Computational Study on the Wealth Conformations of Hepatitis C Virus Envelope Glycoprotein 2 and Role of Its Glycan Coat.

Hepatitis C virus (HCV) is a major cause of chronic liver disease and hepatocellular carcinoma. Antibody development efforts mainly revolve around HCV envelope glycoprotein 2 (E2), which mediates host cell entry by interacting with several cell surface receptors, including CD81. We still have limited knowledge about the structural ensembles and the dynamic behavior of both the CD81 binding sites and the glycans on E2. Here, multiple microsecond-long, all-atom molecular dynamics (MD) simulations, as well as a Markov state model (MSM), were performed to provide an atomistic perspective on the dynamic nature of E2 and its glycans. End-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of E2, which may be exploited in therapeutic efforts. Additionally, the Markov state model built from the simulation maps four metastable states for AS412 and three metastable states for the front layer in CD81 binding sites, while binding with HEPC3 would induce a conformation selection for both of them. Overall, this work presents hitherto unseen functional and structural insights into E2 and its glycan coat, providing a new theoretical foundation to control the conformational plasticity of E2 that could be harnessed for vaccine development.

Assessment of Short-Term Effects of Cell Transplantation in Cirrhosis DUE to HCV.

BACKGROUND AND OBJECTIVES: Recent studies have highlighted the potential of fetal hepatic stem cells in regenerative treatments for liver diseases. This study aimed to evaluate the short-term effects of fetal stem cell transplantation in patients with liver cirrhosis resulting from chronic hepatitis C. MATERIALS AND METHODS: Thirty patients with liver cirrhosis of all Child-Turcotte-Pugh classes due to chronic hepatitis C, aged 18 to 65 years, were selected for this study. A single intravenous dose of 1 ml containing 6*106 fetal hepatic stem cells, diluted in 20.0 ml of 0.9% sodium chloride solution, was administered. The efficacy of the treatment was assessed by measuring levels of ALT, AST, total and direct bilirubin, gamma-glutamyltranspeptidase, alkaline phosphatase, total protein, and albumin before and after cell therapy. RESULTS: Post-treatment, a significant reduction was noted in the Child-Pugh score from 8 [6-9] to 7 [6-8] (p<0.001) and the MELD index from 11 [7-15] to 10 [7-14] (p=0.004). Skin itching decreased from 36.7% to 10%. Complaints of weakness increased significantly from 3.3% to 23.3% after 30 days of therapy (p=0.014), and the incidence of reduced appetite increased from 20% to 46.7% (p=0.021). No statistical differences were observed in the frequency of nosebleeds (86.7% initially vs. 90% at day 30, p=0.655) or drowsiness (63.3% initially vs. 76.7% at day 30, p=0.157). Significant reductions were noted in ALT levels by 35% and total bilirubin by 44%. The lack of significant changes in indicators of hepatic-cell insufficiency, particularly the protein-forming function as reflected in total protein and albumin levels, is likely due to the extent of liver tissue damage and thus a delayed recovery. CONCLUSION: The findings of this study affirm the clinical efficacy and promise of fetal hepatic stem cell therapy as part of a comprehensive treatment regimen for patients with liver cirrhosis.

Evaluation of a Project Integrating Financial Incentives into a Hepatitis C Testing and Treatment Model of Care at a Sexual Health Service in Cairns, Australia, 2020-2021.

