Active HCV Infection Research Articles

Automated Opt-Out Hepatitis C Testing to Reduce Missed Screening Opportunities in the Emergency Department.

We evaluated the impact of implementing automated hepatitis C (HCV) opt-out screening in the emergency department of an urban, academic medical center with high HCV prevalence, in the context of a longstanding HCV opt-in screening model. We compared nine-month periods before and after implementation. HCV testing increased by 502%, and active HCV infection identification increased by 212%. Settings where there is great opportunity for HCV diagnosis, such as emergency department settings, should consider opt-out HCV screening models. (Am J Public Health. Published online ahead of print August 29, 2024:e1-e4. https://doi.org/10.2105/AJPH.2024.307783).

How to better improve the treatment and outcomes of HCV in psychiatric patients: review of a Belgian monocentric psychiatric center.

Hepatitis C (HCV) is one of the major worldwide infections with 58 million infected persons in the world. HCV can lead to chronic liver disease, cirrhosis, and cancer. These past few years, clinical progress allowed a curative rate of 95% of the patients. There are still populations in which, treating the disease is more difficult, especially psychiatric patients, when substance abuse, psychiatric disorders are important risks factors for getting HCV. With the WHO organization establishing goals for clinical management and treatment of HCV, it is important to target where the difficulties lie in getting a better treatment program for those populations. Try to highlight the challenges of treating a certain group of patients compare to the general population. This is a cross sectional monocentric study. 79 patients from a mental facility were included between 2012 and 2022. Inclusion criteria were: >18 years old, an active viral HCV infection. 34.7% of patients with a positive PCR were treated with a significant difference between the closed psychiatric unit and the open one (66.5 vs 22.6%, p<.05). There was an 82.4% eradication rate (Sustained Viral Response at 3 months). There were significantly more schizophrenic disorders in the closed unit and significantly more alcohol abuse in the open one. Treatment of HCV in a psychiatric population is feasible with eradication rate equivalent at those in the general population. Patients with more severe mental illness are better treated in the configuration of a closed psychiatric unit.

Epidemiological characteristics of hepatitis c infection in Nizhny Novgorod at the first stage of infection control program (2016–2021)

Objective. To characterize the peculiarities of the epidemic process of viral hepatitis C in Nizhny Novgorod at the first stage of the infection control program (2016–2021).&#x0D; Materials and Methods. A retrospective analysis of the incidence of registered forms of HCV infection in Nizhny Novgorod was carried out using information of statistical and analytical materials. A total of 78 883 blood serum samples were collected from individuals undergoing pre-hospital screening and admitted to non-infectious hospitals from 2016 to 2021. Laboratory testing included the determination of HCV infection markers: anti-HCV IgM and IgG, antibodies to structural and non-structural proteins (n = 2953). Seropositive samples were tested for the presence of HCV RNA (n = 467) using the Real Time PCR method.&#x0D; Results. A trend towards a decrease in the incidence of registered forms of HCV infection was observed in Nizhny Novgorod from 2016 to 2021. It was found that among the various suspected transmission routes and risk factors for HCV infection, the predominant ones were a history of injected drug used and sexual transmission. The seroprevalence of anti-HCV was 3.6 ± 0.1 % and the prevalence of HCV RNA among the adult population was 1.8 ± 0.1 %. The highest prevalence of active HCV infection was observed in the age groups of 30–39 years (3.3 ± 0.3 %) and 40–49 years (5.7 ± 0.5 %).&#x0D; Conclusions. To achieve the goals of the HCV elimination program, targeted and dynamic seroepidemiological studies are necessary to increase the number of individuals screened for HCV infection markers, with subsequent expansion of access to effective antiviral therapy for those with active infection.

1484. Hepatitis C Virus Infection and Cure by Priority Population Among New York City Ryan White HIV/AIDS Program Part A Clients

