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The structural stability of the hepatitis C model with the proliferation of infected and uninfected hepatocytes is investigated in this paper. The model is clinically verified to accurately reflect the viral dynamics of hepatitis C. It is demonstrated that the limit transition from the hepatitis C model to the Riccati system coupled with the diffusive terms leads to the elimination of the quadratic terms. Such a novel effect leads to the introduction of the concept of the deformed order-1 solitary solutions. The generalized operator of differentiation is used to construct the deformed order-1 solitary solutions to the Riccati system coupled with the diffusive terms. Finally, it is demonstrated that the Riccati system coupled with the diffusive terms admits non-deformed order-1 solitary solutions, which proves the structural instability of the hepatitis C model with the proliferation of infected and uninfected hepatocytes. [ABSTRACT FROM AUTHOR]

In this paper, we explore the bifurcation, chaos, and local stability of a discrete Hepatitis C virus infection model. More precisely, we studied the local stability at fixed points of a discrete Hepatitis C virus model. We proved that at a partial infection fixed point, the discrete HCV model undergoes Neimark-Sacker bifurcation, but no other local bifurcation exists at this fixed point. Moreover, it was also proved that period-doubling bifurcation does not occur at liver-free, disease-free, and total infection fixed points. Furthermore, we also examined chaos control in the understudied discrete HCV model. Finally, obtained theoretical results were confirmed numerically. [ABSTRACT FROM AUTHOR]

The multiple regression model statistical technique is employed to analyze the relationship between the dependent variable and several independent variables. The multicollinearity problem is one of the issues affecting the multiple regression model, occurring in regard to the relationship among independent variables. The ordinal least square is the standard method to evaluate parameters in the regression model, but the multicollinearity problem affects the unstable estimator. Liu regression is proposed to approximate the Liu estimators based on the Liu parameter, to overcome multicollinearity. In this paper, we propose a modified Liu parameter to estimate the biasing parameter in scaling options, comparing the ordinal least square estimator with two modified Liu parameters and six standard Liu parameters. The performance of the modified Liu parameter is considered, generating independent variables from the multivariate normal distribution in the Toeplitz correlation pattern as the multicollinearity data, where the dependent variable is obtained from the independent variable multiplied by a coefficient of regression and the error from the normal distribution. The mean absolute percentage error is computed as an evaluation criterion of the estimation. For application, a real Hepatitis C patients dataset was used, in order to investigate the benefit of the modified Liu parameter. Through simulation and real dataset analysis, the results indicate that the modified Liu parameter outperformed the other Liu parameters and the ordinal least square estimator. It can be recommended to the user for estimating parameters via the modified Liu parameter when the independent variable exhibits the multicollinearity problem. [ABSTRACT FROM AUTHOR]

Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, a guitarist of The Rolling Stones. The present paper provides an updated narrative review of the research devoted to the phenomenon in order to identify and discuss the demographic, lifestyle-related, clinical, viral genotype-related, and host genetic factors underpinning the SC occurrence. The body of evidence indicates that the likelihood of SC is decreased in older individuals, men, Black people, HIV-coinfected subjects, and intravenous drug and alcohol users. In turn, HBV coinfection and specific polymorphism of the genes encoding interferon lambda 3 (particularly at rs8099917) and interferon lambda 4 (particularly at rs12979860) and HLA genes increase the odds of SC. Numerous other host-specific genetic factors could be implicated in SC, but the evidence is limited only to certain ethnic groups and often does not account for confounding variables. SC of HCV infection is a complex process arising from a combination of various factors, though a genetic component may play a leading role in some cases. Understanding factors influencing the likelihood of this phenomenon justifies better surveillance of high-risk groups, decreasing health inequities in particular ethnic groups, and may guide the development of a prophylactic vaccine, which at present is not available, or novel therapeutic strategies. Further research is needed to elucidate the exact mechanisms underlying SC and to explore potential interventions that could enhance this natural antiviral response. [ABSTRACT FROM AUTHOR]

Enzyme-linked immunosorbent assay (ELISA) is widely used for the detection of disease biomarkers. However, it utilizes time-consuming procedures and expensive instruments, making it infeasible for point-of-care (POC) analysis especially in resource-limited settings. In this work, a multicolorimetric ELISA biosensor integrated on a paper/polymer hybrid microfluidic device was developed for rapid visual detection of disease biomarkers at point of care, without using costly equipment. This multicolormetric ELISA platform was built on multiple distinct color variants resulted from the catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) and the etching of gold nanorods (AuNRs). The vivid color changes could be easily distinguished by the naked eye, and their red mean values allowed quantitative biomarker detection, without using any sophisticated instruments. When this multicolorimetric ELISA was integrated on a paper/polymer hybrid analytical device, it not only provided integrated processing and high portability but also enabled fast assays in about 50 min due to the unique advantages of paper/polymer hybrid devices. The limit of detection of 9.1 ng/μL of the hepatitis C virus core antigen, a biomarker for hepatitis C, was achieved using this multicolorimetric ELISA platform. This multicolor ELISA analytical device provides a new versatile, user-friendly, affordable, and portable immunosensing platform with high potential for on-site detections of various viruses, proteins, and biomarkers for low-resource settings such as at home, public venues, rural areas, and developing nations. [ABSTRACT FROM AUTHOR]

Background: Harm reduction is a crucial approach in addressing the multifaceted challenges of injectable drug use. This paper presents an analysis and mapping of the existing literature on harm reduction research in the context of injectable drug use. By reviewing a comprehensive set of scholarly articles, this study identifies research hotspots, knowledge gaps, and future directions in the field. The findings provide valuable insights for researchers, policymakers, and practitioners to guide future research efforts and inform evidence-based harm reduction interventions. Methods: Data for the study was obtained from the Scopus database, using keywords and phrases related to harm reduction and injectable drug use. Validation methods were employed to verify the accuracy and comprehensiveness of the search strategy. Data analysis involved identifying growth patterns, key contributors, mapping frequent terms, identifying research hotspots, and identifying emerging research directions. Results: A total of 971 articles were found, with a notable increase from 2015 to 2022. The International Journal of Drug Policy (n = 172, 17.7%) and the Harm Reduction Journal (n = 104, 10.7%) were the most prolific journals, and the United States (n = 558, 57.5%) had the highest number of publications. The Johns Hopkins University (n = 80, 8.5%) was the most prolific institution. Mapping of frequent author keywords revealed the main keywords, including harm reduction, HIV, hepatitis C, and opioid overdose. The highly cited articles cover a broad time span and focus on topics like naloxone distribution, HIV and hepatitis C transmission, while recent articles concentrate on emerging issues such as the impact of the COVID-19 pandemic, fentanyl-related concerns, stigma reduction, and needle and syringe programs. Both sets of articles share a common focus on harm reduction strategies, but recent publications highlight current challenges and developments in the field. Conclusions: This study provides insights into research landscape on harm reduction in injectable drug use. Research is concentrated in high-income countries, emphasizing the need for more research in low- and middle-income countries. Recent publications focus on emerging challenges like COVID-19 and fentanyl. Research gaps highlight the need for studies in diverse populations, social determinants, program evaluation, and implementation strategies to enhance harm reduction interventions. [ABSTRACT FROM AUTHOR]

