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Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. The Treg cell population – especially the activated Treg cell subpopulation – was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection. [Display omitted] • Increased Tregs persist in patients with chronic HCV after DAA-induced viral clearance. • DAA-induced HCV clearance does not abrogate inflammatory features of Tregs. • HCV clearance does not reverse inflammatory imprinting in the epigenome of Tregs. • Increased TNF+ Tregs persist in patients with chronic HCV after viral clearance. [ABSTRACT FROM AUTHOR]

There is an increasing burden of hepatitis C virus among persons of reproductive age, including pregnant and breastfeeding women, in many regions worldwide. Routine health services during pregnancy present a critical window of opportunity to diagnose and link women with hepatitis C virus infection for care and treatment to decrease hepatitis C virus-related morbidity and early mortality. Effective treatment of hepatitis C virus infection in women diagnosed during pregnancy also prevents hepatitis C virus-related adverse events in pregnancy and hepatitis C virus vertical transmission in future pregnancies. However, linkage to care and treatment for women diagnosed in pregnancy remains insufficient. Currently, there are no best practice recommendations from professional societies to ensure appropriate peripartum linkage to hepatitis C virus care and treatment. We convened a virtual Community of Practice to understand key challenges to the hepatitis C virus care cascade for women diagnosed with hepatitis C virus in pregnancy, highlight published models of integrated hepatitis C virus services for pregnant and postpartum women, and preview upcoming research and programmatic initiatives to improve linkage to hepatitis C virus care for this population. Four-hundred seventy-three participants from 43 countries participated in the Community of Practice, including a diverse range of practitioners from public health, primary care, and clinical specialties. The Community of Practice included panel sessions with representatives from major professional societies in obstetrics/gynecology, maternal fetal medicine, addiction medicine, hepatology, and infectious diseases. From this Community of Practice, we provide a series of best practices to improve linkage to hepatitis C virus treatment for pregnant and postpartum women, including specific interventions to enhance colocation of services, treatment by nonspecialist providers, active engagement and patient navigation, and decreasing time to hepatitis C virus treatment initiation. The Community of Practice aims to further support antenatal providers in improving linkage to care by producing and disseminating detailed operational guidance and recommendations and supporting operational research on models for linkage and treatment. Additionally, the Community of Practice may be leveraged to build training materials and toolkits for antenatal providers, convene experts to formalize operational recommendations, and conduct surveys to understand needs of antenatal providers. Such actions are required to ensure equitable access to hepatitis C virus treatment for women diagnosed with hepatitis C virus in pregnancy and urgently needed to achieve the ambitious targets for hepatitis C virus elimination by 2030. [Display omitted] [ABSTRACT FROM AUTHOR]

Sarcopenia's impact on post-liver transplant outcomes remains a subject of debate, with limited data from South Asia on its association with post-liver transplant hospital stays. This study aims to investigate sarcopenia's influence on post-transplant hospitalization duration in South Asians. In this retrospective study, patients with liver cirrhosis who underwent living-donor liver transplantation (LDLT) at Shifa International Hospital in Islamabad, Pakistan, between January 2022 and January 2023 were included. Computed tomography (CT) images were used to assess the skeletal muscle index (SMI). The areas of the psoas, erector spinae, multifidus, quadratus lumborum, rectus abdominis, transverse abdominis, and internal/external oblique muscles were quantified at the level of L3. The data were analyzed using SPSS version 29.0 (IBM). There was a total of 84 patients. Mean age was 47.4 ± 12.0 years. There were 62 (73.8%) male patients and 22 (26.2%) female patients. Hepatitis C was noted in 36 (42.9%) patients. Twenty-two (26.2%) patients had hepatocellular carcinoma. Sarcopenia was identified in 58 (69.0%) patients. No significant association was observed between sarcopenia and intensive care unit (ICU) or general floor stays. Regression analysis identified pre-transplant model for end-stage liver disease-sodium (MELD-Na) score as the sole significant factor associated with both ICU and total length of stay (P value.002; P value.009). In our population, sarcopenia did not correlate with post-transplant ICU or overall hospital stay. The pre-transplant MELD-Na score emerged as the most influential predictor of length of stay. Therefore, delaying liver transplant procedures based on muscle mass estimations may not be a practical clinical approach for South Asian patients. [ABSTRACT FROM AUTHOR]

The PKC-related kinases (PRKs, also termed PKNs) are important in cell migration, cancer, hepatitis C infection, and nutrient sensing. They belong to a group of protein kinases called AGC kinases that share common features like a C-terminal extension to the catalytic domain comprising a hydrophobic motif. PRKs are regulated by N-terminal domains, a pseudosubstrate sequence, Rho-binding domains, and a C2 domain involved in inhibition and dimerization, while Rho and lipids are activators. We investigated the allosteric regulation of PRK2 and its interaction with its upstream kinase PDK1 using a chemical biology approach. We confirmed the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF)-mediated docking interaction of PRK2 with PDK1 and showed that this interaction can be modulated allosterically. We showed that the polypeptide PIFtide and a small compound binding to the PIF-pocket of PRK2 were allosteric activators, by displacing the pseudosubstrate PKL region from the active site. In addition, a small compound binding to the PIF-pocket allosterically inhibited the catalytic activity of PRK2. Together, we confirmed the docking interaction and allostery between PRK2 and PDK1 and described an allosteric communication between the PIF-pocket and the active site of PRK2, both modulating the conformation of the ATP-binding site and the pseudosubstrate PKL-binding site. Our study highlights the allosteric modulation of the activity and the conformation of PRK2 in addition to the existence of at least two different complexes between PRK2 and its upstream kinase PDK1. Finally, the study highlights the potential for developing allosteric drugs to modulate PRK2 kinase conformations and catalytic activity. [ABSTRACT FROM AUTHOR]

Between 2013 to 2019, several all-oral direct-acting antivirals (DAAs) were launched with the potential to cure patients with hepatitis C virus (HCV). They generated economic value in terms of the health gains for patients and cost-savings for the US healthcare system. We estimated the share of this value allocated to 4 manufacturers vs society. For 2015 to 2019, we estimated the incremental impact of DAAs on HCV health outcomes and costs. We used the Center for Disease Analysis Foundation Polaris Observatory database to estimate utilization. Per-patient projections of lifetime quality-adjusted life-years (QALYs) gained and medical costs avoided were based on a standard 9-state HCV disease-progression model for DAA treatment vs alternatives. Annual QALY gains were valued at $114 000 per QALY. Outcomes and costs were discounted at 3%. Estimated revenues were based on reported sales. An estimated 1 080 000 patients received DAAs: 81.5% would not have received the pre-DAA standard of care. On average, these patients were projected to gain 4.4 QALYs and save $104 400 in lifetime healthcare costs, generating $531.8 billion in value. Those who would have received treatment gained 1.7 QALYs and saved $41 500 in lifetime costs, generating $47.4 billion in economic value. As treatment costs fell nearly 75%, the 4 manufacturers reported $37.4 billion from DAA sales—an allocation of 6.5% of the total value. The significant majority (∼90%) of the economic value of curing HCV with DAAs were health benefits to patients and net cost-savings to society. DAA manufacturers received a minority share (6.5%) of the aggregate economic value generated. • A recent Value in Health special themed section illustrated the increasing interest in viewing innovative medicines from a product lifecycle perspective to better understand how the economic value is allocated to manufacturers as a reward for innovation vs to others in society. • This article addresses this issue by estimating the share of economic value allocated to the competing manufacturers of direct-acting antivirals (DAAs) during the 2015 to 2019 period after a highly visible launch of a curative product. • Despite initial concerns about the prices of DAAs, competitive pressures reduced the market price of these patent-protected DAAs considerably in the first 5 years. The treatments were net cost saving over the entire 5 years. The cost savings grew as the average DAA regimen cost fell from $55 500 in 2015 to $14 400 in 2019. Over the 5 years, from a health sector perspective, manufacturers received a minority share (6.5%) of the economic value generated. [ABSTRACT FROM AUTHOR]