Abstract Background Hepatitis C virus (HCV) infection is a common comorbidity among people with HIV (PWH). HCV-related liver disease is the second leading cause of death among PWH. To identify opportunities to improve service integration and health equity, we examined HCV infection and cure among priority populations identified for New York City (NYC) Ryan White HIV/AIDS Program Part A (RWPA) service delivery. Methods Using a merge of NYC HIV and HCV surveillance data with RWPA program data, we identified RWPA clients receiving services from 01/2019–12/2022. We categorized clients into priority populations: Black or Latina cisgender women; Black or Latino men who have sex with men (MSM); transgender, intersex, gender non-conforming, or non-binary (TIGNCNB) people; people who inject drugs (PWID); and people aging (age &amp;gt;50) with HIV (PAWH). We measured active HCV infections (any positive RNA test during analysis period), and HCV cure­ (negative RNA result on the most recent HCV test &amp;gt;12 weeks after most recent positive RNA result obtained during the analysis period). Using logistic regression, we compared HCV prevalence and HCV cure by population, adjusting for potential confounders. Results Among 15,702 RWPA clients, 15% (n=2,278) had active HCV infection, with 70% (n=1,596) achieving cure. 53% of clients were PAWH, 36% were Black/Latino MSM, 26% were Black/Latina cisgender women, 5% were TIGNCNB people, and 2% were PWID. PWID had the highest proportion of HCV infection (38%), and PAWH had the highest cure proportion (73%) (Table 1). After adjusting for potential confounders, PWID and PAWH had higher odds of HCV infection compared to other clients [adjusted odds ratio (aOR): 4.37, 95% CI: 3.41, 5.59 for PWID; aOR: 4.05, 95% CI: 3.61, 4.54 for PAWH]. Black/Latino MSM and Black/Latina cisgender women had lower odds of infection (aOR: 0.79, 95% CI: 0.71, 0.88 and aOR: 0.60, 95% CI: 0.53, 0.68, respectively) compared to other clients. Among clients with HCV, PWID had lower odds of cure compared to non-PWID (aOR: 0.58, 95% CI: 0.39, 0.85; Table 2). Table 1, Part 1 Table 1, Part 2 Conclusion These findings – particularly the low odds of HCV cure among PWID, who had the highest odds of infection – highlight gaps that can inform resource allocation and targeted integration of HIV/HCV care. Disclosures All Authors: No reported disclosures

Towards SDG30: Fighting HCV with a screening program in Lombardy

Abstract Background The third Sustainable Development Goal, specifically in target 3.3, identifies fighting HCV as a priority. It is estimated that in Italy more than 200.000 patients eligible for HCV treatment are not being treated and 20% are not aware of the infection. Lombardy region to promptly identify and treat patients affected, developed a screening program to be offered to all patients born between 1969 and 1989. Healthcare facilities were divided into first and second-level centers and the campaign was designed in 2 phases: at the first level centres patients were screened with blood tests, if positive they were contacted by second level structures to get a diagnostic test and if confirmed positive to start the therapeutic approach. Methods The screening program started in June 2022 and consisted of an opportunistic offer of free testing for serum anti-HCV antibodies in the context of any healthcare performance offered to eligible patients. Data were uploaded and collected on a web database from which second-level centers could obtain data of positive patients to contact them and set appointment for confirmation tests. Results As of 31st December 2022 120,193 individuals underwent HCV screening in 75 screening centers in Lombardy. The mean age was 44 years, 65.2% were females, and 83.7% were tested at outpatient blood collection centers. 604 (0.50%) patients tested positive with mean age 47 (±5). HCV-RNA was detectable in 125 out of 441 (28.3%) anti-HCV positive subjects with available HCV-RNA. Patients with active HCV infection were aged 46 (±6) and were mostly males (56.8%). Overall, the prevalence of active infection in the general population was 0.10% and was higher in elderly. Conclusions The prevalence of active HCV infection in the general population born between 1969 and 1989 in Lombardy was low. Considering the higher prevalence of active infection in the elderly population, an extension of the screening offer to patients born between 1949-70 could be evaluated. Key messages • Prevalence of active HCV infection in screened population is low. • Extending the screening offer may result in higher number of positive results and more people directed towards treatment.

Lack of associations of microRNAs with severe NAFLD in people living with HIV: discovery case-control study.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people living with HIV (PLWH) and the expression of some microRNAs could be useful as biomarkers for the diagnosis of NAFLD. The aim of this study was to identify patterns of differential expression of microRNAs in PLWH and assess their diagnostic value for NALFD. A discovery case-control study with PLWH was carried out. The expression of miRNAs was determined using HTG EdgeSeq technology. Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, BMI, CD4+ lymphocyte count, active HCV infection, and ART regimen. Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study. Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.

Cost-effectiveness of Kidney Transplantation From Donors at Increased Risk of Blood-borne Virus Infection Transmission.

