Micro-Elimination of Hepatitis C among Patients with Kidney Disease by Using Electronic Reminder System—A Hospital-Based Experience

Background: Little is known about the use of an electronic reminder system for HCV screening among patients with kidney disease. In this study, we tried to determine whether reminder systems could improve the HCV screening rate in patients with kidney disease. Methods: Patients with kidney disease were enrolled from August 2019 to December 2020 to automatically screen and order HCV antibody and RNA testing in outpatient departments. Results: A total of 19,316 outpatients with kidney disease were included, and the mean age was 66.5 years. The assessment rate of HCV antibody increased from 53.1% prior to the reminder system to 79.8% after the reminder system (p < 0.001), and the assessment rate of HCV RNA increased from 71% to 82.9%. The anti-HCV seropositivity rate decreased from 7.3% at baseline to 2.5% after the implementation of the reminder system (p < 0.001), and the percentage of patients with detectable HCV RNA among those with anti-HCV seropositivity decreased from 69.1% at baseline to 46.8% (p < 0.001). Conclusions: The feasibility of an electronic reminder system for HCV screening among patients with kidney disease in a hospital-based setting was demonstrated.

Nonneutralizing FVIII-specific antibody signatures in patients with Hemophilia A and in healthy donors

Previous studies identified nonneutralizing FVIII-specific antibodies in the circulation of severe and non-severe hemophilia A patients without FVIII inhibitors and also in some healthy individuals. To gain a better understanding of the nature of these nonneutralizing antibody responses, we analyzed and compared anti-FVIII antibody signatures in three study cohorts - previously treated severe as well as non-severe hemophilia A patients without FVIII inhibitors, and healthy donors. FVIII-binding IgM, IgG1-4 and IgA antibodies were differentiated, FVIII-specificity was assessed and associated apparent affinity constants were determined. Our results indicate that the nonneutralizing FVIII-specific antibody response in all study cohorts is dominated by IgG1 and IgA. Prevalences, titers and affinities of these nonneutralizing antibodies were higher in the hemophilia A cohorts than in healthy donors. Stratification for the anti-HCV antibody status demonstrated the presence of FVIII-specific IgA with elevated titers in severe hemophilia A patients with an active or past HCV infection when compared to HCV antibody positive non-severe patients or HCV antibody negative patients and healthy donors. Increased titers and affinities of FVIII-specific IgG1 antibodies were observed in a considerable number of hemophilia A patients as opposed to healthy subjects independently of the patients' anti-HCV antibody status. Overall, our findings support the hypothesis that the generation of nonneutralizing anti-FVIII antibodies in healthy individuals and in non-inhibitor hemophilia A patients might be based on similar immune mechanisms. However, differences in prevalences, titers and affinities of these antibodies indicate distinct differences in the antibody evolution between healthy individuals and patients.

Clinical Predictors and Prediction Models for Frequency of Total and Joint Hemorrhage in Severe-Type Patients with Hemophilia a (PwHA) with/without Intermediate-Dose Prophylaxis Therapy with rFVIII