The objective of this study was to estimate prevalence of hepatitis C virus (HCV) exposure and infection among Indigenous and tribal populations globally. Systematic review and meta-analysis. We systematically searched bibliographic databases and grey literature (1/01/2000–16/06/2022). Prevalence estimates were synthesised overall, by World Health Organization region and HCV-risk group. For studies with comparator populations, prevalence ratios were estimated and pooled. Ninety-two studies were included. Globally, among general Indigenous and tribal populations, the median prevalence of HCV antibody (HCV Ab) was 1.3% (interquartile range [IQR]: 0.3–3.8%, I2 = 98.5%) and HCV RNA was 0.4% (IQR: 0–1.3%, I2 = 96.1%). The Western Pacific Region had the highest prevalence (HCV Ab: median: 3.0% [IQR: 0.4–11.9%], HCV RNA: median 5.6% [IQR: 2.0–8.8%]). Prevalence was highest in people who injected drugs (HCV Ab: median: 59.5%, IQR: 51.5–67.6%, I2 = 96.6%; and HCV RNA: median: 29.4%, IQR: 21.8–35.2%, I2 = 97.2%). There was no association between HCV Ab prevalence and Indigenous/tribal status for general populations (prevalence ratio = 0.91; 95% CI: 0.56, 1.49) or key risk groups. Indigenous and tribal peoples from the Western Pacific Region and recognised at-risk sub-populations had higher HCV prevalence. HCV prevalence showed no association with Indigenous/tribal status. However, this review was limited by heterogeneity and poor quality of constituent studies, varying definitions of Indigenous/tribal status, regional data gaps, and limited studies on chronic infection (HCV RNA). Comprehensive quality evidence on HCV epidemiology in Indigenous and tribal peoples is needed to tailor preventive and treatment interventions so these populations are not left behind in elimination efforts. [ABSTRACT FROM AUTHOR]

Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV. [ABSTRACT FROM AUTHOR]

Assess impact of direct-acting antivirals introduction on outcomes after liver resection for hepatocellular carcinoma. 391 patients (1991–2021) treated with resection for hepatocellular carcinoma on Hepatitis C background were divided according to receiving Hepatitis C treatment, treatment type, achievement of sustained virological response (SVR), time of resection pre- (Era 1, 1991–2011) and post-direct acting antivirals introduction (Era 2, 2012–2021). Survival was estimated with Kaplan–Meier curves, Cox regression analysis performed to identify survival predictors. Majority of patients had single lesion (67.8%), diameter >2 cm in 60.6%, no evidence of macroscopic vascular invasion on imaging. Pathology showed vascular invasion in 69.6% of patients, 76.5% microvascular. Recurrence developed in 247 patients (63.2%). 194 patients (49.6%) achieved SVR. Overall survival at 1-, 3-, 5-years was 94.6%, 85.7%, 78.8% for patients who achieved SVR, 80.1%, 48.1%, 29.9% in those who did not (p < 0.001). 220 patients (56.3%) were in Era 1, 171 (43.7%) in Era 2. Survival at 1-, 3-, 5-years was 76.1%, 49%, 36% in Era 1, 94.5%, 82.5%, 70.3% in Era 2 (p < 0.001). SVR was an independent predictor of survival on multiple Cox Regression analysis. While many aspects of HCC management have evolved, SVR following direct-acting antivirals independently improves HCC resection outcomes. [ABSTRACT FROM AUTHOR]

In 2018, Rwanda launched a national program to eliminate the hepatitis C virus (HCV). We aim to assess the impact of the program to date and identify strategies to achieve the World Health Organization's HCV elimination goals by 2030. We developed a microsimulation model to simulate Rwanda's HCV epidemic from 2015 through 2050 and evaluated temporal trends in HCV infection, prevalence, mortality, and the total cost of care for scenarios that could achieve HCV elimination by 2030. Between 2018 and 2022, over 7 million people were screened for HCV, and 60 000 were treated. The study projected that Rwanda could achieve HCV elimination as early as 2027. A feasible strategy of an annual screening rate of 15% and a treatment rate of 100% would achieve all World Health Organization elimination goals by 2028, requiring screening an additional 4 million people and treating 23 900 patients by 2030. The elimination strategy costs $25 million for screening and diagnosis and $21 million for treatment from 2015 to 2050. The national program would avert 4900 hepatocellular carcinoma cases and 6700 HCV-related deaths and save the health system $25.33 million from 2015 to 2050. Rwanda is poised to become one of the first countries in the world to eliminate HCV. Rwanda's program serves as a blueprint for other countries in the African region. By rapid screening and treatment scale-up (eg, by leveraging HIV platforms) and by drug price negotiations, HCV elimination is not only feasible but can be cost-saving in low-income settings. • Existing knowledge: in 2018, Rwanda initiated a national program to combat hepatitis C virus (HCV), aiming to align with the World Health Organization's goal of elimination by 2030. • Paper's contribution: this study reveals that between 2018 and 2022, Rwanda successfully screened over 7 million individuals for HCV and treated 60 000. If Rwanda continue the elimination efforts and can potentially be on track to eliminate HCV by 2027, 3 years ahead of the World Health Organization target. • Insights for healthcare decision making: by emphasizing the importance of rapid screening and treatment expansion, the article highlights the feasibility of HCV elimination, especially in low-income settings, in which leveraging drug price negotiations can not only achieve elimination but also generate substantial health system savings estimated at $25.33 million from 2015 to 2050. Rwanda's approach can serve as a valuable model for other nations in the region. [ABSTRACT FROM AUTHOR]

This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. This was a modified Delphi process. We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of the COVID-19 pandemic on national surveillance of viral hepatitis in Italy. Interrupted time series analysis. Using an interrupted time series analysis with a customised AutoRegressive Integrated Moving Average model on hepatitis cases reported to the Integrated Epidemiological System of Acute Viral Hepatitis from 2006 to 2022, we examined trends in incidence, time to diagnosis and time to epidemiological investigations for hepatitis A, hepatitis B and hepatitis C. The quarterly incidence of hepatitis B (−0.251, P = 0.05) and hepatitis C (−0.243, P = 0.003) significantly decreased with the onset of the pandemic. Surveillance times for hepatitis B (5.496, P < 0.001) and hepatitis C (35.723, P < 0.001), measured as days lost per quarter, significantly increased 12 and 24 months after the pandemic's start. This aligns with a notable rise in quarterly incidence at 36 months for both (0.032, P = 0.030 for hepatitis B; 0.040, P < 0.001 for hepatitis C). The decrease in reported cases could be due to an increase in infection prevention control and containment measures put in place in a pandemic context. However, a delay in the initiation of epidemiological investigations was observed, which could lead to a further increase in incidence in the future. [ABSTRACT FROM AUTHOR]

Baveno VII has defined a clinically significant (i.e. , prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. We retrospectively analysed patients with cACLD (LSM ≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV cure by interferon-free therapies from 15 European centres. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. A total of 2,335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1,002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM change of -5.3 (-8.8 to -2.4) kPa corresponding to -33.9 (-48.0 to -15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p <0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5-year cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5-year cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM decrease of ≥20% (p = 0.550). FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. Liver stiffness measurement (LSM) is increasingly applied as a prognostic biomarker and commonly decreases in patients with compensated advanced chronic liver disease achieving HCV cure. Although Baveno VII proposed criteria for a clinically significant decrease, little is known about the prognostic utility of LSM dynamics (changes through antiviral therapy). Interestingly, in those with a post-treatment LSM of 10-19.9 kPa, LSM dynamics did not provide incremental information, arguing against the consideration of LSM dynamics as prognostic criteria. Thus, post-treatment LSM should guide the management of patients with compensated advanced chronic liver disease achieving HCV cure. [Display omitted] • Post-treatment LSM is key for risk stratification in patients with compensated advanced chronic liver disease after HCV-cure. • Changes in LSM during treatment do not hold significant prognostic information in patients with follow-up LSM of 10-19.9 kPa. • Thus, consideration of LSM dynamics is not of sufficient incremental value in the context of HCV-cure. • Post-treatment LSM should be used to guide clinical decision making. [ABSTRACT FROM AUTHOR]