Demand for donor kidneys outstrips supply. Using kidneys from selected donors with an increased risk of blood-borne virus (BBV) transmission (hepatitis B virus and hepatitis C virus [HCV], human immunodeficiency virus) may expand the donor pool, but cost-effectiveness of this strategy is uncertain. A Markov model was developed using real-world evidence to compare healthcare costs and quality-adjusted life years (QALYs) of accepting kidneys from deceased donors with potential increased risk of BBV transmission, because of increased risk behaviors and/or history of HCV, versus declining these kidneys. Model simulations were run over a 20-y time horizon. Parameter uncertainty was assessed through deterministic and probabilistic sensitivity analyses. Accepting kidneys from donors at increased risk of BBVs (2% from donors with increased-risk behaviors and 5% from donors with active or past HCV infection) incurred total costs of 311 303 Australian dollars with a gain of 8.53 QALYs. Foregoing kidneys from these donors incurred total costs of $330 517 and a gain of 8.44 QALYs. A cost-saving of $19 214 and additional 0.09 QALYs (~33 d in full health) per person would be generated compared with declining these donors. Increasing the availability of kidneys with increased risk by 15% led to further cost-savings of $57 425 and additional 0.23 QALY gains (~84 d in full health). Probabilistic sensitivity analysis using 10 000 iterations showed accepting kidneys from donors at increased risk led to lower costs and higher QALY gains. Shifting clinical practice to accept increased BBV risk donors would likely produce lower costs and higher QALYs for health systems.

Assessing the Feasibility, Acceptability, and Effectiveness of a Pilot Hepatitis C Screening Program at Food Distribution Sites in Cherokee Nation, Oklahoma

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

Real-World Effectiveness and Safety of Direct-Acting Antivirals in Patients with Chronic Hepatitis C and Epilepsy: An Epi-Ter-2 Study in Poland.

In Poland, active HCV infection affects between 0.4 and 0.5% of the population, i.e., about 150,000 people, while the number of patients with epilepsy is estimated to be 350,000-400,000. Currently available antiviral therapies show little interaction with neurological drugs. The aim of our study was to evaluate the effectiveness and safety of the treatment of chronic HCV infection in patients with coexisting epilepsy. A total of 184 epilepsy patients were selected from the group of 10,152 HCV-infected patients treated for HCV infection within the Epiter-2 database from 2015 to 2018. Comparing the effectiveness and safety of anti-HCV regimens between the patients with comorbid epilepsy and 3573 patients without comorbidities was our study's objective. The effectiveness of anti-HCV treatment was high in both the sample and the control group. No statistically significant SVR difference was observed between the sample group, with ITT = 93.5% and mITT = 95.5%, and the control group, with ITT = 95.2% and mITT = 97.5%, regardless of the genotype and the stage of liver disease at the start of therapy. The treatment was safe in patients with epilepsy. The effectiveness and safety of HCV treatment in patients with epilepsy are comparable to those of patients with no significant comorbidities.

Hepatitis C antibody prevalence and active hepatitis C infection in HIV-negative gay, bisexual, and other men who have sex with men in Barcelona and Madrid, Spain (March 2018-March 2021)

ObjectivesHepatitis C virus (HCV) has been recognized as a sexually transmitted infection (STI) in HIV-positive men who have sex with men (MSM), with an increased notification in HIV-negative MSM. The aim of this study was to determine the prevalence of HCV antibody and active HCV infection in HIV-negative gay, bisexual, and other MSM (GBMSM), and their characteristics, in Barcelona and Madrid, from March 2018 to March 2021. MethodsCross-sectional study conducted on 3548 HIV-undiagnosed GBMSM, across four HIV/STI testing centers. Respondents submitted an online, self-administered questionnaire after consultation, which collected information on sociodemographics, sexual health history, HCV knowledge, and substance consumption. Prevalence of HCV antibodies was determined by a reactive result in a rapid anti-HCV test or enzyme-linked immunosorbent assay (ELISA), while active HCV infection was determined by participants who were also positive on an HCV-RNA test. Crude and adjusted Poisson analyses with robust variance are presented for both prevalence and active infection. ResultsIn total, 97.6% of participants (n = 3463) were HIV-negative. Of those, 18 were found to have HCV antibodies (0.52%), of which nine (0.26%) were also HCV-RNA positive. Those with HCV antibodies were associated to have lived with an HCV (+) person (adjusted prevalence ratio [APR]: 7.84, [95% confidence interval: 2.50-24.53]), using injectable drugs for sex (APR: 6.92, [1.20-39.79]) and testing positive for an STI in the previous year (APR: 4.06, [1.09-15.12]). Presenting an active infection was strongly associated with a previous HCV diagnosis (APR: 100.82 [22.16-458.76]), sexualized injectable drug use (APR: 17.53 [2.70-113.76]), and sharing douching material (APR: 7.45, [2.12-25.95]). ConclusionSexual practices with a higher risk of bleeding and sexualized drug use, particularly sexualized injectable drug use, were associated with higher rates of HCV diagnosis in GBMSM. Identifying these practices during consultation, contact tracing new cases and regularly testing those with a previous history of HCV, will facilitate HCV eradication.

