HCV RNA Testing Research Articles

Novel approach to near POC testing for HCV RNA; integration of HCV RNA testing into existing near POC machines used in National TB program, Georgia

Novel approach to near POC testing for HCV RNA; integration of HCV RNA testing into existing near POC machines used in National TB program, Georgia

Evaluation of the Point of Care Molecular Diagnostic Genedrive HCV ID Kit for the detection of HCV RNA in clinical samples.

2. Abstract BACKGROUND Despite the availability of an effective treatment for HCV infection, major bottle neck in the HCV care cascade is difficulty in getting the HCV RNA done on serologically positive (antibody to HCV) patients. This is due to the limited availability of HCV RNA test in the periphery. Nucleic acid amplification testing at point of care might revolutionise the HCV care continuum through its increased sensitivity, decreased turn around time and ease of performance in the field. Genedrive is one such assay which has recently got a CE- IVD certification. OBJECTIVES The diagnostic accuracy of Genedrive HCV ID kit for the qualitative detection of HCV RNA was evaluated by comparing with Abbott HCV RNA in an Indian demographic setting and across a range of different genotypes commonly found in India. STUDY DESIGN For the assay evaluation 150 HCV RNA positive and 170 HCV RNA negative samples as tested by Abbott HCV RNA assay (Abbott, Wiesbaden, Germany) on Automated m2000sp/m2000rt platform, as per the manufacturer’s instructions, that were retrieved from −80°C in the Virology repository were included in the study. All the samples were retrieved and re tested for HCV RNA on Genedrive HCV ID kit and compared with Abbott HCV RNA results. RESULTS Comparison of the Genedrive HCV ID kit with the Abbott Real Time HCV assay revealed a sensitivity of 100 % (95% CI 97.9 to 100) and a specificity of 100 % (95% CI 97.9 to 100) with a positive predictive value and negative predictive value of 100%. Overall diagnostic accuracy of Genedrive was found to be 100% (95% CI 98.9 to 100). CONCLUSION This study demonstrates that Genedrive HCV ID kit can be used for decentralised testing of HCV and ultimately finding the missing million. Highlights Decentralisation of HCV RNA assays is the need of hour for finding the missing millions. Genedrive HCV ID kit is one such assay which can qualitatively detect HCV RNA and can be used as a point of care molecular assay thereby reducing the dropouts and improving the HCV care cascade.

Identifying gaps in the treatment of hepatitis C in patients co-infected with HIV in Edmonton, Alberta

IntroductionWith the availability of direct-acting antivirals, Hepatitis C (HCV) is now considered a treatable disease. Patients who are co-infected with human immunodeficiency virus (HIV) and HCV represent an ideal patient population to treat for HCV, as (1) patients are routinely taking medication for HIV, and therefore would be able to complete HCV drug regimens, and (2) HIV infection has been shown to increase HCV disease progression. ObjectiveWe sought to determine the occurrence of HCV co-infection among HIV patients in our provincial cohort, determine whether they received treatment for HCV, and identify currently viremic patients who can be linked to care. Materials and methodsHCV laboratory testing data (HCV antibody and HCV RNA) and HCV medication dispensation data was collected for all HIV positive patients. Current and previous HCV infection and treatment was assessed. Chart reviews were conducted for HCV viremic patients to assess their HIV care and social determinants. ResultsOf the 2417 HIV positive patients, 392 (16.2%) were identified as being co-infected with HCV. 198 (50.5%) of the HIV-HCV co-infected patients received HCV treatment and 232 (59.2%) were not viremic on the most recent HCV RNA test. 99 (69.2%) had a suppressed HIV infection suggesting they are active in their HIV care and good candidates for HCV treatment. ConclusionDespite the availability of direct-acting antivirals, many patients who are co-infected with HIV and HCV are not being treated for HCV. Routine surveillance of HIV-HCV co-infected patients could improve HCV treatment rates in a high-risk population.