This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33–53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions. [ABSTRACT FROM AUTHOR]

The early diagnosis of active hepatitis C virus (HCV) infection remains a significant barrier to the treatment of the disease and to preventing the associated significant morbidity and mortality seen, worldwide. Current testing is delayed due to the high cost, long turnaround times and high expertise needed in centralised diagnostic laboratories. Here we demonstrate a user-friendly, low-cost pan-genotypic assay, based upon reverse transcriptase loop mediated isothermal amplification (RT-LAMP). We developed a prototype device for point-of-care use, comprising a LAMP amplification chamber and lateral flow nucleic acid detection strips, giving a visually-read, user-friendly result in <40 min. The developed assay fulfils the current guidelines recommended by World Health Organisation and is manufactured at minimal cost using simple, portable equipment. Further development of the diagnostic test will facilitate linkage between disease diagnosis and treatment, greatly improving patient care pathways and reducing loss to follow-up, so assisting in the global elimination strategy. Current HCV nucleic acid-based diagnosis is largely performed in centralised laboratories. Here, the authors present a pan-genotypic RNA assay, based on reverse transcriptase loop mediated isothermal amplification and develop a low-cost prototype paper-based lateral flow device for point-of-care use, providing a visually read result within 40 min. [ABSTRACT FROM AUTHOR]

The paper focuses on the hepatitis C virus (HCV) infection in Egypt, which has one of the highest rates of HCV in the world. The high prevalence is linked to several factors, including the use of injection drugs, poor sterilization practices in medical facilities, and low public awareness. This paper introduces a hyOPTGB model, which employs an optimized gradient boosting (GB) classifier to predict HCV disease in Egypt. The model's accuracy is enhanced by optimizing hyperparameters with the OPTUNA framework. Min-Max normalization is used as a preprocessing step for scaling the dataset values and using the forward selection (FS) wrapped method to identify essential features. The dataset used in the study contains 1385 instances and 29 features and is available at the UCI machine learning repository. The authors compare the performance of five machine learning models, including decision tree (DT), support vector machine (SVM), dummy classifier (DC), ridge classifier (RC), and bagging classifier (BC), with the hyOPTGB model. The system's efficacy is assessed using various metrics, including accuracy, recall, precision, and F1-score. The hyOPTGB model outperformed the other machine learning models, achieving a 95.3% accuracy rate. The authors also compared the hyOPTGB model against other models proposed by authors who used the same dataset. [ABSTRACT FROM AUTHOR]

Background: Aboriginal and Torres Strait Islander Australians are disproportionately impacted by blood-borne viruses (BBVs) and sexually transmissible infections (STIs). Stigma remains one of the key barriers to testing and treatment for BBVs and STIs, particularly among Aboriginal and Torres Strait Islander people. The Deadly Liver Mob (DLM) is a peer-delivered incentivised health promotion program by and for Aboriginal and Torres Strait Islander Australians. The program aims to increase access to BBV and STI education, screening, treatment, and vaccination for Aboriginal and Torres Strait Islander Australians in recognition of the systemic barriers for First Nations people to primary care, including BBV- and STI-related stigma, and institutional racism. This paper presents routinely collected data across nine sites on the 'cascade of care' progression of Aboriginal and Torres Strait Islander clients through the DLM program: hepatitis C education, screening, returning for results, and recruitment of peers. Methods: Routinely collected data were collated from each of the DLM sites, including date of attendance, basic demographic characteristics, eligibility for the program, recruitment of others, and engagement in the cascade of care. Results: Between 2013 and 2020, a total of 1787 Aboriginal and Torres Strait Islander clients were educated as part of DLM, of which 74% went on to be screened and 42% (or 57% of those screened) returned to receive their results. The total monetary investment of the cascade of care progression was approximately $56,220. Data highlight the positive impacts of the DLM program for engagement in screening, highlighting the need for culturally sensitive, and safe programs led by and for Aboriginal and Torres Strait Islander people. However, the data also indicate the points at which clients 'fall off' the cascade, underscoring the need to address any remaining barriers to care. Conclusions: The DLM program shows promise in acting as a 'one stop shop' in addressing the needs of Aboriginal and Torres Strait Islander people in relation to BBVs and STIs. Future implementation could focus on addressing any potential barriers to participation in the program, such as co-location of services and transportation. [ABSTRACT FROM AUTHOR]

Background: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. Methods: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. Results: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. Conclusions: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. Registration: PROSPERO CRD42020180793. [ABSTRACT FROM AUTHOR]

Background: The introduction of Direct-Acting Antivirals (DAAs) transformed Hepatitis C (HCV) treatment, despite this uptake of DAAs remains lower than required to meet the WHO Sustainable Development Goal (3.3). Treatment with interferon was suggested to be able to deliver important outcomes for people who use drugs in addition to a viral cure, such as social redemption, and shift from a stigmatised identity. There is a lack of understanding if DAAs can deliver these transformative outcomes. Methods: This recurrent cross-sectional study combines qualitative semi-structured interviews and demographic data of 15 participants receiving DAAs in Tayside, Scotland. A thematic analysis explored the non-clinical outcomes of DAA treatment viewed through the lens of the Social Identity Model of Recovery (SIMOR) to build understanding of the influence DAAs have in a recovery journey from drug use. Results: Three key themes emerged: identity, relationships and social networks; building recovery capital; and reflecting on re-infection and the shift to DAAs. Concern about the transmission of HCV resulted in self-imposed isolation which weakened support structures. Cure provides a mechanism to strengthen family bonds, however social networks in the wider community remain limited. Participants gained opportunities to undertake activities that build health and wellbeing providing a shift in identity, future plans and aspirations. Social isolation remained for some, revealing unmet need in post-cure support. Conclusion: DAAs may support recovery journeys through the SIMOR, individuals reduced the number of active users within their social network and reconnected with family members, building recovery capital. Individuals, however, remained socially isolated in the context of the wider community. HCV services should support links to community resources to deliver the social inclusion people desire. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, sex workers (SW) were one of the vulnerable groups affected by lockdown measures. COVID-19 had also disrupted HIV/Sexually transmitted infection (STI) testing and treatment services for sex workers due to numerous restrictions in specialist medical care. This study aims to assess the seroprevalence of HIV, syphilis, HBV, and HCV and associated factors among SW as COVID-19 restrictions were lifted. The SW aged over 18 years residing in Chiangmai, Thailand, were recruited between March and December 2022. An interview-based questionnaire was administered. Blood was collected for HIV, syphilis, HBV, and HCV serological testing. Logistic regression models were used to examine factors associated with these serological markers. Of 264 SW recruited, 52.3% were male. The median age was 31 years. Male sex workers (MSW) had higher seroprevalence of HIV (13% vs. 4.8%), syphilis (23.9% vs. 6.4%) and HCV (6.5% vs. 2.4%). Female sex workers (FSW) had higher seroprevalence of HBsAg (9.5% vs. 4.4%). A high proportion were unaware of their HIV/STI infection. MSW reporting receptive anal sex were more likely to be HIV and Treponema Ab positive. MSW reporting drug injection history were more likely to be HCV Ab positive. FSW reporting younger age at first sex were more likely to be HIV Ab positive. In conclusion, SW remains particularly affected by HIV/STIs. Despite the lockdown, HIV/STIs continued to spread, highlighting the need to provide access to HIV/STIs testing, prevention, and treatment services for this population, particularly young men. [ABSTRACT FROM AUTHOR]

Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility of the viral isolate under consideration for use in the CHI model to antiviral treatment before any infections in human volunteers can take place. Humanized mouse models lack adaptive immune responses but provide a unique opportunity to obtain quantitative understanding of early HCV kinetics and develop mathematical models to further understand viral and innate immune response dynamics during acute HCV infection. We show that the models reproduce the measured HCV kinetics in humanized mice, which are consistent with early acute HCV-host dynamics in immunocompetent chimpanzees. Our findings suggest that humanized mice are well-suited to support development of a CHI model. In-silico and in-vivo modeling estimates provide a starting point to characterize candidate viruses for testing in CHI model studies. [ABSTRACT FROM AUTHOR]

Background: People who inject drugs (PWID) are at high risk of blood-borne infections, and injection drug use contributes significantly to hepatitis C virus (HCV) transmission. The WHO has therefore set targets of reducing HCV incidence and prevalence among PWID and increasing treatment coverage to eliminate HCV by 2030. The DRUCK study (2011–2014) found high HCV prevalence and low treatment coverage among PWID in Germany. To assess progress in the elimination of HCV among PWID, we conducted a cross-sectional study in two German federal states that piloted a future monitoring. Methods: PWID aged 16 + who injected drugs (previous 12 months) were recruited in low-threshold drug services and opioid agonist treatment (OAT) practices in Berlin and Bavaria between June 2021 and April 2022. Participants completed a questionnaire on sociodemographics, behaviours and access to care, and were tested for hepatitis B virus (HBV) and HCV, and HIV. Data was analysed regarding HCV prevalence, history of treatment, and risk and prevention behaviours. Results were compared with the DRUCK study. Results: A total of 588 PWID, with a median age of 39 (range: 17–66) years and 68% (399/587) male, were included in the analysis. Of the participants, 61% (353/574) reported receiving OAT and 14% (66/469) recent use of shared needles/syringes during the last 30 days. History of imprisonment was reported by 77% (444/577) and history of homelessness by 75% (428/569) of participants. Among anti-HCV positive participants, viraemic HCV infections decreased by 44% from 66% (904/1361) in 2011–2014 to 37% (160/432) in 2021–2022, while those with cleared HCV infection and treatment history increased from 20% (266/1361) to 34% (148/432). Conclusions: Despite a decrease since 2011–2014, viraemic HCV prevalence among PWID in Germany remains high, and treatment coverage is still insufficient. To achieve the WHO targets, universal health coverage and targeted integrated testing and treatment for PWID are needed. PWID receiving OAT and people in prison should be offered testing and treatment at any contact with the medical system. A nationwide monitoring system will help assess successes and remaining gaps, and track progress towards elimination of HCV among PWID in Germany. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection presents a significant public health challenge globally, particularly in high-burden countries like Nigeria, where an estimated 2.4 million individuals are living with HCV. HCV self-testing (HCVST) can potentially bridge the significant diagnosis gap and help individuals to determine their HCV status in the privacy of their homes. It offers a solution to overcome barriers related to stigma and limited access to healthcare. In Nigeria, Self-testing for hepatitis C has only been implemented in a pilot research context. This study aimed to assess stakeholder and community awareness and perceptions of HCVST in Nigeria. The findings will provide insights that could inform effective policies and future scale-up programs for HCV control. Methods: A cross-sectional descriptive study was conducted using an online social media survey administered through SurveyMonkey. The survey was disseminated across social media platforms and groups between October–November 2023. Participants included Nigerians (both health professionals and non-health professionals) aged 18 years or older residing in any of the 36 states and the Federal Capital Territory (FCT). Data collected include sociodemographic characteristics, awareness and perceptions of HCVST, and perceived benefits and barriers. Results: Of 321 respondents, 94% perceived HCVST as highly important. While 77% of respondents knew about HIVST, only 58% had prior knowledge of HCVST. The analysis also showed that healthcare workers had greater awareness of HIV self-testing (82.3%) compared to non-healthcare workers (50.0%). Most respondents (88%) were highly likely to recommend HCVST and perceived it as a cost-effective alternative to traditional testing. Key perceived benefits included increased disease detection and control (67%), improved access to testing (21%), and reduced stigma (11%). In the unadjusted model, geographical zone (Southern Nigeria: cOR = 0.49, 95% CI: 0.30–0.77, p = 0.002), work experience (more than 20 years: cOR = 2.79, 95% CI: 1.11–8.07, p = 0.039), and prior awareness of HIV self-testing (cOR = 5.24, 95% CI: 3.00–9.43, p < 0.001) were significant predictors of HCVST awareness. However, in the adjusted model, only prior awareness of HIV self-testing remained significant (aOR = 4.77, 95% CI: 2.62–8.94, p < 0.001). Conclusions: The strong support for HCVST among stakeholders in Nigeria highlights its potential to enhance HCV control, especially within the broader context of infectious diseases like STIs. The greater awareness of HIV self-testing among healthcare workers compared to non-healthcare workers indicates the need for targeted awareness campaigns for non-healthcare populations. Addressing these awareness gaps, leveraging lessons from HIVST, and using existing infrastructure will be crucial. Prioritizing public education, outreach, and effective linkage to care will drive the impact of HCVST in achieving HCV elimination goals and position it as a model for expanding similar STI interventions in Nigeria. [ABSTRACT FROM AUTHOR]

