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

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

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

Problematic alcohol use is prevalent in Russia and is deleterious for individuals with HIV and Hepatitis C Virus (HCV). Ethyl glucuronide (EtG) and blood alcohol content (BAC) provide objective biomarkers of drinking that can be compared to self-reported alcohol use. This paper describes patterns of alcohol use measured by biomarkers and self-report along with concordance across measures. Participants were Russian women with HIV and HCV co-infection (N = 200; Mean age = 34.9) from two Saint Petersburg comprehensive HIV care centers enrolled in an alcohol reduction intervention clinical trial. Measures were: (a) urine specimen analyzed for EtG; (b) breathalyzer reading of BAC; and (c) self-reported frequency of drinking, typical number of drinks consumed, and number of standard drinks consumed in the past month. At baseline, 64.0% (n = 128) had a positive EtG (> 500 ng/mL) and 76.5% (n = 153) had a positive breathalyzer reading (non-zero reading). There was agreement between EtG and BAC (kappa = 0.66, p <.001; Phi coefficient = 0.69, p <.001); self-reported alcohol measures were positively correlated with positive EtG and BAC (p's < 0.001). There was concordance between EtG and BAC measures, which have differing alcohol detection windows. Most participants endorsed frequent drinking at high quantities, with very few reporting no alcohol consumption in the past month. Concordance between biomarkers and self-reported alcohol use suggests that underreporting of alcohol use was minimal. Results highlight the need for alcohol screening within HIV care. Implications for alcohol assessment within research and clinical contexts are discussed. [ABSTRACT FROM AUTHOR]

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

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

This paper carries out an analysis of the global properties of solutions of an in-host model of hepatitis C for general values of its parameters. A previously unknown stable steady state on the boundary of the positive orthant is exhibited. It is proved that the model exhibits Hopf bifurcations and hence periodic solutions. A general parametrization of positive steady states is given and it is determined when the number of steady states is odd or even, according to the value of a certain basic reproductive ratio. This implies, in particular, that when this reproductive ratio is greater than one there always exists at least one positive steady state. A positive steady state which bifurcates from an infection-free state when the reproductive ratio passes through one is always stable, i.e. no backward bifurcation occurs in this model. The results obtained are compared with those known for related models of viral infections. [ABSTRACT FROM AUTHOR]

In this paper, we discussed a stochastic optimal control of hepatitis C that minimizes the side effect and reduces the viral load. The control variables represent the drug therapy used for blocking a new infection and virus production. The solution of control problem is solved using the stochastic minimum principle and a four-step scheme. The numerical simulation is carried out to justify the theoretical analysis. The result shows that using both types of drugs for therapy is much more effective. [ABSTRACT FROM AUTHOR]

Pakistan has the second-largest number of HCV infections in the world with homogeneity across provinces and no evidence of decline over the past 30 years (Mahmud et al. in BMC Infect Dis 19(1):1–11, 2019). Currently, one in every 20 Pakistanis is suffering from HCV (Haqqi et al. in Viral Immunol 32(9):402–413, 2019). The disease significantly interferes with the everyday life of the patient (Silberbogen et al. in Psychosomatics 50(2):114–122, 2009; Foster in Viral Hepat 16(9):605–611, 2009). The present research aimed to find the role of gender, family system, and social support in predicting coping in patients with hepatitis C (HCV). A sample of 100 HCV patients was taken using purposive sampling from different public and private hospitals in Lahore, Pakistan. For assessment, the Multidimensional Scale of Perceived Social Support and Brief Cope Inventory were used. Results showed that male hepatitis C patients used a higher level of religious coping. Hepatitis C patients living in a joint family system used a higher level of religious coping. It also showed that there was no significant relationship between social support and coping. Patients suffering from hepatitis C for 2 years or more adopted avoidant coping strategies as compared to the patients diagnosed for 1 year or more. This research has important implications for psychologists, paramedical staff, doctors, social workers, caregivers, peers, and families of patients suffering from HCV. It would help in formulating effective therapeutic interventions. It would also add to the literature in the field of health psychology. [ABSTRACT FROM AUTHOR]

Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate the frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced culture conversion. We also conduct Cox proportional hazard regression analyses to identify factors associated with reversion, including comorbidities, previous treatment, cavitary disease at conversion, low body mass index (BMI) at conversion, time to conversion, and number of likely-effective drugs. Of 1,286 patients, 54 (4.2%) experienced reversion, a median of 173 days (97-306) after conversion. Cavitary disease, BMI < 18.5, hepatitis C, prior treatment with second-line drugs, and longer time to initial culture conversion were positively associated with reversion. Reversion was uncommon. Those with cavitary disease, low BMI, hepatitis C, prior treatment with second-line drugs, and in whom culture conversion is delayed may benefit from close monitoring following conversion. In patients with drug-resistant tuberculosis who receive treatment with new and repurposed drugs, indicators of advanced disease and delayed conversion were associated with an increased risk of reversion. These factors may be targets for close monitoring. [ABSTRACT FROM AUTHOR]

