HCV RNA Testing Research Articles

Evaluation of Quantitative Hepatitis C Virus Core Antigen Testing as a Tool for Screening and Confirmation of HCV Infection.

Hepatitis C is a common viral infection worldwide. Finding the most effective diagnostic methods with low cost is always needed for laboratory improvement. In this study, we evaluated the performance of a quantitative chemiluminescent hepatitis C virus core antigen (HCV cAg) test by comparing it with the HCV confirmatory antibody line immunoblot assay (HCV Ab-LIA) test as well as the HCV quantitate reverse transcription-polymerase chain reaction (qRT-PCR) test. A total of 394 samples were enrolled in the retrospective study. Of these, 225 samples were tested using HCV Ab screening and confirmatory Ab-LIA along with chemiluminescent HCV core Ag testing, while 169 samples were tested using qRT-PCR for HCV RNA and chemiluminescent HCV core Ag testing. Out of these, 225 positive samples tested by HCV Ab screening test were analyzed using the confirmatory Ab LIA and HCV cAg assays, a total of 183 samples (81.3 %) were confirmed to be Ab-positive, and among those, 77 samples (42.1%) were also positive for HCV cAg. Thirty-eight samples (20.76%) were HCV Ab indeterminate, and all of them were HCV cAg negative. Four samples (1.8%) were HCV Ab LIA-negative and negative for HCV cAg. Moreover, 169 samples were measured for qRT-PCR HCV viral load and quantitative HCV cAg test. One hundred and three samples were positive for HCV RNA, while 66 were negative. Among the positives, 96/103 samples were HCV cAg positive and 7/103 samples were negative. Out of the negatives, 4/66 samples were HCV cAg positive but 62/66 samples were negative. The HCV cAg results were concordant with the qRT-PCR results in 158 samples (93.5%); however, 11 samples (6.5%) were found to be discrepant. The sensitivity, specificity, positive predictive value, and negative predictive value of the quantitative HCV cAg were found to be 93%, 94%, 96%, and 90%, respectively. The overall coefficient of correlation between the HCV RNA levels and HCV cAg data was determined to be r2 = 0.9. The HCV cAg test showed a high correlation with the HCV RNA levels and may potentially be used as a more cost-effective alternative to the HCV RNA qRT-PCR test.

1242. Hepatitis C Treatment as a Complement to Syringe Service Programs: Pilot Progress and Pathways Forward

Abstract Background Hepatitis C (HCV) poses a significant chronic infectious disease threat in the United States, and people who inject drugs (PWID) are at elevated HCV risk. We assessed implementation of a program that provided low-barrier services for high-risk PWID, coupling harm reduction with clinical care, including HCV treatment. Methods In 2018, the University of Illinois at Chicago established a program to deliver comprehensive care to PWID in an underserved Chicago neighborhood, including syringe services (SS) and HCV treatment. We performed chart reviews of SS clients who sought HCV care from 09/2018-01/2021. We assessed patient demographics; the proportions prescribed and initiated on HCV treatment; and the proportions with undetectable HCV RNA at treatment week 4, end of treatment, and 12-weeks post-treatment. Results Among 67 patients, 45 (67%) were male, median age was 45 years (IQR 35-57), 22 (33%) were Black, and 11 (16%) were Hispanic. 66 (99%) reported current or former drug use and 62 (93%) injection drug use, and 3 (4%) sex work. 36 (54%) were undomiciled or lived in unstable housing, 22 (33%) were unemployed, 19 (28%) had been incarcerated within the past year, and 30 (45%) had a history of psychiatric illness. Median pre-treatment HCV RNA was 701,626 IU/L (IQR 39,944-1,979,898). 40 (60%) were prescribed HCV treatment and 31 (46%) initiated treatment (Figure). Of these, 21/31 (68%) completed HCV RNA testing at treatment week 4, of whom 18/21 (86%) had an undetectable viral load; 16/31 (52%) completed end of treatment testing, of whom 16/16 (100%) had an undetectable viral load; and 15/31 (48%) completed 12-week post-treatment testing, of whom 13/15 (87%) had an undetectable viral load. Of the 2 patients who did not achieve sustained viral suppression following treatment, 1 missed four weeks of treatment due to incarceration and 1 reported full adherence to treatment. Numbers and percentages of patients at each step in the treatment cascade Conclusion This comprehensive program offering SS and HCV care successfully reached PWID in an underserved area before and during the pandemic. Losses along the HCV treatment cascade were high: Only 60% were prescribed treatment and less than one-third of those prescribed treatment achieved sustained viral suppression. Among those who remained in care, over 80% achieved sustained viral suppression. Disclosures All Authors: No reported disclosures.