The prevalence of transfusion-transmissible infections (TTIs) among blood donors is critical for ensuring blood safety. Aim: To provide an updated assessment of TTIs at a tertiary care hospital in Mexico over a ten-year period. We conducted a retrospective cross-sectional study. Blood samples were analyzed from potential donors at tertiary care hospital between 2012 and 2022. Donors completed a questionnaire and were screened for HIV, syphilis, hepatitis B, and hepatitis C using nucleic acid testing and serological tests. Prevalence and trends were estimated. Among the 117,756 donors analyzed, 0.48% were positive for syphilis, with a significant annual decrease of −5.9% (p < 0.001), although notable fluctuations occurred, including a peak in 2021. HIV showed a significant annual increase of 9.8% (p = 0.029), with a peak in approximately 2019–2020. Hepatitis C maintained a stable trend, with a slight annual decrease of −5.6% (p = 0.170). Hepatitis B consistently decreased, with an annual decrease of −11.3% (p = 0.06). This study highlights the importance of continuous monitoring and screening of blood donors to ensure blood safety. These findings underscore the need for localized public health interventions, particularly to address the increasing incidence of HIV. Further research should focus on enhancing donor screening practices and public health strategies to reduce the prevalence of TTIs. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) infection, a global health concern, can lead to chronic liver disease. The HCV core antigen (HCVcAg), a viral protein essential for replication, offers a cost-effective alternative to HCV RNA testing, particularly in resource-limited settings. This review explores the significance of HCVcAg, a key protein in the hepatitis C virus, examining its structure, function, and role in the viral life cycle. It also evaluates its clinical use in diagnosis and treatment monitoring, comparing its performance to the standard HCV RNA assay using data from PubMed and Google Scholar. HCVcAg assays show high pooled sensitivity (93.5%) and pooled specificity (99.2%) compared to HCV RNA assays, correlating closely (r = 0.87) with HCV RNA levels. Hence, HCVcAg testing offers a cost-effective way to diagnose active HCV infections and monitor treatment, especially in resource-limited settings, but its sensitivity can vary and standardization is needed. HCVcAg also predicts liver disease progression and assesses liver damage risk, aiding patient management. It helps to identify patients at risk for fibrosis or carcinoma, making it vital in hepatitis C care. HCVcAg testing can expand access to HCV care, simplify management, and contribute to global elimination strategies, especially in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: With the advent of direct acting antivirals (DAAs) the World Health Organisation (WHO) adopted global strategy to eliminate hepatitis C virus (HCV) infection by 2030. In Europe, people who inject drugs (PWID) account for the majority of new cases, however testing and treatment remain suboptimal. The aim was to monitor progress in HCV policy and cascade-of-care for PWID, led by the civil society organisations (CSO) that provide harm reduction services for PWID across Europe. Methods: In period 2020–2023, CSOs representing focal points of Correlation-European Harm Reduction Network were annually invited to complete online questionnaire on use/impact of HCV test-and-treat guidelines for PWID, availability/functioning of continuum-of-care, and role/limitations of harm reduction services for PWID. A retrospective longitudinal analysis of responses to questions answered each year by the same respondents was performed, and a comparison among the studied years was made. Results: Twenty-five CSOs from cities in 25 European countries were included and responded to 25 questions. Between 2020 and 2023, there was positive trend in number of HCV treatment guidelines, separate guidelines for PWID, and their positive impact on acess to testing/treatment (24/25, 5/25, and 16/25 in 2023, respectively). DAAs were available in all countries, predominantly prescribed by specialist physicians only (slight increase at primary care), with restrictions including active drug use, stage of liver fibrosis or/and reimbursement policies (2/25, 4/25, and 3/25 in 2023, respectively). A decrease in HCV testing sites was noted. Treatment was consistently most common at clinical settings, however an increase outside the specialist settings was detected, particularly in prisons (12/25 and 15/25 in 2020–2021, respectively). Comparing 2022–2023, number of HCV-testing services increased in many cities with positive dynamic in nearly all the settings; increase in treatment at harm reduction services/community centres was noted (6/25 to 8/25, respectively). Between 2020 and 2023 the frequency of various limitations to CSOs addressing HCV was oscillating, presenting an increase between 2022 and 2023 (9/25 to 14/25, respectively). Conclusion: The overall progress towards WHO HCV elimination goals across Europe remains insufficient, most probably also due to the influence of Covid-19 pandemic. Further improvements are needed, also by including CSOs for PWID in continuum-of-care services, and in monitoring progress. [ABSTRACT FROM AUTHOR]

In this review, recent advances in the combination of CRISPR–Cas systems with graphene-based electrolyte-gated transistors are discussed in detail. In the first part, the functioning of CRISPR–Cas systems is briefly explained, as well as the most common ways to convert their molecular activity into measurable signals. Other than optical means, conventional electrochemical transducers are also developed. However, it seems that the incorporation of CRISPR/Cas systems into transistor devices could be extremely powerful, as the former provides molecular amplification, while the latter provides electrical amplification; combined, the two could help to advance in terms of sensitivity and compete with conventional PCR assays. Today, organic transistors suffer from poor stability in biological media, whereas graphene materials perform better by being extremely sensitive to their chemical environment and being stable. The need for fast and inexpensive sensors to detect viral RNA arose on the occasion of the COVID-19 crisis, but many other RNA viruses are of interest, such as dengue, hepatitis C, hepatitis E, West Nile fever, Ebola, and polio, for which detection means are needed. [ABSTRACT FROM AUTHOR]

Hepatitis C is a disease for which in approximately 30 years we have gone from the discovery of the causative agent in 1989, to the introduction of direct-acting antiviral (DAAs) therapies starting from 2011, and to a proposal for its elimination in 2016, with some countries being on track for this goal. Elimination efforts, in the absence of a vaccine, rely on prevention measures and antiviral therapies. However, treatment rates have declined in recent years and are not considered adequate to achieve this goal at a global level. This poses a great epidemiological challenge, as HCV in many countries still causes a significant burden and most infected people are not yet diagnosed. Consequently, efforts are needed at different levels with common purposes: to facilitate access to screening and diagnosis and to improve linkage to care pathways. In this review, we discuss the latest epidemiological findings on HCV infection, the obstacles to its elimination, and strategies that are believed to be useful to overcome these obstacles but are applied unevenly across the world. [ABSTRACT FROM AUTHOR]

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The Deadly Liver Mob (DLM) is a peer-delivered incentivised health promotion program by and for Aboriginal and Torres Strait Islander Australians, and was introduced in response to the disproportionate number of Aboriginal and Torres Strait Islander Australians who are impacted by blood borne viruses (BBVs) and sexually transmitted infections (STIs). The goal of the program is to increase access to BBV and STI education, screening, treatment, and vaccination in recognition and response to the systemic barriers that Aboriginal and Torres Strait Islander peoples face in accessing health care. This commentary introduces a series of papers that report on various aspects of the evaluation of the Deadly Liver Mob (DLM) program. In this paper, we explain what DLM is and how we constructed an evaluation framework for this complex health promotion intervention. [ABSTRACT FROM AUTHOR]

Background: With the advent of direct acting antivirals, the World Health Organisation proposed eliminating Hepatitis C as a public health threat by 2030. To achieve this, countries need to diagnose, engage in care and treat their undiagnosed populations. This will require sensitisation campaigns. However previous media campaigns have had mixed impact. We conducted a scoping review to identify and understand the impact of previous Hepatitis C media campaigns. These findings could inform the delivery of future campaigns. Methods: We searched five electronic databases for published literature on media campaigns conducted for Hepatitis C awareness, testing, and treatment in Organisation for Economic Co-operation and Development (OECD) countries since 2010. Two independent reviewers screened citations for inclusion. Additionally, we spoke to stakeholders in the Hepatitis C field in the UK and conducted a Google search to identify any unpublished literature. A quantitative synthesis was conducted to identify targeted populations, strategies and media used, aims and impact of the campaigns. Results: A title and year of publication screening of 3815 citations resulted in 113 papers that had a full abstract screen. This left 50 full-text papers, 18 were included of which 9 (50%) were from Europe. 5 (27.8%) of campaigns targeted minority ethnicities, and 9 (50%) aimed to increase testing. A Google search identified 6 grey literature sources. Most campaigns were not evaluated for impact. Discussions with stakeholders identified several barriers to successful campaigns including lack of targeted messaging, stigmatising or accusatory messaging, and short-lived or intermittent campaign strategies. Conclusion: Future campaigns will likely need to be multifaceted and have multiple tailored interventions. Campaigns will need to be sizeable and robust, integrated into health systems and viewed as an ongoing service rather than one-offs. [ABSTRACT FROM AUTHOR]