#3928 NEPHROTIC SYNDROME IN LIVER DISEASES: PRESENTATION OF TWO UNUSUAL AND INSTRUCTIVE CASES

Abstract Background and Aims However, there are known associations between chronic liver diseases and glomerulopathies, here we report two rare cases, where diagnostic and therapeutic challenges influenced the patients’ care. Method The patients’ medical parameters were obtained from the electronical charts of the hospital. Kidney biopsy samples were examined with immunofluorescence (frozen samples), light microscopy (paraffin embedded tissue, 2-3 um sections) and electron microscopy (1 um, toluidine blue). The follow-up time was 24 months for case 1 and 23 months for case 2. Both patients gave written consent to the presentation of the reports. Results Case 1: A 42-year-old man with recent pulmonary embolism was presented in our hospital with nephrotic syndrome and reduced kidney function (estimated glomerular filtration rate (eGFR): 43 ml/min/1.73 m2, urinary protein/creatinine ratio (UPCR): 2124 mg/mmol, serum albumin: 24 g/L). Kidney biopsy confirmed primary membranous nephropathy (MN). The anti-phospholipase-A-2 receptor (aPLA2R) was positive in high titer, and PLA2R positivity was also seen in the renal sample. Additionally, an active hepatitis C (HCV) infection with viremia was confirmed. The nephrotic syndrome was worsened with severe edema requiring ultrafiltration; therefore, after one-week direct anti-HCV therapy, methylprednisolone was started. Immunosuppressive therapy had to be determined soon due to severe infections. With combined direct antiviral treatment, HCV PCR test became negative, which was followed by the disappearance of the aPLA2R antibodies. The patient's kidney function stabilized and there are no symptoms of nephrotic syndrome (eGFR: 52 ml/min/1.73 m2, serum albumin: 37 g/L, UPCR: 321 mg/mmol). Case 2: A 66-year-old woman was admitted to the hospital with coronavirus disease (COVID)- associated pneumonia. At admission, nephrotic syndrome was diagnosed (eGFR: 29 ml/min/1.73 m2, serum albumin: 22 g/L, proteinuria: 8 g/day). Additionally, elevated gamma glutamyl transferase was registered. Immune serology was negative for aPLA2R, but antinuclear antibodies (anti-cytoplasm, chromatin, Ro), and anti-mitochondrial antibodies (AMA-M2) were positive. Biopsies were performed after the COVID infection. Liver biopsy confirmed primary biliary cholangitis (stage 1-2), while the kidney biopsy showed secondary membranous nephropathy with signs of potential monoclonal gammopathy (monoclonal immunoglobulin-G1-kappa deposits). After the exclusion of malignancies, monoclonal gammopathy, and potential other causes of the secondary MN, PBC-associated MN was diagnosed. Based on case reports in the literature, cyclosporine A treatment was started. The patient reached complete remission in 5 months (no significant proteinuria, stable eGFR around 34 ml/min/1.73 m2). Conclusion The association of an active HCV infection and an aPLA2R positive MN has not been reported in the literature. Nephrotic syndrome and the aPLA2R positivity disappeared related to the direct antiviral treatment, which may indicate a diagnosis of secondary MN. PBC-associated secondary MN is a known but rare entity, where calcineurin inhibitor treatment may reduce the symptoms of nephrotic syndrome.

Efficacy of a comprehensive strategy for the detection and treatment of hepatitis C infection in a population attending addiction centers.