1249. Rise in ALT after Hepatitis C Treatment is a Highly Sensitive Marker of Treatment Failure

Abstract Background Hepatitis C nucleic acid testing to confirm sustained virological response (SVR) after antiviral treatment is technical and expensive, hampering scale-up and decentralisation of care in resource-poor settings. Serial liver function testing may offer a cheaper means of screening for treatment failure. Methods In an HCV treatment shortening study in Vietnam (n=51), we analysed whether a change in ALT or AST from EOT to EOT+ 12 weeks (ΔALT; ΔAST) was a sensitive surrogate for HCV RNA in detecting treatment failure. We compared ΔALT and ΔAST between cures (38) and failures (13), and assessed sensitivity, specificity and area under receiver-operator curves (AUROC) vs gold standard HCV RNA. We validated our findings in a second, larger study population from a UK treatment shortening study (n=202). Both study populations had mild liver disease, and all participants were treated with 4-8 weeks direct acting antiviral therapy. Results In Vietnam, among 46 HCV genotype 1 or 6-infected individuals who supressed ALT on therapy, 11 failed to achieve SVR. Median ΔALT was -1 IU/L in cures vs +24 IU/L in treatment failures (p< 0.001). Increase in ALT (ΔALT > 0) after end-of-treatment was 100% (95% C.I. [66.4 – 100]) sensitive and 48% [26.8 – 69.4] specific vs HCV RNA in identifying failures (AUROC = 0.99). These results were validated among 193 genotype 1 or 4-infected individuals who supressed ALT on treatment in a UK study (in which 60 failed to achieve SVR). Median ΔALT was +1 IU/L in cures vs +45 IU/L in treatment failures (p< 0.001). ΔALT > 0 was 100% sensitive (95% C.I. [94.6 – 100]) and 47% [38.3-56.3] specific (AUC = 0.98). ΔAST performed similarly. Figure 1Change in ALT from EOT to EOT+12 in cures and from EOT to start of retreatment (EOT+6 to 24) in treatment failures in a) Vietnam study b) UK study Conclusion ΔALT from EOT to EOT+12 is a highly sensitive screen for identifying DAA treatment failures. Using this strategy, only around half of treated individuals require HCV RNA testing 12 weeks after end of treatment, offering substantial benefits in terms of cost reductions and decentralisation of care. Disclosures All Authors: No reported disclosures.

Sustained virological response after treatment with direct antiviral agents in individuals with HIV and hepatitis C co-infection.

Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing. We included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment. A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered. Our estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.

Spontaneous elimination of the Hepatitis C virus at the CMN la Raza specialty hospital

This study aimed to estimate risk factors for viral exposure in patients with spontaneous elimination of HCV in the Hepatitis clinic of CMN La Raza. Retrospective, observational, descriptive, cross-sectional and single-center study. Records of patients with antibodies against HCV determined by third-generation ELISA from July 2017 to February 2020 were reviewed; those that did not have sufficient information to carry out the analysis were eliminated, patients with the positive anti-HCV test were selected, confirmatory test with HCV PCR detectable by Abbot's real-time PCR. Risk factors for exposure to HCV and demographic data were collected. The results were analyzed with measures of relative frequencies and obtaining percentages, mean and average. Sixty patients (12.4%) with undetectable anti HCV+/PCR were included; 22 were men (35%) and 40 were women (65%), mean age of 54.4 years. Risk factors for exposure to HCV were: surgery (90%), transfusions (37%), dental interventions (10%). None presented a clinical picture suggestive of viral hepatitis. Associated comorbidities: systemic arterial hypertension (25%), Diabetes mellitus 2 (14%), obesity (8%). All the patients studied had risk factors for exposure to HCV, as reported in the literature. A higher frequency of spontaneous elimination of HCV was found in the female gender. All patients with an anti-HCV + test must undergo an HCV RNA test to confirm infection and start antiviral treatment since the spontaneous elimination of HCV is low. The resources used in this study were from the hospital without any additional financing The authors declare no potential conflicts of interest.