BACKGROUND: Understanding the effectiveness of novel models of care in community-based settings is critical to achieving hepatitis C elimination. We conducted an evaluation of a hepatitis C model of care with financial incentives that aimed to improve engagement across the hepatitis C cascade of care at a sexual health service in Cairns, Australia. METHODS: Between March 2020 and May 2021, financial incentives were embedded into an established person-centred hepatitis C model of care at Cairns Sexual Health Service. Clients of the Service who self-reported experiences of injecting drugs were offered an AUD 20 cash incentive for hepatitis C testing, treatment initiation, treatment completion, and test for cure. Descriptive statistics were used to describe retention in hepatitis C care in the incentivised model. They were compared to the standard of care offered in the 11 months prior to intervention. RESULTS: A total of 121 clients received financial incentives for hepatitis C testing (antibody or RNA). Twenty-eight clients were hepatitis C RNA positive, of whom 92% (24/28) commenced treatment, 75% (21/28) completed treatment, and 68% (19/28) achieved a sustained virological response (SVR). There were improvements in the proportion of clients diagnosed with hepatitis C who commenced treatment (86% vs. 75%), completed treatment (75% vs. 40%), and achieved SVR (68% vs. 17%) compared to the pre-intervention comparison period. CONCLUSIONS: In this study, financial incentives improved engagement and retention in hepatitis C care for people who inject drugs in a model of care that incorporated a person-centred and flexible approach.

Comprehensive assessment of circulatory miRNAs as potential diagnostic markers in HCV recurrence post liver transplantation.

HCV recurrence after liver transplantation is one of the causal agents for graft rejection. This study aims to profile non-invasive biomarkers in patients with HCC who had liver transplants. One hundred participants were categorized into three groups (20 control, 32 recurrent HCV (RHCV), and 48 non-RHCV). The expression of six miRNAs (hsa-miR-124-3p, hsa-miR-155-5p, hsa-miR-205-5p, hsa-miR-499a-5p, hsa-miR-574-3p, and hsa-miR-103a-3p) and two mRNAs IL-1ß, STAT1 were quantified. RHCV group has higher levels of hsa-miR-574-3p and hsa-miR-155-5p and lesser levels of hsa-miR-499a-5p than control groups (p = 0.024, 0.0001, 0.002; respectively). RHCV and non-RHCV groups revealed a significant reduction in levels of IL-1ß and STAT1 mRNA compared to the control (p = 0.011, 0.014; respectively). According to ROC analysis, miR-155-5p can differentiate among the patients' groups, while miR-574-3p, IL-1ß, and STAT1 mRNA can discriminate between RHCV and control groups. In conclusion, RHCV patients have dysregulated expression of five transcripts compared to non-RHCV and control groups.

Epidemiology of acute hepatitis C and hepatitis C virus-related cirrhosis in reproductive-age women, 1990-2019: An analysis of the Global Burden of Disease study.

Background: The current study uniquely focuses on the global incidence and temporal trends of acute hepatitis C (AHC) and hepatitis C virus (HCV)-related cirrhosis among women of reproductive age (15-49 years) from 1990-2019. The risk of vertical transmission and adverse perinatal outcomes associated with HCV infection underscores the importance of prioritising these women in HCV prevention efforts. Methods: Leveraging the Global Burden of Disease 2019 data, we calculated age-standardised incidence rates (ASIR) and assessed temporal trends via the average annual percent change from joinpoint regression. The age-period-cohort model was employed to understand further the effects of age, period, and birth cohort. Results: Over the 30 years, global incidences of AHC and HCV-related cirrhosis in reproductive-age women increased by 46.45 and 72.74%, respectively. The ASIR of AHC was highest in low sociodemographic index regions but showed a declining trend. Conversely, the ASIR of HCV-related cirrhosis displayed unfavourable trends in low, low-middle, and high sociodemographic index regions. Special attention is necessary for sub-Saharan Africa, high-income North America, Eastern Europe, and Central Asia due to their high incidence rates or increasing trends of AHC and HCV-related cirrhosis. Notably, the age-period-cohort model suggests a recent resurgence in AHC and HCV-related cirrhosis risk. Conclusions: The current study is the first to thoroughly evaluate the trends of AHC and HCV-related cirrhosis among reproductive-age women, shedding light on previously unexplored aspects of HCV epidemiology. Our findings identify critical areas where health care systems must adapt to the changing dynamics of HCV infection. The detailed stratification by region and nation further enables the development of localised prevention and treatment strategies.