The burden hepatitis C infection in people with history or current drug use suppose a high risk of hepatic complications and transmission infectious disease. This population is poor linked to heath system and is difficult to achieve them and support treatment because they have high rates of lost follow-up. Our aim was to evaluate an intervention for the diagnosis and treatment of chronic hepatitis C and HIV in this population. Six-hundred and eighty-three people attended in Drugs and Addictions Centers (DAC) were asked to participate in health counseling and provide blood sample for test HCV, HIV, and syphilis from April 2019 to June 2020. Totally 556 subjects were surveyed and tested. All of them were assigned to a patient navigation program to improve health education and linking to the sanitary system. Hepatitis C infection patients were evaluated in an ampliated medical consult to evaluate hepatic stage with transient liver elastography and initiated Direct Acting Antivirals to achieve Sustained Viral Response. Of the 556 patients who agreed to participate in the study, 33 (5.9%) had active HCV infection. Of the 33 patients infected with HCV, three were lost to follow-up once the diagnosis of HCV infection was made. Twenty-eight patients (93.3%) completed treatment and 26 achieved Sustained Viral Response (78.8%). Of the 30 patients, seven (23.3%) had advanced fibrosis, and of these, four (16.6%) had liver cirrhosis. One of the cirrhotic patients had hepatic space-occupying lesions at the baseline evaluation and was diagnosed with hepatocarcinoma. Our study suggests that the implementation of strategies based on personalized intervention models can contribute to the control of HCV infection in DAC users.

The impact of hepatitis B virus and hepatitis C virus infections in patients with Hodgkin's and non-Hodgkin's lymphoma.

This study aimed to determine the prevalence of HCV and occult HBV among newly diagnosed pre-treatment Egyptian lymphoma patients and evaluate patients' outcomes based on the presence of the viral infections. The study included 80 therapy-naïve lymphoma patients including 71 non-Hodgkin lymphoma (NHL) and 9 Hodgkin lymphoma disease (HD) in addition to 100 healthy volunteers. HBV screening using HBsAg and anti-HBc IgM and HCV using AB/Ag ELISA and real-time RT-PCR were screened in tested and control groups. The diagnosis was confirmed by histopathology. Overall survival (OS) and progression-free survival (PFS) were conducted to diseased patients. Healthy patients showed 4/100, (4%) active HCV infection and 1/100, (1%) active HBV infection and no occult HBV infection. Among NHL patients, 28 were positive for HBV (6 active and 22 occult HBV infection). Occult HBV was also detected in 5/9 HD patients. HCV was detected in (30/71, 42.3%) of NHL patients and in a single HD patient. Ten occult HBV NHL patients showed a mixed infection with HCV. The incidence of both HCV and HBV are higher in NHL than HL patients. After antitumor treatment, complete remission for lymphoma was achieved in 45% of patients. Both overall survival (OS) and progression-free survival (PFS) were correlated and significantly associated with patients' LDH levels. Our findings claim the suggestive role of HCV and occult HBV infections in NHL but not HL patients in comparison to healthy control, suggesting pre-screening of related factors including occult HBV in for potential better therapy response.

1241. Hepatitis C Cascade of Care in a Multidisciplinary Substance Use Bridge Clinic Model

Abstract Background Hepatitis C virus (HCV) infection is common among persons who inject drugs. Treating HCV in patients who present for treatment of substance use disorder (SUD) is an opportunity to improve linkage to and retention in care. The Vanderbilt University Medical Center (VUMC) Bridge Clinic serves a unique patient population that includes individuals with opioid use disorder who recently presented to VUMC for complications related to substance use. These patients are treated by a multidisciplinary team for addiction with opioid agonist therapy as well as comorbid medical conditions. The aim of this study is to further characterize the HCV cascade of care (CoC) in a bridge clinic setting and identify barriers to HCV treatment. Methods We performed a single-center, ambispective cohort study of patients enrolled in the VUMC Bridge Clinic from 7/1/20 through 6/30/21. Data collection was continued through 12/31/21. All patients enrolled in the Bridge Clinic were reviewed, and patients with active HCV infection were monitored from initial evaluation through treatment and sustained virologic response (measured at least 12 weeks after completing therapy (SVR12). Descriptive statistics including demographics and progression through the CoC are presented. Results Characteristics of the 230 patients screened for HCV are reflected in Table 1. The CoC is reflected in Figure 1. Of these 230 patients, 96 (42%) had detectable virus as measured by blood HCV RNA. Of these 96 patients, 39 (40%) were approved for treatment, 33 (34%) initiated treatment, 25 (26%) completed treatment, and 13 (14%) achieved SVR12 with laboratory confirmation. The largest number of patients who did not progress through the CoC were those not approved for treatment; the most common reasons were loss to follow-up or incomplete workup. The majority of patients received opioid agonist therapy as part of their multidisciplinary treatment plan. Conclusion This study demonstrates opportunities and challenges for treating HCV in individuals with SUD in a bridge clinic model. Ongoing efforts should focus on linkage to care and strategies to keep individuals with SUD engaged throughout HCV treatment. Disclosures David Marcovitz, MD, Better Life Partners LLC: Stocks/Bonds|Silver Pines LLC: Stocks/Bonds.