Hepatitis C core antigen testing to diagnose active hepatitis C infection among haemodialysis patients

BackgroundHepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost.MethodsWe conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test.ResultsWe recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients.ConclusionsAlthough HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.

Look-Back Study of Transfusion-Transmitted Hepatitis C Virus Infection in Iran

Background: With the identification of blood donors with a subsequent positive result in HCV screening and the possibility of HCV transmission via their previous negative donations, the role of look-back investigation has been crucial in enhancing blood safety. A retrospective study was conducted to identify the fate of blood components from donors subsequently found to be confirmed HCV positive cases with previous negative donations. Objectives: This look-back study aimed to determine the transfusion-induced hepatitis C virus infection through previous HCV-negative donations of subsequent HCV positive blood donors in Iran. Methods: In this study, all serologically confirmed HCV positive blood donors across the country from December 2015 to June 2017 were included. A look-back process was conducted by tracing back previous HCV negative donations of subsequent HCV-positive blood donors to specific recipients, according to the IBTO instructions. The HCV RNA testing was carried out using an in-house one-step TaqMan real-time RT-PCR assay. Results: During the study period, 280 serologically confirmed HCV-positive blood donors were included, with 267 as first-time, nine as repeated, and three as regular donors. Of the participants, the first-time donors were excluded, the repeated donors were not eligible, and only the regular donors were selected for the look-back study. The HCV RNA was detected in one regular donor, but HCV infection was not detected in his previous donation recipient. In addition, more than two HCV risk factors were reported by each regular blood donor. Conclusions: According to the results, evidence of HCV transmission via previous blood transfusions and the risk of HCV infection was not observed among recipients. Due to the reporting of some HCV risk factors by the subjects, paying proper attention to the donor selection process is highly recommended.

Acute hepatitis C treatment in advanced renal failure using 8 weeks of pan-genotypic daclatasvir and reduced-dose sofosbuvir.

Sofosbuvir is not recommended in persons with estimated glomerular filtration rate (eGFR) <30 mL/min. We report the results of treatment with an off-label 8-week regimen of daclatasvir and half-dose sofosbuvir in patients with acute infection withhepatitis C virus ( HCV) and eGFR <30 mL/min. Clinic records were searched to identify treatment-naïve, noncirrhotic adults with acute hepatitis C (HCV viremia and a ≥10-fold elevation of serum alanine aminotransferase activity) and eGFR <30 mL/min, who had been treated with a sofosbuvir-based regimen. Treatment response was assessed using serum HCV RNA testing at 4 weeks of treatment, end of the 8-week treatment and 12 weeks after stopping treatment. Of the 31 patients with acute hepatitis C, 27 [median age (range): 36 (18-74) years; 20 (74%) male] were started on treatment with 200 mg sofosbuvir and 60 mg daclatasvir daily for 8 weeks, irrespective of HCV genotype. All the 27 completed the planned 8-week treatment. One patient died 10 weeks after completing the treatment of an unrelated cause. All the 27 patients had undetectable HCV RNA after 4 weeks of and at the end of treatment. At 12 weeks after completion of treatment, only one tested HCV RNA positive and 25 were negative, with sustained virological response rate of 25/27 (92.6%) and 25/26 (96.2%) on intention-to-treat and per-protocol basis, respectively. Eight-week course of daclatasvir and half-dose sofosbuvir is effective for acute hepatitis C in patients with eGFR <30 mL/min and could be a useful alternative to costly, kidney-safe anti-HCV oral drugs in resource-constrained settings.

Monitoring hepatitis C virus treatment rates in an Opioid Treatment Program: A longitudinal study.