Changes in Use of Hepatitis C Direct-Acting Antivirals After Access Restrictions Were Eased by State Medicaid Programs.

Importance: Direct-acting antivirals (DAAs) are safe and highly effective for curing hepatitis C virus (HCV) infection, but their high cost led certain state Medicaid programs to impose coverage restrictions. Since 2015, many of these restrictions have been lifted voluntarily in response to advocacy or because of litigation. Objective: To estimate how the prescribing of DAAs to Medicaid patients changed after states eased access restrictions. Design, Setting, and Participants: This modified difference-in-differences analysis of 39 state Medicaid programs included Medicaid beneficiaries who were prescribed a DAA from January 1, 2015, to December 31, 2019. DAA coverage restrictions were measured based on a series of cross-sectional assessments performed from 2014 through 2022 by the US National Viral Hepatitis Roundtable and the Center for Health Law and Policy Innovation. Exposure: Calendar quarter when states eased or eliminated 3 types of DAA coverage restrictions: limiting treatment to patients with severe liver disease, restricting use among patients with active substance use, and requiring prescriptions to be written by or in consultation with specialists. States with none of these restrictions at baseline were excluded. Main Outcomes and Measures: Quarterly number of HCV DAA treatment courses per 100 000 Medicaid beneficiaries. Results: Of 39 states, 7 (18%) eliminated coverage restrictions, 25 (64%) eased restrictions, and 7 (18%) maintained the same restrictions from 2015 to 2019. During this period, the average quarterly use of DAAs increased from 669 to 3601 treatment courses per 100 000 Medicaid beneficiaries. After states eased or eliminated restrictions, the use of DAAs increased by 966 (95% CI, 409-1523) treatment courses per 100 000 Medicaid beneficiaries each quarter compared with states that did not ease or eliminate restrictions. Conclusions and Relevance: The results of this study suggest that there was greater use of DAAs after states relaxed coverage restrictions related to liver disease severity, sobriety, or prescriber specialty. Further reductions or elimination of these rules may improve access to a highly effective public health intervention for patients with HCV.

Cost effectiveness of hepatitis C direct acting agents.

INTRODUCTION: Introduction of direct acting antivirals (DAA) has transformed treatment of chronic hepatitis C (HCV) and made the elimination of HCV an achievable goal set forward by World Health Organization by 2030. Multiple barriers need to be overcome for successful eradication of HCV. Availability of pan-genotypic HCV regimens has decreased the need for genotype testing but maintained high efficacy associated with DAAs. AREAS COVERED: In this review, we will assess the cost-effectiveness of DAA treatment in patients with chronic HCV disease, with emphasis on general, cirrhosis, and vulnerable populations. EXPERT OPINION: Multiple barriers exist limiting eradication of HCV, including cost to treatment, access, simplified testing, and implementing policy to foster treatment for all groups of HCV patients. Clinically, DAAs have drastically changed the landscape of HCV, but focused targeting of vulnerable groups is needed. Public policy will continue to play a strong role in eliminating HCV. While we will focus on the cost-effectiveness of DAA, several other factors regarding HCV require on going attention, such as increasing public awareness and decreasing social stigma associated with HCV, offering universal screening followed by linkage to treatment and improving preventive interventions to decrease spread of HCV.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

[Cost-effectiveness of HCV testing strategies for hepatitis C elimination in general population in China].