Awareness of chronic hepatitis C in the Western Black Sea Region.

Chronic hepatitis C (CHC) can be cured with oral antivirals. Awareness of CHC is a substantial barrier to the World Health Organization's goal of eradicating HCV by 2030. This study aimed at evaluating CHC awareness among different departments in a Western Black Sea Region University Hospital. Anti-HCV and HCV RNA test results of all patients admitted to our center for whatever reason and who underwent anti-HCV screening between January 2017 and January 2022 were analyzed. CHC awareness has been defined as the presence of HCV RNA testing for anti-HCV positives. Of the 63,963 patients who underwent anti-HCV testing, anti-HCV positivity was observed in 2%. HCV RNA was tested in 647 (48.8%) patients who had tested positive for anti-HCV. The HCV RNA was positive in 212 (32.7%) patients tested. Only 66 (29.7%) of those with positive HCV RNA test results had received antiviral therapy. The distribution of HCV RNA testing rates for patients with positive anti-HCV by different departments were as follows: 33% (n=78/232) in medical inpatient clinics, 78% (n=539/685) in medical outpatient clinics, 7% (n=16/223) in surgical inpatient clinics, 7% (n=14/183) in surgical outpatient clinics, and 0% in the emergency department. The prevalence of anti-HCV positivity in our region was 2%. Less than half of the patients tested for anti-HCV had HCV RNA testing, and less than a third of the HCV RNA-positive patients received antiviral therapy. To meet the WHO's HCV eradication target by 2030, it is necessary to increase physicians' awareness of CHC.

Management of Anti-Hepatitis C Virus-Antibody-Positive Patients in Non-Hepatology Departments in an Acute Care, General Hospital in Japan

In Japanese hospitals, patients undergoing invasive procedures or surgery are screened for anti-HCV antibodies; however, the majority of possible HCV careers are not referred to hepatologists. In addition to the conventional alert email system, a hepatologist extracted monthly lists of anti-HCV-antibody-positive patients who had been tested two months previously and checked medical records to determine whether the doctors who ordered the tests had properly dealt with the positive results. If the doctors had not yet properly followed up, the hepatologist would send emails to both the doctor and a medical clerk to inform them to conduct an HCV-RNA test and to refer HCV-RNA-positive patients to hepatologists. In total, 130 patients managed in the pre-intervention period and 151 patients managed in the post-intervention period were included in this study. The number of anti-HCV-positive patients whose results were not properly handled showed a significant decrease after the introduction of the double alert system (p = 0.034). Among patients undergoing screening anti-HCV antibody testing, a significant number of patients with probable chronic HCV hepatitis were overlooked by the email alert system and their results were not properly handled. The double alert system was useful for reducing the number of positive anti-HCV antibody patients whose results were not properly handled.

S3317 Acute Hepatitis C Infection Accounts for Suspected Isoniazid Hepatitis in a Patient With Controlled HIV Infection on Antiretroviral Therapy

