bluuebunny/crossref_metadata_2025_split huggingface dataset:
906. Characteristics of Chronic Hepatitis B Patients with Severe Outcomes in a Large Integrated Healthcare System - 2008-2019
Authors: Florea Ana , Gounder Prabhu , Sahota Amandeep , Pak Katherine J , Hong Vennis , Im Theresa M , Tartof Sara 
Published: December 2021

Abstract

Background
It is estimated that there are 1.59 million cases of chronic hepatitis B virus (HBV) infection (CHB) in the United States. HBV infection is highest among men and non-Hispanic Asian adults. CHB can lead to liver damage, cirrhosis, hepatocellular carcinoma, or death. However, the population that is most likely to develop severe outcomes is not as well-defined.

Methods
We evaluated electronic health record data from Kaiser Permanente Southern California adult members from 2008-2019 with at least 1 year of continuous membership, and with 2 successive, positive HBV lab results (HBV DNA, or HBsAg, or HBeAg) at least 6 months apart (indicative of CHB). Severe outcomes included incident hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant and death, and prevalent and incident liver cirrhosis. For each outcome, we estimated the distribution of characteristics including age, sex, race/ethnicity, and lab values (alanine aminotransferase [ALT], alpha-fetoprotein [AFP], MELD score).

Results
Our final study population included 5,427 CHB-diagnosed patients with 411 (7.6%) cases of liver cirrhosis, 123 (2.3%) of hepatic decompensation, 65 (1.2%) of HCC, 8 (0.1%) of liver transplant, and 164 (3.0%) deaths. Compared to the total cohort, those who developed severe outcomes were older (median age for each outcome &gt;50 years vs. 47 years in total CHB population). Among those with severe outcomes, the majority were male ( &gt;56%) and Asian. Diabetes was more prevalent in patients with hepatic decompensation, HCC, and death versus the entire cohort (25% vs. 8%, respectively, P&lt; 0.0001), and twice as prevalent among those with cirrhosis. All severe outcomes were associated with &gt;2 x upper limit of normal ALT levels.

Conclusion
The characteristics of those with severe outcomes were consistent with those of overall CHB, although there was a 2-3 times higher prevalence of diabetes in those with severe outcomes. Identifying characteristics that are more prevalent in those with severe outcomes can help inform screening and management of CHB.

Disclosures
Ana Florea, PhD MPH, Gilead Inc. (Grant/Research Support) Prabhu Gounder, MD, Gilead Inc. (Grant/Research Support) Amandeep Sahota, MD, MS, Gilead Inc (Grant/Research Support) Katherine J. Pak, MS, Gilead (Grant/Research Support) Vennis Hong, MPH, Gilead Inc. (Research Grant or Support) Theresa M. Im, MPH, Gilead Inc. (Grant/Research Support) Sara Tartof, PhD, Gilead (Grant/Research Support, Scientific Research Study Investigator)
908. Dismantling Barriers to Hepatitis Elimination: Automated Hepatitis C Screening with Care and Cure by a Primary Care Based Team
Authors: Xu Binghong , Brogden Ruth P , Patel Ammie J , Gallipani Alyssa , Yango Jaymie , Adedeji Mary O , Wang Su 
Published: December 2021

Abstract

Background
Liver cancer rates are rising in the US, viral hepatitis accounting for more than 65% of the cases. Yet more than half of viral hepatitis infections remain undiagnosed. In response to the rise in HCV due to the opioid epidemic, the Centers for Disease Control and Prevention began recommending a one-time HCV test for all adults in 2020. Screening, linkage to care (LTC) and access to HCV curative therapy must be scaled up to reach the WHO goal of eliminating hepatitis by 2030.

Methods
In 2018, automated HCV screening utilizing electronic medical record protocols began in the emergency department (ED) based on the date of birth. Drug testing and peer recovery consults were added as eligibility criteria. Screening became universal and expanded to the inpatient units in 2020. Patient navigators (PN) received alerts of positive results and worked with patients to arrange LTC, one site being a primary care-based practice (PCP) where internists provided HCV care and support from ambulatory care clinical pharmacists.

