Universal Screening for Hepatitis C Virus in the ED Using a Best Practice Advisory.

INTRODUCTION: In 2019 the United States Preventive Services Task Force (USPSTF) released draft guidelines recommending universal hepatitis C virus (HCV) screening for individuals aged 18-79. We aimed to assess the efficacy of an emergency department-based HCV screening program, by comparing screening practices before and after its implementation. METHODS: We performed a retrospective cohort analysis of two temporally matched, 11-month study periods, corresponding to before and after the implementation of a best practice advisory (BPA). Patients were screened for anti-HCV antibody (Ab), and positive results were followed by HCV viral load (VL) testing. The primary implementation outcome was ED testing volume (number of tests performed/month). The primary screening outcomes were the seroprevalence of anti-HCV Ab and HCV VL. We describe data with simple descriptive statistics. RESULTS: The median age of patients was similar between periods (pre: 50 years [interquartile range [IQR] 34-62], post: 47 years [IQR 33-59]). Patients screened were more likely to be males in the pre-BPA period (Male, pre: 60%, post: 49%). During the pre-BPA study period, a total of 69,604 patients were seen in the ED, and 218 unique patients were screened for HCV (mean 19.8 tests/month). During the post-BPA study period, a total of 68,225 patients were seen in the ED, and 14,981 unique patients were screened for HCV (mean 1361.9 tests/month). Anti-HCV Ab seroprevalence was 23% (51/218) and 9% (1340/14,981) in the pre-BPA and post-BPA periods, respectively. In the pre-BPA period, six patients with a positive anti-HCV Ab level had follow-up VL testing (detectable in three). In the post-BPA period, reflex VL testing was performed in most patients (91%, 1225/1,340), and there were 563 patients with detectable VLs, indicating active infection. CONCLUSION: Our study shows that using a universal BPA-driven screening protocol can dramatically increase the number of patients screened for HCV and increase the number of new HCV diagnoses.

Hepatitis C Among High-Risk Alabamians: Disease Burden and Screening Effectiveness.

BACKGROUND: The effectiveness of hepatitis C testing and linkage-to-care (LTC) is poorly characterized in low-resource jurisdictions facing gaps in harm reduction, including illegality of syringe exchange services. Effectiveness of a community-based test/LTC program was evaluated in Alabama. METHODS: In 2016-2018, shelters, drug treatment centers (DTCs), AIDS organizations, and Federally Qualified Health Centers (FQHCs) engaged in screening/LTC. A coordinator navigated individuals to confirm viremia and link to substance use treatment or primary care with hepatitis C prescribers. RESULTS: Point-of-care (POC) tested 4293 individuals (10% [427] antibody-positive, 71% [299/419] RNA performed, 80% [241/299] viremia confirmed) and 93% linked to care (225/241). Electronic medical record (EMR)-based reflex strategy screened 4654 (15% [679] antibody positive, 99% [670/679] RNA performed, 64% [433/679] viremia confirmed) and 85% linked to care (368/433). We observed higher odds of RNA confirmation in EMR-based reflex versus POC (OR, 2.07; P < .0001) and higher odds of LTC in EMR-based reflex versus POC (OR, 1.51; P < .0001). Overall, 53% individuals tested were nonbaby boomers. CONCLUSIONS: In Alabama, screening at high-risk settings identified significant hepatitis C burden and reflex testing outperformed point-of-care linkage indicators. Colocating testing in DTCs and treatment in FQHCs provided key LTC venues to at-risk younger groups.

Crowdsourcing to promote hepatitis C testing and linkage-to-care in China: a randomized controlled trial protocol.