African Americans have the highest prevalence of chronic Hepatitis C virus (HCV) infection. Racial disparities in outcome are observed after elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). This study sought to identify if disparities in treatments and outcomes exist between Black and White patients who have HCV prior to elective THA and TKA. Patient demographics, comorbidities, HCV characteristics, perioperative variables, in-hospital outcomes, and postoperative complications at 1-year follow-up were collected and compared between the 2 races. Patients who have preoperative positive viral load (PVL) and undetectable viral load were identified. Chi -square and Fisher's exact tests were used to compare categorical variables, while 2-tailed Student's Kruskal-Wallis t -tests were used for continuous variables. A P value of less than.05 was statistically significant. The liver function parameters, including aspartate aminotransferase and model for end-stage liver disease scores, were all higher preoperatively in Black patients undergoing THA (P =.01; P <.001) and TKA (P =.03; P =.003), respectively. Black patients were more likely to undergo THA (65.8% versus 35.6%; P =.002) and TKA (72.1% versus 37.3%; 0.009) without receiving prior treatment for HCV. Consequently, Black patients had higher rates of preoperative PVL compared to White patients in both THA (66% versus 38%, P =.006) and TKA (72% versus 37%, P <.001) groups. Black patients had a longer length of stay for both THA (3.7 versus 3.3; P =.008) and TKA (4.1 versus 3.0; P =.02). The HCV treatment prior to THA and TKA with undetectable viral load has been shown to be a key factor in mitigating postoperative complications, including joint infection. We noted that Black patients were more likely to undergo joint arthroplasty who did not receive treatment and with a PVL. While PVL rates decreased over time for both races, a significant gap persists for Black patients. [ABSTRACT FROM AUTHOR]

Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management. [ABSTRACT FROM AUTHOR]

Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be provided quickly in the event of an overdose. OPCs are programs that are established in Canada and have recently become legally sanctioned in only a few United States jurisdictions. We conducted a systematic review that summarizes and identifies gaps of economic evidence on establishing OPCs in North America to guide future expansion of OPCs. We included 16 final studies that were evaluated with the Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists. Eight studies reported cost-effectiveness results (eg, cost per overdose avoided or cost per quality-adjusted life-year), with 6 also including cost-benefit; 5 reported only cost-benefit results, and 3 cost offsets. Health outcomes primarily included overdose mortality outcomes or HIV/hepatitis C virus infections averted. Most studies used mathematical modeling and projected OPC outcomes using the experience of a single facility in Vancouver, BC. OPCs were found to be cost-saving or to have favorable cost-effectiveness or cost-benefit ratios across all studies. Future studies should incorporate the experience of OPCs established in various settings and use a greater diversity of modeling designs. • Overdose prevention centers (OPCs) help to provide a safe space for people who use drugs and provide essential public health services that can help reduce opioid overdose fatalities. There is scant health economic evidence on OPCs and no systematic review. • This systematic review found the optimal number of OPCs varied within the studies, but all suggested opening at least 1 OPC as economically viable. • The findings from this review suggest that jurisdictions looking for strategies to stem the opioid overdose crisis should establish budgets for supporting OPCs in North America because they are projected to result in favorable economic and health impact. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR. Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined. The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04–1.16; p <0.001) even among participants with ≥14 consecutive missed days. High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR. People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers. NCT02824640. [Display omitted] • The recent US nationwide HERO RCT study randomized 755 PWIDs living with HCV. • Electronic blister packs measured day-by-day adherence to 12-week DAA regimen. • Greater adherence is associated with SVR among those with <50% adherence rate. • Treatment interruption and early discontinuation are associated with lower SVR. • High SVR (>90%) can be achieved even with adherence as low as 50%. [ABSTRACT FROM AUTHOR]

/Purpose: To achieve the World Health Organization goal of eliminating viral hepatitis by 2030, a key strategy in resource-limited areas is to identify the areas with high prevalence and to prioritize screening and treatment intervention. We hypothesized that a hospital-based laboratory database could be used to estimate the township- and village-specific anti-hepatitis C virus (HCV) prevalence. Yunlin County Public Health Bureau has been collecting anti-HCV test data from eight major hospitals. Township- and village-specific screening testing rates and anti-HCV prevalence were calculated for residents 40 years or older. A township with a wide range of anti-HCV prevalence rates was selected for outreach universal screening and for validating the village-specific prevalence of anti-HCV in the analysis of the data from the hospitals. The overall anti-HCV screening testing rate in Yunlin County was 30.4 %, whereas the anti-HCV prevalence rate for persons 40 years or older was 15.4 %. The village-specific anti-HCV prevalence rates ranged from 3.8 % to 85.8 %. Community-based screening was conducted in Kouhu Township. The village-specific anti-HCV prevalence rates ranged from 0 % to 18.8 %. Three of the four villages had the highest village-specific anti-HCV prevalence in the community-based study and the hospital-based study. Additionally, 95.8 % of the new HCV cases detected by universal screening received anti-HCV therapy. The hospital-based database provided a framework for identifying the villages with high anti-HCV prevalence. Additionally, community-based universal screening should be prioritized for villages with high prevalence in hospital-based databases. [ABSTRACT FROM AUTHOR]

• This retrospective study investigated the risk factors for developing metabolic syndrome components after liver transplantation. • Diabetes mellitus was associated with every component of metabolic syndrome after liver transplantation. • Preoperative abdominal aortic calcification was associated with the development of metabolic syndrome components after liver transplantation. This study aimed to assess the risk factors for components of metabolic syndrome, such as diabetes mellitus, hypertension, and dyslipidemia, more than a year after liver transplantation. This study included 164 patients with liver failure secondary to acute and chronic liver disease or hepatocellular carcinoma who underwent liver transplantation between 2000 and 2019. Univariate and multivariate analyses were performed to identify the risk factors associated with metabolic syndrome components after liver transplantation. The median follow-up period was 10.5 years. Of the 164 patients who underwent liver transplantation, 144 (87.8%) developed components of metabolic syndrome after liver transplantation. The most common cause of liver failure was hepatitis C virus infection (34.1%). The incidence of hepatocellular carcinoma was 36.0%. In univariate analysis, preoperative diabetes mellitus was a significantly more common component of metabolic syndrome than the others. In multivariate analysis, preoperative abdominal aortic calcification was a risk factor for the new onset of all components of metabolic syndrome after liver transplantation, despite the varying degree of calcification at risk of development (odds ratio for diabetes mellitus = 3.487, P =.0069; odds ratio for hypertension = 2.914, P =.0471; odds ratio for dyslipidemia = 3.553, P =.0030). Preoperative abdominal aortic calcification was significantly associated with the development of each metabolic syndrome component after liver transplantation. [ABSTRACT FROM AUTHOR]

The need to expand the pool of available organs for transplantation has meant that the use of marginal organs is increasingly widespread. The advent of antiviral therapy for hepatitis C virus (HCV) has made it possible to consider the donation of organs from HCV-positive donors and even from viremic donors. In HCV-positive to HCV-negative antibody donor transplantation, the development of antibodies to HCV is uneven, depending on the organ transplanted and with differences in the time of appearance. Whether the subsequent disappearance is attributed to the development of antibodies or the transmission of immunity between donor and recipient remains unclear. In transplantation from an HCV-infected donor to a HCV-seronegative recipient, the administration of antiviral therapy to the recipient before transplantation or a few days after transplantation achieves sustained response in almost all cases. We wanted to deepen the argument by studying the data in the literature, focusing on kidney transplantation, considering that this could be of interest, particularly for possible long-term renal damage. HCV infection both ongoing and previous, as well as the presence of HCV antibodies alone, can be responsible for kidney damage. Direct-acting anti-HCV therapy has revolutionized the treatment of HCV disease and the therapeutic possibilities of transplantation. However, we believe it is useful to keep in mind the pathophysiology of HCV-related damage especially in patients with a long life expectancy, using all emerging strategies to minimize the risk of transmission of infection or development of viremia. [ABSTRACT FROM AUTHOR]