Aim: This paper presents the development of the METRIC toolkit, aimed at enhancing primary healthcare interventions in the context of hepatitis C control, thus contributing to the World Health Organization's global strategy to achieve the elimination of the disease by 2030. Background: At the global level, most people living with hepatitis C are unaware of their condition. As such, the eradication of hepatitis C necessitates comprehensive strategies within primary healthcare settings, as it provides an opportunity to reach the general population, facilitates the identification of potential patients who may be unfamiliar with hepatitis C, and guides them toward adequate care. Herein, we propose the METRIC toolkit as a means to optimize the efficiency and efficacy of healthcare services dedicated to hepatitis C control. Methods: The development of the METRIC toolkit was guided by a thorough review of pertinent literature, focusing on primary healthcare interventions in hepatitis C control. Key components were identified, encompassing systematic problem identification, solution formulation, outcome evaluation, and feedback integration. Findings: The METRIC toolkit represents a valuable resource for strengthening primary healthcare interventions in hepatitis C control. By fostering a culture of continuous improvement and data-driven decision-making, this framework holds promise in advancing the global agenda towards hepatitis C elimination. However, its successful application requires careful consideration of contextual factors and ongoing adaptation to local needs and circumstances. [ABSTRACT FROM AUTHOR]

Background/Aims World Health Organization has set a goal to end the endemic of viral hepatitis C by 2030. Increasing linkage to care and treatment success for HCV patient is essential. Daegu Catholic University Medical Center introduced an in-hospital HCV alarm system on July 6, 2022, to notify the responsible physician of HCV antibody detection. This study aims to evaluate the effectiveness of this alarm system in improving linkage to care for hepatitis C. Methods This is a retrospective study using electronic medical records of DCUMC for each patient screened for HCV between September 2020 and May 2024. Linkage is defined as referring a HCV Ab detected patient to a hepatologist. We compared the differences in RNA test implementation rates and linkage success rates before and after the alarm system. We evaluated factors associated with RNA testing failure, using logistic regression analysis. Results Before and after the alarm system, 24,713 and 25,498 patients were screened respectively. HCV antibodies were detected in 446 (1.8%) and 479 (1.9%) patients. Among the HCV Ab detected patients, 260 (58.3%) and 338 (70.6%) completed HCV RNA testing (p<0.001). Linkage was 278 (62.3%) and 377 (78.7%), respectively (p <0.001). These factors were associated with RNA testing failure; patient’s department; surgical department (OR, 3.63; 95% CI, 2.43-5.42); emergency medicine (OR, 2.18; 95% CI, 1.36-3.47); without alarm (OR, 1.96; 95% CI, 1.42-2.70). Conclusion The implementation of the in-hospital HCV alarm system not only encourages HCV RNA testing for HCV Ab detected patients but also improves their linkage to hepatologists. Additionally, HCV RNA testing failures are more likely to occur in surgical and emergency departments than in medical departments. These suggest that the alarm system, along with the cooperation of surgical and emergency medical doctors, is essential to improve linkage to care. [ABSTRACT FROM AUTHOR]

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the NLRP3 inflammasome. The NLRP3 inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well as IL-18 and IL-1β production. Acute and chronic liver diseases are characterized by a massive influx of pro-inflammatory stimuli enriched in reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs) that promote the assemblage and activation of the NLRP3 inflammasome. As the major cause of inflammatory cytokine storm, the NLRP3 inflammasome exacerbates liver diseases, even though it might exert protective effects in regards to hepatitis C and B virus infection (HCV and HBV). Here, we summarize the current knowledge concerning NLRP3 inflammasome function in both acute and chronic liver disease and in the post liver transplant setting, focusing on the molecular mechanisms involved in NLRP3 activity. [ABSTRACT FROM AUTHOR]

Background Worldwide, more than 39 million individuals are living with human immunodeficiency virus (HIV), 296 million with chronic hepatitis B (HBV), and 58 million with chronic hepatitis C (HCV). Despite successful treatments for these blood-borne viruses (BBVs), >1.7 million people die per annum. To combat this, the World Health Organization recommended implementing triple testing for HIV, HBV, and HCV. This systematic review aims to provide evidence for this policy, by identifying the prevalence of these BBVs and discussing the costs of available triple tests. Methods Medline, Embase, and Global Health were searched to identify articles published between 1 January and 24 February 2023. Included studies reported the prevalence of HIV (anti-HIV 1/2 antibodies), HBV (hepatitis B surface antigen) and HCV (anti-HCV antibodies). Results were stratified into risk groups: blood donors, general population, healthcare attendees, individuals experiencing homelessness, men who have sex with men, people who use drugs, pregnant people, prisoners, and refugees and immigrants. Results One hundred seventy-five studies sampling >14 million individuals were included. The mean prevalence of HIV, HBV, and HCV was 0.22% (standard deviation [SD], 7.71%), 1.09% (SD, 5.80%) and 0.65% (SD, 14.64%) respectively. The mean number of individuals testing positive for at least 1 BBV was 1.90% (SD, 16.82%). Therefore, under triple testing, for every individual diagnosed with HIV, another 5 would be diagnosed with HBV and 3 with HCV. Testing for all 3 viruses is available for US$2.48, marginally more expensive than the lowest-priced isolated HIV test ($1.00). Conclusions This article highlights a potential avenue for healthcare improvement by implementing combination testing programs. Hopefully, this will help to achieve the Sustainable Development Goal of elimination of these BBV epidemics by 2030. [ABSTRACT FROM AUTHOR]