BACKGROUNDDirect-acting antivirals (DAAs) are recommended for the treatment of hepatitis C virus (HCV) infection in patients treated with methadone or buprenorphine.AIMTo assess HCV treatment rates in an Opioid Treatment Program (OTP).METHODSThis longitudinal study included 501 patients (81.4% men, median age: 45 years; interquartile range: 39-50 years) enrolled in an OTP between October 2015 and September 2017. Patients were followed until September 2019. Data on socio-demographics, substance use, HCV infection, human immunodeficiency virus (HIV) infection and laboratory parameters were collected at entry. We analyzed medical records to evaluate HCV treatment. Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors.RESULTSPrevalence of HCV and HIV infection was 70% and 34%, respectively. Among anti-HCV-positive (n = 336) patients, 47.2%, 41.3%, and 31.9% used alcohol, cannabis, and cocaine, respectively. HCV-RNA tests were positive in 233 (69.3%) patients. Twentyeight patients (8.3%) cleared the infection, and 59/308 (19.1%) had received interferon-based treatment regimens before 2015. Among 249 patients eligible, 111 (44.6%) received DAAs. Treatment rates significantly increased over time from 7.8/100 person-years (p-y) (95%CI: 5.0-12.3) in 2015 to 18.9/100 p-y (95%CI: 11.7-30.3) in 2019. In a multivariate analysis, patients with HIV co-infection were twice as likely to receive DAAs (HR = 1.94, 95%CI: 1.21-3.12) than patients with HCV mono-infection. Current drug use was an independent risk factor for not receiving treatment against infection (HR = 0.48, 95%CI: 0.29-0.80).CONCLUSIONHCV treatment is evolving in patients with HCV-HIV co-infection. Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.

HCV micro-elimination in two prisons in Milan, Italy: A model of care.

People in prison represent a high-risk population for HCV infection control. With the advent of new direct antiviral agents (DAAs) HCV micro-elimination in prison setting became a feasible strategy. We assessed the impact of an intervention for HCV testing and treatment in 2017 and 2018 in a jail (San Vittore,SV) and a prison for sentenced individuals (Opera,OP). A dedicated protocol was applied and implemented over the two years. We collected data on demographics, HCV testing and treatment on all inmates present on 31 October 2017 and 2018. In the two facilities, there were 2,366 and 2,369 inmates in 2017 and 2018 respectively; the majority were men (95.6%; 96.4%) and Italians (57.0%; 61.9%) with a median age of 41years. Prevalence of lifetime reported drug use remained high (46.5%; 44.2%). HCV screening coverage was 89% in both years, while HCV RNA test coverage increased (90.6%; 99.0%). HCV seroprevalence remained stable (10.1%; 9.2%). In 2017 among inmates with HCV chronic infection 90 (42.4%) individuals had started DAAs treatment and 106 (54.6%) in 2018; of whom 38 (17.9%) and 74 (38.1%) achieved the SVR. The viremic pool decreased significantly over time (SV,24.4%; 15.4%;OP, 16.1%; <1%). Among inmates with HCV-positive serology in 2018, 121 (81.0%) were never linked to care before incarceration. Our study showed how a targeted and well-implemented HCV test-and-treat intervention in prison was feasible and effective in achieving micro-elimination. Viral hepatitis elimination agenda may help drawing interest onto this neglected population and bringing prison health higher up in the global public health agenda.

Innovative procedures for micro-elimination of HCV infection in persons who use drugs.

People who use drugs are a key population in global HCV control. We evaluated the efficacy of an innovative model to eliminate HCV infection in a high-risk population of PWUD in a service for substance use disorder (SUD). Between January 2018 and December 2018, we conducted a prospective, interventional, before and after study, based on audits performed by Infectious Diseases physicians in a SUD facility in Piedimonte Matese, in southern Italy, to improve the knowledge about HCV infection; a shared protocol for screening and linkage to care of patients was implemented. The pre-intervention period was defined as January-December 2017 and the post-intervention period as January-December 2018. The subjects followed up at SUD facility in the pre-intervention and post-intervention periods were 318 and 275, respectively. Compared with the pre-intervention period, the number of anti-HCV-positive subjects tested for HCV RNA was higher in the post-intervention period (91% vs 27%, P<.0001), as was the number who started directly acting antivirals (DAAs). Of the 18 HCV RNA-positive subjects in the pre-intervention period, only 3 (16.6%) started DAA, a percentage decisively lower than that observed after the start of the programme, 63 (84%) of 75 subjects (P<.0001), and all obtained SVR. The data were similar for people who inject drugs (PWID) and non-PWID sub-populations. The use of our innovative model with close interaction between the Infectious Disease Unit and the SUD facility determined a significant increase in HCV RNA testing, linkage to care and the start of DAA in the PWUD population.