Hepatitis C, a particularly dangerous form of viral hepatitis caused by hepatitis C virus (HCV) infection, is a major socio-economic and public health problem. Due to the rapid development of deep learning, it has become a common practice to apply deep learning to the healthcare industry to improve the effectiveness and accuracy of disease identification. In order to improve the effectiveness and accuracy of hepatitis C detection, this study proposes an improved denoising autoencoder (IDAE) and applies it to hepatitis C disease detection. Conventional denoising autoencoder introduces random noise at the input layer of the encoder. However, due to the presence of these features, encoders that directly add random noise may mask certain intrinsic properties of the data, making it challenging to learn deeper features. In this study, the problem of data information loss in traditional denoising autoencoding is addressed by incorporating the concept of residual neural networks into an enhanced denoising autoencoder. In our experimental study, we applied this enhanced denoising autoencoder to the open-source Hepatitis C dataset and the results showed significant results in feature extraction. While existing baseline machine learning methods have less than 90% accuracy and integrated algorithms and traditional autoencoders have only 95% correctness, the improved IDAE achieves 99% accuracy in the downstream hepatitis C classification task, which is a 9% improvement over a single algorithm, and a nearly 4% improvement over integrated algorithms and other autoencoders. The above results demonstrate that IDAE can effectively capture key disease features and improve the accuracy of disease prediction in hepatitis C data. This indicates that IDAE has the potential to be widely used in the detection and management of hepatitis C and similar diseases, especially in the development of early warning systems, progression prediction and personalised treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) and liver cancer are two of the leading causes of cancer death in the United States and persistent disparities in CRC and liver cancer incidence and outcomes exist. Chronic hepatitis C virus (HCV) infection is one of the main contributors to liver cancer. Effective screening for both CRC and HCV exist and are recommended for individuals based upon age, regardless of gender or sex assigned at birth. Recommendations for both screening behaviors have been recently updated. However, screening rates for both CRC and HCV are suboptimal. Targeting adoption of multiple screening behaviors has the potential to reduce cancer mortality and disparities. Objective: To examine psychosocial factors associated with completion of CRC and HCV screenings in order to inform a multi-behavioral educational intervention that pairs CRC and HCV screening information. Methods: A cross-sectional survey was conducted with participants (N = 50) recruited at two community health centers in Florida (United States). Kruskal-Wallis and Fisher's exact tests were used to examine associations between completion of both CRC and HCV screening, CRC and HCV knowledge, Preventive Health Model constructs (e.g., salience and coherence, response efficacy, social influence), and sociodemographic variables. Results: Most participants were White (84%), female (56%), insured (80%), and reported a household income of $25,000 or less (53%). 30% reported ever previously completing both CRC and HCV screenings. Prior completion of both screening behaviors was associated with higher educational attainment (p =.014), having health insurance (p =.022), being U.S.-born (p =.043), and higher salience and coherence scores for CRC (p =.040) and HCV (p =.004). Conclusions: Findings demonstrate limited uptake of both CRC and HCV screenings among adults born between 1945 and 1965. Uptake was associated with multiple sociodemographic factors and health beliefs related to salience and coherence. Salience and coherence are modifiable factors associated with completion of both screening tests, suggesting the importance of incorporating these health beliefs in a multi-behavioral cancer education intervention. Additionally, health providers could simultaneously recommend and order CRC and HCV screening to improve uptake among this age cohort. [ABSTRACT FROM AUTHOR]

Obesity is a global health problem and has been increasing in Egypt over the last several decades. A national population screening program for hepatitis C included screening for obesity. Here we report the outcome of body mass index (BMI) calculation for the screened population and for patients with hepatitis C. Methods Adults 18 years and older (a target population of 62.5 million) were invited to participate in a screening program between October 2018 and April 2019. Persons had their BMI calculated. All data were entered in real-time to a central database via cellular networks. BMI data for patients with hepatitis C virus (HCV) infection before starting direct antiviral therapy were obtained from the National Committee for the Control of Viral Hepatitis (NCCVH) Findings 49.6 million persons (25.6 million females and 24.0 million males) voluntarily participated and had valid height and weight data. 12.7 million females (49.51%) and 7.09 million males (29.53%) were affected by obesity (BMI ≥ 30kg/m2). Obesity increased with age, was more prevalent in females, was more prevalent in the Nile Delta states and in urban areas. Detailed district-level prevalence for the whole country is identified. Prevalence of obesity among 335,504 patients with HCV was higher in females, increased with age, and was significantly lower overall and in males and females than in the screened general population. Conclusion This is the largest population screening program for obesity. We show that obesity prevalence in the general population is currently among the highest in the world, starting in young adults, and highlight the high prevalence areas. Prevalence is lower in patients with HCV. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69–0.92) and cirrhosis (RR 0.39, 95% CI 0.24–0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55–0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23–0.78) and liver decompensation (RR 0.52, 95% CI 0.33–0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality. [ABSTRACT FROM AUTHOR]

Purpose of Review: Direct-acting antivirals (DAA) have revolutionized the field of hepatitis C in the last decade; however, significant challenges remain in eliminating the disease specifically among difficult-to-reach populations. This paper reviews the barriers to viral elimination with a specific emphasis on people who inject drugs and incarcerated patients. Recent Findings: People who inject drugs face challenges at every stage of the "cascade of care"—screening, diagnosis, accessing medications, and completing treatment. Despite this, evidence suggests that treatment of these high-risk groups is essential to the elimination of the virus in the population. Summary: Although DAAs have very high efficacy, their effectiveness at eliminating the virus will be limited without special attention to people who inject drugs. Addressing these challenges in people who inject drugs might best be achieved through proactive programs for incarcerated patients. [ABSTRACT FROM AUTHOR]

Compared with other racial and ethnic groups in the United States, American Indian and Alaska Native (AI/AN) people experience the highest incidence of acute hepatitis c (HCV). Cherokee Nation Health Services (CNHS) implemented a pilot health screening program from January through May 2019 to assess whether conducting HCV and other preventive health screenings at food distribution sites is a feasible, acceptable, and effective strategy to increase health screening among underserved community members. Data were collected among 340 eligible participants. Most (76%) participants reported being very comfortable receiving health screenings at food distribution sites and that getting screened at food distribution sites is very easy (75.4%). Most (92.1%, n = 313) participants received HCV screening, with 11 (3.5%) individuals testing positive for HCV antibodies. Of the 11 HCV seropositive individuals, six were confirmed to have active HCV infection of which four initiated treatment. Most (55.7%) participants exhibited a body mass index in the obese range, 33.1% exhibited high hemoglobin A1C (> 6.0), 24.5% exhibited high (> 200) cholesterol, 44.6% exhibited high blood pressure (> = 140/90), and 54.8% did not have a current primary care provider. This project demonstrated that conducting HCV and other health screenings at food distribution sites within Cherokee Nation was an effective strategy to engage AI/AN people in preventive health screenings. Future programs are needed to scale-up preventive health screenings outside of traditional medical facilities as these types of screenings may help to decrease the HCV disparities among AI/AN people. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are amongst the most common causative agents of viral hepatitis with its severe complications, including liver cirrhosis, decompensation, and hepatocellular carcinoma (HCC). Elimination of viral hepatitis, a significant challenge, has become an adopted global goal with certainly designed targets set by the World Health Assembly to be met by 2030. While many countries, including Egypt, have started executive plans for viral hepatitis elimination and achieved remarkable progress, the emergence of the COVID-19 pandemic has markedly affected all the machinery of the healthcare systems and specifically laid countries off their track in their viral hepatitis elimination process. The pandemic disrupted most healthcare services, and health staff and hospital resources were recruited mainly for managing the crisis, which significantly negatively impacted the management of other less severe diseases, including viral hepatitis. Social distancing and restrictive measures applied by most countries to contain the pandemic have affected medical services offered to patients with hepatitis. All supply chains of medications and vaccinations concerned with treating and preventing viral hepatitis have been markedly compromised. Many efforts and strategies are required to combat the severe and deleterious implications of the pandemic on the management of viral hepatitis worldwide in an attempt to get the situation under control and resume the pathway towards viral hepatitis elimination. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection causes a substantial economic burden, not only in terms of healthcare costs, but also in labour productivity losses. The main objective of this study is to provide objective and comparable information about the trend in labour productivity losses caused by premature HCV-associated deaths in Spain in recent years (2009–2018). We used nationwide data from several official sources to create a simulation model based on the human capital approach and to estimate the flows in labour productivity losses due to deaths identified in the period considered. Based on a pessimistic scenario, the annual number of deaths due to HCV infections decreased by 19.7% between 2009 and 2018. The years of potential labour productive life lost (YPLPLL) decreased by 38.1%. That reduction led to a decrease in annual labour productivity losses from €236 million in 2009 to €156 million in 2018 (–33.8%). The aggregate HCV-related labour productivity losses between 2009 and 2018 ranged from €1742 million (optimistic scenario) to €1949 million (pessimistic scenario), with an intermediate estimation of €1846 million (moderately optimistic scenario). These results show a substantial reduction in annual deaths, working-age deaths, YPLPLL, and labour productivity losses associated with HCV infection over this period. [ABSTRACT FROM AUTHOR]