1980. A Case Series of Serratia Marcescens Endocarditis in Persons Who Inject Drugs

Abstract Background Serratia marcescens is a gram-negative bacillus that is widespread in the environment and has been recognized as a rare cause of infective endocarditis (IE), particularly in persons who inject drugs (PWID). The literature consists of a 19 person case series in the 1970s followed by just a handful of case reports and small case series. At AHWFB (Atrium Health Wake Forest Baptist), we have noticed an increasing number of severe infections, including IE, with Serratia marcescens in PWID. Methods We conducted a retrospective chart review of all cases of Serratia grown from sterile culture sites in the AHWFB system between 8/1/2016 -10/31/2021. Charts were reviewed to confirm status of injection drug use in the 3 months prior to admission, ≥18 years old, and possible or definite IE by Modified Duke’s criteria. Results Twenty two participants were included in the study. The median age was 29.5 years. Eighteen (90%) were white and 16 (73%) were female. Sixteen (73%) had injection of opioids and 3 (14%) had injection of stimulants clearly indicated. Ten (45.5%) had stimulant use documented but the route was not clear. Nineteen (95%) had evidence of active or resolved HCV infection. The median duration of bacteremia was 2 days. Two cases of IE involved the aortic valve, 8 mitral, 3 pulmonic, and 10 tricuspid. Four (18%) of the participants had prosthetic valve IE. Nine (41%) of the participants had a history of previous IE episode. Eighteen participants had evidence of septic emboli: 10 pulmonary, 7 cerebral, and 5 major arterial. In terms of disposition, 4 (18%) patients died, 4 left against medical advice, 12 (54%) remained at a facility for the duration of their antibiotics. One patient was transferred to another facility and one was discharged to complete antibiotic therapy via peripheral IVs in an infusion center. Two patients expired before a final antibiotic regimen could be determined. Ten participants were treated with beta lactam monotherapy, 1 with fluoroquinolone monotherapy, and 9 with dual therapy with a beta lactam and fluoroquinolone. Conclusion Serratia marcescens, a rare cause of IE, has been found in a population of PWID in a North Carolina hospital system. More research is necessary to understand why this unusual infection is clustering in this population and the optimal treatment regimen. Disclosures All Authors: No reported disclosures.

S1210 Catching Hepatitis C: Universal Hepatitis C Screening in a Primary Care Setting in California’s Central Valley

Introduction: An estimated 2.4 million people in the United States are living with chronic hepatitis C (HCV). Approximately 40% of HCV patients are unaware of their diagnosis. Socioeconomic status and the ongoing opioid crisis are important risk factors for HCV infection. The rates of intravenous and intranasal drug use in California’s Central Valley are among the highest in the nation and many are socioeconomically disadvantaged, creating a perfect scenario for HCV propagation. Identification and treatment of HCV is imperative to prevent morbidity and mortality as well as the spread of infection. Methods: A universal HCV screening program was implemented in the internal and family medicine teaching clinics at a large federally qualified health center in the Central Valley. The electronic medical record identifies eligible patients based on current CDC guidelines. Once identified, an automatic prompt alerts the provider and HCV labs (HCV antibody test with reflex to genotype and RNA level) are auto-populated and available to be signed at the end of the visit. Patients with active HCV infection (positive RNA level) are contacted by the designed project coordinator, who facilitates linkage to care to a primary care provider as well as to the provider experienced in treating HCV. Linkage to care is defined as, completion of the first medical appointment. Results: Universal screening was implemented on July 1, 2021. The data here was collected between July 1, 2021 and November 30, 2021. A total of 1152 patients were eligible for screening and 1084 patients completed the screening. Twenty-three patients tested positive for HCV Ab and 11 patients (9 male and 2 female) tested positive for HCV RNA. Most HCV RNA positive patients were Hispanic (36%) and African American (27%). The most common genotype was 1a (45%). Fifty-four percent of HCV RNA positive patients were linked to care. Conclusion: Prior to the implementation of universal screening, only 54% eligible patients were screened in a 12-month period. Based on preliminary data, we screened 94% eligible patients within a 5-month period. In addition, only 31% of HCV patients prior to universal screening were linked to care compared to the 54% linked to care through our initiative. Our project encouraged providers to screen patients which helped identify HCV in the community. Although data collection is ongoing, we suspect this initiative will surpass the total number of patients screened and linked to care compared to previous practices.