BACKGROUND: Hepatitis C virus (HCV) is a growing public health problem with a large disease burden worldwide. In China many people living with HCV are unaware of their hepatitis status and not connected to care and treatment. Crowdsourcing is a technique that invites the public to create health promotion materials and has been found to increase HIV testing uptake, including in China. This trial aims to evaluate crowdsourcing as a strategy to improve HCV awareness, testing and linkage-to-care in China. METHODS: A randomized controlled, two-armed trial (RCT) is being conducted in Shenzhen with 1006 participants recruited from primary care sectors of The University of Hong Kong-Shenzhen Hospital. Eligible participants are ≥30 years old; a resident in Shenzhen for at least one month after recruitment; no screening for HCV within the past 12 months and not known to have chronic HCV; and, having a WeChat social media account. Allocation is 1:1. Both groups will be administered a baseline and a follow-up survey (4-week post-enrollment). The intervention group will receive crowdsourcing materials to promote HCV testing once a week for two weeks and feedback will be collected thereafter, while the control group will receive no promotional materials. Feedback collected will be judged by a panel and selected to be implemented to improve the intervention continuously. Those identified positive for HCV antibodies will be referred to gastroenterologists for confirmation and treatment. The primary outcome will be confirmed HCV testing uptake, and secondary outcomes include HCV confirmatory testing and initiation of HCV treatment with follow-ups with specialist providers. Data will be collected on Survey Star@ via mobile devices. DISCUSSION: This will be the first study to evaluate the impact of crowdsourcing to improve viral hepatitis testing and linkage-to-care in the health facilities. This RCT will contribute to the existing literature on interventions to improve viral hepatitis testing in primary care setting, and inform future strategies to improve HCV care training for primary care providers in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry. ChiCTR1900025771. Registered September 7th, 2019, http://www.chictr.org.cn/showprojen.aspx?proj=42788.

Antibody avidity-based approach to estimate population-level incidence of hepatitis C.

BACKGROUND & AIMS: Accurate HCV incidence estimates are critical for monitoring progress towards HCV elimination goals, including an 80% reduction in HCV incidence by 2030. Moreover, incidence estimates can help guide prevention and treatment programming, particularly in the context of the US opioid epidemic. METHODS: An inexpensive, Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level primary HCV incidence using 1,840 HCV antibody and RNA-positive samples from 875 individuals enrolled in 5 cohort studies in the US and India. Using samples collected <2 years following HCV seroconversion, the mean duration of recent infection (MDRI) was calculated by fitting a maximum likelihood binomial regression model to the probability of appearing recent. Among samples collected ≥2 years post-HCV seroconversion, an individual-level false recent ratio (FRR) was calculated by estimating the probability of appearing recent using an exact binomial test. Factors associated with falsely appearing recent among samples collected ≥2 years post seroconversion were determined by Poisson regression with generalized estimating equations and robust variance estimators. RESULTS: An avidity index cut-off of <40% resulted in an MDRI of 113 days (95% CI 84-146), and FRRs of 0.4% (95% CI 0.0-1.2), 4.6% (95% CI 2.2-8.3), and 9.5% (95% CI 3.6-19.6) among individuals who were HIV-uninfected, HIV-infected, and HIV-infected with a CD4 count <200/µl, respectively. No variation was seen between HCV genotypes 1 and 3. In hypothetical scenarios of high-risk settings, a sample size of <1,000 individuals could reliably estimate primary HCV incidence. CONCLUSIONS: This cross-sectional approach can estimate primary HCV incidence for the most common genotypes. This tool can serve as a valuable resource for program and policy planners seeking to monitor and reduce HCV burden. LAY SUMMARY: Determining the rate of new hepatitis C virus (HCV) infections in a population is critical to monitoring progress toward HCV elimination and to appropriately guide control efforts. However, since HCV infections are most often initially asymptomatic, it is difficult to estimate the rate of new HCV infections without following HCV-uninfected people over time and repeatedly testing them for HCV infection. Here, we present a novel, resource-efficient method to estimate the rate of new HCV infections in a population using data from a single timepoint.

Eliminación de la hepatitis C. Documento de posicionamiento de la Asociación Española para el Estudio del Hígado (AEEH) / Elimination of hepatitis C. Positioning document of the Spanish Association for the Study of the Liver (AEEH)

La Asociación Española para el Estudio del Hígado (AEEH) está convencida de que la eliminación de la hepatitis C en España es posible siempre y cuando seamos capaces de emplear los recursos y las herramientas necesarias para la misma. Este documento refleja la posición de la AEEH respecto a la eliminación del virus de la hepatitis C (VHC), estableciendo una amplia serie de recomendaciones que se pueden agrupar en cinco categorías: 1) cribado del VHC en función de la edad, de la existencia de factores de riesgo clásicos de adquisición de la infección, búsqueda activa de pacientes diagnosticados con anterioridad y desarrollo de estrategias de microeliminación en poblaciones vulnerables; 2) simplificación del diagnóstico del VHC (diagnóstico en un solo paso y diagnóstico en el punto de atención del paciente); 3) simplificación del tratamiento de los pacientes y mejora de los circuitos asistenciales; 4) medidas de política sanitaria, y, finalmente, 5) establecimiento de indicadores de eliminación del VHC