Introduction: Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) is the first direct-acting antiviral (DAA) therapy approved for patients who have previously failed a DAA-containing regimen including NS5A inhibitors. In clinical trials, SOF/VEL/VOX was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. However, the effectiveness and safety of SOF/VEL/VOX in the real world remained uncertain. We aimed to perform a systematic review and meta-analysis to assess the real world effectiveness and safety of SOF/VEL/VOX. Methods: We systematically searched the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for relevant real world studies published before January 28, 2022. Patients with previous treatment failure who received SOF/VEL/VOX were included. The primary outcome was the percentage of patients achieving SVR12. Secondary outcome included adverse events (AEs) during treatment. Results: Fifteen studies with a total of 1796 HCV-infected patients with previous treatment failure were included. SVR12 rates were 93% (95% CI 91–95) in the ITT populations (n = 1517, 11 cohorts) and 96% (95% CI 95–97) in the PP populations (n = 1187, 10 cohorts). SVR12 rates were significantly higher in non-GT3-infected patients (OR = 2.29, 95% CI 1.23–4.27, P = 0.009) and non-cirrhotic patients (OR = 2.22, 95% CI 1.07–4.60, P = 0.03) than in GT3-infected patients and cirrhotic patients. Furthermore, the SVR12 rates of previous treatment of SOF/VEL were significantly lower than those of other regimens in both ITT and PP populations (P ≤ 0.001). Adverse events (AEs) were reported in 30% (228/760) of patients. Serious AEs (SAEs) were reported in 3.82% (29/760) of patients. The most frequently reported AEs were headache, asthenia, nausea, fatigue, and diarrhea, which were mostly mild in severity. AE-related treatment discontinuations were reported in 0.66% (5/760) of patients. Conclusions: Consistent with clinical trials, the real world evidence indicates that SOF/VEL/VOX is a well-tolerated and highly effective salvage therapy for HCV-infected patients with previous treatment failure. However, there may still be a risk of treatment failure for patients with GT3 infection, cirrhosis, or SOF/VEL treatment failure. The protocol of this study was registered at PROSPERO, registration no. CRD 42022306828. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are amongst the most common causative agents of viral hepatitis with its severe complications, including liver cirrhosis, decompensation, and hepatocellular carcinoma (HCC). Elimination of viral hepatitis, a significant challenge, has become an adopted global goal with certainly designed targets set by the World Health Assembly to be met by 2030. While many countries, including Egypt, have started executive plans for viral hepatitis elimination and achieved remarkable progress, the emergence of the COVID-19 pandemic has markedly affected all the machinery of the healthcare systems and specifically laid countries off their track in their viral hepatitis elimination process. The pandemic disrupted most healthcare services, and health staff and hospital resources were recruited mainly for managing the crisis, which significantly negatively impacted the management of other less severe diseases, including viral hepatitis. Social distancing and restrictive measures applied by most countries to contain the pandemic have affected medical services offered to patients with hepatitis. All supply chains of medications and vaccinations concerned with treating and preventing viral hepatitis have been markedly compromised. Many efforts and strategies are required to combat the severe and deleterious implications of the pandemic on the management of viral hepatitis worldwide in an attempt to get the situation under control and resume the pathway towards viral hepatitis elimination. [ABSTRACT FROM AUTHOR]

Background: Regression of fibrosis and improvement of portal hemodynamics after achievement of sustained viral response (SVR) in patients with chronic hepatitis C (HCV) is a subject of debate in different studies. Some studies reported improvement in the degree of fibrosis, while others did not find significant changes. Objective: We aimed to evaluate changes in liver fibrosis, portal hemodynamics and clinical outcomes in patients with chronic HCV-related liver cirrhosis after the achievement of SVR with direct-acting antiviral drugs (DAAs). Patients and methods: In our prospective longitudinal study, a total of 100 patients with chronic HCV infection-related liver cirrhosis were recruited, received DAAs, and completed the follow-up period. Clinical evaluation for assessment of liver disease severity using MELD and Child–Pugh class and scores were done. A noninvasive assessment of liver fibrosis using serum biomarkers (APRI index & FIB4 score) and share wave elastography (SWE) was done. Portal hemodynamic evaluation using Doppler ultrasound was done. All were done at baseline and 3 and 12 months after the end of therapy. Results: A significant reduction in the degree of fibrosis was observed. Share wave elastography (SWE) readings showed 19.79% and 30.45% reduction 3 and 12 months after the end of therapy respectively (P < 0.001). Regarding the FIB4 score, the percentage of score reduction was 19.8% and 26.46% 3 and 12 months after the end of therapy, respectively (P < 0.01). APRI scores showed 22.6% and 41.09% reduction 3 and 12 months after the end of therapy respectively (P < 0.001). Significant improvement in Child–Pugh scores 3 and 12 months after the end of treatment was observed. Doppler ultrasound showed a significant increase in portal vein flow velocity, a significant decrease in time average mean velocity, and cross-section area 12 months after the end of treatment. Conclusion: There was a considerable degree of reduction of liver fibrosis, improvement of portal hemodynamics, and Child–Pugh score in cirrhotic HCV patients who achieved SVR after DAAs. Trial registration: ClinicalTrials.gov, ID: NCT03241823. Registered on 08 May 2017. [ABSTRACT FROM AUTHOR]