Objective: To evaluate the cost-effectiveness of hepatitis C screening in general population in China, and find the age group in which hepatitis C screening can achieve the best cost-effectiveness. Methods: A decision-Markov model was constructed by using software TreeAge pro 2019 to simulate the outcomes of hepatitis C disease pregression of 100 000 persons aged 20-59 years. The cost-effectiveness of the strategies were evaluated from societal perspectives by using incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). One-way sensitivity analysis and probability sensitivity analysis were used to evaluate the uncertainty of parameters and model. Results: Hepatitis C screening was cost-effective in people aged 20- 59 years and the cost effectiveness was best in age group 40-49 years. Compared with non-screening strategy of hepatitis C in people aged 20-59 years, the incremental cost was 161.24 yuan, the incremental utility was 0.003 6 quality adjusted life years (QALYs)/per person, ICER was 45 197.26 yuan/QALY, ICER was less than the willing payment threshold. The ICER and NMB in all age groups were 42 055.06-53 249.43 yuan/QALY and 96.52-169.86 yuan/per person. Hepatitis C screening in people aged 40-49 years had the best cost-effectiveness. The results of one-way sensitivity analysis showed that the discount rate, anti-HCV detection cost, anti-HCV infection rate and the cost of direct antiviral agents were the main factors influencing economic evaluation. The results of the probability sensitivity analysis indicated that the model analysis was stable. Conclusions: Implementing hepatitis C screening based on medical institutions is cost-effective in people aged 20- 59 years, especially in those aged 40-49 years. Implementing the HCV screening strategy of be willing to test as far as possible in general population can reduce hepatitis C disease burden in China.

Kentucky Outreach Service Kiosk (KyOSK) Study protocol: a community-level, controlled quasi-experimental, type 1 hybrid effectiveness study to assess implementation, effectiveness and cost-effectiveness of a community-tailored harm reduction kiosk on HIV, HCV and overdose risk in rural Appalachia.

INTRODUCTION: Many rural communities bear a disproportionate share of drug-related harms. Innovative harm reduction service models, such as vending machines or kiosks, can expand access to services that reduce drug-related harms. However, few kiosks operate in the USA, and their implementation, impact and cost-effectiveness have not been adequately evaluated in rural settings. This paper describes the Kentucky Outreach Service Kiosk (KyOSK) Study protocol to test the effectiveness, implementation outcomes and cost-effectiveness of a community-tailored, harm reduction kiosk in reducing HIV, hepatitis C and overdose risk in rural Appalachia. METHODS AND ANALYSIS: KyOSK is a community-level, controlled quasi-experimental, non-randomised trial. KyOSK involves two cohorts of people who use drugs, one in an intervention county (n=425) and one in a control county (n=325). People who are 18 years or older, are community-dwelling residents in the target counties and have used drugs to get high in the past 6 months are eligible. The trial compares the effectiveness of a fixed-site, staffed syringe service programme (standard of care) with the standard of care supplemented with a kiosk. The kiosk will contain various harm reduction supplies accessible to participants upon valid code entry, allowing dispensing data to be linked to participant survey data. The kiosk will include a call-back feature that allows participants to select needed services and receive linkage-to-care services from a peer recovery coach. The cohorts complete follow-up surveys every 6 months for 36 months (three preceding kiosk implementation and four post-implementation). The study will test the effectiveness of the kiosk on reducing risk behaviours associated with overdose, HIV and hepatitis C, as well as implementation outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: The University of Kentucky Institutional Review Board approved the protocol. Results will be disseminated in academic conferences and peer-reviewed journals, online and print media, and community meetings. TRIAL REGISTRATION NUMBER: NCT05657106.

Hepatitis C virus antibody seropositivity is associated with albuminuria but not peripheral artery disease in patients with type 2 diabetes.