Results
From Mar 2018 to Mar 2021, 50,873 people were screened for HCV, with 977 (1.9%) testing HCV Ab+, and 259 (0.5%) had confirmed infection by reflex HCV RNA. LTC 86.6% of patients, and 128 (49.4%) were newly diagnosed. Universal screening led to 35,482 testings from Jan 2020-Mar 2021. People born out of the 1945-65 birth cohort made up 75.8% of the screened and 39.1% of the infected. The PCP evaluated 47 HCV patients, initiated therapy in 38; 36 required prior authorization and 15 needed financial assistance. Treatment breakdown was: 29 (76.3%) glecaprevir/pibrentasvir, 6 (15.8%) sofosbuvir/velpatasvir & 3 (7.9%) ledipasvir/sofosbuvir. Pharmacist intervention with prior authorizations and financial assistance significantly reduced the cost (table 1). Thus far, 35 achieved cure with undetectable HCV RNA at 12 weeks.
Table 1. The Cost of Treatment before and after Pharmacist Assistance

Conclusion
Automated universal testing was an effective and seamless way to scale up HCV screening. Warm handoffs from a PN were important for engaging patients in care. A team approach assisted with removing barriers in therapy access, including prior authorization, specialist requirements, and financial assistance. Novel strategies utilizing ED and hospitals for testing with coordination to PCP are needed to find the missing millions and achieve hepatitis elimination.

Disclosures
Su Wang, MD MPH, Gilead Sciences (Grant/Research Support)Gilead Sciences (Grant/Research Support)
909. Treating Hepatitis C Virus (HCV) in Young Adult Active Drug Users Is Possible
Authors: Nahass Ronald G , Seneca Kathleen H , Homer Ruth A 
Published: December 2021

Abstract

Background
Successful treatment of HCV in persons who inject drugs (PWIDS), has been reported for patients who were older or who had used drugs more than 6 months prior. The young, &lt; 35 year of age (yoa), active user has not been well studied or reported. We performed a pilot treatment study in a young cohort of PWIDS to evaluate cure rates of HCV in this population.

Methods
Young, active PWIDS using &lt; 6months earlier, &lt; 35 yoa were identified. Treatment for HCV with glecaprevir/pibrentasvir (G/P) and concurrent treatment for opiate use disorder with XR Naletrexone (XR-NTX) was provided. Two patients chose methadone. Patients were followed up to 12 months after enrollment. Patients were evaluated for adherence, side effects, alanine aminotransferase (ALT) levels, urine drug screens (UDS) and opioid craving scores using a visual analog scale (VAS) while on XR-NTX to assess management of their addiction. Rates of treatment completion, SVR 4 & 12 were determined.

Results
30 patients were recruited: 18 were women. Average age was 28 with a range of 23-35. Recent injection drug use was common with 22 (73%) having injected within the 30 days and all having injected within 3 months of recruitment. The average ALT on enrollment was 106. Genotypes were 1 (15), 3a (11), and unknown (4). Of the 30 patients, 15 failed to come for the required 2 visits prior to starting G/P. Lost to follow up occurred due to relapse of addiction (9), overdose death (1), lost communication and suspected relapse (4). 15 began and completed G/P. 15 were cured of their HCV infection. 17 patients receive one or more doses of XR-NTX. On average patients were on XR-NTX for 4.8 months. Sobriety was measured for patients on XR-NTX using Opiate Craving Scores using the Visual Analogue Scale (VAS) and UDS (Figure 1) demonstrating excellent control of craving and significant declines positive UDS. Toxicities were uncommon with no treatment limiting adverse events. Adverse effects of XR-NTX included mild injection site irritation. No ALT abnormalities were noted.

Conclusion
Young active PWIDS can successfully be cured of HCV. Their addiction can be concurrently managed with XR-NXT. Our findings suggest it is safe to treatment active users with active HCV with XR-NXT improving elimination goals.

Disclosures
Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau) Kathleen H. Seneca, MSN, Abbvie (Research Grant or Support)Alkermes (Research Grant or Support)Gilead (Speaker’s Bureau) Ruth A. Homer, MSW, Abbvie (Grant/Research Support)Alkermes (Grant/Research Support)
910. Evaluation of an Enzymatic Immunoassay System for Detection and Differentiation of Rat Hepatitis E Virus Infection in Humans
Authors: Sridhar Siddharth , Situ Jianwen , Lo Kelvin Hon Yin , Cai Jianpiao 
Published: December 2021

Abstract

Background
Previously, hepatitis E in humans was believed to be caused exclusively by species A variants of the Orthohepevirus genus (HEV-A) of the family Hepeviridae. However, we have previously demonstrated that Orthohepevirus species C (HEV-C), also known as rat hepatitis E virus, also causes hepatitis in humans. Due to high sequence divergence between HEV-A and HEV-C, serological tests based on HEV-A are often insensitive for HEV-C diagnosis. Therefore, we developed an enzymatic immunoassay (EIA) system for differentiating HEV-A and HEV-C antibody signatures in patient sera.