In this work, we analyse the dynamics of a five-dimensional hepatitis C virus infection mathematical model including the spatial mobility of hepatitis C virus particles, the transmission of hepatitis C virus infection by mitosis process of infected hepatocytes with logistic growth, time delays, antibody response and cytotoxic T lymphocyte (CTL) immune response with general incidence functions for both modes of infection transmission, namely virus-to-cell as well as cell-to-cell. Firstly, we prove rigorously the existence, the uniqueness, the positivity and the boundedness of the solution of the initial value and boundary problem associated with the new constructed model. Secondly, we found that the basic reproductive number is the sum of the basic reproduction number determined by cell-free virus infection, determined by cell-to-cell infection and determined by proliferation of infected cells. It is proved the existence of five spatially homogeneous equilibria known as infection-free, immune-free, antibody response, CTL response and antibody and CTL responses. By using the linearization methods, the local stability of the latter is established under some rigorous conditions. Finally, we proved the existence of periodic solutions by highlighting the occurrence of a Hopf bifurcation for a certain threshold value of one delay. [ABSTRACT FROM AUTHOR]

An effective preventive vaccine for hepatitis C virus (HCV) remains a major unmet need. Antigenic region 3 (AR3) on the E1E2 envelope glycoprotein complex overlaps with the CD81 receptor binding site and represents an important epitope for broadly neutralizing antibodies (bNAbs) and is therefore important for HCV vaccine design. Most AR3 bNAbs utilize the VH1-69 gene and share structural features that define the AR3C-class of HCV bNAbs. In this work, we identify recombinant HCV glycoproteins based on a permuted E2E1 trimer design that bind to the inferred VH1-69 germline precursors of AR3C-class bNAbs. When presented on nanoparticles, these recombinant E2E1 glycoproteins efficiently activate B cells expressing inferred germline AR3C-class bNAb precursors as B cell receptors. Furthermore, we identify critical signatures in three AR3C-class bNAbs that represent two subclasses of AR3C-class bNAbs that will allow refined protein design. These results provide a framework for germline-targeting vaccine design strategies against HCV. The burden of chronic hepatitis C virus infection is exacerbated by the lack of an effective vaccine. In this work, authors use a recombinant permuted (E2E1) HCV glycoprotein design to analyze the binding of different VH1-69-derived AR3-directed broadly neutralizing antibodies to the viral envelope glycoprotein. [ABSTRACT FROM AUTHOR]

Although hepatitis B (HBV) and C (HCV) virus infections are still global health issues, measuring sero-markers by standard venipuncture is challenging in areas limited with the adequate human resources and basic infrastructure. This study aimed to inform the usefulness of dried blood spot (DBS) sampling technique for epidemiological study of HBV and HCV in the resources limited areas. We compared specimen recovery rate expressed as analytical sensitivity ratio of HBsAg, HBcAb and anti-HCV between serum specimens and DBS samples (HemaSpot vs Whatman903). Sensitivity ratio was calculated as the ratio of the measured value from DBS to the measured value from serum. Then both the qualitative and quantitative comparisons of HBsAg detection by DBS were done using Cambodian samples. HBsAg, HBcAb and anti-HCV sensitivity ratios for the highest sample dilution (8-fold) were 31.2:1, 38.9:1 and 32.0:1 for Whatman903 card and 17.6:1, 23.5:1 and 26.3:1 for HemaSpot respectively. Detection efficacy of HemaSpot (80%) was not inferior to Whatman903 (60%) after 1 month storage, and no significant difference in any hepatitis virus sero-markers was observed in HemaSpot-spotted patient samples stored for 2 weeks at −25 °C and 29 °C. All reference HemaSpot -spotted 400 HBsAg sero-negative samples showed negative. Sensitivity and specificity of HBsAg in HemaSpot were 92.3% and 100%. The recovery expressed as analytical sensitivity ratio of HBsAg, HBcAb and anti-HCV of HemaSpot specimen were not inferior to Whatman903. Therefore, DBS with its usefulness proved as an acceptable tool for large epidemiological study of HBV and HCV in resources limited remote area. [ABSTRACT FROM AUTHOR]

In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33–0.43) for sustained virologic response (SVR) and 1.70 (1.61–1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19–0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19–0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens. Data sources: This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords. Results: Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing. Conclusion: The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy. [ABSTRACT FROM AUTHOR]

Estimates of the population size of people who inject drugs (PWID) are essential for efficient program planning and for monitoring key targets. Existing estimates in Greece are based on the capture-recapture method applied to drug treatment sources. We aimed to obtain estimates based on data collected from a community-based program addressing PWID in Athens, Greece. The program was implemented in 2012–2013 to increase diagnosis and treatment for HIV among PWID during an HIV outbreak. Five Responden-Driven Sampling (RDS) rounds were used to recruit participants. A unique code was used to identify participants among rounds. Capture-recapture was applied to estimate the population size in 2013 (PWID with injection in the past 12 months; active PWID with injection in the past 30 days). Log-linear models were applied. In 2013, the estimated number of active PWID in Athens was 4,117 [95% confidence interval (CI): 3,728–4,507] (vs. 1,956 [95% CI: 1,525–2,565] the existing population size estimate). Based on this estimate, the coverage of needle and syringe programs in 2013 was 103 syringes/PWID/year (vs. 216 based on the existing estimate). The population prevalence of injecting drug use in Athens (past 12 months) was 0.222% (95% CI: 0.200–0.245). The inclusion of data from community-based programs in the estimation of the PWID population size resulted in 2.1-fold higher estimates, compared to the official estimates obtained from drug treatment data, and indicates the need for re-evaluation of necessary resources for harm reduction and elimination of HIV and hepatitis C in PWID. [ABSTRACT FROM AUTHOR]

Introduction: With the advent of direct-acting antivirals (DAAs), the past decade has seen a paradigm shift in the management of hepatitis C (HCV) infection in children. In this review, we summarize the various treatment options for pediatric HCV infection, highlighting the recent changes in the management. Methods: A literature search was performed using the PubMed database with the relevant keywords. Filters included were human, ages 0–18 years, and the English language. Results: Initial phase of HCV treatment using conventional or pegylated interferon and ribavirin combination regimens yielded poor outcomes in children, especially in genotypes 1 and 4, with an overall sustained virologic response of 58%. Also, treatment with interferon and ribavirin combination was associated with significant side effects in up to 52% of those treated. Presently, various combinations of direct-acting antivirals (DAAs) have been approved in children above three years of age with documented evidence of high efficacy (SVR12 of 92% to 100%) and excellent safety, and the current standard of care. Conclusion: With various DAA regimens now being approved for children above three years of age, the treatment of active HCV infection (HCV-RNA positive) in children has become simple. Besides the effectiveness of DAA therapy, public awareness about HCV transmission, better screening, and making the DAAs available at a subsidized price in the public sectors are necessary to eliminate HCV infection in India. [ABSTRACT FROM AUTHOR]