The Spanish Association for the Study of the Liver (AEEH) is convinced that the elimination of hepatitis C virus (HCV) in Spain is possible as long as we are able to use the resources and tools necessary for it. This document reflects the position of the AEEH regarding the elimination of HCV, establishing a wide range of recommendations that can be grouped into five categories: 1) Screening of HCV according to age, of the existence of classic acquisition risk factors of infection, active search of previously diagnosed patients and development of microelimination strategies in vulnerable populations; 2) Simplification of HCV diagnosis (one-step diagnosis and diagnosis at the point of patient care); 3) Simplification of patient treatment and improvement of care circuits; 4) Health policy measures, and, finally, 5) Establishment of HCV elimination indicators

Evaluation of the diagnostic accuracy of laboratory-based screening for hepatitis C in dried blood spot samples: A systematic review and meta-analysis.

The dried blood spot (DBS) is increasingly used for the hepatitis C virus (HCV) screening. Our objective was to perform a meta-analysis of the methodology for HCV screening in DBS samples, particularly in the type of diagnostic assay used. We performed a meta-analysis of all eligible studies published to date (March 2018). The literature search revealed 26 studies: 21 for detection of anti-HCV antibodies and 10 for detection of HCV-RNA. Statistical analyses were performed using Meta-DiSc and STATA (MIDAS module). For detection of HCV antibodies, pooled diagnostic accuracy measures were as follows: sensitivity 96.1%, specificity 99.2%, positive likelihood ratio (PLR) 105, negative likelihood ratio (NLR) 0.04, diagnostic odds ratio (DOR) 2692.9, and summary receiver operating characteristic (SROC) 0.997 ± 0.001. For detection of HCV-RNA, the pooled diagnostic accuracy measures were as follows: sensitivity 97.8%, specificity 99.2%, PLR 44.8, NLR 0.04, DOR 1966.9, and SROC 0.996 ± 0.013. Similar values of pooled diagnostic accuracy measures were found according to the type of anti-HCV antibody detection assay (enzyme-linked immunosorbent assay, rapid diagnostic test, and chemiluminescence assays) and HCV-RNA detection assay (real-time polymerase chain reaction and transcription-mediated amplification). The analysis of external validity showed a high negative predicted value (NPV) for both approaches, but a low positive predicted value (PPV) when prevalence was < 10%, particularly in HCV-RNA tests. Finally, this meta-analysis is subject to limitations, especially publication bias and significant heterogeneity between studies. In conclusion, HCV screening in DBS samples has an outstanding diagnostic performance, with no relevant differences between the techniques used. However, external validity may be limited when the HCV prevalence is low.

Hepatitis aguda C seronegativa: informe de dos casos / Acute seronegative hepatitis C: two case reports

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Hepatitis C Virus Potentially Transmitted by Opioid Drug Diversion from a Nurse - Washington, August 2017-March 2018.

During January 22-March 23, 2018, a local health department in Washington was notified of two patients who received a diagnosis of acute hepatitis C virus (HCV) infection. Neither patient had behavioral risk factors associated with HCV acquisition; however, both had received injectable narcotic (opioid) drugs from the same nurse during separate visits to an emergency department (ED) at a local hospital on December 6 and December 16, 2017. Investigation revealed that the nurse had accessed the automated drug dispensing system at a higher frequency than had other staff members, admitted diverting* patients' injectable narcotic and antihistamine drugs for personal use, and tested positive for HCV antibodies (anti-HCV) on March 19, 2018, but did not have quantifiable HCV RNA. Specimens from both patients were sent to CDC for genetic testing, and HCV viral variants analysis found a significant level of genetically similar HCV variants in both patients, indicating a common source of infection. Further investigation was conducted to confirm the infection source, identify other potentially exposed patients, and treat any new patients who received an HCV diagnosis. Monitoring frequency of access to drug dispensing systems can help identify staff members with abnormal dispensing patterns, including diversion activities (1). U.S. health care facilities are required to prevent, identify, and report any loss, diversion, or theft of controlled substances (2).