Background: There are reported studies of Hepatitis C and chronic kidney disease association. However, how this liver virus infection affects the general population's susceptibility to the onset of the kidney disease is still unknown. Methods: To determine if a positive anti-HCV serologic status is linked to a greater incidence of chronic kidney disease in the general adult population, a systematic evaluation of the published medical literature since 2015 was conducted. A summary estimate of the relative risk of chronic kidney disease with HCV was produced using a random-effects model. Moreover, stratified analysis and meta-regression were performed. Results: Twelve studies (n = 605858 patients) were filtered and included. Meta-analyses were conducted according to the outcome. Pooling results of longitudinal studies (n = 06 studies, n = 347120 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD. The summary estimate for adjusted hazard ratio was 1.21 with (95% confidence interval 1.13; 1.29, P = 0.001), and between studies heterogeneity was noted (P value by Q test < 0.001). In the subset of Asian surveys, the risk of the occurrence of chronic kidney disease linked to HCV was 1.70 (95% confidence interval 1.40; 2.00) without heterogeneity (P value by Q test = 0.6). Conclusions: We found a strong correlation between HCV infection and a higher risk of chronic renal disease in general global population. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the psychometric properties of the Spanish-language version of the HIV-Symptom Index (HIV-SI) questionnaire in Spanish patients undergoing antiretroviral therapy. Methods: Between 2014 and 2016, an observational, multicenter, prospective cohort study was conducted in seventeen Spanish hospitals to validate HIV-SI questionnaire in terms of: construct validity (confirmatory factor analysis), internal consistency (Cronbach's alpha), convergent validity (Pearson's correlation coefficient) and Known-group validity. In addition, a sensitivity to change analysis was also performed. Results: A total of 232 patients were included in the study. They had a mean age of 46.17 (SD9.82) and were 75% male. The median overall score for the HIV-SI was 10 (IQR 4– 19.5) and the most common symptoms reported were feelings of nervousness or anxiety, fatigue or energy loss, feeling sad or depressed, stomach pain or bloating, and difficulty sleeping. In the current study, the Spanish HIV-SI questionnaire showed a high internal consistency (α = 0.89) and adequate construct validity (CFI and TLI > 0.90). When contrasted with the MOS-HIV questionnaire, an inverse correlation was found. It showed a good association with the mental (r=-0.61; P < 0.0001) and physical score (r=-0.60; P < 0.0001). In a multivariate analysis, the age of the patient, female condition, hepatitis C coinfection, concomitant treatment and non-adherence resulted in a higher HIV-SI score. Conclusions: Our study has shown that the Spanish HIV-SI is a valid and reliable self-administered PROM for routine measurement of patient- reported symptoms among Spanish patients on antiretroviral treatment. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug–drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit. [ABSTRACT FROM AUTHOR]

Viral hepatitis (A–E) presents a major global health challenge. In 2015, the World Health Organization (WHO) launched an initiative to eliminate viral hepatitis, with the aim of reducing new infections by 90% and deaths by 65% by 2030. Mexico is one of 38 focus countries identified by the WHO, collectively accounting for 80% of global infections and deaths. While hepatitis B and C are commonly diagnosed in Mexico, routine diagnosis for hepatitis D and E is lacking, with no specific epidemiological data available. In 2020, Mexico implemented the National Hepatitis C Elimination Program, focusing on preventing new infections, reducing complications like cirrhosis and hepatocellular carcinoma, ensuring access to treatment, and improving patient care. However, this program has not been extended to hepatitis B and E. Addressing the challenges of viral hepatitis control in Mexico requires increased resource allocation, expanded diagnosis, vaccination for hepatitis A and B, and treatment coverage for hepatitis B and C, along with multisectoral engagement. This work provides an overview of Mexico's response to the global initiative, highlighting its progress, challenges, and areas of opportunity. [ABSTRACT FROM AUTHOR]

The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. The infection's distribution and genotype prevalence vary widely across the continent. Even with the availability of highly effective direct-acting antiviral (DAA) therapies, HCV infection is far from being controlled. A significant proportion of patients remain undiagnosed, contributing to the ongoing transmission of the virus. Additionally, several barriers hinder the widespread use of DAAs, including high treatment costs, stigma, poor linkage to care, and considerable geographical variations in prevalence and transmission routes. The World Health Organization has set ambitious targets to reduce liver-related deaths, decrease new viral hepatitis infections, and ensure that 90% of infected individuals are diagnosed by 2030. However, most European countries face challenges, highlighting the need for screening programs, funding mechanisms, and public health strategies to effectively control HCV infection in Europe. [ABSTRACT FROM AUTHOR]

Background: Cryptococcal meningitis (CM) is a central nervous system (CNS) infection that occurs mainly in immunocompromised individuals such as those with human immunodeficiency virus (HIV) infection. However, the prevalence of CM in immunocompetent patients has increased. Although CM has been reported in patients with hepatitis C virus (HCV) infection, it has not yet been fully established whether there is an association between both conditions. CM has also been reported in patients with intravenous drug use (IVDU), which is related to the immunosuppression caused by these drugs. Case Presentation: We report the case of a 24-year-old man who presented with meningitis secondary to Cryptococcus gattii infection. He had a history of IVDU and HCV infection, was HIV-negative and without antiviral treatment. The patient received adequate antifungal treatment during induction, consolidation, and maintenance phases. His condition relapsed, requiring dose adjustment, with an excellent response during clinical follow-up for both meningitis and HCV infection. A brain biopsy was requested during relapse to rule out other co-infection. Conclusion: The case of an individual diagnosed with cryptococcal meningitis, who had a history of IVDU and HCV infection, is presented. The coexistence of such events could shadow the prognosis of this group of subjects, related to immunosuppression that can be caused through different pathways. Having HCV and being a IVDU simultaneously could increase the risk of Cryptococcus infection. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the efficacy of combining automated machine learning (AutoML) and explainable artificial intelligence (XAI) in identifying metabolomic biomarkers that can differentiate between hepatocellular carcinoma (HCC) and liver cirrhosis in patients with hepatitis C virus (HCV) infection. Methods: We investigated publicly accessible data encompassing HCC patients and cirrhotic controls. The TPOT tool, which is an AutoML tool, was used to optimize the preparation of features and data, as well as to select the most suitable machine learning model. The TreeSHAP approach, which is a type of XAI, was used to interpret the model by assessing each metabolite's individual contribution to the categorization process. Results: TPOT had superior performance in distinguishing between HCC and cirrhosis compared to other AutoML approaches AutoSKlearn and H2O AutoML, in addition to traditional machine learning models such as random forest, support vector machine, and k-nearest neighbor. The TPOT technique attained an AUC value of 0.81, showcasing superior accuracy, sensitivity, and specificity in comparison to the other models. Key metabolites, including L-valine, glycine, and DL-isoleucine, were identified as essential by TPOT and subsequently verified by TreeSHAP analysis. TreeSHAP provided a comprehensive explanation of the contribution of these metabolites to the model's predictions, thereby increasing the interpretability and dependability of the results. This thorough assessment highlights the strength and reliability of the AutoML framework in the development of clinical biomarkers. Conclusions: This study shows that AutoML and XAI can be used together to create metabolomic biomarkers that are specific to HCC. The exceptional performance of TPOT in comparison to traditional models highlights its capacity to identify biomarkers. Furthermore, TreeSHAP boosted model transparency by highlighting the relevance of certain metabolites. This comprehensive method has the potential to enhance the identification of biomarkers and generate precise, easily understandable, AI-driven solutions for diagnosing HCC. [ABSTRACT FROM AUTHOR]