Introduction: Acute hepatitis C (HCV) infection is rising in intravenous drug users/non-monogamy. Isoniazid (INH), commonly used for tuberculosis, may cause idiosyncratic drug-induced liver injury (DILI). Acute HCV infection was reported in 1.5% of suspected DILI. We here report a case of acute HCV infection for suspicious INH hepatitis in a patient with controlled human immunodeficiency virus (HIV) infection on antiretroviral therapy (ART). Case Description/Methods: A 54 years-old Caucasian male was admitted for several days of fatigue/nausea/abdominal pain with elevated ALT/AST at 179/93. He has a history of controlled HIV infection on dolutegravir/tenofovir/emtricitabine, non-monogamy (men having sex with men), marijuana/herbal use, and latent tuberculosis (with a normal liver test/negative HCV antibody) treated with INH for 3 months. Serology for acute hepatitis A, B, C infection, other work-ups, and abdominal ultrasound/CT were negative. INH rather than ART/herbals was suspected as the possible culprit for hepatotoxicity and was continued due to ALT < 5 times upper normal limit. Patient was discharged after a negative esophagogastroduodenoscopy and symptomatic improvement. He presented again 2 days later with ALT/AST of 287/153 then to 984/388 on the 9th day after INH cessation. Total bilirubin and INR had remained normal with minimally elevated ALP. HCV RNA was detected at 16.5 million IU/ml. A liver biopsy was performed for rising liver enzymes and excluding autoimmune hepatitis. Moderate portal/lobular inflammation with abundant hepatocyte apoptosis and mild intra-canalicular cholestasis without autoimmune hepatitis was reported, suggesting possible DILI with viral hepatitis per pathologist. However, with a strong competing diagnosis of acute HCV hepatitis, persistently rising ALT/AST despite cessation of INH, and only possible causality score for INH-DILI, the suspected INH hepatitis was adjudicated as acute HCV infection. Sofosbuvir-velpatasvir treatment was initiated with rapid normalization of ALT/AST and decreasing HCV RNA. Discussion: This is the first reported case of acute HCV infection for suspected INH hepatitis in a patient with controlled HIV infection on ART. The case emphasizes the importance of early HCV RNA testing for diagnosing/excluding acute HCV infection in suspicious DILI due to delayed seroconversion of HCV antibody. Prompt treatment with highly potent antiviral agents leads to eradication of HCV with potential public health benefit.

Universal versus targeted screening for HCV infection in pregnancy in a diverse, multi-ethnic population: Universal screening is more comprehensive.

Universal hepatitis C screening in pregnancy is not recommended by NICE due to a lack of effective interventions to prevent mother to child transmission (MTCT) and is only offered to pregnant women at increased risk of infection (intra-venous drug use [IVDU] or with a HCV positive family member). No testing is offered to patients from high endemic areas. However, data regarding true seroprevalence in multi-ethnic inner-city populations in the UK are required. This study aimed to determine test positivity rates of HCV infection in an unselected South East London ethnically diverse population of pregnant women by universal screening during routine antenatal care compared with a "targeted" screening approach. "Targeted" risk-based screening was performed in two eras (2016, n=1002) and subsequently in 2018, after modifying the HCV risk questionnaire (n=1122). Universal opt out screening was similarly performed in two eras in 2017 (n=1012) and again in 2019 (n=1057). During screening for HBV, HIV and syphilis, anti-HCV was tested, followed by an iterative HCV RNA test in those positive for anti-HCV. All anti-HCV-positive women were referred to the specialist hepatology service, and testing was offered to all family members. All HCV RNA-positive patients were followed during pregnancy and post-delivery period and were offered treatment. All infants of HCV RNA-positive mothers were linked to care with paediatric team. In the 2016 "targeted" screening cohort 212/1002 had a risk of BBV (blood borne viral) infection and (0.6%) were anti-HCV positive and HCV RNA positive. 0.3% patients were newly diagnosed. In the 2017 universal screening cohort, 1012/1038 pregnant women consented to testing. 0.96% were anti-HCV positive and 0.86% women were HCV RNA positive with 0.67% newly diagnosed. After modification of the risk-based questionnaire, a second risk-based targeted cohort were tested in 2018: 342/1122 (31%) were assessed as at risk and were offered an anti-HCV test. 0.71% were anti-HCV positive and 0.27% were HCV RNA positive. In the 2019 cohort tested by universal screening, 1049/1057 women were tested and 0.85% tested positive for anti-HCV, 0.28% women were HCV RNA positive. All newly diagnosed patients were born abroad. All patients had mild liver disease and had normal pregnancies. All patients were treated post-delivery and achieved SVR. All patients were negative for other BBV infections. In conclusion, the anti-HCV test positive rate in this ethnically diverse pregnant cohort ranged between 0.96% and 0.6% (whole cohort) but the rate depended upon the era and screening methodology used. Universal screening detected a higher numbers of anti-HCV positive women during pregnancy, including those not previously aware of their hepatitis C. While there was not significant drop in seroprevalence in pregnant women between 2016 and 2019, we observed that the ratio of HCV RNA positive to anti-HCV positive women has declined over time, from 0.86% in 2016 (100% HCV RNA+) to 0.28% in 2019 (33% HCV RNA+) for whole cohort probably due to increased HCV treatment rates from 2016. These data have important implications for hepatitis C testing in pregnancy and the appropriate methodology to use for maximal accuracy.