There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We evaluated the HRQoL and associated factors among a cohort of PWID in Australia. Participants were enrolled in an observational cohort study (the Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study) from May 2018 to September 2019 (wave 1) and November 2019 to June 2021 (wave 2). Participants completed the EQ-5D-5L survey at enrolment. Two-part models were used to assess the association of clinical and socioeconomic characteristics with EQ-5D-5L scores. Among 2395 participants (median age, 43 years; 66% male), 65% reported injecting drug use in the past month, 20% had current hepatitis C virus (HCV) infection, and 68% had no/mild liver fibrosis (F0/F1). Overall, the mean EQ-5D-5L and EQ-visual analog scale scores were 0.78 and 57, respectively. In adjusted analysis, factors associated with significantly lower EQ-5D-5L scores include older ages, female (marginal effect = −0.03, P =.014), being homeless (marginal effect = −0.04, P =.040), and polysubstance use (marginal effect = −0.05, P <.001). Factors associated with significantly higher EQ-5D-5L scores were being Aboriginal/Torres Strait Islander (marginal effect = 0.03, P =.021) and recent injecting drug use in the past 12 months. Current HCV infection and liver fibrosis stage were not associated with reduced HRQoL among the study participants. PWID experienced a lower HRQoL compared with the general population. Further research is needed to understand HRQoL in this population to facilitate the development of multifaceted care models for PWID beyond HCV cure and inform health economic analyses for identifying optimal health strategies for PWID. • There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). Previous studies reporting health utility scores for PWID have been limited by either small sample sizes or the lack of health utility information stratified by important subgroups, such as hepatitis C virus (HCV) infection status and liver disease staging. • PWID in this study experienced a lower HRQoL compared with the general population. Factors associated with lower EQ-5D-5L scores included older ages, being female, being homeless and polysubstance use. However, EQ-5D-5L could not discriminate between participants with different stages of liver disease, nor between participants with and without HCV infection. • This study has provided health utility scores among PWID to inform health economic analyses for identifying optimal health strategies to enhance HCV elimination and improve health outcomes among this population. Further research is needed to validate the use of EQ-5D-5L among PWID and understand factors associated with lower HRQoL. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. Cost-effectiveness Analysis; Level III. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has reached a turning point. The non-pharmaceutical interventions for preventing COVID-19 are lifting. Vaccination uptake is increasing in general, but this strategy is continuously challenged by the rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of note, the Omicron subvariants spread globally for at least one year, and the most recently developed subvariants show strong immune evasion to preexisting immunity, either from previous infection, vaccination or both. Therefore, early and appropriate antiviral agents to treat patients at risk for severe COVID-19 or death is crucial to decrease morbidities and mortalities, to restore the healthcare capacities and to facilitate a return to the new normal. Current antiviral therapy for COVID-19 consist of neutralizing monoclonal antibodies (mAbs) and direct antiviral agents. Each agent has been proved for early ambulatory treatment of COIVD-19, but suffer from variable effectiveness and limitations due to patients' comorbidities, drug properties, or antiviral resistance. Besides, some specific mAbs are indicated for prophylaxis of COVID-19 before or after close contact with confirmed COVID-19 patients. This review article summarizes the evidence and unmet needs of the currently available antiviral agents for management of COVID-19 in the context of the Omicron subvariants. [ABSTRACT FROM AUTHOR]

Direct-acting antiviral agents (DAAs) have shown higher cure rates for treating hepatitis C virus (HCV) by directly interfering with different steps of the HCV life cycle. To optimize drug combinations and accurately quantify the antiviral effect of DAAs treatments, mathematical models should include the intracellular virus replication processes. In this study, we develop a two-strain multiscale age-structured model that includes intracellular viral RNA replication and extracellular viral infection. We prove the existence, positivity, and boundedness of the solution, and derive the conditions for the existence and stability of the three steady states (non-infection steady state, boundary steady state, and coexistence steady state). Under certain biologically reasonable assumptions, we obtain the approximate solutions of the viral load decline of the two virus strains (sensitive and drug-resistant virus strains) during treatment, and the long-term approximation is shown to be in good agreement with the solution of the original model. We also carry out numerical simulations using the long-term approximate solution, providing insights into the influence of antiviral effects on the viral load change of the two virus strains during treatment with DAAs. • A multiscale mixed-ODE-PDE model is developed to study HCV infection. • The model includes intracellular RNA replication and extracellular viral infection. • We studied the existence and stability of the three steady states. • The approximate analytical solution is convenient for data comparison. [ABSTRACT FROM AUTHOR]

Le virus de l'hépatite C (VHC) est un virus à ARN hépatotrope, capable d'établir des infections aiguës et chroniques chez l'humain. Le VHC induit dans la majorité des cas une infection persistante à l'origine d'une hépatite chronique associée à des degrés divers à une activité nécrotico-inflammatoire et à une fibrose hépatique. Les principales complications sont la cirrhose et le carcinome hépatocellulaire (CHC) à l'origine de près de 270 000 décès dans le monde chaque année. Le développement de thérapies antivirales puissantes et bien tolérées et la mise à disposition de nouveaux outils virologiques ont révolutionné la prise en charge. Au regard des objectifs de l'Organisation mondiale de la santé (OMS), il est urgent de simplifier et d'élargir le dépistage et le diagnostic de l'infection par le VHC, de simplifier le parcours de soins et d'augmenter l'accès au traitement. Hepatitis C virus (HCV) is a hepatotropic RNA virus capable of establishing acute and chronic infections in humans. In the majority of cases, HCV induces persistent infections leading to chronic hepatitis, associated to various degrees with necrotic-inflammatory activity and hepatic fibrosis. The main complications are cirrhosis and hepatocellular carcinoma (HCC), responsible for almost 270,000 deaths a year world-wide.The development of potent, well-tolerated antiviral therapies and the availability of new virological tools have revolutionized management of hepatitis C infection. In line with the objectives of the World Health Organization (WHO), there is an urgent need to simplify and expand screening and diagnosis of HCV infection, simplify the cascade of care and increase access to antiviral treatment. [ABSTRACT FROM AUTHOR]

Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous clinical studies. This trial evaluates the pharmacokinetics of 400 μg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 μg. Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 μg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed. T max was 154.003 h and T 1/2 was 114.273 h. The C max was 29.823 ng mL−1. AUC last was 9364.292 h∗ng mL−1 and AUC inf was 11084.317 h∗ng mL−1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL−1. Ropeginterferon alfa-2b at 400 μg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 μg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications. [ABSTRACT FROM AUTHOR]