Reduced incidence of hepatitis C in 9 villages in rural Egypt: Progress towards national elimination goals

Egypt has a major HCV burden and a well established treatment programme, with an ambitious goal of HCV elimination. Our aim was to assess the impact of a comprehensive HCV prevention, test and treat programme on the incidence of new HCV infections in 9 villages in rural Egypt. An HCV "educate, test and treat" project was implemented in 73 villages across 7 governorates in Egypt between 06/2015 and 06/2018. In 2018, in 9 of the villages we re-tested individuals who originally tested HCV antibody (HCV-Ab) and HBsAg negative using rapid diagnostic tests (RDTs); confirmatory HCV RNA testing was performed for positive cases. The incidence rate per 1,000 person-years (py) was calculated, and risk factors for incident HCV infections assessed through an interviewer-administered questionnaire in 1:3 age- and gender-matched cases and controls. Out of 20,490 individuals who originally tested HCV-Ab negative in the 9 villages during the 2015-2016 implementation of the "educate, test and treat" programme, 19,816 (96.7%) were re-tested in 2018. Over a median of 2.4 years (IQR 2.1-2.7), there were 19 new HCV infections all of which were HCV RNA positive (incidence rate 0.37/1,000 py) (95% CI 0.24-0.59). Compared to a previous estimate of incidence in the Nile Delta region (2.4/1,000 py) from 2006, there was a substantial reduction in overall incidence of new HCV infections. Exposures through surgery (odds ratio 51; 95% CI 3.5-740.1) and dental procedures (odds ratio 23.8; 95% CI 2.9-194.9) were significant independent predictors of incident infections. This is the first study to show a substantial reduction in incidence of new HCV infections in a sample of the general population in Egypt following attainment of high testing and treatment coverage. New infections were significantly associated with healthcare-associated exposures. Egypt has a major national HCV testing and treatment programme with the goal of eliminating HCV infection. We assessed the impact of a comprehensive HCV prevention, test and treat programme in 73 villages that achieved high coverage of testing and treatment on the subsequent incidence of new HCV infections in nine of the villages. We re-tested people who were previously HCV antibody negative and found that the rate of new HCV infections was greatly reduced compared to previous estimates. We also found that exposure through surgery and dental procedures were associated with these new infections. This highlights the importance of continued strengthening of infection control and prevention measures, alongside treatment scale-up.

Emergency department targeted screening for hepatitis C does not improve linkage to care.

BACKGROUNDHepatitis C virus (HCV) infection is a leading cause of chronic liver disease worldwide. New treatments for HCV revolutionized management and prompted the world health organization to set the goal of viral elimination by 2030. These developments strengthen the need for HCV screening in order to identify asymptomatic carriers prior to development of chronic liver disease and its complications. Different screening strategies have been attempted, most targeting high-risk populations. Previous studies focusing on patients arriving at emergency departments showed a higher prevalence of HCV compared to the general population.AIMTo identify previously undiagnosed HCV carriers among high risk emergency room attendees and link them to care for anti-viral treatment.METHODSIn this single center prospective study, persons visiting the emergency department in an urban hospital were screened by a risk factor-specific questionnaire. The risk factors screened for were exposure to blood products or organ transplantation before 1992; origins from countries with high prevalence of HCV; intravenous drug use; human immunodeficiency virus carriers; men who have sex with men; those born to HCV-infected mothers; prior prison time; and chronic kidney disease. Those with at least one risk factor were tested for HCV by serum for HCV antibodies, a novel oral test from saliva (OraQuick®) or both.RESULTSFive hundred and forty-one participants had at least one risk factor and were tested for HCV. Eighty four percent of all study participants had only one risk factor. Eighty five percent of participants underwent OraQuick® testing, 34% were tested for serum anti-HCV antibodies, and 25% had both tests. 3.1% of patients (17/541) had a positive result, compared to local population incidence of 1.96%. Of these, 82% were people who inject drugs (current or former), and 64% served time in prison. One patient had a negative HCV-RNA, and two patients died from non-HCV related reasons. On review of past medical records, 12 patients were found to have been previously diagnosed with HCV but were unaware of their carrier state. At 1-year follow-up none of the remaining 14 patients had completed HCV-RNA testing, visited a hepatology clinic or received anti-viral treatment.CONCLUSIONTargeted high-risk screening in the emergency department identified undiagnosed and untreated HCV carriers, but did not improve treatment rates. Other strategies need to be developed to improve linkage to care in high risk populations.