Introduction: It was well-known that severe-type patients with hemophilia A (PwHA) had great variability in bleeding phenotypes. Factors effecting bleeding patterns of PwHA include at least treatment modality and interindividual various procoagulant and anticoagulant levels. We aimed to investigate what clinical variables could predict bleeding frequency of severe PwHA and to develop models for predicting bleeding phenotypes among severe PwHA with/without FVIII prophylaxis therapy. Methods and materials: Totally 51 severe-type previously-treated PwHA from two Hemophilia Centers in Taiwan were enrolled, who received standard half life (SHL) rFVIII products with complete consecutive bleeding records at least more than 6 months, and their medical charts 2017－2018 were retrospectively viewed. The clinical data were collected for analysis, including age, body mass index (BMI), body weight (BW), ABO blood groups, hemoglobin (Hb), hematocrit (Hct), HCV infecton, HIV infection, treatment modality, baseline VWF levels, and genetic defects. Baseline VWF activity meant the data via VWF:ACL activity or VWF:RCo. Clinical variables for annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were evaluated by multivariate linear regression (MVLR) analysis. Results: The cohort of 51 severe-type PwHA included 8 boys and 43 adults, aged 8-64. For treatment modality, there were 19 patients receiving episodic treatment (ET) and 32 receiving prophylaxis therapy (PT) with intermediate-dose standard half life (SHL) rFVIII. The mean study period was 11.9 months, range 10－14.5 months. Among them, there were 31 with HCV infection and 4 with HIV infection. PwHA with non-O blood group were 31 and those with O blood group 20. The mean baseline VWF:Ag was 115.6±55.5%, range 50%－294.7%. The mean baseline VWF:activity was 105.4±52.1%, range 41.3%－307%. ABR of ET group and PT group were 46.1±29.2 and 6.8±7.1, respectively. (p&lt;0.0001***) AJBR of ET group and PT group were 37.3±27.7 and 6.0±6.8, respectively. (p=0.0001***) By MVLR analysis, both treatment modality and baseline VWF:Ag were recognized as inverse predictors of ABR and AJBR, and HCV infection recognized a predictor for AJBR. Age, inhibitor histroy, BMI, BW, ABO blood groups, Hct, Hb, HIV infection, and missense mutation or not were eliminated as predictors. The predictive equations by MVLR were as the following two: (1) Predictive ABR = 56.5 - 37.8 * (Treatment model) - 11.8 * baseline VWF:Ag (IU/mL). (2) Predictive e AJBR = 41.9 - 28.6 * (Treatment model) - 12.0 * baseline VWF:Ag (IU/mL) + 10.0 * (HCV infection). (1 if Treatment model is PT, 0 if Treatment model is ET. 1 if HCV infection or anti-HCV antibody is positive, 0 if HCV infection or HCV antibody is negative.) Separate prediction models developed from MVLR analysis could explain 52.51% of the ABR variability and 50.56% of the AJBR variability. The correlation between predicted and observed bleeding frequency was significantly strong.(P-rank&gt;0.7, p-value&lt;0.0001***) Mean difference between predicted ABRs and observed ABRs was 1.75 and that between predicted AJBRs and observed AJBRs was 1.27. Predicted ABR deviated &lt;21 (&lt;2 per month) of observed ABR in 42/50 patients (84%). Predicted AJBR deviated &lt; 24 (&lt;2 per month) ofobserved AJBR in 44/50 patients (88%). Conclusion: Prophylaxis therapy and baseline VWF:Ag levels were the strongest two inverse predictors for ABR and AJBR. Positive HCV infection was another predictor for AJBR. The prediction models provided with an insight into personal bleeding quantified patterns and may identify PwHA with high bleeding risks based on individual characteristics of treatment modality, baseline VWF:Ag, and HCV infection. Our approach is of help for individualized treatment and refining of dosing strategies. Disclosures No relevant conflicts of interest to declare.

920. Automated Hepatitis C Screening and Linkage to Care among Hospitalized Patients Born Between 1945-1965

Background Hepatitis C virus (HCV) infects 4.1 million people in the United States, of whom 50% are unaware of their status. In 2016, Pennsylvania introduced a law mandating HCV screening for patients born between 1945-1965 in inpatient settings. However, HCV screening during hospital admissions has remained low in part due to limited knowledge on HCV testing requirements, interpretation of results, and treatment approaches. To overcome these barriers, we implemented a quality improvement initiative to automate HCV screening as part of hospital admission order sets, facilitate linkage to HCV treatment, and sought to evaluate its effectiveness. Methods Between September 2020 and May 2021, the automated inpatient HCV screening strategy was implemented at a single 328-bed academic hospital in Philadelphia, PA. Patients born between 1945-1965 without documentation of HCV screening or diagnosis in the electronic medical record had a HCV antibody with reflexive confirmatory RNA assay automatically populated in the admission order set. Admitting providers could opt out of the screening as appropriate. All patients with reactive HCV antibody were approached by the Hepatitis Linkage Team for result disclosure, counseling, and linkage to treatment for those with HCV viremia. Cascade of care was detailed for those linked to providers within the health system. Results During the initial 8 months of the program, 2,203 patients were screened for HCV, identifying 156 with reactive HCV antibody (7.1% seroprevalence). Among 147 with completed HCV RNA assay, 51 were viremic (34.7%). Fourteen viremic patients were not linked to care, including six with a terminal illness, two who declined linkage, and six who did not respond to linkage attempts. Nine were linked to care at other health systems. Among the 28 patients linked to providers in the health system, 50% completed initial visits, 42.8% were prescribed direct acting antivirals (DAA), and 21.4% completed therapy by May 2021. One person achieved sustained virologic response 12 weeks after treatment as of May 2021 (Figure 1). Figure 1. Cascade of HCV Care Among Patients Screened During Hospital Admission from September 2020 to May 2021 Conclusion Automated inpatient HCV screening is a viable strategy to identify people with HCV and facilitate linkage to care. Optimal strategies to ensure patients access and maintain care require further study. Disclosures All Authors: No reported disclosures