Study of XPD Gene Polymorphism in HCV Positive HCC Egyptian Patients

Background: Hepatocellular carcinoma (HCC) is one of the most frequently occurring tumorous cells globally, but its pathogenesis is unknown. Xeroderma pigmentosum gene D (XPD) is a critical Repair of DNA gene that has been implicated in protein mutation. Aim: The objectives of this research were to assess the relationship between the XPD gene polymorphism (rs13181) (codon 751, Lys to Gln) and susceptibility to hepatocellular neoplasms, as well as to investigate the relationship between HCV and XPD polymorphisms. Methods: Seventy-nine HCC patients and 63 patients with active HCV infection, and 52 healthy controls were involved. Real-time PCR carried out for genotyping of XPD Lys751Gln (rs 13181). Results: Patients with XPD Lys751Gln AC genotype have a great risk of HCC development (p = 0.01, OR =1.505). Conclusion: Our finding was that XPD Lys751Gln (A/C) polymorphism exhibit a major function in HCC early detection susceptibility in Egyptian patients. It has the potential to be a valuable noninvasive molecular indicator for evaluating the HCC threat. Keywords: HCC; RT-PCR; XPD gene polymorphism

An open-label, multicenter, phase 1 study of RP3 as a single agent and in combination with nivolumab in patients (pts) with solid tumors.

TPS2705 Background: RP3 is a genetically modified herpes simplex virus 1 (HSV-1) that contains insertions for the gibbon ape leukemia virus surface glycoprotein (GALV-GP) with the R- sequence deleted (R-), an anti–cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody-like molecule, CD40 ligand, and 4-1BB ligand. Together, these insertions are expected to increase oncolytic potency, cell-to-cell spread, immunogenic cell death, and systemic immune activation. RP3 has demonstrated antitumor activity in preclinical models using viruses similar to RP3 expressing murine versions of anti-CTLA-4, CD40L, and 4-1BBL both alone and in combination with PD1-1 blockade. Methods: This is an open-label, multicenter, Phase 1 study evaluating RP3 as monotherapy or in combination with nivolumab (nivo) in patients (pts) with solid tumors (NCT04735978). Part 1 evaluated escalating doses of RP3. Pts in Part 1 received IT injections of up to 10 mL RP3 into superficial, nodal, or visceral lesions Q2W x 5 across two dose levels (DL1: 105 plaque-forming units (PFU)/mL once, then 106 PFU/mL x 4; DL2: 106 PFU/mL once, then 107 PFU/mL x4). The RP2D is 106 PFU/mL once, followed by 107 PFU/mL IT Q2W. In Part 2, pts are being enrolled into expansion cohorts of 45 patients with GI (including HCC), lung, breast, and squamous cell carcinoma of the head and neck treated with RP1 combined with nivo. Additional cohorts will enroll patients treated with RP3 followed by nivo, RP3 monotherapy to further explore biomarkers in injected and uninjected tumors, and with the potential to also open a cohort in melanoma. Pts in both Part 1 and Part 2 may receive up to 8 additional doses of RP3 if protocol-specified criteria are met. Key inclusion criteria: confirmed advanced or metastatic non-neurological solid tumors, at least one measurable tumor ≥ 1 cm and injectable tumors ≥ 1 cm in aggregate, ECOG ≤1, and adequate hematologic, hepatic, and renal function. In Cohorts 1, 2, and 4, approximately 50% of the pts with lung, breast, and GI cancer must have liver lesions intended for injection. Exclusion criteria include prior oncolytic virus treatment, need for immunosuppressive therapy, an autoimmune disease requiring systemic therapy, active significant herpetic infections or prior complications of HSV-1 infection, active or chronic HBV or HCV infection, known HIV infection, or prior active malignancy within 3 years. Clinical trial information: NCT04735978.