Background: Homeless and marginally housed (HAMH) individuals experience significant health disparities compared to housed counterparts, including higher hepatitis C virus (HCV) rates. New direct-acting antiviral (DAA) medications dramatically increased screening and treatment rates for HCV overall, but inequities persist for HAMH populations. Objective: This study examines the range of policies, practices, adaptations, and innovations implemented by Veteran Affairs Medical Centers (VAMCs) in response to Veterans Health Administration (VHA)'s 2016 HCV funding allocation to expand provision of HCV care. Design: Ethnographic site visits to six US VAMCs varying in size, location, and availability of Homeless Patient-Aligned Care Teams. Semi-structured qualitative interviews informed by the HCV care continuum were conducted with providers, staff, and HAMH patients to elicit experiences providing and receiving HCV care. Semi-structured field note templates captured clinical care observations. Interview and observation data were analyzed to identify cross-cutting themes and strategies supporting tailored HCV care for HAMH patients. Participants: Fifty-six providers and staff working in HCV and/or homelessness care (e.g., infectious disease providers, primary care providers, social workers). Twenty-five patients with varying homeless experiences, including currently, formerly, or at risk of homelessness (n=20) and stably housed (n=5). Key Results: All sites experienced challenges with continued engagement of HAMH individuals in HCV care, which led to the implementation of targeted care strategies to better meet their needs. Across sites, we identified 35 unique strategies used to find, engage, and retain HAMH individuals in HCV care. Conclusions: Despite highly effective, widely available HCV treatments, HAMH individuals continue to experience challenges accessing HCV care. VHA's 2016 HCV funding allocation resulted in rapid adoption of strategies to engage and retain vulnerable patients in HCV treatment. The strategies identified here can help healthcare institutions tailor and target approaches to provide sustainable, high-quality, equitable care to HAMH individuals living with HCV and other chronic illnesses. [ABSTRACT FROM AUTHOR]

Background: While hepatitis A and B are well-known causes of acute liver failure (ALF), few well-documented cases of hepatitis C virus (HCV) infection (absent preexisting liver disease or other liver insults) have been described that result in ALF. We reviewed the Acute Liver Failure Study Group registry for evidence of HCV as a primary or contributing cause to ALF. Methods: From January 1998 to January 2017, 2,332 patients with ALF (INR ≥ 1.5, any degree of hepatic encephalopathy) and 667 with acute liver injury (ALI; INR ≥ 2.0, no hepatic encephalopathy) were enrolled. Anti-HCV testing was done routinely, with confirmatory RT-PCR testing for HCV RNA where necessary. Results: A total of 136 patients were anti-HCV-antibody positive, as follows: 56 HCV RNA negative, 65 HCV RNA positive, and 8 with no result nor sera available for testing. Only three subjects with ALI/ALF were determined to represent acute HCV infection. Case 1: 47-year-old female with morbid obesity (BMI 52.4) developed ALF and recovered, experiencing anti-HCV seroconversion. Case 2: 37-year-old female using cocaine presented with ALI and fully recovered. Case 3: 54-year-old female developed ALF requiring transplantation and was anti-HCV negative but viremic prior to transplant experiencing anti-HCV seroconversion thereafter. Among 1636 APAP overdose patients, the 52 with concomitant chronic HCV had higher 3-week mortality than the 1584 without HCV (31% vs 17%, p = 0.01). Conclusions: ALI/ALF solely related to acute hepatitis C infection is very rare. Chronic HCV infection, found in at least 65 (2.2%) of ALI/ALF patients studied, contributed to more severe outcomes in APAP ALI/ALF; ClinicalTrials.gov number, NCT000518440. Trial Registration ClinicalTrials.gov number NCT000518440. [ABSTRACT FROM AUTHOR]

In the United States, approximately 25% of people with HIV (PWH) are co-infected with hepatitis C (HCV). Since 2014, highly effective and well-tolerated direct-acting antivirals (DAAs) have revolutionized HCV treatment. Uptake of DAAs by people with HIV/HCV co-infection has improved but remains suboptimal due to system, provider, and patient-level barriers. To explore patient-level issues by better understanding their attitudes towards DAA treatment, we conducted qualitative interviews with 21 persons with HIV/HCV co-infection who did not consent to DAA treatment or delayed treatment for at least 1 year after diagnosis. We found PWH perceived DAA treatment barriers and facilitators on multiple levels of the social-ecological environment: the individual (HCV disease and treatment literacy), interpersonal (peer influence), institutional (media and healthcare provider relationship), and structural levels (treatment cost and adherence support). Recommendations to improve DAA treatment uptake include HCV-treatment adherence support, HCV disease and treatment literacy training (particularly for substance use and DAA treatment interactions), and encouraging PWH who have successfully completed DAA treatment to speak with their peers. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus, a member of Flaviviridae is a single-stranded positive-sense RNA virus infecting 62–79 million people around the globe. This blood-borne virus is one of the leading causes of liver diseases worldwide. This review aims to identify novel potential genes linked to cellular host factors, as well as revise the roles of each gene in hepatitis C Virus infection. This review also aims to provide a comprehensive insight into therapeutic advancements against HCV. Methods: For this review article, 190 articles were searched via PubMed Central, Bio-One, National Academy of Science, Google Scholar, and Worldwide Science. 0ut of these 190 studies, 55 articles were selected for this review. The inclusion of articles was done on the criteria of high citation and Q1 ranking. Results: The information gathered from previously published articles highlighted a critical link between host-cellular factors that are important for HCV infection. Conclusion: Although many advancements in HCV treatment have been made like DAAs and HTAs, the development of a completely effective HCV therapy is still a challenge. Further research on combinations of DAAs and HTAs can help in developing a better therapeutic alternative. Keywords: Hepatitis C virus, Replication cycle, Non-structural proteins, Host-cellular factors, Treatment strategies [ABSTRACT FROM AUTHOR]