Probing the Antigenicity of HCV Envelope Glycoproteins by Phage Display Antibody Technology.

The envelope glycoproteins E1 and E2 of hepatitis C virus form a heterodimeric complex on the viral surface. They are the targets of neutralizing antibodies and are being investigated as potential vaccine antigens. Because of the high level of cysteine residues and N-glycosylation sites in the polypeptide sequences, it is technically challenging to produce pure, folded recombinant E1, E2, and E1E2 complex for downstream analysis. In this chapter, the methods we used to isolate a panel of human antibodies specific to diverse antigenic regions on the glycoproteins are discussed. The antibodies have been found to be valuable reagents for the study of HCV envelope glycoproteins, including the determination of the first E2 core domain structure.

Isolation of HCV Neutralizing Antibodies by Yeast Display.

Yeast surface display (YSD) enables efficient screening and selection of single chain variable fragments (scFvs) of heavy (VH) and light (VL) chains that bind to target antigen with different affinities. Assembly of a scFv library from cDNA usually involves adding different primers and linkers (Gly4/Ser)3 through multiple rounds of PCR amplification and purification. We describe here a simplified scFv assembly method by creating a modified YSD vector with a built-in linker that reduces the time of assembly and decreases accumulated base exchanges due to PCR errors. In addition, we describe a bias screening strategy toward maximizing novel antibodies of interest by a combination of memory B cell selection and depletion by binding to mutant antigens that do not bind to previously identified monoclonal antibodies.

Detection of Antibodies to HCV E1E2 by Lectin-Capture ELISA.

Enzyme-linked immunosorbent assays (ELISAs) enable rapid detection and quantitation of antibodies in samples. Such assays can be highly sensitive and can be performed in most laboratories with basic equipment. Although detecting binding antibodies to the surface proteins of most pathogens by ELISA is not always indicative of antibody function, i.e., neutralizing activity of antibodies, the results can be used as a first step toward more in-depth analysis of antibody responses. Here we describe a method that can be used to standardize ELISAs for the detection of HCV envelope antibodies across laboratories and provide adaptations of the method to further characterize antibody responses in serum samples.

Prevalence of hepatitis C virus infection and its impact on the prognosis of head and neck cancer patients.

OBJECTIVE: Several studies have shown a higher prevalence of hepatitis C virus (HCV) infection among patients with head and neck cancer (HNC) compared to the general population. In Brazil, the prevalence of HCV infection is considered low (1.38%). The aim of this study was to determine HCV prevalence and how this can modify outcomes of patients with HNC. STUDY DESIGN: Retrospective cohort. METHODS: Patients with a diagnosis of malignant neoplasm in the head and neck (HN) region and who had serology performed for HCV were included. Patients were classified into two groups: head and neck squamous cell carcinoma (HNSCC) and other head and neck malignant neoplasms (OHNMN). Descriptive statistics were performed for all variables of interest. Means were compared using ANOVA and proportions using chi-square tests. Survival data were compared by Kaplan-Meier curves and log-rank test. RESULTS: Global HCV prevalence in patients with HNC was 7.8%, reaching 12.8% in HNSCC and 3.4% in OHNMN (p = 0.003). There was a higher risk of developing a second primary neoplasm in HNSCC compared to OHNMN patients (20.6% versus 4.6%; p = 0.001). The mean survival was not different between HCV-positive and HCV-negative patients (6.0 years versus 6.6 years, respectively, p = 0.516). CONCLUSION: The prevalence of HCV infection was higher in HNC patients compared to the general Brazilian population. It seems reasonable to consider that HCV infection is associated with an increased risk of HNC, but HCV infection does not worsens the prognosis of HNC patients.

Microenvironment Eradication of Hepatitis C: A Novel Treatment Paradigm.

OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Our aim was to create a permanent program of HCV elimination in a prison based on a "test and treat" strategy. METHODS: This open-label clinical trial was conducted in the Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015 Spanish Guidelines. A teleconsultation program was established to follow-up patients from the hospital. Non-responders were submitted for a phylogenetic analysis and offered retreatment. An evaluation of new cases of HCV infection was performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%) inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and 86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and had

Assessing Disparities in the Rates of HCV Diagnoses Within American Indian or Alaska Native Populations Served by the U.S. Indian Health Service, 2005-2015.

Hepatitis C virus (HCV) disproportionately affects American Indians/Alaska Natives (AI/AN). The Indian Health Service (IHS), via federal and tribal health facilities provides medical services to an estimated 2.2 million AI/AN people in the United States. HCV diagnoses, defined by International Classification of Diseases 9th Revision, Clinical Modification (ICD-9-CM) codes, were analyzed from 2005 to 2015. Results showed 29,803 patients with an HCV diagnosis; 53.4% were among persons born 1945-1965 and overall HCV burden was higher among males than females. These data will help inform local, regional, and national efforts to address, plan for and carry out a national strategy to provide treatment for HCV infected patients and programs to prevent new HCV infections.

Expression of a functional intrabody against hepatitis C virus core protein in Escherichia coli and silkworm pupae.

It has been shown that the single-domain intrabody 2H9-L against the hepatitis C virus (HCV) capsid (core) protein inhibits the viral propagation and NF-κB promoter activity induced by the HCV core. In this study, 2H9-L fused with the FLAG tag sequence was expressed in both Escherichia coli and silkworm pupae and then purified. In addition, the full-length and its C terminal deletions of the HCV core protein, i.e., 1-123 amino acid residues (C123), 1-152 amino acid residues (C152), 1-177 amino acid residues (C177) and 1-191 amino acid residues (C191), were expressed as fusion proteins with a 6 × His tag at their N-terminus in E. coli and then purified. Approximately 175 and 132 µg of the intrabody were purified from 100 ml of E. coli culture and 10 silkworm pupae, respectively, by affinity chromatography. The C123, C152, C177 and C191 HCV core protein variants were purified to approximately 152, 127, 103 and 155 µg, respectively, from 100 ml of E. coli culture. An ELISA in which the intrabodies were immobilized revealed that the intrabodies purified from both hosts were bound to all HCV core protein variants. However, their binding to the C191 appeared to be weak compared to their bindings to the other HCV core protein variants. When C152 was immobilized in the ELISA, the binding of each intrabody to the core protein was also observed. These purified intrabodies can be used in biochemical analyses of the inhibitory mechanism of HCV propagation and as protein interference reagents, thus providing a potential pathway to developing a new type of antiviral drug.

Systematic review with meta-analysis: performance of dried blood spots for hepatitis C antibodies detection.

OBJECTIVES: Dried blood spots (DBS) specimens can be used for hepatitis C virus (HCV) infection screening in cases where serum specimens are difficult to obtain. However, uncertainties surround the sensitivity and specificity of DBS for HCV antibodies (anti-HCV) serology testing. We aimed to evaluate the accuracy of DBS use to screen for HCV infection. STUDY DESIGN: We carried out a systematic review and meta-analysis. METHODS: Medline and EMBASE databases were searched for articles published between 1989 and November 2016. We included studies comparing DBS to plasma/serum specimens to detect anti-HCV in adults. Two authors extracted data and assessed the quality of the studies using an adapted standards for reporting diagnostic accuracy studies (STARD) and independently checked the data for accuracy. Meta-analysis was computed with the bivariate and the hierarchical summary receiver-operating characteristic models. RESULTS: Twelve studies (3307 specimens) were analyzed, where 11 of them evaluated the anti-HCV using enzyme immunoassays (EIAs), and the remaining one used rapid diagnostic tests. The studies were mostly case-controls (83.3%) and from developed countries (66.7%). The overall pooled sensitivity (95% confidence interval; CI) and specificity (95% CI) of DBS to detect anti-HCV was 98.1% (96.1-99.1%) and 99.7% (98.9-99.9%), respectively. In studies using EIAs, the pooled sensitivity and specificity were 97.3% (94.3-98.8%) and 99.6% (98.5-99.9%), respectively. Considering only studies using EIAs, sensitivity analysis excluding one study carried out in people who inject drugs showed the pooled sensitivity of 97.8% (96.2-98.8%) and specificity of 99.5% (98.5-99.9%). CONCLUSIONS: In testing for anti-HCV by means of EIAs, the efficacy of DBS is found to be similar or slightly lower than that of serum specimens. However, the risk of finding negative and positive results that are both false when using DBS remains present. Therefore, further work including optimal storage and processing methodologies are recommended. This is to help establish consensus guidelines for use of DBS specimens for anti-HCV screening.