Nested-PCR based Detection of Hepatitis C Virus: Low-cost Strategy in Pakistan

One of the most common blood-borne illnesses is hepatitis C virus (HCV), Hepatitis C is referred to as the inflammation of the liver and caused by the HCV virus, HCV is estimated to cause 53000 fatalities per year over the world. The majority of HCV-infected patients are unaware of their infection. No vaccine is available for HCV although Interferon is used to treat HCV but effective only 20-38 %, but at present, only a minority of infected persons have been tested and are aware of their diagnosis. The expense of testing may play a substantial role in patients' ability to get rid of the hepatitis C virus (HCV). Costs in many low- and middle-income nations, including Pakistan, force the development of novel and economically advantageous testing methods. The major aim of this study is about the effective diagnostic procedure for detecting Hepatitis C in the samples obtained from Balochistan, for this purpose the samples were collected from the health organization BINUQ (Balochistan Institute of Nephrology and Urology Quetta). Twenty (20) HCV antibodies positive patients in the Molecular Laboratory Department of Biotechnology were processed and then subjected to RNA extraction. cDNA was synthesized by reverse transcriptase enzyme. cDNA was used for qualitative analysis of HCV-RNA through nested PCR. According to the study, 09 samples were detected as positive and 7 samples were HCV negative out of 16 patients’ samples. The findings of the present study show comparison of the price for HCV- RNA tests per sample from patients with hepatitis C at various labs. When compared to the other five PCR-based tests in the laboratory-conducted anti-HCV, HCV qualitative, quantitative, and genotyping tests, Shoukat Khanum laboratory reported the most expensive costs for HCV -RNA tests. Dow laboratory HCV-RNA test is comparatively lower than Shoukat Khanum laboratory, while reported lowest and most cost-effective test of Molecular Diagnostic laboratory for anti-HCV. So, our molecular tests for HCV- RNA detection and quantitation showed very good diagnostic and clinical performance over all five public health laboratories.

Real-life validation of a sample pooling strategy for screening of hepatitis C

ObjectivesTo test a real-life sample pooling screening strategy which contributes to increasing the diagnostic capacity of clinical laboratories and expanding access to massive screening of hepatitis C. MethodsAfter evaluating the sensitivity of the pooling strategy for seven different commercial assays which are used to determine the concentration of hepatitis C virus (HCV)-RNA in the plasma or serum, consecutive samples submitted for HCV diagnosis during the first 3 weeks of November 2021 were tested for HCV antibodies and, in parallel and in a blinded way, were pooled into 100 samples and tested for HCV-RNA. When the result was positive, a strategy to un-mask the positive(s) pool(s), which needed up to 15 total HCV-RNA tests, was used. ResultsAll platforms were able to detect the presence of HCV-RNA in a single sample from a patient with viremic HCV present in pools of up to at least 10 000 HCV-RNA-free samples. A total of 1700 samples (17 pools) were analysed, with an overall prevalence of anti-HCV and HCV-RNA of 0.24%. After pooling, we could detect all samples previously detected using standard diagnosis tests (reflex testing) with a specificity and sensitivity of 100% (CI, 99.78–100%). Given the median current prices of anti-HCV and HCV-RNA on the market in Spain as well as personnel costs, testing using the pooling strategy would have resulted in a save of 3320€. ConclusionsHere, we demonstrated that by improving cost effectiveness, with no loss of sensitivity and specificity, the strategy of pooling samples may serve as an appropriate tool for use in large-scale screening of HCV.

Meta-analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct-acting antivirals.

Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) is monitored by assessing plasma HCV-RNA load. However, detection of HCV core antigen (HCVcAg) may be an alternative. To evaluate the diagnostic performance of the HCVcAg assay to monitor the efficacy of DAAs in HCV-infected patients METHODS: We performed searches in multiple electronic databases until 6 July 2022, of studies evaluating the HCVcAg detection in plasma or serum compared with the HCV-RNA test (gold standard). We calculated pooled measurement at 2 and 4 weeks of treatment, and at end-of-treatment (EOT), as well as sustained virological response (SVR; 12 weeks after EOT). We selected 16 studies from 2016 to 2022, with 3237 patients and 8958 samples. Overall, the diagnostic performance and clinical utility of the HCVcAg assay were poor at week 2 (sensitivity=0.40, specificity=0.96, positive likelihood ratio (PLR)=9.16, negative likelihood ratio (NLR)=0.63, and area under the summary receiver operating curve (SROC)=0.57), fair at week 4 (sensitivity=0.30, specificity=0.90, PLR=3.18, NLR=0.77, and AUC=0.79), acceptable at EOT (sensitivity=0.40, specificity =0.98, PLR=16.54, NLR=0.62, and AUC=0.97) and excellent for SVR (sensitivity=0.94, specificity=0.99, PLR=107.54, NLR=0.06, and AUC=0.99). The HCVcAg assay may be helpful for monitoring the efficacy of HCV treatment with DAAs in HCV-infected patients at EOT and for documenting SVR, but not at weeks 2 and 4 of treatment due to poor diagnostic performance.

A cross-sectional study of hepatitis C prevalence and correlates among persons who inject drugs in rural and non-rural communities.

Persons who inject drugs (PWID) have been experiencing a higher burden of new hepatitis C (HCV) due to the opioid epidemic. The greatest increases in injection have been in rural communities. However, less is known about the prevalence of HCV or its risk factors in rural compared to non-rural communities. This study compared HCV infection history, current infection, and associated behavioural and sociodemographic correlates among PWID recruited from rural and non-rural communities from Upstate New York (NY). This cross-sectional study recruited 309 PWID, using respondent-driven sampling. Blood samples were collected through finger stick for HCV antibody and RNA tests. A survey was also self-administered for HCV infection history, sociodemographics and behavioural correlates to compare by setting rurality. HCV seropositivity was significantly higher among PWID from rural than non-rural communities (71.0% vs. 46.8%), as was current infection (41.4% vs. 25.9%). High levels of past year syringe (44.4%) and equipment (62.2%) sharing were reported. Factors associated with infection history include syringe service program utilization, non-Hispanic white race, sharing needles and methamphetamine injection, which was higher in rural vs. non-rural communities (38.5% vs. 15.5%). HCV burden among PWID appears higher in rural than non-rural communities and may be increasing possibly due to greater levels of methamphetamine injection. On-going systematic surveillance of HCV prevalence and correlates is crucial to respond to the changing opioid epidemic landscape. Additionally, improving access to harm reduction services, especially with special focus on stimulants, may be important to reduce HCV prevalence among PWID in rural settings.

Comparative evaluation of the Geenius HCV supplemental assay and Inno-LIA HCV score assay in detecting anti-HCV antibodies.

This study compared two assays aimed at confirming the presence of anti-HCV antibodies (Ab) after a positive screening: Geenius HCV supplemental assay (Bio-Rad, Marne la Coquette, France) and the Inno-LIA HCV score assay (Fujirebio, Les Ulis, France). A total of 180 archived samples were investigated including 119 samples collected at different stages of HCV infection in 25 hemodialyzed patients who underwent HCV seroconversion, 14 samples from 4 commercial seroconversion panels, 47 Ab positive/HCV-RNA positive blood donations of which 7 showing an single reactivity in confirmatory assays. Samples were investigated and results were interpreted with the two assays according to the manufacturers' instructions. Overall, Geenius and Inno-LIA were concordant for 84% (151/180) samples: 38 negative, 17 indeterminate and 96 positive. Of the 29 discrepant results, 26 were overclassified with Inno-LIA. HCV seroconversion was detected with Inno-LIA 4 and 7 days prior to Geenius in two panels. The high positive rate observed with Inno-LIA (64%) compared to Geenius (54%) was mainly due to low reactivities considered positive according to interpretation criteria, which could affect specificity. Although HCV supplemental assays are not recommended for the diagnostic of HCV infection, which is primarily based on HCV-RNA testing, both assays are suitable as second line anti-HCV tests when Ab screening is positive and RNA testing cannot be performed. Moreover, Geenius system provides an objective result in less than 30minutes, which is compatible when a rapid diagnostic is required.