Model-based cost-effectiveness estimates of testing strategies for diagnosing hepatitis C virus infection in Central and Western Africa.

Whereas 72% of hepatitis C virus (HCV)-infected people worldwide live in low- and middle-income countries (LMICs), only 6% of them have been diagnosed. Innovative technologies for HCV diagnosis provide opportunities for developing testing strategies more adapted to resource-constrained settings. However, studies about their economic feasibility in LMICs are lacking. Adopting a health sector perspective in Cameroon, Cote-d'Ivoire, and Senegal, a decision tree model was developed to compare 12 testing strategies with the following characteristics: a one-step or two-step testing sequence, HCV-RNA or HCV core antigen as confirmative biomarker, laboratory or point-of-care (POC) tests, and venous blood samples or dried blood spots (DBS). Outcomes measures were the number of true positives (TPs), cost per screened individual, incremental cost-effectiveness ratios, and nationwide budget. Corresponding time horizon was immediate, and outcomes were accordingly not discounted. Detailed sensitivity analyses were conducted. In the base-case, a two-step POC-based strategy including anti-HCV antibody (HCV-Ab) and HCV-RNA testing had the lowest cost, €8.18 per screened individual. Assuming a lost-to-follow-up rate after screening > 1.9%, a DBS-based laboratory HCV-RNA after HCV-Ab POC testing was the single un-dominated strategy, requiring an additional cost of €3653.56 per additional TP detected. Both strategies would require 8-25% of the annual public health expenditure of the study countries for diagnosing 30% of HCV-infected individuals. Assuming a seroprevalence > 46.9% or a cost of POC HCV-RNA < €7.32, a one-step strategy based on POC HCV-RNA dominated the two-step POC-based strategy but resulted in many more false-positive cases. POC HCV-Ab followed by either POC- or DBS-based HCV-RNA testing would be the most cost-effective strategies in the study countries. Without a substantial increase in funding for health or a dramatic decrease in assay prices, HCV testing would constitute an economic barrier to the implementation of HCV elimination programs in LMICs.

A simple risk-based strategy for hepatitis C virus screening among incarcerated people in a low- to middle-income setting

BackgroundHepatitis C virus (HCV) is among the highest priority diseases in custodial settings; however, the diagnosis remains suboptimal among people in custody. This study aimed to validate a short survey for identifying people with HCV infection in a provincial prison in Iran.MethodsBetween July and December 2018, residents and newly admitted inmates of Gorgan central prison completed a questionnaire, including data on the history of HCV testing, drug use, injecting drug use, sharing injecting equipment, and imprisonment. Participants received rapid HCV antibody testing, followed by venipuncture for RNA testing (antibody-positive only). Each enrollment question (yes/no) was compared with the testing results (positive/negative).ResultsOverall, 1892 people completed the questionnaire, including 621 (34%) who were currently on opioid agonist therapy (OAT); 30% of participants had been tested for HCV previously. About 71% had a history of drug use, of whom 13% had ever injected drugs; 52% had ever shared injecting equipment. The prevalence of HCV antibody and RNA was 6.9% (n = 130) and 4.8% (n = 90), respectively. The antibody prevalence was higher among people on OAT compared to those with no history of OAT (11.4% vs. 4.0%). History of drug use was the most accurate predictor of having a positive HCV antibody (sensitivity: 95.2%, negative predictive value: 98.9%) and RNA testing (sensitivity: 96.7%, negative predictive value: 99.5%). The sensitivity of the drug use question was lowest among people with no OAT history and new inmates (87% and 89%, respectively). Among all participants, sensitivity and negative predictive value of the other questions were low and ranged from 34 to 54% and 94 to 97%, respectively.ConclusionsIn resource-limited settings, HCV screening based on having a history of drug use could replace universal screening in prisons to reduce costs. Developing tailored screening strategies together with further cost studies are crucial to address the current HCV epidemic in low- to middle-income countries.