Mothers of children with chronic hepatitis C virus (HCV) infection experience anxiety about the health of their children. In this study we assessed an impact of treating children with chronic HCV infection on the psychological burden of their mothers. This was a multicenter, questionnaire survey conducted at six institutions in Japan. A newly-developed questionnaire for this study was used to assess changes in the mothers' various concerns regarding HCV infection and thoughts about their child's HCV infection. Responses at the time of diagnosis and at the time of the survey were compared between mothers of children who had received treatment and those without treatment. Responses were received from 36 of 37 eligible mothers (11 and 25, non-treatment and treatment groups, respectively). All children in treatment group had successfully eliminated the virus. Mothers in both groups were psychologically stressed in various ways, including concern about their child's health in the present and future at the time of diagnosis, concern about school, employment, and marriage, concern about the behavior of others towards them and infecting others with HCV, and feelings of guilt regarding their child. These concerns were significantly lower in the present compared to at the time of diagnosis in treatment group, and the rate of decrease was significantly higher in treatment group compared to non-treatment group. Successful treatment greatly reduced mothers' concerns about their children's HCV infection, indicating that treatment during childhood is beneficial from the perspective of the mothers' psychological burden. [ABSTRACT FROM AUTHOR]

T cell exhaustion is a hallmark of hepatitis C virus (HCV) infection and limits protective immunity in chronic viral infections and cancer. Limited knowledge exists of the initial viral and immune dynamics that characterise exhaustion in humans. We studied longitudinal blood samples from a unique cohort of individuals with primary infection using single-cell multi-omics to identify the functions and phenotypes of HCV-specific CD8+ T cells. Early elevated IFN-γ response against the transmitted virus is associated with the rate of immune escape, larger clonal expansion, and early onset of exhaustion. Irrespective of disease outcome, we find heterogeneous subsets of progenitors of exhaustion, based on the level of PD-1 expression and loss of AP-1 transcription factors. Intra-clonal analysis shows distinct trajectories with multiple fates and evolutionary plasticity of precursor cells. These findings challenge the current paradigm on the contribution of CD8+ T cells to HCV disease outcome and provide data for future studies on T cell differentiation in human infections. The early immune response following exposure to HCV is not fully explored. Here the authors use single cell analysis and immune profiling to relate the infection sequence and immune response to early HCV infection showing that exhausted phenotypes of T cells arise early post infection. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization. E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits. [ABSTRACT FROM AUTHOR]

SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir's apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir. [ABSTRACT FROM AUTHOR]

Dynamic resource allocation for prevention, screening, and treatment interventions in population disease management has received much attention in recent years due to excessive healthcare costs. In this paper, our goal is to design a model and an efficient algorithm to optimize sequential intervention policies under resource constraints to improve population health outcomes. We consider a discrete-time finite-horizon budget allocation problem with disease progression within a closed birth-cohort population. To address the computational challenges associated with large-state and multiple-period dynamic decision-making problems, we propose a low-fidelity approximation that preserves the population dynamics under a stationary policy. To improve the healthcare interventions in terms of population health outcomes, we then embed the low-fidelity approximation into a high-fidelity optimization model to efficiently identify a good non-stationary sequential intervention policy. Our approach is illustrated by a numerical example of screening and treatment policy implementation for chronic hepatitis C virus (HCV) infection over a budget planning period. We numerically compare our Multi-Fidelity Rollout Algorithm (MF-RA) to a grid search approach and demonstrate the similarity of sequential policy trends and closeness of overall health outcomes measured by quality-adjusted life-years (QALYs) and the total number of individuals that undergo screening and treatment for different annual budgets and birth-cohorts. We also show how our approach scales well to problems with high dimensionality due to many decision periods by studying time to elimination of HCV. [ABSTRACT FROM AUTHOR]

This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored. [ABSTRACT FROM AUTHOR]

In this paper we propose two methods to give a first rough estimate of the actual number of hepatitis C virus (HCV)-infected individuals (prevalence) taking into account the notification rate of newly diagnosed infections (incidence of notification) and the size of the liver transplantation waiting list (LTWL) of patients with liver failure due to chronic HCV infection. Both approaches, when applied to the Brazilian HCV situation converge to the same results, that is, the methods proposed reproduce both the prevalence of reported cases and the LTWL with reasonable accuracy. We use two methods to calculate the prevalence of HCV that, as a first, and very crude approximation, assumes that the actual prevalence of HCV in Brazil is proportional to the reported incidence to the official notification system with a constant denoted $$\kappa $$ . In the paper we discuss the limitations and advantages of this assumption. With the two methods we calculated $$\kappa $$ , which reproduces both the reported incidence and the size of the LTWL. With the value of $$\kappa $$ we calculated the prevalence I( a) (the integral of which resulted in 1.6 million people living with the infection in Brazil, most of whom unidentified). Other variables related to HCV infection (e.g., the distribution of the proportion of people aged a who got infected n years ago) can be easily calculated from this model. These new variables can then be measured and the model can be recursively updated, improving its accuracy. [ABSTRACT FROM AUTHOR]

Health state utilities are global measurements of quality of life and have been used to evaluate health outcomes for the cost-utility analysis. This study aimed to estimate the health state utilities of patients with hepatitis B (HB), hepatitis C (HC), and hepatitis-related diseases in Japan. We distributed a self-administered questionnaire, including the EuroQol 5-Dimension 5-Level (EQ-5D-5L), to 9,952 outpatients with several clinical conditions caused by HB or HC virus infection (such as asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis) and estimated the condition-specific utilities of patients with HB or HC. In patients with more severe conditions (patients with acute hepatitis, fulminant hepatitis, and hepatocellular carcinoma and patients undergoing post-liver transplantation), the utilities of these severe conditions were estimated by three hepatitis experts using the EQ-5D-5L. The means of the utilities for acute hepatitis, fulminant hepatitis, asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, compensated cirrhosis, hepatocellular carcinoma stage I/II, hepatocellular carcinoma stage III/IV, and post-liver transplantation were 0.529, − 0.111, 0.904, 0.868, 0.845, 0.722, 0,675, 0,428, and 0.651 and 0.876, 0.821, 0.737, 0.671, 0.675, 0.428, and 0.651 in HB and HC, respectively. To the best of our knowledge, this is the first study that comprehensively assessed the health state utilities of patients with HB, HC and hepatitis-related conditions from a nationwide survey in Japan using the EQ-5D-5L. [ABSTRACT FROM AUTHOR]

