OBJECTIVE: Universal opt-out antenatal screening for Hepatitis C virus (HCV) is not currently recommened and it is recommended that maternity services offer risk-based testing. We aimed to investigate antenatal HCV testing and adherence to testing guidance.
METHODS: A cross-sectional survey was circulated to maternity service providers between November-December 2020 which included testing policy, training for healthcare staff, and management of women found to be HCV positive. Descriptive data are presented.
RESULTS: A total of 75 questionnaires were returned, representing 48 % of English maternity service providers. 87 % of providers reported offering antenatal HCV risk-based testing. Risk factors used to identify pregnant women for testing varied. Less than 15 % of respondents considered women that were ever homeless or with history of incarceraton or from higher HCV prevalence areas as high risk.
CONCLUSIONS: Current antenatal HCV testing practices are inadequate and HCV infection likely goes undiagnosed in pregnancy, especially among vulnerable population groups. In the absence of universal antenatal screening, re-framing antenatal HCV risk-based testing and management as a quality improvement initiative and developing HCV specific pathway guidance for maternity units is required.

Current management of HCV infection is based on Direct-Acting Antiviral Drugs (DAAs). However, resistance-associated mutations, especially in the NS3 and NS5B regions are gradually decreasing the efficacy of DAAs. Among the most effective HCV NS3/4A protease drugs, Sofosbuvir also develops resistance due to mutations in the NS3 and NS5B regions. Four mutations at positions A156Y, L36P, Q41H, and Q80K are classified as high-level resistance mutations. The resistance mechanism of HCV NS3/4A protease toward Sofosbuvir caused by these mutations is still unclear, as there is less information available regarding the structural and functional effects of the mutations against Sofosbuvir. In this work, we combined molecular dynamics simulation, molecular mechanics/Generalized-Born surface area calculation, principal component analysis, and free energy landscape analysis to explore the resistance mechanism of HCV NS3/4A protease due to these mutations, as well as compare interaction changes in wild-type. Subsequently, we identified that the mutant form of HCV NS3/4A protease affects the activity of Sofosbuvir. In this study, the resistance mechanism of Sofosbuvir at the atomic level is proposed. The proposed drug-resistance mechanism will provide valuable guidance for the design of HCV drugs.

Bacillus pumilus (B. pumilus) is a ubiquitous spore-forming bacteria that has rarely been implicated in extraintestinal infections, mostly in immunocompromised hosts. The authors report a case of B. pumilus cellulitis with bacteremia in a person who injects drugs living with human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infection. Although similar cases have been reported for some species of the genus, namely Bacillus anthracis (B. anthracis) and Bacillus cereus (B. cereus), this case reinforces the importance of considering other Bacillus spp. as potential pathogens in skin and soft tissue infections and bloodstream infections related to intravenous drug use.

BACKGROUND: Hepatitis C virus (HCV) infection is a major global concern, with Indigenous Peoples bearing the highest burden. Previous studies exploring HCV prevalence within Indigenous populations have predominantly used a pan-Indigenous approach, consequently resulting in limited availability of Métis-specific HCV data. The Métis are one of the three recognized groups of Indigenous Peoples in Canada with a distinct history and language. The Métis Nation of Ontario (MNO) is the only recognized Métis government in Ontario. This study aims to examine the prevalence of self-reported HCV testing and positive results among citizens of the MNO, as well as to explore the association between sociodemographic variables and HCV testing and positive results.
METHODS: A population-based online survey was implemented by the MNO using their citizenship registry between May 6 and June 13, 2022. The survey included questions about hepatitis C testing and results, socio-demographics, and other health related outcomes. Census sampling was used, and 3,206 MNO citizens responded to the hepatitis C-related questions. Descriptive statistics and bivariate analysis were used to analyze the survey data.
RESULTS: Among the respondents, 827 (25.8%, CI: 24.3-27.3) reported having undergone HCV testing and 58 indicated testing positive, resulting in a prevalence of 1.8% (CI: 1.3-2.3). Respondents with a strong sense of community belonging, higher education levels, and lower household income were more likely to report having undergone HCV testing. Among those who had undergone testing, older age groups, individuals with lower education levels, and retired individuals were more likely to test positive for HCV.
CONCLUSIONS: This study is the first Métis-led and Métis-specific study to report on HCV prevalence among Métis citizens. This research contributes to the knowledge base for Métis health and will support the MNO\'s health promotion program and resources for HCV. Future research will examine the actual HCV incidence and prevalence among MNO citizens.

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).

OBJECTIVE: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated.
METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested.
METHODS: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence.
RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5).
CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.

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.

There is an urgent need for the identification of new drugs that inhibit HCV-induced hepatocellular carcinoma (HCC). Our work demonstrates that cyclophilin inhibitors (CypIs) represent such new drugs. We demonstrate that the nonimmunosuppressive cyclosporine A (CsA) analog (CsAa) rencofilstat possesses dual therapeutic activities for the treatment of HCV infection and HCV-induced HCC. Specifically, we show that the HCV infection of humanized mice results in the progressive development of HCC. This is true for the four genotypes tested (1 to 4). Remarkably, we demonstrate that rencofilstat inhibits the development of HCV-induced HCC in mice even when added 16 weeks after infection when HCC is well established. Importantly, we show that rencofilstat drastically reduces HCC progression independently of its anti-HCV activity. Indeed, the CypI rencofilstat inhibits HCC, while other anti-HCV agents such as NS5A (NS5Ai) and NS5B (NS5Bi) fail to reduce HCC. In conclusion, this study shows for the first time that the CypI rencofilstat represents a potent therapeutic agent for the treatment of HCV-induced HCC.

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.

During January 2017-March 2020, approximately 2.2 million noninstitutionalized civilian US adults had hepatitis C; one-third were unaware of their infection. Prevalence was substantially higher among persons who were uninsured or experiencing poverty. Unrestricted access to testing and curative treatment is needed to reduce disparities and achieve 2030 elimination goals.