A Testing Campaign Intervention Consisting of Peer-Facilitated Engagement, Point-of-Care HCV RNA Testing, and Linkage to Nursing Support to Enhance Hepatitis C Treatment Uptake among People Who Inject Drugs: The ETHOS Engage Study.

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018–September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.

Timely Hepatitis C RNA Testing and Treatment in the Era of Direct-Acting Antiviral Therapy among People with Hepatitis C in New South Wales, Australia.

This study aimed to identify the factors associated with timely (within four weeks) HCV RNA testing and timely (within six months) DAA initiation following HCV notification in the DAA era. We conducted a cohort study of people with an HCV notification in NSW, Australia. Notifications of positive HCV serology were linked to administrative datasets. Weights were applied to account for spontaneous clearance. Logistic regression analyses were performed. Among 5582 people with an HCV notification during 2016–2017, 3867 (69%) were tested for HCV RNA, including 2770 (50%) who received timely testing. Among an estimated 3925 people with chronic HCV infection, 2372 (60%) initiated DAA therapy, including 1370 (35%) who received timely treatment. Factors associated with timely HCV RNA testing included age (≥30 years), female sex, non-Aboriginal ethnicity, country of birth being Australia, and no history of drug dependence. Factors associated with timely treatment were age (≥30 years), male sex, non-Aboriginal ethnicity, country of birth being Australia, no history of drug dependence, and HCV/HIV co-infection. In the DAA era, 50% of people with an HCV notification did not receive timely HCV RNA testing. Most people with an HCV infection received therapy; however, DAA initiation was delayed among many.

Declining prevalence of current HCV infection and increased treatment uptake among people who inject drugs: The ETHOS Engage study.

Evaluating trends in HCV treatment and prevalence is crucial for monitoring elimination. We evaluated the change in current infection and treatment among people who inject drugs (PWID) between 2018-2019 and 2019-2021. ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participant enrolment occurred over two periods, Wave 1 (May 2018-September 2019, 25 sites) and Wave 2 (November 2019-June 2021, 21 sites), with baseline questionnaire completion and point-of-care HCV RNA testing (Xpert®HCV Viral Load Fingerstick). Logistic regression wasused to identify factors associated with current HCV infection and historic HCV treatment. 2,395 individuals were enrolledacross the two recruitment waves (66% male, median age 43, 72% current opioid agonist therapy, and 65% injecting in the previousmonth). HCV prevalence decreased from 24% to 17% between 2018-2019 and 2019-2021, respectively (p=0.003). HCVtreatment increased from 66% to 74% between 2018-2019 and 2019-2021, respectively (p<0.001). After adjusting, there was a reduction in current HCV infection in 2019-2021 (adjusted odds ratio [aOR] 0.62; 95% CI, 0.50, 0.77) compared to 2018-2019. Other factors associated with currentinfection included homelessness (aOR, 1.70; 1.26, 2.30), incarceration (vs. never; historic: aOR 1.69; 95%CI 1.31, 2.19; recent: aOR 1.85; 95%CI, 1.35, 2.54), and recentlyinjecting drugs(vs. >12 months ago;previous month <daily: aOR 2.03; 95%CI, 1.37, 3.02;≥daily: aOR 2.90; 95%CI, 1.94, 4.32). The increase in HCV treatment and decrease in prevalence among PWID provides evidence of further progress towards HCV elimination; however, sub-populations may require additional support to enhance elimination. PWID are a priority population to facilitate HCV elimination and temporal data are crucial to understand trends in HCV infection and treatment in this group. Among a cohort of PWID recruited during two different waves and in an era of unrestricted DAA therapy, prevalence of HCV infection decreased and the proportion who had received HCV treatment increased. Sub-populations of PWID-including people who are homeless, people who have been incarcerated, people who frequently inject drugs, younger people, women, and people not engaged in OAT-may require additional support to enhance HCV elimination efforts.