Halophilic archaea is considered an promising natural source of many important metabolites. This study focused on one of the surface-active biomolecules named biosurfactants produced by haloarchaeon Natrialba sp. M6. The production trend was optimized and the product was partially purified and identified using GC–Mass spectrometry. Sequential optimization approaches, Plackett–Burman (PB) and Box–Behnken Designs (BBD) were applied to maximize the biosurfactants production from M6 strain by using 14 factors; pH, NaCl, agitation and glycerol; the most significant factors that influenced the biosurfactant production were used for Response Surface Methodology (RSM). The final optimal production conditions were agitation (150 rpm), glycerol (3%), NaCl (20.8%), pH (12) and cultivation temperature (37°C). GC–Mass spectrometry for the recovered extract revealed the presence of a diverse group of bipolar nature, hydrophobic hydrocarbon chain and charged function group. The majority of these compounds are fatty acids. Based on results of GC–MS, compositional analysis content and Zetasizer, it was proposed that the extracted biosurfactant produced by haloarchaeon Natrialba sp. M6 could be a cationic lipoprotein. The antiviral activity of such biosurfactant was investigated against hepatitis C (HCV) and herpes simplex (HSV1) viruses at its maximum safe doses (20 μg/mL and 8 μg/mL, respectively). Its mode of antiviral action was declared to be primarily via deactivating viral envelopes thus preventing viral entry. Moreover, this biosurfactant inhibited RNA polymerase- and DNA polymerase-mediated viral replication at IC50 of 2.28 and 4.39 μg/mL, respectively also. Molecular docking studies showed that surfactin resided well and was bound to the specified motif with low and accepted binding energies (ΔG = − 5.629, − 6.997 kcal/mol) respectively. Therefore, such biosurfactant could be presented as a natural safe and effective novel antiviral agent. [ABSTRACT FROM AUTHOR]

Background and Aims: The burden of hepatocellular carcinoma (HCC) is increasing, and certain groups may be at higher risk. Methods: We analyzed trends in HCC-related mortality in the USA (1999–2018) using national death data. Age-adjusted trends in death rates (annual percentage change, APC) were calculated using joinpoint regression analysis. Results: HCC-related death rates increased by 2.1% (95% CI 1.9 to 2.3) annually. Hepatitis C (HCV)-related HCC death rates increased from 1999 to 2012 (8.9%, 95% CI 7.6 to 10.2) followed by a −1.3% (95% CI −3.5 to 0.9) decrease annually. For adults > 65 years, HCV-related HCC death rates increased (7.3% annually, 95% CI 6.5 to 8.1), especially for rural areas (11.1% annually, 95% CI 6.9 to 15.5) with high rates among African-Americans and Hispanics. Increases in non-HCV-related HCC death rates were larger: 13.5% annually (95% CI 3.6 to 24.3, 2005–2010) followed by 4.2% annually (95% CI 2.3 to 6.2, 2010–2018). Annual rates of increase were similar for men (6.8%, 95% CI 5.9 to 7.8) and women (7.0%, 95% CI 5.5 to 8.4) from 1999 to 2018. Rate of increase across races was Whites 8.3% (95% CI 7.2 to 9.4, 1999–2018), African-Americans 11.2% (95% CI −6.6 to 32.3, 2015–2018), and Hispanics 3.7% (95% CI 1.0 to 6.5, 2012–2018). Conclusion: HCC-related mortality has increased, driven by increases in non-HCV-related mortality with important demographic and regional trends. In addition, HCV-HCC mortality remains high particularly in older persons and those in rural areas despite advances in HCV therapy. These data underscore the need for targeted approaches to mitigate the burden of HCC-related mortality similar to efforts for other cancers. [ABSTRACT FROM AUTHOR]

Introduction: As a country that is heavily burdened by hepatitis C, China's successful responses to this public health threat have significant implications for the achievement of the global elimination goal. Methods: This article reviews China's strategies for prevention, screening, diagnosis, access to direct-acting antiviral agents (DAA) therapy, and patient management of hepatitis C. It also analyses the major challenges and summarizes the valuable successful international experiences that have implications for China to achieve the elimination goal. Results: To promote the achievement of elimination, China has taken a series of proactive measures to promote the prevention and treatment of hepatitis C. Compared with other middle-income countries, there is still much room for China to achieve universal screening, diagnosis and treatment based on a streamlined disease management procedure. A stronger role of primary care in an integrated healthcare delivery system and integration of hepatitis C with other infectious disease programs should also be the focus of China's efforts. Conclusions: As a developing country with a large population, a "micro-elimination" strategy with focused screening and proactive diagnosis and treatment for the vulnerable population may be a more practical approach to eliminating hepatitis C in China. Continued efforts are needed to fully overcome the intellectual property barriers of sofosbuvir for forming the more competitive pan-genotype DAA combinations based on the locally developed DAAs. Meanwhile, the safety net for patients in economic hardship needs to be further strengthened. More importantly, it is necessary to promote patients' willingness and compliance with standard treatment through increased awareness of hepatitis C. The development of an integrated healthcare delivery system, a disease management procedure which is suitable for primary care, and full compliance of the primary care providers are also important to achieve effective cascade care management. [ABSTRACT FROM AUTHOR]

Background: In 2015, the Swedish government in an unprecedented move decided to allocate 150 million € to provide funding for new drugs for hepatitis C. This was triggered by the introduction of the first second generation of direct-acting antivirals (DAAs) promising higher cure rates and reduced side effects. The drugs were cost-effective but had a prohibitive budget impact. Subsequently, additional products have entered the market leading to reduction in prices and expansions of the eligible patient base. Methods: We estimated the social surplus generated by the new DAAs in Stockholm, Sweden, for the years 2014–2019. The actual use and cost of the drugs was based on registry data. Effects on future health care costs, indirect costs and QALY gains were estimated using a Markov model based primarily on Swedish data and using previous generations of interferon-based therapies as the counterfactual. Results: A considerable social surplus was generated, 15% of which was appropriated by the producers whose share fell rapidly over time as prices fell. Most of the consumer surplus was generated by QALY gains, although 10% was from reduced indirect costs. QALY gains increased less rapidly than the number of treated patients as the eligibility criteria was loosened. Conclusions: The transfer of funds from the government to the regions helped generate substantial surplus for both consumers and producers with indirect costs playing an important role. The funding model may serve as a model for the financing of innovative treatments in the future. [ABSTRACT FROM AUTHOR]