Seroprevalencia de hepatitis C en población con factores de riesgo del suroeste de la Comunidad de Madrid / Hepatitis C seroprevalence in an at-risk population in the southwest Madrid region of Spain

INTRODUCCIÓN: La seroprevalencia estimada del VHC en España es del 1,7%, cifra que es muy superior en la población con factores de riesgo. Se desconoce cuál sería la estrategia de cribado más eficiente en nuestro país. OBJETIVOS: Estimar la prevalencia del VHC en la población con factores de riesgo atendida en Atención Primaria (AP) y conocer su perfil epidemiológico. MATERIAL Y MÉTODOS: Estudio descriptivo transversal de prevalencia que incluyó a pacientes adultos con factores de riesgo de infección por VHC asistidos en AP de la zona suroeste de la Comunidad de Madrid entre 2010 y 2012. RESULTADOS: Se incluyó a 158 pacientes (H: 51,3%) con una edad media de 46 años (DE=16,6). Los factores de riesgo más frecuentes fueron la hipertransaminasemia (44,3%) y cirugía mayor (13,3%). La inmigración, las prácticas sexuales de riesgo y los tatuajes o piercing fueron más prevalentes en los menores de 45 años. Del total de pacientes, 15 (9,5%) presentaron anti-VHC positivo, de ellos 9 tenían ARN-VHC positivo (5,7%). De los pacientes positivos, 4 (44,4%) presentaron fibrosis significativa al diagnóstico (F3-F4). Los pacientes varones presentaron una mayor tasa de anti-VHC positivo (13,8 vs. 5,3%; p = 0,072), y también los pacientes mayores de 45 años (12,8 vs. 6,3%; p = 0,167). El uso de drogas parenterales se asoció a mayor tasa de anti-VHC positivo (50 vs. 8,5%; p = 0,005), así como el uso de drogas vía nasal (66,7 vs. 8,4%; p = 0,001). CONCLUSIONES: Los pacientes con factores de riesgo de infección por VHC presentan una elevada seroprevalencia. Por tanto, es necesario implantar programas de detección de la infección VHC en esta población en AP

INTRODUCTION: The estimated seroprevalence of hepatitis C virus (HCV) in Spain is 1.7%, but is much higher in the at-risk population. The most efficient national screening strategy is unclear. AIMS: To estimate the prevalence of HCV among the at-risk population seen in primary care (PC), and to determine their epidemiological profile. MATERIALS AND METHODS: Cross-sectional descriptive prevalence study that included adult patients with risk factors for HCV infection seen in PC in the southwest Madrid region between 2010 and 2012. RESULTS: A total of 158 patients (men=51.3%), mean age 46 years (SD=16.6), were included. The most common risk factors were hypertransaminasaemia (44.3%) and major surgery (13.3%). Immigration, unsafe sexual practices, and tattoos or body piercing were more prevalent in patients younger than 45 years of age. Fifteen patients (9.5%) were positive for anti-HCV; 9 of these (5.7%) were HCV-ARN positive. Of the positive patients, 4 (44.4%) had significant fibrosis at diagnosis (F3-F4). Male patients had a higher rate of positive anti-HCV results (13.8 vs. 5.3%; P=.072), as did patients older than 45 years of age (12.8 vs. 6.3%; P=.167). Intravenous and intranasal drug use were associated with a higher rate of positive anti-HCV results (50 vs. 8.5%; P=.005 and 66.7 vs. 8.4%; P=.001, respectively). CONCLUSIONS: Patients with risk factors for HCV infection have high seroprevalence. Screening programmes must therefore be implemented to detect HCV infection in this population in PC

Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance.

Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins. Five E1E2 broadly reactive antibodies were isolated: 3 antibodies showed potent neutralization of genotype 1 to 4 using HCV pseudotyped particles, whereas the other 2 antibodies neutralized genotype 1, 2 and 3 or 1 and 2 only. All antibodies recognized non-linear epitopes on E2. Finally, except for antibody AT12-011, which recognized an epitope consisting of antigenic domain C /AR2 and AR5, all other four antibodies recognized epitope II and domain B. These data show that a subject, who spontaneously cleared HCV infection 25 years ago, still has circulating memory B cells that are able to secrete broadly neutralizing antibodies. Presence of such memory B cells strengthens the argument for undertaking the development of an HCV vaccine.

Birth Cohort Testing for Hepatitis C Virus - Indian Health Service 2012-2015.

Hepatitis C virus (HCV) infection is a substantial and largely unrecognized public health problem. An estimated 3.5 million persons in the United States are currently living with HCV infection, at least half of whom are unaware of their infection (1-3). Persons born during 1945-1965 (the "baby boomer" birth cohort) have a sixfold higher prevalence (2.6%) than adults of other ages, and represent 81% of all persons chronically infected with HCV (4). Therefore, in addition to recommending testing for all persons at risk for HCV infection, CDC and the U.S. Preventive Services Task Force (USPSTF) recommend one-time HCV testing for the birth cohort (5,6). Compared with the national average, American Indian/Alaska Native (AI/AN) persons have approximately twofold the rate of acute HCV incidence and HCV associated mortality (2). In June 2012, the Indian Health Service (IHS) implemented HCV testing in the 1945-1965 birth cohort and created a nationally standardized performance measure to monitor implementation of the recommendation. As of June 2015, the proportion of the birth cohort screened for HCV increased from a baseline of 7.9% (14,402/182,503) to 32.5% (68,514/211,014) among the AI/AN population served by IHS nationwide; provider training and the use of clinical decision tools were associated with increases in HCV testing. With this fourfold increase in testing in just 3 years, IHS needs to prepare for the challenges associated with increased identification of persons living with HCV infection.

Identification and Clinical Management of Persons with Chronic Hepatitis C Virus Infection - Cherokee Nation, 2012-2015.

An estimated 3.5 million persons in the United States are living with hepatitis C virus (HCV) infection, resulting in approximately 20,000 deaths each year, primarily from cirrhosis or hepatocellular carcinoma (1,2). American Indian/Alaska Native (AI/AN) populations have the highest incidence of acute HCV infection among all U.S. racial/ethnic groups and are at greater risk for HCV-related mortality compared with the general population (3). In 2013, new antiviral drugs became available that make possible 8-12 week treatment regimens with fewer adverse events and are able to achieve sustained virologic response (SVR) in >90% of treated patients (4), equivalent to a cure of HCV infection. Also of note, HCV testing recommendations were expanded in 2012 by CDC and in 2013 by the U.S. Preventive Services Task Force to include one-time testing of persons born during 1945-1965 (the "baby boomer" cohort) in addition to anyone at increased risk for HCV infection (5,6). Given the availability of new HCV drugs, expanded testing recommendations, and high incidence of HCV infection in AI/AN populations, in October 2012, Cherokee Nation Health Services (CNHS) implemented a tribal HCV testing policy.* As part of the policy, CNHS added a reminder in the electronic health record (EHR) for clinical decision support and provided HCV education to primary care clinicians. From October 2012 to July 2015, among 92,012 persons with at least one CNHS clinic encounter, the cumulative number who received HCV screening for the first time increased from 3,337 (3.6%) to 16,772 (18.2%). The largest percentage of HCV screening was among persons born during 1945-1965. Of 715 persons who tested positive for HCV antibodies, 488 (68.3%) were tested for HCV RNA; among those 488 persons, 388 (79.5%) were RNA positive and were thus confirmed to have chronic HCV infection. Treatment was initiated for 223 (57.5%) of the 388 with chronic infection; 201 (90.1%) completed treatment, of whom 180 (89.6%) achieved SVR. CNHS has successfully increased HCV testing and treatment and is now collaborating with CDC and other external partners to develop an HCV elimination program for the Cherokee Nation that might serve as a model for similar settings.