Here, we describe a rare case of malignant lymphoma after liver transplantation for liver cirrhosis caused by human immunodeficiency virus (HIV) and hepatitis C virus (HCV) co-infection. A male patient was diagnosed with hemophilia A at 8 months of age. Since then, he had been receiving blood products, which led to HIV and HCV co‐infection. His HIV viral load was suppressed with antiretroviral therapy, and a sustained virologic response was achieved for HCV using direct-acting antivirals. However, his decompensated liver cirrhosis progressed, and deceased donor liver transplantation was performed. A post-transplant lymphoproliferative disorder (PTLD) developed 105 days after liver transplantation, with enlarged para-aortic and hilar lymph nodes, a right renal mass, and masses in the small and large intestines. Histopathological examination confirmed monomorphic PTLD (diffuse large B-cell lymphoma). Against the treatment (reduction of immunosuppression, rituximab, and chemotherapy), the response was poor, and the patient died 94 days after the outbreak of PTLD. Both transplantation and HIV infection are risk factors for lymphoproliferative diseases. To the best of our knowledge, this is one of the very few reports of PTLD in a patient with HIV/HCV co-infection. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) epidemic remains a public health problem worldwide. A systematic review and meta-analysis were conducted to provide evidence of outcomes attained across the HCV care cascade in the era of direct-acting antivirals. Studies from North America, Europe, and Australia (January 2014 through March 2021) reporting on HCV care cascade outcomes (screening to cure) were included. When calculating the proportions of individuals completing each step, the numerator for Steps 1–8 was the number of individuals completing each step; the denominator was the number of individuals completing the previous step for Steps 1–3 and Step 3 for Steps 4–8. In 2022, random effects meta-analyses were conducted to estimate pooled proportions with 95% CIs. Sixty-five studies comprising 7,402,185 individuals were identified. Among individuals with positive HCV ribonucleic acid test results, 62% (95% CI=55%, 70%) attended their first care appointment, 41% (95% CI=37%, 45%) initiated treatment, 38% (95% CI=29%, 48%) completed treatment, and 29% (95% CI=25%, 33%) achieved cure. HCV screening rates were 43% (95% CI=22%, 66%) in prisons or jails and 20% (95% CI=11%, 31%) in emergency departments. Linkage to care rates were 62% (95% CI=46%, 75%) for homeless individuals and 26% (95% CI=22%, 31%) for individuals diagnosed in emergency departments. Cure rates were 51% (95% CI=30%, 73%) in individuals with substance use disorder and 17% (95% CI=17%, 17%) in homeless individuals. Cure rates were lowest in the U.S. Despite the availability of effective all-oral direct-acting antiviral therapies, persistent gaps remain across the HCV care cascade, especially among traditionally marginalized populations. Public health interventions targeting identified priority areas (e.g., emergency departments) may improve screening and healthcare retention of vulnerable populations with HCV infection (e.g., substance use disorder populations). [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. This study aimed to assess serum human telomerase enzyme (hTERT) levels and their relation to the progression of liver disease. Also, it aimed to assess the effect of hepatitis C virus (HCV) core protein on memory T-cells in HCV patients with or without HCC and the correlation between memory cell phenotype and the progression of the disease in the same patients. HTERT level in serum was assessed through relative quantitative RT-PCR. Flow cytometric analysis was used to assess T-cell responsiveness (as IFN- γ secretion) before and after stimulation with HCV core protein and the memory CD8+ cell phenotype using several differentiation markers. HTERT was found to be increased in a stepwise manner upon comparing its level in controls, chronic hepatitis patients, cirrhotic patients, and HCC patients. T-cells showed a similar manner of stepwise decrease in response (decreased IFN- γ secretion) in HCC patients compared to HCV patients without HCC and controls. Also, late differentiated memory cells (CD8+, CD27−, CD28−, CD45RA+, and CCR7−) were depleted in HCC patients compared to HCV patients without HCC. These results suggest a negative correlation between hTERT and IFN- γ secretion by T-cells in HCV patients and that this relationship, along with the depletion of late differentiated memory cells, could help the progression of liver disease to HCC. [Display omitted] • The progression of HCV infection to HCC is a major health problem that involves multiple molecular interactions and pathways. • hTERT levels showed a stepwise increase upon comparing its level in controls, chronic hepatitis, cirrhotic, and HCC patients. • Late differentiated CD8+ and IFN-γ response to HCV core protein showed a stepwise decrease in control, HCV, and HCC patients. • The negative correlation between hTERT and IFN-γ levels in HCV patients could help the progression of liver disease to HCC. [ABSTRACT FROM AUTHOR]

• Unusual genotype 4 subtypes 4n, 4o, and 4v were detected in four (8.3%) patients. • Baseline NS5A-RASs are frequent, with complex patterns in unusual genotype 4. • Sequencing surveillance programs are needed in Africa and Asia. • Minority populations of NS5A-NS3-RASs are infrequent. To investigate the molecular characteristics of Hepatitis C Virus (HCV) detected in patients with chronic HCV infection in Jordan. The study included 48 Jordanian treatment-naïve patients with active chronic HCV recruited from seven governorates. HCV genotype and the resistance-associated substitutions (RAS) profile were investigated by next-generation sequencing of the NS5B, NS5A, and NS3 regions of HCV. "Unusual genotype 4 subtypes" were detected in four (8.3%) patients (4n-n = 1, 4o-n = 2, 4v-n = 1); one patient (2.1%) was co-infected by genotypes 1b+4a. Overall prevalence of NS5A RASs was 38.3% (3% cutoff); genotype 4a showed the highest NS5A RAS prevalence (n = 11, 55.0%). Overall prevalence of NS3 RASs was 21.8% (7/32), all genotype 1a-infected patients. We report, for the first time in Jordanian patients with chronic HCV infection, the detection of unusual genotype 4 subtypes 4n, 4o, and 4v. Baseline RASs in NS5A are frequent, with complex RASs patterns in some of the unusual subtypes. Our data support the need for sequencing surveillance programs in sub-Saharan Africa, Asia, and the Middle East and North African region to monitor response to treatment in these subtypes and to facilitate the World Health Organization's 2030 elimination strategy. [Display omitted] [ABSTRACT FROM AUTHOR]

The role of the Emergency Department (ED) as a vital constituent in Hepatitis C (HCV) screening has become increasingly evident. A key component of the ED's role in HCV screening is the ability to effectively link HCV-RNA positive patients to definitive, HCV-specific care, to include direct-acting antiviral (DAA) medication with resultant sustained virologic response (SVR). We sought to consider the rate of HCV-specific linkage, DAA initiation, and SVR obtained in HCV patients identified from an ED screening program. A retrospective chart review was conducted in February of 2022 of all individuals who participated in an opt-out ED-based HCV screening program between January 2018 and December 2019. Data was disaggregated by race, gender, age/birth cohort, insurance status, and achievement of sustained virologic response (SVR). Bivariate analysis using Pearson's chi-square was utilized to compare outcomes based on insurance status, race, sex, and birth cohort. Of 66,634 individuals screened for HCV during the study period, 885 (1.33%) patients were RNA-positive. Of those individuals, 121 (13.67%) were linked to HCV-specific care. Of those linked, the majority (66.9%) were male, white (66.1%; 33.1% Black), baby boomers or older (53.7%) and publicly insured (57.9%; private insurance 23.1%, self-pay 19%). Among linked patients, 88 (72.7%) started DAA medication. Mirroring linked demographics, majority were male (64.8%), white (64.8%), baby boomers or older (52.3%), and publicly insured (57.6%). White patients initiated on DAA were more likely to obtain SVR (64.9% versus 41.9% Black; p =.04) and uninsured patients were more likely to obtain SVR (82.4% versus 50.7% insured; p =.02). Bivariate consideration of SVR-patients specifically demonstrates that Black patients tended to be older, with significant overrepresentation of Baby boomers (77.5%) as compared to whites (37.5%; p <.0001). Black patients were also more likely to be publicly insured (82.5%) while white patients were more likely to have private insurance (28.8%) or be uninsured (26.3%) than their Black counterparts (12.5% and 5% respectively; p <.05). An ED-based HCV screening program can result in successful HCV-specific linkage and care, to include DAA initiation and ultimately, SVR. Among linked patients, specific cohort considerations may demonstrate differences in age and insurance status which may have implications on DAA application and adherence, and therefore, individual ability to achieve SVR. [ABSTRACT FROM AUTHOR]