Hepatitis C virus (HCV) infection is prevalent in patients with type 2 diabetes mellitus (DM). We aimed to investigate whether HCV antibody (Ab) seropositivity is associated with diabetic micro- and macro-vascular diseases. In this hospital-based cross-sectional study, we retrospectively collected data from patients who participated in the diabetes pay-for-performance program and underwent HCV Ab screening in the annual comprehensive assessment between January 2021 and March 2022. We examined the relationships of HCV Ab seropositivity with the spot urinary albumin-to-creatinine ratio (UACR) and ankle-brachial index (ABI) in patients aged ≥ 50 years with type 2 DM. A total of 1758 patients were enrolled, and 85 (4.83%) of the enrolled patients had HCV Ab seropositivity. Multivariable regression analyses revealed that albuminuria showed a dose-dependent association with HCV Ab seropositivity (UACR [30-299 mg/g]: odds ratio [OR] = 1.463, 95% confidence interval [CI] 0.872‒2.456); UACR [≥ 300 mg/g]: OR = 2.300, 95% CI 1.160‒4.562; P for trend = 0.015) when compared with normal albuminuria (UACR < 30 mg/g). However, the proportion of patients with peripheral arterial disease, defined as an ABI ≤ 0.9, was not significantly different between the groups with and without HCV Ab seropositivity (3.5% vs. 3.9%, P = 0.999). In conclusion, severely increased albuminuria, but not the ABI, showed a significant association with HCV Ab seropositivity in patients aged ≥ 50 years with type 2 DM.

Real-world economic burden of hepatitis C and impact of direct-acting antivirals in France: A nationwide claims data analysis.

BACKGROUND AND AIMS: The economic impact of managing patients with hepatitis C virus (HCV) infection remains unknown. This study aimed to assess the economic burden of chronic HCV infection from a national health insurance perspective and the impact of direct-acting antivirals (DAAs) using nationwide real-world data. METHODS: Patients with chronic HCV infection were identified from the French Health Insurance Claims Databases (SNDS) and matched for age and sex to the general population. Health resource utilization and reimbursements were summarized according to healthcare expenditure items from 2012 to 2021. The economic burden attributable to chronic HCV infection was evaluated over a 10-year period. Finally, the impact of DAAs was estimated using economic data derived from the SNDS. RESULTS: A total of 145 187 patients with chronic HCV infection were identified. Among the patients eligible for DAA therapy, 81.5% had received DAA by the end of 2021. Over a 10-year period, managing patients with chronic HCV infection resulted in an additional cost of €9.71 billion (95% confidence interval [CI]: €9.66-€9.78 billion) or €9191 (95% CI: €9134-€9252) per patient per year compared to the general population. After DAA therapy, patients with chronic HCV infection had a higher economic burden than the general population, with an additional cost of €5781 (95% CI: €5540-€6028) per patient at the fifth-year post-DAA therapy. CONCLUSIONS: A significant economic burden persists among patients with HCV infection after DAA treatment. The high proportion of patients not treated with DAA therapy supports reinforcing policies for universal access.

Universal screening and treatment towards the elimination of chronic hepatitis C in China: an economic evaluation.

OBJECTIVES: China has the largest number of hepatitis C virus (HCV) infection in the world, but current levels of diagnosis and treatment are low. The objective of this study was to assess the cost-effectiveness of various universal HCV screening and treatment strategies in China and inform decisions on health policy. STUDY DESIGN: A cost-effectiveness analytical study. METHODS: We developed a Markov model to investigate cost-effectiveness of different HCV screening and treatment strategies in China. We simulated several screening scenarios for Chinese people aged 18-70 years. We estimated incremental cost-effectiveness ratios (ICERs) of different intervention scenarios compared with status quo. RESULTS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups (Scenario S5) was the most cost-effective strategy (ICER: USD $11,667.71/quality-adjusted life-year [QALY] gained), which resulted in great reduction in HCV-related diseases and deaths, with a 67.11% reduction in cases of chronic HCV. Universal HCV screening and treatment implementation remains a cost-effective strategy when delayed until 2025 (ICER: USD $17,093.69/QALY), yet the delayed strategy is less effective in reducing HCV-related deaths. CONCLUSIONS: Expanded HCV screening and treatment strategy with prioritisation for high-risk groups is the most cost-effective strategy and has lead to a significant reduction in both HCV morbidity and mortality in China, which would essentially eliminate HCV as a public threat.

Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Exploring azomethine ylides reactivity with acrolein through cycloaddition reaction and computational antiviral activity assessment against hepatitis C virus.

CONTEXT: The regioselectivity and diastereoselectivity of the 1,3-dipolar cycloaddition reaction between azomethine ylides and acrolein were investigated. The DFT studies revealed that the favored pathway leads to the formation of cis-cycloadduct pyrrolidine and these computational findings align with experimental observations. The cis-cycloadduct pyrrolidine product serves as an advanced intermediate in the synthesis of a hepatitis C virus inhibitor. For this, the antiviral activity of cis-cycloadduct pyrrolidine against cyclophilin A, the co-factor responsible for hepatitis C virus, was also evaluated through molecular docking simulations which revealed intriguing interactions and a high C-score, which were further confirmed by molecular dynamics simulations, demonstrating stability over a 100-ns simulation period. Furthermore, the cis-cycloadduct pyrrolidine exhibits favorable drug-like properties and a better ADMET profile compared to hepatitis C virus inhibitor. METHODS: Chemical reactivity studies were performed using DFT method by the functional B3LYP at 6-31G (d, p) computational level by GAUSSIAN 16 program. Frontal molecular orbitals theory used to investigate HOMO/LUMO interactions between azomethine ylides and acrolein. Findings of this approach were confirmed by global reactivity indices and electron displacement was investigated based on Fukui functions. Furthermore, the activation energies were determined after frequency calculations using TS Berny algorithm and transition states were confirmed by the presence of a single imaginary frequency. Moreover, antiviral activity of cis-cycloadduct was explored through molecular docking using Surflex-Dock suite SYBYL X 2.0, and molecular dynamics simulation using GROMACS program. Finally, drug-like properties were investigated with SwissADME and ADMETlab 2.0.

Treating Hepatitis C Before Total Knee Arthroplasty is Cost-Effective: A Markov Analysis.

BACKGROUND: Patients who have the hepatitis C virus (HCV) have increased mortality and complication rates following total knee arthroplasty (TKA). Recent advances in HCV therapy have enabled clinicians to eradicate the disease using direct-acting antivirals (DAAs); however, its cost-effectiveness before TKA remains to be demonstrated. The aim of this study was to perform a cost-effectiveness analysis comparing no therapy to DAAs before TKA. METHODS: A Markov model using input values from the published literature was performed to evaluate the cost-effectiveness of DAA treatment before TKA. Input values included event probabilities, mortality, cost, and health state quality-adjusted life-year (QALY) values for patients who have and do not have HCV. Patients who have HCV were modeled to have an increased rate of periprosthetic joint infection (PJI) infection (9.9 to 0.7%). The incremental cost-effectiveness ratio (ICER) of no therapy versus DAA was compared to a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to investigate the effects of uncertainty associated with input variables. RESULTS: Total knee arthroplasty in the setting of no therapy and DAA added 8.1 and 13.5 QALYs at a cost of $25,000 and $114,900. The ICER associated with DAA in comparison to no therapy was $16,800/QALY, below the willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses demonstrated that the ICER was affected by patient age, inflation rate, DAA cost and effectiveness, HCV-associated mortality, and DAA-induced reduction in PJI rate. CONCLUSION: Direct-acting antiviral treatment before TKA reduces risk of PJI and is cost-effective. Strong consideration should be given to treating patients who have HCV before elective TKA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

Socio-economic factors associated with loss to follow-up among individuals with HCV: A Dutch nationwide cross-sectional study.

