SDMA), as markers of oxidative stress, and total antioxidant capacity (TAC), as a marker of the antioxidant defence, in 4 groups: group A - HCV positive patients with LP (n=12), group B - HCV positive patients without LP (n=12), group C - HCV negative patients with LP (n=31) and group D - control group (n=26). Results. In LP patients, we have identified an increased level of lipid peroxidation (4-HNE - group A - 8.41±1.11 μg/mL, group B - 7.97±2.17 μg/mL, group C - 7.81±1.96 μg/mL and group D - 6.15±1.17 μg/mL) and alterations in arginine methylation (SDMA - group A - 1.10±0.24 μmol/L, group B - 1.03±0.16 μmol/L, group C - 0.84±0.19 μmol/L and group D - 0.50±0.06 μmol/L) associated with a diminished antioxidant defence (TAC - group A - 234.50±49.96, μmol/L group B - 255.83±41.41 μmol/L, group C - 269.83±43.33 μmol/L and group D - 316.46 ±29.33 μmol/L), processes augmented by the association with HCV infection. Conclusion. There is an imbalance between oxidants and antioxidants in patients with LP, an imbalance that is augmented by the presence of HCV infection. SDMA could be regarded as a novel biomarker of oxidative stress among these patients. To the best of our knowledge this is the first study to investigate the influence of HCV infection on oxidative stress in LP patients.

BACKGROUND: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs).
METHODS: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate.
RESULTS: Five hundred and twenty HCV-infected PWID treated with all-oral DAA-based regimens were enrolled; a total of 168 (32.3%) patients presented genotype 1a, 109 (21.0%) genotype 1b, and 174 (33.5%) genotype 3; a total 152 of the 520 subjects (29.2%) were cirrhotics; a total 118 (22.7%) and 373 (71.7%) were treated with DAA regimens of second and third generation, respectively; a total 169 (33.6%) patients were receiving an opioid agonist at the start of antiviral therapy. Only 11 subjects (2.1%) did not show an SVR12. A significant correlation was found between treatment with opioid substitution therapy (p < 0.001), Human Immunodeficiency Virus (HIV) coinfection (p = 0.002), and treatment with first- or second-generation regimens (p = 0.0015) and HCV failure. Upon multivariate analysis, treatment with a first- or second-generation DAA was the only factor independently associated with failure (OR 10.4, 95% CI: 1.43 to 76.1, p = 0.02).
CONCLUSIONS: Treatment with DAAs led to a high SVR12 rate (97.9%) in a large cohort of HCV-infected PWID. The only predictor of viral failure found in our analysis was treatment with first- and second-generation DAA.

UNASSIGNED: The prevalence of transfusion transmitted infections (TTIs) among blood donors varies across different geographical populations. Establishing the sero-prevalence of the disease among blood donors is important to informing the direction of preventive and control strategies.
UNASSIGNED: The aim of this study was to determine the sero-prevalence of transfusion transmitted infections among voluntarily blood donors at Dessie Blood Bank, North East Ethiopia.
UNASSIGNED: A cross-sectional study was conducted from November 10 to December 12, 2018. A total of 384 blood donors were conveniently included in this study. Socio-demographic data and other factors were collected using a pre-tested structured questionnaire. Five milliliters of venous blood was collected using a sterile test tube from each blood donor and the blood was allowed to clot; then, serum was separated by centrifugation for laboratory investigation. Serum samples from blood donors were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of hepatits B surface antigen (HBsAg), and antibodies to human immunodeficiency virus (HIV-1/2), hepatits C virus (HCV), and Treponema pallidum. Logistic regression was used to explore risk factors associated with each transfusion transmissible infection.
UNASSIGNED: From a total of 384 blood donors, 24 (6.25%) of them had serological evidence for at least one infection. The overall sero-prevalence rates of HBV, HCV, HIV, and syphilis among blood donors were 4.2%, 0%, 0.26%, and 1.82%, respectively. Educational status was significantly associated with HBV infection. Multiple sexual behaviors had statistically significant association with syphilis.
UNASSIGNED: In conclusion, 6.25% of blood donors still harbor transfusion transmissible infections despite recent blood donation safety improvements with the greater majority (4.2%) of cases caused by HBV infection.

Aim of this study was to evaluate the prevalence of blood-borne chronic viral infections in immigrants living in southern Italy and identify factors associated to viral infections.
A prospective screening program was performed in seven clinical centers operating in Campania, Apulia and Calabria regions in southern Italy, in order to identify immigrants with HBV, HCV or HIV infections.
Of 4,125 immigrants observed in the study period, 3,839 (93.0%) agreed to be screened: 381 (9.9%) resulted HBsAg-positive, 136 (3.5%) anti-HCV, 62 (1.6%) anti-HIV and 1,448 (37.7%) HBsAg-negative and anti-HBc-positive. Ongoing or previous HBV infection was observed more frequently in males (p = 0.02 and p < 0.001, respectively), whereas HIV infection in females (p = 0.01). Immigrants from western Africa showed a higher rate of HBsAg positivity (p < 0.0001), HBsAg negativity/anti-HBc positivity (p < 0.0001) and anti-HIV positivity (p = 0.004) compared with those from other geographical areas. At multivariate analysis, ongoing HBV infection was associated with male sex (OR 1.49, 95% CI: 1.04-2.14) and origin from western Africa (OR 4.67, 95% CI: 1.70-12.80) and eastern Europe (OR 3.44, 95% CI: 1.17-10.08). HCV infection showed the tendency to be more frequent among males (OR 1.84, 95% CI: 0.99-3.42). HIV infection was associated with an older age (OR 1.04, 95% CI: 1.01-1.06), origin from western Africa (OR 4.09, 95% CI: 1.26-13.29) and female sex (OR 2.38, 95% CI: 1.29-4,39; p = 0.006).
The high prevalence of HBV, HCV and HIV infections in our large cohort of immigrants should definitively prompt Italian Healthcare Authorities to develop adequate cost-effective screening policies.

UNASSIGNED: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy.
UNASSIGNED: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used.
UNASSIGNED: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic.
UNASSIGNED: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.