Prisons are key venues for scaling-up hepatitis C virus (HCV) testing and treatment. Complex clinical pathways and frequent movements of people in prison remain barriers to HCV care. This study evaluated the impact of a 'one-stop-shop' point-of-care HCV RNA testing intervention on treatment uptake compared with standard of care among people recently incarcerated in Australia. PIVOT was a prospective, non-concurrent, controlled study comparing HCV treatment uptake during 'standard of care' (n = 239; November 2019–May 2020) and a 'one-stop-shop' intervention (n = 301; June 2020–April 2021) in one reception prison in Australia. The primary endpoint was uptake of direct-acting antiviral treatment at 12 weeks from enrolment. Secondary outcomes included the time taken from enrolment to each stage in the care cascade. A total of 540 male participants were enrolled. Median age (29 vs. 28 years) and history of injecting drug use (48% vs. 42%) were similar between standard of care and intervention phases. Among people diagnosed with current HCV infection (n = 18/63 in the standard of care phase vs. n = 30/298 in the intervention phase), the proportion initiating direct-acting antiviral treatment within 12 weeks from enrolment in the intervention phase was higher (93% [95% CI 0.78–0.99] vs. 22% [95% CI 0.64–0.48]; p <0.001), and the median time to treatment initiation was shorter (6 days [IQR 5–7] vs. 99 days [IQR 57–127]; p <0.001) compared to standard of care. The 'one-stop-shop' intervention enhanced treatment uptake and reduced time to treatment initiation among people recently incarcerated in Australia, thereby overcoming key barriers to treatment scale-up in the prison sector. This study provides important insights for policymakers regarding optimal HCV testing and treatment pathways for people newly incarcerated in prisons. The findings will improve health outcomes in people in prison with chronic HCV infection by increasing testing and treatment, thereby reducing infections, liver-related morbidity/mortality, and comorbidities. The findings will change clinical practice, clinical guidelines, and international guidance, and will inform future research and national and regional strategies, in particular regarding point-of-care testing, which is being rapidly scaled-up in various settings globally. The economic impact will likely include health budget savings resulting from reduced negative health outcomes relating to HCV, and health system efficiencies resulting from the introduction of simplified models of care. This study is registered at Clinicaltrials.gov (NCT04809246). [Display omitted] • The proportion tested for HCV was higher in the intervention (99%) compared with the control phase (26%). • The proportion treated for HCV was higher in the intervention (93%) compared with the control phase (22%). • Median time from diagnosis to treatment initiation was shorter in the intervention than in the control phase (6 vs. 25 days). • Combining all key HCV assessments into a single visit improved efficiencies and enhanced testing and treatment uptake. [ABSTRACT FROM AUTHOR]

Sofosbuvir (S), daclatasvir (D), ledipasvir, or velpatasvir (V) containing first-line hepatitis C virus (HCV) treatment regimens fail to cure viremia in 5–10%. We report our experience of HCV retreatment using these first-line drugs, in a setting where second-line anti-HCV drugs are not available. Adults, who had relapsed after first complete course of a sofosbuvir-containing first-line, pegylated interferon free, anti-HCV treatment regimen with or without ribavirin (Riba) were included. Retreatment regimen, tailored to the failed anti-HCV regimen, was based on principle of using first-line drugs for 24 weeks with ribavirin and swapping between pangenotypic and genotype-specific regimens. Retreatment outcome was categorized as successful (achieved undetectable HCV RNA at the end of treatment [ETR] and sustained viral response at week 12 [SVR12]), non-responder (failed to achieve ETR), or relapse (achieved ETR but not achieved SVR12). Twelve patients (9 male; 7 cirrhosis; all genotype 3) who had relapsed to prior anti-HCV treatment (4 SD12, 4 SD24, 1 SDRiba12, 1 SDRiba24, 2 SV12) were included. Following retreatment (2 SDRiba24, 10 SVRiba24), all achieved ETR but only 9 (75%) achieved SVR12. Two among three, in whom retreatment failed, achieved SVR12 following another course of sofosbuvir/velpatasvir/ribavirin for 24 weeks. Overall, 11/12 (92%) patients achieved SVR12 following retreatment with the first-line anti-HCV drugs. HCV retreatment could be a treatment option if second-line anti-HCV drugs are not available. Successful retreatment could be achieved, in a large proportion, with the use of first-line drugs for 24 weeks with ribavirin and swapping of pangenotypic/genotype-specific regimens (NCT03483987). [ABSTRACT FROM AUTHOR]

• HCV infection is not associated with hepatic iron levels in TM. • Chronic HCV infection significantly increases the risk of diabetes in TM. • Chronic HCV infection is a prospective risk marker of cardiac complications in TM. No study has evaluated the effect of hepatitis C virus (HCV) infection on the wide spectrum of complications affecting patients with thalassemia. This multicenter study prospectively assessed the relationship of HCV infection with diabetes mellitus and cardiovascular complications in patients with thalassemia major (TM). We considered 1057 TM patients (539 females; 29.79±10.08 years) enrolled in the MIOT Network and categorized into 4 groups: negative patients (group 1a, N=460), patients who spontaneously cleared the virus within 6months (group 1b, N=242), patients who eradicated the virus after the treatment with antiviral therapy (group 2, N=102), and patients with chronic HCV infection (group 3, N=254). Group 1a and 1b were considered as a unique group (group 1). For both groups 1 and 3, a match 1:1 for age and sex with group 2 was performed. The effective study cohort consisted of 306 patients (three groups of 102 patients). During a mean follow-up of 67.93±39.20months, the group 3 experienced a significantly higher % increase/month in aspartate transaminase levels and left ventricular mass index than both groups 1 and 2. The changes in iron overload indexes were comparable among the three groups. Compared to group 1, the chronic HCV group showed a significantly higher risk of diabetes (hazard ratio-HR=5.33; p=0.043) and of cardiovascular diseases (HR=3.80; p=0.034). Chronic HCV infection is associated with a significant higher risk of diabetes mellitus and cardiovascular complications in TM patients and should be approached as a systemic disease in which extrahepatic complications increase the weight of its pathological burden. [Display omitted] [ABSTRACT FROM AUTHOR]

Liver disease accounts for two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and non-alcoholic fatty liver disease. Hepatotropic viruses are the aetiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents. [ABSTRACT FROM AUTHOR]

• Blood transfusion safety was prioritized in Georgia as part of a pioneering national hepatitis C elimination program. • Successful implementation of blood donor nucleic acid testing for HCV, HBV and HIV has afforded insight into the epidemiology and risk of the three major transfusion transmissible viruses. • Pairing of blood safety with a public health program affords dual benefits, promoting safer transfusion while removing a neglected source of viral transmission. In 2015, the country of Georgia initiated its hepatitis C virus (HCV) elimination program. Given a high background incidence of HCV infection, centralized nucleic acid testing (NAT) of blood donations was prioritized for implementation. Multiplex NAT screening for HIV, HCV and hepatitis B virus (HBV) was launched in January 2020. An analysis was conducted of serological and NAT donor/donation data for the first year of screening (through December 2020). A total of 54,116 donations representing 39,164 unique donors were evaluated. Overall, 671 donors (1.7%) tested positive for at least one infectious marker by serology or NAT, with the highest prevalence among donors aged 40–49 years (2.5%; n = 200), male (1.9%; n = 524), replacement (2.8%; n = 153) and first time (2.1%; n = 642) donors. Sixty donations were seronegative but NAT positive, and therefore would not have been found by traditional serology testing alone. These were more likely among female vs. male (adjusted odds ratio [aOR] 2.06; 95% confidence interval [95%CI]: 1.05–4.05), paid (aOR 10.15; 95%CI: 2.80–36.86) or voluntary (aOR 4.30; 95%CI: 1.27–14.56) vs replacement, and repeat vs. first time (aOR 13.98; 95%CI: 4.06–48.12) donors. On repeat serological testing (including HBV core antibody [HBcAb] testing), 6 HBV + donations, 5 HCV + donations and 1 HIV + donations were deemed NAT yield (detected through the implementation of NAT, and would have otherwise been missed by serology screening alone). This analysis offers a regional model for NAT implementation, demonstrating the feasibility and clinical utility in a nationwide blood program. [ABSTRACT FROM AUTHOR]

At the 74th World Health Assembly, the WHO issued a strategy for the prevention and control of several major infectious diseases. To achieve the WHO-initiated targets for these infectious diseases, the elimination of mother-to-child transmission is essential. To date, a systematic review of the global and regional prevalence of infections with relevant mother-to-child transmission and outside the spectrum of congenital infections is lacking. We aimed to systematically review the prevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis in pregnant women. MEDLINE, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang database and China Biology Medicine disc database, and five WHO Regional Index Medicus databases. Original studies reporting the prevalence of infection or coinfection of HIV, HBV, HCV, and syphilis in pregnant women. This systematic review followed the preferred reporting items for systematic reviews and meta-analyses 2020 checklist. We used random-effects models to generate pooled prevalence estimates for each infection. The global pooled prevalence in pregnant women of HIV, HBV, HCV, and syphilis was 2.9% (95% CI, 2.4–3.4%), 4.8% (3.8–5.8%), 1.0% (0.8–1.3%), and 0.8% (0.7–0.9%). The pooled prevalence of HIV, HBV, HCV, and syphilis in low-income countries was higher than the global level (HIV: 5.2% [1.6–10.5%); HBV: 6.6% (5.4–7.9%); HCV: 2.7% (1.6–4.1%); syphilis: 3.3% (2.2–4.6%]). The pooled prevalence of HIV, HBV, HCV, and syphilis in lower-middle-income countries was higher than the global level (HIV: 2.9% [0.8–6.1%]; HBV: 4.9% [3.8–6.1%]; HCV: 2.3% [1.2–3.6%]; syphilis: 1.5% [1.0–2.2%]). The prevalence of these infections among pregnant women was particularly high in resource-poor settings. The relevance and feasibility of current global practice guidelines for the prevention of mother-to-child transmission of these infections in lower-middle-income countries must be evaluated, including timely access to screening and therapeutics. [ABSTRACT FROM AUTHOR]