FRI318 - Progress towards hepatitis C elimination: the feasibility and success of a nurse and harm reduction practitioner led model of care utilising rapid point of care HCV RNA testing at a medically supervised injecting room in Melbourne, Australia

FRI318 - Progress towards hepatitis C elimination: the feasibility and success of a nurse and harm reduction practitioner led model of care utilising rapid point of care HCV RNA testing at a medically supervised injecting room in Melbourne, Australia

Determining the frequency and characteristics of Hepatitis C reinfections in North East England.

Hepatitis C virus infection (HCV) is common, and injecting drug use is the major risk factor for acquisition. Understanding HCV reinfection following treatment is an important consideration for HCV elimination programmes. The aim of this work was to assess the frequency and patterns of HCV reinfection in our region to develop avoidance strategies. All individuals who completed anti-HCV treatment with a known outcome in Tyne and Wear, England between January 2016 and May 2021 were included. This was a retrospective analysis of prospectively collected data. HCV reinfection was defined as positive HCV RNA after achieving sustained virological response 12 (SVR12). 788 of 840 patients (76% male; mean age 45.7 ± 11.9 years; 47% Genotype 1; 11% Cirrhosis; 20% started in prison) achieved SVR (94%). 443 patients (56%) had HCV RNA testing post-SVR after a median 0.82 (range 0.1-5.2) years. 56 reinfections (7.1% of all SVRs and 12.6% of SVRs who had post-SVR testing) were diagnosed. The median time to reinfection was 1.37 (range 0.1-4.0) years and the rate of reinfection was 10.5 /100 person years. 45 (80%) reinfections became chronic, 17 of whom were retreated and achieved SVR. 5 individuals developed a second reinfection. Younger age was the only factor independently associated with reinfection (HR 0.91 [0.88-0.94] p < .001). In conclusion, HCV reinfection is common and may slow our HCV elimination efforts. In order to address high reinfection rates, harm minimization approaches need improved, and we have implemented an 'HCV track and trace' pilot to try to reduce onwards HCV transmission.

Elimination of Hepatitis C in Southern Italy: A Model of HCV Screening and Linkage to Care among Hospitalized Patients at Different Hospital Divisions.

Background: Free-of-charge HCV screening in some key populations and in 1969–1989 birth cohorts has been funded in Italy as the first step to diagnosing individuals who are infected but asymptomatic. The aim of this study is to evaluate the feasibility of an opportunistic HCV screening and its linkage to care. Methods: A hospital-based HCV screening was conducted as a routine test for in-patients admitted to the Evangelical Hospital Betania of Naples from January 2020 to May 2021. All consecutive in-patients were screened for the HCV antibody (HCV-Ab) at the time of their admission to the hospital, and those born prior to year 2000 were included in the study. HCV-RNA testing was required for those not previously treated and without antiviral treatment contraindications. For in-patients with an active infection, treatment started soon after hospital admission. Results: Among 12,665 inpatients consecutively screened, 510 (4%) were HCV-Ab positive. The HCV-Ab positivity rate increased with age, reaching the highest prevalence (9.49%) in those born before 1947. Among patients positive for HCV, 118 (23.1%) had been previously treated, 172 (33.9%) had been discharged before being tested for HCV-RNA, and 26 (5.1%) had not been tested for short life expectancy. Of 194 (38% of HCV-Ab+) patients who were tested for HCV-RNA, 91 (46.2%) were HCV-RNA positive. Of patients with active infection, 33 (36%) were admitted to the liver unit with signs of liver damage either not previously diagnosed or diagnosed but unlinked to care for HCV infection. Of the patients positive for HCV-RNA, 87 (95.6%) started treatment; all achieved sustained virological response. Conclusion: HCV active infection has been frequently found in patients with comorbidities admitted in the hospital in Southern Italy. To achieve HCV elimination in Italy, broader screening strategies are required. In addition to screening of the 1969–1989 birth cohort of individuals unaware of their infection status, diagnosis and linkage to care of patients with known liver damage is strictly required. Hospital screening is feasible, but prompt reflex testing for identifying HCV-active infections is necessary to increase diagnosis and subsequent linkage to care.