913. Re-engagement using Historical Hepatitis C Antibody Results: Is it Worth the Effort?

Background The World Health Organisation aim to eliminate hepatitis C (HCV) as a public health concern by 2030. One aspect of Public Health England’s (PHE) strategy to meet this target is to use historical surveillance data of anti-HCV positive patients identified by PHE to re-engage with offers of PCR testing and treatment if RNA-positive. Operational Delivery Networks (ODN) are responsible for enacting this initiative across 22 regions in England. We present an interim analysis and evaluation of the effectiveness of using this data to re-engage HCV-infected persons in the West Midlands ODN of England. Methods A dataset of historical anti-HCV positive antibody patients provided to the West Midlands ODN by PHE was cross-referenced with HCV RNA data from 01/01/1996 to 01/01/2019 from 5 regional laboratories and regional treatment databases. If HCV RNA positive, letters were sent to the general practitioner and to the patient to invite them for further testing and, if necessary, treatment to achieve SVR. This received no additional funding or support and occurred in addition to the routine clinical workload. Results From a dataset of 4,540 anti-HCV antibody results, 31.7% (n=1,440) had a PCR result: 48.1% (n=693) were PCR positive for HCV RNA with no evidence of cure. 693 letters were sent to GPs from Oct 2019 to Feb 2020 with responses from 14.2% (n=99). From July to Oct 2020 only 212 patient letters were sent (due to significant interruption due to the COVID-19 pandemic) and 11.3% (n=24) replied by May 2021. 17 presented for PCR testing and 4 were found to be viraemic. To date, one patient has achieved SVR and three have completed treatment awaiting SVR. Re-Engagement Process Flow diagram of re-engagement of patients with historical antibody-positive results for hepatitis C virus. * Of the 17 deemed not suitable to contact by the GP: 4 treated elsewhere, 3 had negative PCR elsewhere, 1 was unknown reason, 2 were under care of another hospital, 7 had died Conclusion The use of historical anti-HCV antibody results to re-engage people into testing and treatment for hepatitis C in this format is low yield. Rollout was limited by ongoing clinical work and the COVID-19 pandemic. Dedicated time and resources with a less restrictive cohort might improve yields. Disclosures All Authors: No reported disclosures

914. The Relationship Between Buprenorphine Maintenance Therapy and Hepatitis C Virus Infection, Testing, and Treatment in Southern Appalachian Ohio

Background The hepatitis C virus (HCV) epidemic in the United States is primarily among young people who use drugs (PWUD), especially in rural and Appalachian regions. Buprenorphine maintenance therapy (BMT) may indirectly prevent HCV infection by reducing injection drug use. We aim to assess the relationship between BMT and HCV infection, testing, and treatment among rural PWUD. Methods We conducted a cross-sectional respondent driven sampling survey of 243 PWUD adults in southern Appalachian Ohio from May to November 2019. Participants completed audio computer-assisted self-interview and were tested for HCV antibodies. We defined recent BMT use as self-reported BMT in the past 30 days and prior BMT use as self-reported BMT any time prior to the past 30 days. HCV antibody positive participants were incentivized to receive confirmatory HCV RNA testing. We fit log-binomial regression models to assess the relationship between BMT and HCV infection, testing, and treatment. Results 72% of participants were HCV antibody positive (n=175). 31% (n=54) of antibody positive participants received an RNA test; of those, 96% (n=52) were HCV RNA positive. Compared to participants with no history of BMT, those with prior BMT were more likely to be HCV antibody positive (PR=1.3, 95% CI: 1.1-1.6) and to have been tested for HCV (PR=1.3 95% CI: 1.1-1.5); they were somewhat more likely to have been treated for HCV (PR=1.3 95% CI: 0.5-3.4). Compared to participants with no history of BMT, those reporting recent BMT had similar HCV antibody positivity (PR=1.1 95% CI: 0.9-1.5) but were more likely to have been tested (PR=1.3 95% CI: 1.1-1.6) and possibly more likely to have been treated for HCV (PR=2.0 95% CI: 0.6-5.9). Compared to those with a prior BMT, people with recent BMT use had slightly lower HCV antibody positivity (PR=0.8 95% CI: 0.7-1.1) and possibly higher prevalence of HCV treatment (PR=1.5 95% CI: 0.6-3.8) but had similar prevalence of HCV testing (PR=1.0 95% CI: 0.9-1.2). Conclusion Participants with a recent history of BMT were more likely to have been tested for HCV and possibly to have received prior treatment. Participants with prior BMT were more likely to be antibody positive and to have tested for HCV. Improved coordination between BMT and HCV care may increase HCV treatment among rural PWUD. Disclosures All Authors: No reported disclosures

Frequency and genotype distribution of hepatitis C virus infection in patients with diabetes type 2 in Ahvaz, Iran