Background: Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients.Methods: The Medline was searched for “HCV infection”, “HCV treatment”, “Directly acting antivirals”,“HCV resistance”.Results: Most patients who did not achieve an SVR have been found to be infected with HCV mutant strains with a reduced susceptibility to these drugs. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A regions and rarely in the NS5B region. Treatment-induced mutants resistant to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration.Conclusions: Patients who have failed HCV treatment with DAA agents have several re-treatment options, but re-treatment selection may be intricate and resistance testing is recommended to optimize this choice. It is, therefore, important to bear in mind that the correct determination of HCV genotype and subtype and the identification of RASs are essential elements for choosing the optimal re-treatment. It is supposed that it is useful to give readers some other suggestions regarding therapeutic reprocessing. [ABSTRACT FROM AUTHOR]

Nebraska has one of the highest numbers of refugees per capita in the U.S. A high number of Somalis have resettled in Nebraska due to job opportunities and the low cost of living. In this paper, we report the process and the results of a cervical and breast cancer education program for Somali women conducted through a collaboration among public health, academia, and community entities. The curriculum was built to be suitable for the literacy level and cultural values of this community. Topics include female reproductive anatomy; breast and cervical cancer knowledge and screening; hepatitis C and liver cancer; and preparing for a health screening visit. Two community members trained as lay health workers conducted a pilot and an actual education session. The 2-day education program was attended by 52 women. Qualitative data showed the intervention to be promising for this and other African refugee populations. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this paper is to provide a thorough overview of methods used for recruitment, network data collection, and network data management in a network-based study of rural people who use drugs (PWUD) and to offer methodological recommendations for future research on rural drug use.Recent Findings: The Social Networks among Appalachian People (SNAP) study recruited a cohort of 503 rural PWUD via respondent-driven sampling (RDS) and has retained more than 80% of eligible participants over 7-9 years. SNAP has yielded important methodological insights, including that (1) RDS referral was non-random and disproportionately involved kin and (2) interviewer-administered questionnaires were successful in eliciting accurate name and age information about network members.Summary: The SNAP experience suggests that RDS was a successful recruitment strategy for rural PWUD and questionnaires administered by community-based interviewers in the context of a Certificate of Confidentiality could elicit detailed data on PWUD risk networks. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the fourth in Egypt. Persistent inflammation and specific somatic mutations in driving genes play a major role in the development of HCC. One of these somatic mutations is CTNNB1 mutations with subsequent activation of β-catenin in HCC, associated with a risk of malignant transformation. In this study, we investigate the clinical utility of peripheral blood circulating tumor DNA (ctDNA) CTNNB1 (rs121913407) in HCC patients compared to pathological chronic hepatitis C virus (HCV) patients and healthy controls. Methods: Our study is a case-control study at the Ain Shams Centre for Organ Transplantation, Ain Shams University Hospitals, enrolling twenty-eight adult HCC patients (twelve early HCC patients and sixteen advanced HCC patients), ten patients with chronic hepatitis C as a disease control group, and ten healthy controls. We collected plasma and stored at −80 °C. We detected mutations in the gene locus CTNNB1 rs121913407 by real-time PCR. Results: All of our studied cases (early and advanced HCC) in addition to HCV and healthy control groups were CTNNB1 wild (TT) genotype. There was statistical significant difference between early and late cases of HCC as regards AFP and AST. Conclusions: None of our recruited subjects showed CTNNB1 rs121913407 gene mutation. Further studies on larger number of patients are needed to clarify and confirm the clinical utility of CTNNB1 single-nucleotide polymorphism in the pathogenesis of HCC related to HCV in Egyptian population. [ABSTRACT FROM AUTHOR]

Objectives: Non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid–enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of progressing to hepatocellular carcinoma (HCC). The presence of NHHNs is a strong risk factor for HCC development in patients with chronic hepatitis C virus (HCV) infection after the achievement of sustained virologic response (SVR). However, it is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection. We therefore explored serum markers that potentially indicate the presence of NHHNs. Methods: Three serum markers, alpha-fetoprotein (AFP), FIB-4 index, and Wisteria floribunda agglutinin–positive Mac-2 binding protein glycan isomer (M2BPGi), were measured in 481 patients with HCV infection and no history of HCC who underwent EOB-MRI. The associations between these serum marker levels and the presence of NHHNs were investigated. Results: All three markers were associated with the presence of NHHNs. M2BPGi predicted the presence of NHHNs more accurately than AFP and FBB-4 index; M2BPGi had the highest area under the receiver operating characteristic curve. Multivariate analysis identified male gender and high M2BPGi as factors associated with the presence of NHHNs. When patients were stratified by the degree of liver fibrosis, M2BPGi increased with the progression of fibrosis. In addition, NHHNs were more prevalently detected in patients with higher M2BPGi (COI > 3.46) in patients with similar fibrosis degree. Conclusions: M2BPGi is a serum marker that potentially identifies HCV patients with high risk of the presence of NHHNs, for whom EOB-MRI should be considered. Key Points: • Non-hypervascular hypointense nodule on EOB-DTPA-enhanced MRI is pre-HCC nodule with high likelihood of progressing to HCC, which is a strong predictor for HCC that develops after the eradication of HCV in patients with HCV infection. • It is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection due to limited access, limited availability of MRI equipment, and high costs. • Serum Wisteria floribunda agglutinin–positive Mac-2 binding protein glycan isomer (M2BPGi) levels effectively indicate the presence of NHHNs and can be used to identify patients with high risk of their presence, for whom EOB-DTPA-enhanced MRI should be considered. [ABSTRACT FROM AUTHOR]

The direct impact of chronic hepatitis B and hepatitis C on neurocognition remains elusive due to the frequent comorbidities, and the domains of the neurocognitive functions affected have rarely been investigated comprehensively. We cross-sectionally assessed the neurocognitive functions of the individuals with chronic hepatitis B, chronic hepatitis C, treated chronic hepatitis C with a sustained virologic response, and their healthy control counterparts. Laboratory examinations were used to investigate the impact of inflammation on neurocognition, exclude the medical conditions that could interfere with neurocognition assessment, and assess liver function and fibrotic severity of the liver of the participants. This study found the detrimental impact of chronic hepatitis B on language and executive functions. In contrast, individuals with chronic hepatitis C showed deficits in executive functions, psychomotor speed, memory, and attention. Successful elimination of hepatitis C resulted in improved liver function, but not neuropsychological test performance. Moreover, erythrocyte sedimentation rate level was found to mediate the deficits in the attention of individuals with chronic hepatitis C. These results demonstrate the neurocognitive deficits and the difference in the profiles of neurocognitive deficits in individuals with chronic hepatitis B and chronic hepatitis C. Our study also provided results suggesting the mediation by systemic inflammation on the attention deficit in individuals with chronic hepatitis C. [ABSTRACT FROM AUTHOR]