Data are limited regarding the long-term durability of sustained virologic response (SVR) in solid organ transplant recipients who achieve SVR 12 with direct-acting antivirals (DAAs) for hepatitis C virus (HCV). We reported the virologic outcomes in 42 recipients who received DAAs for acute or chronic HCV infection after heart, liver, and kidney transplantation. After achieving SVR 12 , all recipients received HCV RNA surveys at SVR 24 , and biannually until the last visit. If HCV viremia was detected during the follow-up period, direct sequencing and phylogenetic analysis were performed to confirm late relapse or reinfection. Sixteen (38.1%), 11 (26.2%), and 15 (35.7%) patients underwent heart, liver and, kidney transplantation. Thirty-eight (90.5%) received sofosbuvir (SOF)-based DAAs. No recipients had late relapse or reinfection after a median (range) of post-SVR 12 follow-up 4.0 (1.0–6.0) years. We demonstrate that the durability of SVR in solid organ transplant recipients is excellent once SVR 12 is achieved with DAAs. [ABSTRACT FROM AUTHOR]

Liver transplantation offers live-saving therapy for patients with complications of cirrhosis and stage T2 hepatocellular carcinoma. The demand for organs far outstrips the supply, and innovations aimed at increasing the number of usable deceased donors as well as alternative donor sources are a major focus. The etiologies of cirrhosis are shifting over time, with more need for transplantation among patients with alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease and less for viral hepatitis, although hepatitis B remains an important indication for transplant in countries with high endemicity. The rise in transplantation for alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease has brought attention to how patients are selected for transplantation and the strategies needed to prevent recurrent disease. In this review, we present a status report on the most pressing topics in liver transplantation and future challenges. [ABSTRACT FROM AUTHOR]

Surgical interventions and invasive diagnostic/therapeutic procedures are known routes of transmission of viral hepatitis. Using data from the Italian surveillance system for acute viral hepatitis (SEIEVA), the aim of this study was to investigate the association between specific types of invasive procedures and the risk of acute HBV and HCV infections. Data from SEIEVA (period 2000-2021) were used. The association between acute HBV and HCV infection and potential risk factors, i.e. surgical interventions and diagnostic/therapeutic procedures (given according to the ICD-9-CM classification), was investigated in comparison to age-matched hepatitis A cases, used as controls, by conditional multiple logistic regression analysis. A total of 8,176 cases with acute HBV, 2,179 with acute HCV, and the respective age-matched controls with acute HAV infection were selected for the main analysis. Most of the procedures evaluated were associated with the risk of acquiring HBV or HCV. The strongest associations for HBV infection were: gynaecological surgery (odds ratio [OR] 5.19; 95% CI 1.12-24.05), otorhinolaryngological surgery (OR 3.78; 95% CI 1.76-8.09), and cardiac/thoracic surgery (OR 3.52; 95% CI 1.34-9.23); while for HCV infection, they were: neurosurgery (OR 11.88; 95% CI 2.40-58.85), otorhinolaryngological surgery (OR 11.54; 95% CI 2.55-52.24), and vascular surgery (OR 9.52; 95% CI 3.25-27.87). Hepatitis C was also strongly associated with ophthalmological surgery (OR 8.32; 95% CI 2.24-30.92). Biopsy and/or endoscopic procedures were significantly associated with both HCV (OR 3.84; 95% CI 2.47-5.95) and, to a lesser extent, HBV infection (OR 1.48; 95% CI 1.16-1.90). Despite the progress made in recent years, invasive procedures still represent a significant risk factor for acquiring parenterally transmitted hepatitis viruses, thus explaining the still numerous and unexpected cases diagnosed among the elderly population in Italy. Our results underline the importance of observing universal precautions to control the iatrogenic transmission of hepatitis viruses. Cases of parenterally transmitted acute viral hepatitis in the elderly population, that are difficult to explain based on the most widely recognised risk factors, continue to be diagnosed in Italy. Based on the Italian SEIEVA surveillance of acute viral hepatitis data, this study highlights an increased risk of acquiring hepatitis B and C following exposure to invasive procedures, which might explain the observed cases in elderly individuals. Furthermore, this finding emphasises the need to observe universal precautions strictly, in healthcare settings, including in the case of minor surgical procedures. [Display omitted] • An increased risk of acquiring hepatitis B and C following exposure to invasive procedures was observed. • Compared with hepatitis A (controls), the risk was two times higher for HBV and over five times higher for HCV. • Most of the procedures (surgical specialties) evaluated were associated with the risk of acquiring HBV or HCV. • Minor surgeries, biopsy and endoscopy showed the greater association with both HCV and HBV infection. • Complying with universal precautions in healthcare settings is crucial. [ABSTRACT FROM AUTHOR]

Concerning data have revealed that viral hepatitis and hepatocellular carcinoma (HCC) disproportionally impact non-White patients and those from lower socioeconomic status. A recent study found that HCC clusters were more likely to be in high poverty areas in New York City. We aim to investigate the impacts of neighborhood characteristics on those with viral hepatitis and cirrhosis, particularly with advanced HCC diagnosis. Patients with cirrhosis and viral hepatitis admitted to a New York City health system between 2012 and 2019 were included. Those with prior liver transplants were excluded. Neighborhood characteristics were obtained from US Census. Our primary outcome was HCC and advanced HCC diagnosis. This study included 348 patients; 209 without history of HCC, 20 with early HCC, 98 with advanced HCC, and 21 patients with HCC but no staging information. Patients with advanced HCC were more likely to be older, male, Asian, history of HBV, and increased mortality. They were more likely to live in areas with more foreign-born, limited English speakers, and less than high school education. After adjusting for age, sex, and payor type, Asian race and low income were independent risk factors for advanced HCC. Neighborhood factors were not associated with mortality or readmissions. We observed that in addition to age and sex, Asian race, lower household income, lower education, and lower English proficiency were associated with increased risk of advanced HCC. These disparities likely reflect suboptimal screening programs and linkage to care among vulnerable populations. Further efforts are crucial to validate and address these concerning disparities. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is an infection of the liver, which contributes to over 15,000 deaths in the United States annually. When treated, HCV has a 90% or greater cure rate, however testing for HCV remains low. To assess patient perspectives on HCV screenings in the community pharmacy setting including awareness of screening, willingness to be screened, barriers to screening, and willingness to pay for HCV screening. This study used a cross-sectional survey design. The surveys were distributed by staff at an independent community pharmacy participating in an HCV screening initiative through the state department of public health. Eligible patients were born between 1945 and 1965. Descriptive statistics were calculated for survey variables. Open-ended responses were analyzed for additional context. Fifty-seven surveys were returned and analyzed. The majority of the respondents were White (94%), female (56%), and had some college education (26%). Only 7% were aware that a finger-stick point-of-care test was available and 67% were unaware of the Centers for Disease Control and Prevention (CDC) recommendation for testing. The most frequently reported barrier or hesitation to screening was the patient not thinking they were at risk (29%) followed by uncertainty about cost (14%). Over half of respondents (63%) were either somewhat interested or very interested in testing in a community pharmacy, however, the majority (71%) were not willing to pay or only willing to pay less than $20. Survey respondents were largely unaware of the recommendations and availability of finger-stick HCV screenings at community pharmacies but many were willing to be tested if low-cost. Providing patient education on the importance of HCV screenings and CDC recommendations may bolster interest in screening. [ABSTRACT FROM AUTHOR]