Background: Analyzing hospitalizations of patients with hepatitis C virus (HCV) infection is essential for an effective action plan to eliminate hepatitis C as a public health threat. This study aimed to explore trends in hospitalizations of patients with HCV infection and factors related to these hospitalizations. Methods: This 11-year retrospective study (2012–2022) explored trends in hospitalizations of patients with HCV infection in Poland based on data from the Nationwide General Hospital Morbidity Study. Results: The mean age of individuals was 55 years, with hospitalization rates among men and women of 15.5 and 13.7 per 100,000 population, respectively. Hospitalizations were 1.8-fold higher among urban residents. The most frequent comorbidities were digestive (24%) and cardiovascular (18%) diseases. During the studied period, the hospitalization rates significantly decreased from 31.9 per 100,000 in 2012 to 5.0 per 100,000 in 2022, with stays requiring 0–3, 4–7, and ≥8 days becoming 8-fold, 6-fold, and 4-fold less frequent, respectively. The flattening of hospitalizations was apparent across all age groups, including children. Conclusions: While significant progress has been made in managing HCV in Poland, continued efforts are required to eliminate disparities in care and to sustain the momentum toward HCV elimination, particularly through enhanced political commitment and the implementation of comprehensive national screening programs. [ABSTRACT FROM AUTHOR]

Nearly 60 million people worldwide are infected with Hepatitis C Virus (HCV), a bloodborne pathogen which leads to liver cirrhosis and increases the risk of hepatocellular carcinoma. Those with limited access to healthcare resources, such as injection drug users and people in low- and middle-income countries, carry the highest burden. The current diagnostic algorithm for HCV is slow and costly, leading to a significant barrier in diagnosis and treatment for those most at risk from HCV. There remains no available vaccine for HCV, and infection is often asymptomatic until significant cirrhosis has occurred, which makes screening incredibly important to prevent liver damage and transmission. Recent investigation has sought to address these issues through improvements in various aspects of the diagnostic procedure, using methods such as isothermal amplification techniques for viral RNA amplification, the use of viral protein as an analyte, and the incorporation of streamlined, self-contained testing systems to reduce administrative skill requirements. This review provides a comprehensive overview of current commercial standards and novel improvements in HCV diagnostics, as well as a framework for future integration of these improvements to develop a one-step diagnostic that meets the needs of those most affected. [ABSTRACT FROM AUTHOR]

To clarify the risk factors for the aggravation of esophagogastric varices (EGVs) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGVs were aggravated in 42 (25%) patients despite SVR. The cumulative 1-, 3-, 5-, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified a platelet count < 11.0 × 104/μL, LSM ≥ 18.0 kPa, total bile acid ≥ 33.0 μmol/L, and a diameter of left gastric vein (LGV) ≥ 5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that met all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGVs tend to worsen as two or more of these risk factors increase. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C (HCV) is a virus that causes chronic liver disease, end-stage cirrhosis, and liver cancer, yet most infected individuals remain undiagnosed or untreated. Kenya is a country located in Sub-Saharan Africa (SSA) where the prevalence of HCV remains high but with uncertain disease burden due to little population-based evidence of the epidemic. We aimed to highlight the HCV disease burden in Kenya with a summary of the available data. Methods: The study was performed as per the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We searched publications reporting HCV prevalence and genotypes in Kenya between January 2000 to December 2022. The effect size, i.e., the HCV prevalence, was defined as the proportion of samples testing positive for HCV antibody. Study quality was assessed by the Joanna Briggs Institute (JBI) critical appraisal checklist. Due to high study heterogeneity, the studies were categorized into low-, intermediate-, and high-risk for HCV infection. The pooled estimate prevalence per category was determined by the random effects model. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023401892). Results: A total of 29 studies with a sample size of 90,668 met our inclusion criteria, a third of which were from the capital city Nairobi (34.5%). Half of the studies included HIV-infected individuals (31%) or injection drug users (20.7%). HCV genotype 1 was the most common, with genotype 4 only slightly less common, and together they accounted for 94% of cases. The pooled prevalence for the low-, intermediate- and high-risk groups were 2.0%, 3.4%, and 15.5%, respectively. Over 80% of the studies had a score of > 6 on the JBI scale, indicating a low risk of bias in terms of study design, conduct and analysis. Conclusion: Our findings demonstrate that there is a higher prevalence of HCV in key populations such as HIV-infected individuals and drug users than in the general population in Kenya. We found that HCV genotypes 1 and 4 were the most common genotypes. More data from the general population is required in order to establish baseline data on the prevalence and genotypes of HCV in Kenya. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child–Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child–Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy. [ABSTRACT FROM AUTHOR]

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Hepatitis C (HCV) treatment for people who use drugs (PWUD) decreases injection drug use and injection equipment sharing. We examined changes in injection drug use and injection equipment sharing following HCV treatment in a randomized trial comparing peer-assisted telemedicine for HCV treatment (TeleHCV) versus peer-assisted usual care in rural PWUD. We hypothesize that TeleHCV reduces risky behaviors and peers facilitate this change. We used mixed-effects logistic regression to describe participant-level (n = 203) associations between both injection drug use and injection equipment sharing and randomized groups, frequency of peer contact, HCV treatment initiation, HCV cure, and time. Risky behaviors were surveyed at baseline and 12 and 36 weeks after HCV treatment completion. Injection drug use declined more over time in TeleHCV participants vs. control at 12 weeks (adjusted odds ratio [aOR] = 0.42, 95% CI 0.20–0.87, p = 0.02) and 36 weeks (aOR = 0.48, 95% CI 0.21–1.08, p = 0.076). Injection drug use decreased more with a greater number of peer interactions, with reductions among participants in the 3rd quartile exceeding those in the 1st quartile of peer interactions at 12 weeks (aOR = 0.75, 95% CI 0.57–0.99, p = 0.04). Similarly, injection equipment sharing decreased over time, with reductions among participants in the 3rd quartile exceeding those in the 1st quartile of peer interactions at 36 weeks (aOR = 0.08, 95% CI 0.01–0.97, p = 0.047). Peer-assisted telemedicine for HCV treatment decreases injection drug use and injection equipment sharing; peers contribute to this effect. [ABSTRACT FROM AUTHOR]

Background: The main mode of transmission of Hepatitis C in North America is through injection drug use. Availability of accessible care for people who inject drugs is crucial for achieving hepatitis C elimination. Objective: The objective of this analysis is to compare the changes in injection drug use frequency and high-risk injection behaviors in participants who were randomized to accessible hepatitis c care versus usual hepatitis c care. Methods: Participants who were hepatitis C virus RNA positive and had injected drugs in the last 90 days were enrolled and randomized 1:1 to an on-site, low threshold accessible care arm or a standard, referral-based usual care arm. Participants attended follow-up appointments at 3, 6, 9, and 12 months during which they answered questions regarding injection drug use frequency, behaviors, and treatment for opioid use disorder. Primary outcomes: The primary outcomes of this secondary analysis are the changes in the frequency of injection drug use, high-risk injection behaviors, and receiving medication for opioid use disorder in the last 30 days. Results: A total of 165 participants were enrolled in the study, with 82 participants in the accessible care arm and 83 participants in the usual care arm. Participants in the accessible care arm were found to have a statistically significant higher likelihood of reporting a lower range of injection days (accessible care-by-time effect OR = 0.78, 95% CI = 0.62–0.98) and injection events (accessible care-by-time effect OR = 0.70, 95% CI = 0.56–0.88) in the last 30 days at a follow-up interview relative to those in the usual care arm. There were no statistically significant differences in the rates of decrease in receptive sharing of injection equipment or in the percentage of participants receiving treatment for opioid use disorders in the two arms. Conclusion: Hepatitis C treatment through an accessible care model resulted in statistically higher rates of decrease in injection drug use frequency in people who inject drugs. [ABSTRACT FROM AUTHOR]