Management of hepatitis C in opioid agonist therapy patients of the Swiss canton Aargau within and outside the cohort study.

With regard to HCV elimination in opioid agonist therapy patients by 2030, case finding and regular screening for new and re-infections remain a challenge, especially for non-cohort patients in a decentralised setting. Documentation of the HCV sero- and RNA status of each opioid agonist therapy&nbsp; patient by the cantonal physician and a yearly HCV screening reminder sent to the opioid agonist therapy prescriber combined with capillary HCV antibody and HCV RNA testing might facilitate the implementation of the FOPH guidelines. Prescription of direct-acting antivirals directly by the opioid agonist therapy prescriber could increase awareness and improve linkage to care.

Nucleic Acid Testing for Diagnosis of Perinatally Acquired Hepatitis C Virus Infection in Early Infancy.

Most US children with perinatal hepatitis C virus (HCV) exposure fail to receive the recommended anti-HCV antibody test at age ≥18 months. Earlier testing for viral RNA might facilitate increased screening, but sensitivity of this approach has not been established. We hypothesized that modern HCV-RNA RT-PCR platforms would adequately detect infected infants. Nationwide Children's Hospital electronic health records from 1/1/2008 to 30/6/2018 were reviewed to identify perinatally exposed infants tested by HCV-RNA RT-PCR at age 2-6 months. Diagnostic performance was determined using a composite case definition: (1) infected children had positive repeat HCV-RNA testing or positive anti-HCV at age ≥24 months; (2) uninfected children lacked these criteria and had negative anti-HCV at age ≥18 months. 770 perinatally exposed infants underwent HCV-RNA testing at age 2-6 months. Of these, 28 (3.6%) tested positive; viremia was confirmed in all who underwent repeat testing (n = 27). Among 742 infants with negative HCV-RNA results, 226 received follow-up anti-HCV testing at age ≥18 months, of whom 223 tested negative. Three children had low-positive anti-HCV results at age 18-24 months that were negative upon retesting after age 24 months, possibly indicating waning maternal antibodies. Using the composite case definitions, early HCV-RNA screening demonstrated sensitivity of 100% (87.5-100%, Wilson-Brown 95% CI) and specificity of 100% (98.3-100%). Modern HCV-RNA RT-PCR assays have excellent sensitivity for early diagnosis of perinatally acquired infection and could aid HCV surveillance given the substantial loss to follow-up at ≥18 months of age.

Viral Interference Between Dengue Virus and Hepatitis C Virus Infections.

Both dengue virus (DENV) and hepatitis C virus (HCV) belong to the Flaviviridae family and could induce hepatitis. We aimed to investigate the interference between them. In total, 515 patients confirmed with dengue fever (DF) were enrolled. Thirty-two patients (6.21%) were seropositive for anti-HCV; 12 of 32 anti-HCV-positive patients had detectable HCV-RNA at presentation of DF. The proportion of dengue hemorrhagic fever was comparable between patients with or without anti-HCV and between those with or without HCV-RNA. Eleven of 32 patients received HCV-RNA testing during a median interval of 23 months after DF, which revealed significantly increased HCV-RNA levels (5.43 ± 0.77 vs 3.09 ± 1.24 log IU/mL, follow-up vs acute-DF phase; P = .003). Four of 11 patients with baseline HCV-RNA values before DF demonstrated a nadir viremia during acute DF. We also included age-, sex-, and follow-up duration–matched HCV-monoinfected patients as controls; higher delta HCV-RNA changes were demonstrated in patients with DF than in controls during the follow-up period (2.34 ± 1.15 vs –0.27 ± 0.76 log IU/mL; P < .001). Further in vitro experiments showed that HCV nonstructural protein 5A was downregulated in Con1 HCV replicon cells infected by DENV1. These clinical and experimental findings suggested possible viral interference in DENV/HCV. However, HCV viremia did not affect the disease outcomes of DF.