Previous initiatives have described the feasibility of conducting point-of-care testing (POCT) for hepatitis C virus (HCV) within community pharmacies. Limited research has been conducted to evaluate the role of student pharmacists and technicians in providing these services. Describe the implementation of a student pharmacist–run HCV POCT initiative within an independent community pharmacy and evaluate the linkage to care process. One specialty and 3 community pharmacies managed by one independent pharmacy chain. Pharmacy students screened participants for HCV and referred those with a reactive result or reporting untreated HCV to a partnering medical facility for confirmatory testing. Individuals with confirmed HCV had the option to receive their prescriptions, along with monthly telephonic monitoring services from the independent pharmacy's specialty pharmacy. Researchers evaluated the number of participants who screened reactive or reported current HCV infection, successful referrals to medical care, and prescriptions dispensed by the specialty pharmacy for HCV treatment. From September 2020 to September 2022, 236 individuals were screened for HCV at the pharmacy, of whom 11 screened reactive (4.7%) and 4 participants reported untreated HCV infection. In total, 15 participants were referred to care and 4 of these participants (26.7%) were successfully linked. One participant received prescriptions and telephonic monitoring for HCV treatment from the specialty pharmacy as a direct result of Project IMPACT (Innovating the Model for Student Pharmacists to Increase Access to Hepatitis C Testing). Project IMPACT demonstrated that community pharmacies can increase access to HCV screenings by using student pharmacists and technicians. Potential strategies to improve the linkage to care process include enhancing the quality of patient education and implementing telehealth services. [ABSTRACT FROM AUTHOR]

People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life. • No significant improvement in health-related quality of life was observed among people who inject drugs after hepatitis C virus (HCV) direct-acting antiviral treatment. • A modest but significant improvement in employment was observed during study follow-up. • This study suggests the need for HCV care models addressing a range of issues beyond HCV treatment to improve quality of life among people who inject drugs. [ABSTRACT FROM AUTHOR]

Hepatitis C is a disease that is often asymptomatic, so that it is detected completely by chance. However, it is worth remembering that untreated hepatitis C can lead to a number of serious complications, such as post-inflammatory cirrhosis and hepatocellular carcinoma, among others. Therefore, diagnosis and proper treatment are very important here. Appropriate data mining techniques can be helpful here and can support the work of medical. This work analyzed the data of 73 patients who have been diagnosed with hepatitis C through serological and histopathological testing. During the initial phase of the study, the data underwent classification. Then feature selection was carried out, followed by the same classifiers again. Finally, the obtained classification rules are also presented. [ABSTRACT FROM AUTHOR]

Despite expert-based recommendations, real-world adherence to immune thrombocytopenia (ITP) guidelines is unclear. The impact of geographic and socioeconomic disparities on the quality of care and outcomes is unknown. We sought to determine the association between geographic remoteness and material deprivation on ITP care and outcomes. We conducted a multi-centre retrospective cohort study of adults with chronic ITP requiring a second-line therapy between 2012 and 2019 in the province of Alberta, Canada. Socioeconomic status was measured using the Pampalon material deprivation index quintiles. Geographic disparities were assessed by the driving distance to a major centre, with geographic remoteness defined as >200 km from major centre. We examined the impact of geographic and material deprivation on quality of care, resource utilization (hospitalizations, transfusions), and outcomes (major bleeding, all-cause mortality and ITP-related mortality). Cox proportional hazards models were used to examine the impact of geographic remoteness, rural residence and material deprivation on overall survival and ITP-related survival. We included 326 ITP patients, median age of ITP diagnosis was 57 years, 182 (56 %) were female. Most patients (58 %) lived within 20 km of a major centre, whereas 49 (15 %) lived in a geographically remote area (>200 km). Geographic remoteness was significantly associated with material deprivation and lower likelihood of management by hematologists (84 % vs 99 %, P = 0.0001). It was also associated with lower rates of hepatitis C (71 % vs 89 %, P = 0.005) and hepatitis B testing (69 % vs 86 %, P = 0.03), and a non-significant trend towards lower rates of HIV testing (73 % vs 83 %, P = 0.051) compared with those <20 km from a major centre. Incomplete hyposplenic vaccinations among splenectomized patients (52 %), early splenectomy within 12 months of ITP diagnosis (35 %), inappropriate platelet transfusions (41 %), and inappropriate hospitalizations for asymptomatic thrombocytopenia (16 %) were common regardless of geographic distribution. There were 28 (9 %) ITP-related deaths (major bleeding or infections), most occurred within the first year of ITP diagnosis. Material deprivation, but not geographic remoteness, was an independent predictor of all-cause mortality (aHR 1.9, 95 % CI 1.1–3.3 in the most deprived quintile vs least deprived quintile). Rural residence trended towards increased hazard of ITP-related deaths (aHR 1.7, 95 % CI 0.9–3.2). We demonstrated substantial deviations of ITP care from consensus guidelines, and geographic disparities in access to care and diagnostic workup. Future quality improvement initiatives are critical to improve the quality of care and reduce inequities. • It is unclear whether geographic remoteness or socioeconomic status affects quality of care in immune thrombocytopenia (ITP). • Multicentre cohort study evaluating impact of geographic remoteness and material deprivation on quality of care and outcomes. • Remoteness was associated with lower rates of hematology referral, while material deprivation was a predictor of mortality. • Socioeconomic disparities impact quality of care and outcomes in ITP, and require further attention to reduce inequities. [ABSTRACT FROM AUTHOR]

HCV test and treat campaigns currently exclude pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine. Country-specific probabilistic decision models were developed to simulate a cohort of pregnant women. We compared five strategies: S0, targeted risk-based screening and deferred treatment (DT) to after pregnancy/breastfeeding; S1, World Health Organization (WHO) risk-based screening and DT; S2, WHO risk-based screening and targeted treatment (treat women with risk factors for HCV vertical transmission [VT]); S3, universal screening and targeted treatment during pregnancy; S4, universal screening and treatment. Maternal and infant HCV outcomes were projected. S0 resulted in the highest proportion of women undiagnosed: 59% and 20% in Egypt and Ukraine, respectively, with 0% maternal cure by delivery and VT estimated at 6.5% and 7.9%, respectively. WHO risk-based screening and DT (S1) increased the proportion of women diagnosed with no change in maternal cure or VT. Universal screening and treatment during pregnancy (S4) resulted in the highest proportion of women diagnosed and cured by delivery (65% and 70%, respectively), and lower levels of VT (3.4% and 3.6%, respectively). This is one of the first models to explore HCV screening and treatment strategies in pregnancy, which will be critical in informing future care and policy as more safety/efficacy data emerge. Universal screening and treatment in pregnancy could potentially improve both maternal and infant outcomes. In the context of two lower middle-income countries with high HCV burdens (Egypt and Ukraine), we designed a decision analytic model to explore five different HCV testing and treatment strategies for pregnant women, with the assumption that treatment was safe and efficacious for use in pregnancy. Assuming direct-acting antiviral treatment during pregnancy would reduce vertical transmission, our findings indicate that the provision of universal (rather than risk-based targeted) screening and treatment would provide the greatest maternal and infant benefits. While future trials are needed to assess the safety and efficacy of direct-acting antivirals in pregnancy and their impact on vertical transmission, there is increasing recognition that the elimination of HCV cannot leave entire subpopulations of pregnant women and young children behind. Our findings will be critical for policymakers when developing improved screening and treatment recommendations for pregnant women. [Display omitted] • In Egypt and Ukraine, universal screening and treatment in pregnancy may improve both maternal and infant outcomes. • The proportion of women cured by delivery would be 65% in Egypt and 70% in Ukraine, vs. 0% with standard of care. • The proportion of infants infected at the age of 6 months would decrease by 50% compared to standard of care. [ABSTRACT FROM AUTHOR]