BACKGROUND AND AIMS: The path to hepatitis C virus (HCV) elimination is complicated by individuals who become lost to follow-up (LTFU) during care, particularly before receiving effective HCV treatment. We aimed to determine factors contributing to LTFU and whether LTFU is associated with mortality. METHODS: In this secondary analysis, we constructed a database including individuals with HCV who were either LTFU (data from the nationwide HCV retrieval project, CELINE) or treated with directly acting antivirals (DAA) (data from Statistics Netherlands) between 2012 and 2019. This database was linked to mortality data from Statistics Netherlands. Determinants associated with being LTFU versus DAA-treated were assessed using logistic regression, and mortality rates were compared between groups using exponential survival models. These analyses were additionally stratified on calendar periods: 2012-2014, 2015-2017 and 2018-2019. RESULTS: About 254 individuals, LTFU and 5547 DAA-treated were included. Being institutionalized (OR = 5.02, 95% confidence interval (CI) = 3.29-7.65), household income below the social minimum (OR = 1.96, 95% CI = 1.25-3.06), receiving benefits (OR = 1.74, 95% CI = 1.20-2.52) and psychiatric comorbidity (OR = 1.51, 95% CI = 1.09-2.10) were associated with LTFU. Mortality rates were significantly higher in individuals LTFU compared to those DAA-treated (2.99 vs. 1.15/100 person-years (PY), p < .0001), while in those DAA-treated, mortality rates slowly increased between 2012-2014 (.22/100PY) and 2018-2019 (2.25/100PY). CONCLUSION: In the Netherlands, individuals who are incarcerated/institutionalized, with low household income, or with psychiatric comorbidities are prone to being LTFU, which is associated with higher mortality. HCV care needs to be adapted for these vulnerable individuals.

Trends and prediction in the incidence rate of hepatitis C in Shandong Province in China from 2004 to 2030.

BACKGROUND: Hepatitis C threatens human health and brings a heavy economic burden. Shandong Province is the second most populous province in China and has uneven regional economic development. Therefore, we analyzed the incidence rate trend and regional differences of hepatitis C in Shandong Province from 2004 to 2021. METHODS: The monthly and annual incidence rates of hepatitis C in Shandong Province from 2022 to 2030 were predicted by fitting Autoregressive Integrated Moving Average model (ARIMA), Long Short-Term Memory (LSTM) and ARIMA-LSTM combined model. RESULTS: From 2004 to 2021, annual new cases of hepatitis C in Shandong Province increased from 635 to 5834, with a total of 61,707 cases. The incidence rate increased from 0.69/100 thousand in 2004 to 6.40/100 thousand in 2019, with a slight decrease in 2020 and 2021. The average annual incidence rate was 3.47/100 thousand. In terms of regional distribution, the hepatitis C incidence rate in Shandong Province was generally high in the west and low in the east. It is estimated that the hepatitis C incidence rate in Shandong Province will be 9.21 per 100 thousand in 2030. CONCLUSION: The hepatitis C incidence rate in Shandong Province showed an increasing trend from 2004 to 2019 and a decreasing trend in 2020 and 2021. Significant regional variations in incidence rate existed. An upward trend in incidence rate is predicted from 2022 to 2030. It is necessary to strengthen the prevention and control of hepatitis C to achieve the goal of eliminating viral hepatitis by 2030.

Incarceration, Inequality, and Hepatitis C Treatment: The Story of Two Southern States.

Hepatitis C virus (HCV) infection causes liver-related morbidity/mortality and disproportionately affects people who are incarcerated and non-Hispanic Black populations, largely due to social and policy issues that contribute to poor health. With the advent of highly efficacious treatment, HCV is now curable. However, most states' departments of corrections do not offer universal HCV testing or treatment. Two southern states-Tennessee and Louisiana-provide examples of divergent approaches to addressing HCV infection. While Tennessee has offered treatment on a limited basis, resulting in a class action lawsuit, the state of Louisiana recently adopted a new approach. In establishing the 2019 Hepatitis Elimination Plan, the state created a standard of care for HCV infection that included robust testing and treatment in state prison facilities while capping costs. Louisiana has demonstrated the feasibility of HCV testing and treatment programs within state prisons, an important step towards achieving health equity.