Hepatitis C screening and referral for further investigation and treatment in a tertiary care hospital.

Hepatitis C virus infection is a major cause of cirrhosis and liver cancer worldwide. The knowledge of physicians about what should they do in case of any anti-HCV positivity in screening tests is of great importance. In this study the awareness and knowledge of physicians is evaluated by analyzing the rate of the referrals of anti-HCV positive patients to HCV RNA test and their treatment by different clinics. The patients tested for anti-HCV in internal medicine, surgery, gastroenterology and infectious disease clinics between 1 January and 31 December 2017 were evaluated retrospectively in a tertiary care hospital. Anti-HCV testing was performed in 32,803 patients. Anti-HCV positivity was detected in 95 (0.28%) patients aged 88 years of age or younger (mean 60.89 ± 16.96 years), 57.89% of them were female. HCV RNA was tested in 50 (%52,63) of anti-HCV positive patients and it was found positive in 18 (36%) patients. In anti-HCV positive patients HCV RNA testing was requested most by infectious disease (100%) and gastroenterology (70.58%) clinics and least by surgery and other clinics (21% and 25% respectively). These differences were found to be statistically significant ( =33.65, p < 001). Our study highlights the significant deficiencies existed in the referring patients with anti-HCV positivity for further examination and treatment by the attending physicians especially in surgical clinics. Performing HCV screening in the different steps of medical care and using electronic reminder systems directing physicians at appropriate diagnostic and treatment protocols can maximize the likelihood of the detection and treatment of HCV- infected patients.

Evaluation of the Xpert HCV VL Fingerstick point-of-care assay and dried blood spot HCV-RNA testing as simplified diagnostic strategies among people who inject drugs in Catalonia, Spain

BackgroundCatalonia requires decentralized and simplified strategies for the diagnosis of viremic HCV infection among people who inject drugs (PWID). We aimed to perform a direct comparison of the diagnostic performance between two, single-step strategies for the screening and diagnosis of viremic HCV infection in PWID attending a drug consumption room (DCR) in Barcelona: i) on-site HCV-RNA testing using the point-of-care test (PoCT) Xpert HCV VL Fingerstick; and ii) on-site dried blood spots (DBS) collection for HCV-RNA testing at the laboratory (in-house assay). Additionally, we aimed to assess participants’ preferences in receiving HCV-RNA testing results and feasibility of same-day delivery of PoCT results. MethodsThe real-world, clinical performance of these two strategies was established in comparison with the reference method (HCV viral load testing with the Xpert HCV Viral Load assay at the laboratory from venous plasma collected at the DCR). HCV genotypes/subtypes and HIV status were also determined by sequencing and serology, respectively. A questionnaire including preferences regarding the delivery of test results was administered. ResultsThe prevalence of HCV-RNA was 63.0% (of which 25.8% were co-infected with HIV). The RNA-PoCT showed a sensitivity of 98.4% for detectable viral loads (>4 IU/mL) and of 100% for quantifiable viral loads (≥10, ≥1000 and ≥3000 IU/mL). For the DBS-based assay, a sensitivity of 93.7% was obtained for detectable viral loads, 96.7% for the quantifiable ≥10 IU/mL threshold, and 98.3% for both the quantifiable ≥1000 and ≥3000 IU/mL thresholds. No significant differences were detected between the sensitivity values of these two strategies, and the specificity was 100% in both cases. Half of the participants preferred to receive the HCV-RNA result on the same day, and 80% of participants received their RNA-PoCT results on the same day. ConclusionsBoth the HCV-RNA PoCT and the DBS-based assay are highly reliable tools for the simplified diagnosis of viremic HCV infection among current PWID. These strategies allow for on-site sample collection and delivery of test results, facilitating decentralized care in harm reduction services.