Background: Direct acting antivirals (DAAs) as a curative treatment of hepatitis C have been available for several years and have replaced interferon-containing therapies. However, treatment rates of people who inject drugs (PWID) are declining in Germany, putting the elimination of hepatitis C by 2030 at risk. This study aimed at elucidating the knowledge of, and attitude towards, hepatitis C treatment in a clinical sample of PWID. Methods: Participants were recruited between February 2019 and October 2020 at two opioid agonist therapy (OAT) clinics and two in-patient drug detoxification wards. Based on the European Addiction Severity Index (Europ-ASI), a standardized interview focusing on: sociodemographic data, drug history, risky behavior, infection with hepatitis C virus (HCV) and HIV, and previous experience with HCV treatment was carried out. In addition, participants filled in a questionnaire evaluating 13 statements relating to HCV treatment (right/wrong) and 15 statements on their personal ‘pros and cons’ views to start such a treatment assessed with the means of a 6-point Likert scale. Results: A total of 153 patients (average age 45 years, male 78%; 106 (69.3%) currently in opioid maintenance treatment, 47 (30.7%) currently admitted to an inpatient detoxification) with an opioid use disorder were investigated. All of them reported having injected drugs at least once in their lives; 97 participants (63.3%) stated that they had been previously diagnosed with HCV infection. Among them, 27/97 patients (27.8%) reported a previous treatment with interferon; 27/97 (27.8%) with DAAs; and 32/97 (33.0%) reported a currently active hepatitis C. Most patients knew about the availability and efficacy of DAAs. However, DAAs’ low rate of side effects, their short treatment duration, and their replacement of interferon, were not correctly evaluated by up to 50.3% of patients. 25–40% of 32 patients with currently active hepatitis C prioritized handling of social and other medical issues, e.g., reduction of heroin use, over treatment of hepatitis C. Conclusions: Although current levels of risky behavior have reportedly been reduced by active PWID over the past few years, educational and motivational interventions to increase hepatitis C treatment uptake should address the gaps in patients’ knowledge. [ABSTRACT FROM AUTHOR]

Background: Participatory approaches have become a widely applied research approach. Despite their popularity, there are many challenges associated with the evaluation of participatory projects. Here we describe an evaluation of a community-based participatory research study of underserved communities in Ho Chi Minh City (HCMC), Vietnam at risk for hepatitis C virus. The goals of our evaluation were to explore the main benefits and challenges of implementing and participating in a participatory study and to describe study impacts. Methods: We conducted two meetings with leaders and members of the participating groups followed by in-depth interviews with 10 participants. We then held a dissemination meeting with over 70 participants, including the representatives of each group, researchers from non-governmental organizations (community-based, national and international), and govenrment officials from the Vietnam Ministry of Health and the Department of Health of HCMC. Results: Results include four categories where we describe first the participatory impacts, followed by the collaborative impacts. Then we describe the benefits and challenges of creating and belonging to one of the groups, from members' and leaders' points of view. Finally, we describe the key suggestions that participants provided for future research. Conclusion: In conclusion, the evaluation approach led to both a research reflection on the 'success' of the project and enabled participants themselves to reflect on the outcomes and benefits of the study from their point of view. Plain English Summary : Participatory approaches in research aim to include participants in an array of aspects of the study, including developing research questions, collecting data, conducting analysis, etc. It has become a more popular method, however there are still challenges surrounding the evaluation of these projects. Here we describe an evaluation of a community-based participatory research study of underserved communities in Ho Chi Minh City (HCMC), Vietnam at risk for hepatitis C virus. The goals of the evaluation were to discuss and explore the main benefits and challenges with those who participated, as well as assess study impacts. To conduct the evaluation, we conducted two meetings with leaders and members of the participating groups followed by interviews with 10 people who were involved. The evaluation results included four categories including impacts for members as well as wider impacts in the community. Then we describe the benefits and challenges of creating and belonging to one of the groups, from members' and leaders' points of view. Finally, we describe the key suggestions that participants provided for future research. In conclusion, the evaluation approach led to both a research reflection on the 'success' of the project and enabled participants themselves to reflect on the outcomes and benefits of the study from their point of view. [ABSTRACT FROM AUTHOR]

Simple Summary: The mortality of hepatocellular carcinoma (HCC) is rising globally, against the trend of other cancers. People with liver cirrhosis, even after hepatitis C treatment still face a high risk of HCC, requiring ongoing enrolment in HCC surveillance, and new technologies to improve diagnostic sensitivity are being explored. However, their impact on HCC survival remains uncertain relative to improving adherence to existing surveillance methods. This study uses mathematical modeling to assess how different strategies can reduce deaths from liver cancer in people with cirrhosis after being cured of hepatitis C. We compared the impact of improved adherence to ultrasound screening with increased HCC imaging sensitivity on HCC survival. Notably, we found that even modest enhancements in surveillance adherence (5–10 percentage point increases) exhibited significant survival benefits for people with hepatitis C-related cirrhosis, outperforming improvements in diagnostic sensitivity. Background & Aims: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. Methods: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. Conclusions: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy. [ABSTRACT FROM AUTHOR]

This study is a secondary analysis of a randomized clinical trial (October 2013–April 2017) involving 150 People Who Inject Drugs (PWIDs) with hepatitis C virus (HCV) seen in opioid agonist treatment programs in the Bronx, New York, and investigates the impact of distrust in the healthcare system on adherence to Direct-Acting Antivirals (DAAs) HCV treatment therapy among PWIDs. The distrust was scaled on a 9-item instrument and the adherence to DAA medications was measured using electronic blister packs. This study demonstrated a significant inverse relationship between levels of distrust and medication adherence: 71.8 ± 2.2% (se) vs. 77.9 ± 1.8%, p = 0.024 between participants with higher and lower distrust levels. Despite the absence of significant association of distrust with sociodemographic or substance use characteristics, these findings suggest that building trust within the healthcare system is paramount for improving adherence to DAAs among PWIDs. The results call for a healthcare approach that emphasizes trust-building through patient-centered care, sensitivity training, peer support, and health system reform to effectively address the treatment needs of this marginalized population. [ABSTRACT FROM AUTHOR]