Telemedicine Improves HCV Elimination among Italian People Who Use Drugs: An Innovative Therapeutic Model to Increase the Adherence to Treatment into Addiction Care Centers Evaluated before and during the COVID-19 Pandemic.

Simple SummaryPeople who use drugs represent a category of patients to be prioritized for antiviral treatment for the purpose of hepatitis C elimination, due to their younger age and the major risk of viral transmission, acting as a virus reservoir. The treatment challenges for hepatitis C in this population are related to an ineffective linkage to care, poor adherence to treatment, and follow-up and the risk of re-infection. The COVID-19 pandemic has further exacerbated these conditions, increasing the concerns among clinicians regarding the effectiveness of their treatment. In our study, we describe a novel “patient-tailored” model-of-care for people who use drugs. The antiviral therapy was adapted to the needs of the patient and monitored remotely by a hepatological specialist, in order to decentralize the point of care within the addiction center. The study was conducted before and during the COVID-19 pandemic, clearly demonstrating the model’s high effectiveness in the linkage to care, adherence, and response to antiviral therapy.People who use drugs (PWUDs) are generally considered “hard-to-treat” patients, due to adherence to HCV antiviral therapy or re-infection concerns. Linkage-to-care still remains a significant gap for HCV elimination, worsened by the COVID-19 pandemic. To reduce time-to-treat and improve treatment adherence, we have developed a patient-tailored model-of-care, decentralized within the addiction center and supervised remotely by hepatologists. From January 2017 to December 2020, patients were enrolled in one addiction care center in Southern Italy, where a complete hepatologic assessment, including blood chemistry, ultrasound, and transient elastography examination, was provided. DAAs treatment has been adapted on clinical features, also performing a daily administration during an outpatient visit, and monitored remotely by specialists via telemedicine interactions. Adherence was evaluated on the accomplishment of therapy or on the percentage of attended visits. From a total of 690 PWUDs, 135 had an active HCV infection and were enrolled in the study. All patients started the treatment within 3 weeks after HCV diagnosis. Six drop-outs were recorded, obtaining a sustained virological response at week 12 (SVR12) in 98.5% of PWUDs. There were only two cases of treatment failure, one of which is re-infection. No differences were found between the SVR12 rates before and during the COVID-19 pandemic. We obtained a high SVR12 rate, providing a comprehensive assessment within the addiction care center, tailoring the drug administration with a hepatologic remote stewardship. Our therapeutic model should improve the time-to-treat and treatment adherence in PWUDs.

Seroprevalence of Hepatitis B, C and D in Vietnam: A systematic review and meta-analysis

SummaryBackgroundVietnam has one of the greatest disease burdens from chronic viral hepatitis. Comprehensive prevalence data are essential to support its elimination as a public health threat.MethodsWe searched Medline and Embase from 1990 to 2021 for seroprevalence data relating to Hepatitis B (HBV), C (HCV) and D (HDV) in Vietnam. We estimated pooled prevalence with a DerSimonian-Laird random-effects model and stratified study populations into i) low-risk ii) high-risk exposure and iii) liver disease. We further estimated prevalence by decade and region and rates of HIV-coinfection.FindingsWe analysed 72 studies, including 120 HBV, 114 HCV and 23 HDV study populations. Pooled HBV prevalence was low in blood donors (1.86% [1.82-1.90]) but high in antenatal populations (10.8% [10.1-11.6]) and adults in the general population (10.5% [10.0-11.0]). It was similar or modestly increased in groups at highest risk of exposure, suggesting the epidemic is largely driven by chronic infections acquired in childhood. HCV pooled prevalence in the general population was lower than historical estimates: 0.26% (0.09-0.51) have active infection defined by detectable antigen or HCV RNA. In contrast, there is an extremely high prevalence of active HCV infection in people who inject drugs (PWID) (57.8% [56.5-59.1]), which has persisted through the decades despite harm-reduction interventions. HDV appears mainly confined to high-risk groups.InterpretationBlood safety has improved, but renewed focus on HBV vaccination at birth and targeted HCV screening and treatment of PWID are urgently required to meet elimination targets. Large cross-sectional studies are needed to better characterize HDV prevalence, but mass screening may not be warranted.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.