Dried blood spot self-sampling at home is a feasible technique for hepatitis C RNA detection.

To facilitate HCV diagnosis, we developed an HCV-RNA testing service, which involved home-sampled dried blood spots (DBS). The main objective of this study was to evaluate the feasibility of self-sampling at home. Furthermore, to optimise the processing of DBS samples for RNA detection, we evaluated two elution buffers: phosphate-buffered saline (PBS) and L6-buffer. 27 HCV-RNA and 12 HIV-1 RNA positive patients were included. Laboratory spotted DBS (LabDBS) were made by a technician from blood samples drawn at inclusion. Patients received a DBS home-sampling kit and were requested to return their self-sampled DBS (ssDBS) by mail. We compared the RNA load of PBS and L6-eluted labDBS, and of L6-eluted ssDBS, L6-eluted labDBS and plasma. LabDBS load measurements were repeated after 7-13 and 14-21 days to evaluate RNA stability. All 39 plasma samples provided quantifiable RNA loads. In 1/39 labDBS sample, RNA could not be detected (plasma HCV load: 2.98 log10 IU/ml). L6-eluted samples gave a 0.7 log10 and 0.6 log10 higher viral load for HCV and HIV-1 respectively, compared to PBS-eluted samples. Strong correlations were found between labDBS and ssDBS HCV RNA (r = 0.833; mean difference 0.3 log10 IU/mL) and HIV-1 RNA results (r = 0.857; mean difference 0.1 log10 copies/mL). Correlations between labDBS and plasma values were high for HCV (r = 0.958) and HIV-1 (r = 0.844). RNA loads in DBS remained stable over 21 days. Our study demonstrates that self-sampling dried blood spots at home is a feasible strategy for the detection of HCV and HIV-1 RNA. This could facilitate one-step diagnostics and treatment monitoring in communities with high HCV prevalence.

Per-Contact Infectivity of Hepatitis C Virus Acquisition in Association With Receptive Needle Sharing Exposures in a Prospective Cohort of Young Adult People who Inject Drugs in San Francisco, California.

BackgroundSharing needles and ancillary injecting equipment is a primary risk exposure for hepatitis C virus (HCV) infection among people who inject drugs (PWID); however, infectivity of these exposures is not well quantified. We aimed to estimate per-event HCV infectivity associated with receptive needle sharing (RNS) among susceptible PWID.MethodsParticipants in a prospective cohort study of young adult PWID who were anti-HCV and HCV RNA negative at baseline and attended at least 2 follow-up study visits between 2003 and 2014 were eligible. Data were selected from the first HCV-negative through the first HCV-positive visit (or last HCV-negative among those uninfected). Anti-HCV and HCV-RNA tests were used to determine infection status. A probabilistic exposure model linking observed HCV infection outcomes to self-reported exposure events was applied to estimate infectivity.ResultsAmong 344 participants, a maximum likelihood estimate considering RNS yielded a pooled population per RNS event HCV probability of 0.25% (95% confidence interval [CI], 0.10%–0.43%), and 1.12% (95% CI, 0.48%–2.35%) among those who acquired any HCV infection (primary or reinfection).ConclusionsHCV is highly infectious in association with RNS, a primary injection-related risk exposure. Our infectivity estimate among participants who acquired any HCV infection is 1.7 times higher than that estimated for HIV infection in PWID and 2.24 times higher than that estimated among health care workers exposed through needle sticks. The strengths of this study include the assessment of receptive needle sharing events, the prospective design, and relatively short recall and testing periods. These results can inform transmission models and research to prevent HCV infection.