Background and Objectives: Diabetes is recognized as a great concern and a public health problem worldwide. Several factors including environmental and genetic factors have been involved. Recently, infectious agents such as hepatitis C virus (HCV) have been reported to be associated with diabetes. Thus, this study was conducted to determine the frequency of HCV infection among patients with diabetes type 2 in Ahvaz city, Iran. Materials and Methods: A case-control study design was conducted at Ahvaz Jundishapur University of Medical Sciences. A total of 600 study subjects were included in this research. All the patient sera were tested for Anti- HCV antibody, HBsAg, and HIV antibody. The sera of positive Anti-HCV antibody, were assayed for 5'- UTR and core regions of the HCV genome by Nested RT-PCR. Finally, the HCV genotyping was determined by sequencing. Results: The prevalence of HCV in type 2 diabetes and nondiabetic controls was 2% and 0.33%, respectively. The distribution of HCV genotypes among the HCV-positive patients were 3a (1.66%) and 1a (0.33%). Conclusion: To control and improve the treatment, the screening of HCV infection with anti-HCV antibody was followed by molecular techniques such as PCR and HCV genotyping which should be implemented for all patients with diabetes type 2.

In Egyptian Patients with Hepatocellular Carcinoma the role of MicroRNA-215

Introduction/Objective MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs which are make a contribution in the regulation of gene expression and protein translation, and they play vital roles in differentiation, cell growth, and the development of diverse types of cancers. Methods/Case Report Our research was done in hepatology and gastroenterology department at the National Liver Institute, Menoufia University. It included 135 patients and 60 healthy subjects serving as control group. We have 3 groups: Group I (Control) This group included 60 apparently healthy individuals. They were 32 males and 28 females, whose ages ranged from 39 to 67 years old (mean ±SD= 51.67 ± 6.40 years). Group II (Cirrhosis) This group included 75 patients with liver cirrhosis due to chronic HCV infection. They were 41 males and 34 females whose ages ranged from 41 to 68 years old (mean ±SD= 54±6.73 years). Group III (HCC) Sixty patients with HCC were included. They were 35 males and 25 females, whose ages ranged from 41 to 70 years old (mean ±SD= 53.97±6.15 years). Laboratory Investigations Complete blood count (CBC), Liver tests: aspartate transaminase (AST) and alanine transaminase (ALT), serum albumin, total and direct bilirubin, alkaline phosphatase and INR were measured. Serum creatinine was also measured. The analysis of serum alpha fetoprotein (AFP) (ng/ml) was done. Chronic HCV infection was diagnosed by detection of HCV antibody and HCV RNA by real time PCR. Anti-HCV antibody was detected by means of a third generation enzyme immunoassay. Quantification of HCV RNA level was performed by means of COBAS Taqman 84 (Roche) real time HCV RNA Assay with lower detection limit 15 IU/ml. Results (if a Case Study enter NA) In control group, miRNA-215 ranged from 1.60 to 21.30 with a median value of 6.89. In cirrhotic patients group, it ranged from 0.70 to 14.65 with a median value of 2.85. In patients with HCC group, it ranged from 0.03 to 10.95 with a median value of 0.52 (pg/ml). MiRNA-215 and AFA mean levels showed a statistically significant difference (p &lt;0.001) between the three studied groups. Conclusion In conclusion, MicroRNA-215 was proved to be significantly lower in HCC patients compared to cirrhotic patients and control group. This marker might be used as a potential serologic marker for HCC and a complementary diagnostic tool in monitoring cirrhotic patients for detection of HCC.

Spontaneous clearance of vertically acquired hepatitis c infection: implications for testing and treatment

Background. Current guidelines recommend that infants born to women with hepatitis C (HCV) viremia are screened for HCV antibody at age 18 months, and if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based in part on analyses suggesting 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. Methods. Data on 179 infants with RNA and/or anti-HCV evidence of vertically acquired viraemia (single PCR+) or confirmed infection (2 PCR+ or anti-HCV beyond 18 months) in three prospective European cohorts were investigated. Ages at clearance of viremia and confirmed infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in infants in whom RNA was not detectable until after 6 weeks. Results. Clearance rates decline rapidly over the first 6 months. An estimated 90.6% (95%CrI: 83.5-95.9) of viremia cleared by 5 years, most within 3 months, and 65.9% (50.1-81.6) of confirmed infection cleared by 5 years, at a median 12.4 (7.1-18.9) months. If treatment began at age 6 months, 18 months or 3 years, at least 59.0% (42.0-76.9), 39.7 (17.9-65.9), and 20.9 (4.6-44.8) of those treated would clear without treatment. In seven (6.6%) confirmed infections, RNA was not detectable until after 6 weeks, and in 2 (1.9%) not until after 6 months. However, all such cases subsequently cleared. Conclusions. Most viraemia clears within 3 months, and most confirmed infection by 3 years. Delaying treatment avoids but does not eliminate over-treatment and should be balanced against loss to follow-up.