Methods
HEV-A and HEV-C peptide homologs spanning the entire immunogenic E2s region of HEV ORF2 capsid protein were expressed in E. coli. These peptides, HEV-A4 p239 and HEV-C p241, form virus-like particles (figure 1). Both peptides were coated in separate 96-well plates. Sera obtained from patients with RT-PCR confirmed acute HEV-A infection (n = 54), HEV-C infection (n = 15), and uninfected HEV seronegative controls (n = 126) were tested in parallel in HEV-A4 p239 and HEV-C p241 EIAs for respective IgG antibodies. Sample optical densities (ODs) were divided by mean OD + 3SD of the seronegative controls to generate signal/noise (S/N) ratios. S/Ns marking positivity in either assay were determined by ROC analysis. An algorithm for assay interpretation was developed (table 1) and the performance of this algorithm was measured against the RT-PCR gold standard.
HEV-A4 p239 and HEV-C1 p241 virus like particles

Transmission electron microscopy images of the two peptides used in this study
Diagnostic testing algorithm interpretation

Interpretation of results of testing using parallel enzymatic immunoassays

Results
Using cutoffs determined by ROC analysis (figure 2), HEV-A4 p239 and HEV-C p241 EIAs detected species-specific antibody responses well (sensitivity: 92.6% and 80% respectively) and were specific (92.9% and 98.3% respectively). The DC was 100% congruent with HEV-C RT-PCR and 88.9% congruent with HEV-A RT-PCR in RT-PCR positive samples. Incorporating all three cutoffs into the algorithm, we derived a 3×3 confusion matrix of RT-PCR sample assignation vs EIA algorithm classification (table 2). The Cohen’s κ value was 0.883 indicating excellent inter-rater reliability.
ROC analysis for determining S/N cutoffs

Curve for A/A represents analysis for HEV-A4 p239 EIA. Curve for C/¬C represents analysis for HEV-C p241 EIA. Curve for r(C/A) represents analysis for the differentiating ratio.
3×3 confusion matrix comparing sample assignations by RT-PCR vs. EIA algorithm

Conclusion
A parallel EIA system accurately differentiated HEV-A and HEV-C serological signatures in acute patient sera. This method can now be applied to seroprevalence studies to determine seroprevalence of rat hepatitis E in human populations.

Disclosures
Siddharth Sridhar, FRCPath, Abbott (Other Financial or Material Support, Speaker’s honoraria)
911. Rapid Hepatitis C Treatment Initiation in Young People Who Inject Drugs: Final Results from the HCV-Seek, Test and Rapid Treatment (HCV-ST&RT) Randomized Pilot Clinical Trial
Authors: Eckhardt Benjamin , Kapadia Shashi , Smith Melinda , Aponte-Melendez Yesenia , Fong Chunki , Davis La , Mateu-Gelabert Pedro , Marks Kristen , Marks Kristen 
Published: December 2021

Abstract

Background
Young people who inject drugs (PWID) have higher HCV incidence and lower treatment initiation rates compared to their older peers. Novel, simplified care models need to be developed to engage, treat and cure hard to reach patient populations, such as young PWID.

Methods
We present final data from the randomized pilot clinical trial HCV-Seek Test & Rapid Treatment (HCV-ST&RT) for curing HCV in young PWID. Eligible participants were 18-29 years of age, HCV Ab+, treatment naïve, and had injected drugs in the past 30 days. Participants were randomized 1:1 to the Rapid Treatment or Usual Care arm. Participants randomized to Rapid Treatment received a same-day medical evaluation, confirmatory and baseline lab testing, and 7-day starter pack of sofosbuvir/velpatasvir. Participants in Usual Care received same-day HCV confirmatory testing and, if positive, facilitated referral to local providers. The primary endpoint was sustained virologic response (SVR12) in RNA+ participant within 12 months of enrollment.

Results
Among 47 eligible participants, 38 were enrolled and randomized. 14/18 in the Rapid Treatment arm and 11/20 in the Usual Care arm were confirmed HCV RNA+ and included in the intention-to-treat analysis. Demographics of the RNA+ participants were similar in the two arms with a mean age of 26 years; 24% women; 36% Hispanic and 4% non-Hispanic black. At baseline 24% were homeless, 52% received medication for opioid use disorder in the prior 90 days, and participants injected a median of 20 of the last 30 days. In the intention-to-treat analysis, 9/14 (64%) of the Rapid Treatment arm and 2/11 (18%) of the Usual Care arm had confirmed SVR12 (p=0.042). Of the 5 participants in the Rapid Treatment arm who did not achieve SVR12, 1 had treatment failure, 1 never started DAA therapy, 1 had an on-treatment response with pending SVR12 confirmation, and 2 were lost to follow-up.

Conclusion
Among young HCV RNA+ PWID, significantly higher rates of cure were achieved using the Rapid Treatment model with same day, low-threshold, simplified HCV care compared to facilitated referral. Meeting young PWID where they’re at and initiating HCV treatment ‘in the moment’ without the need for repeat visits appears to be a promising strategy for treating this hard to reach population.

Disclosures
Benjamin Eckhardt, MD, MS, Gilead Sciences (Grant/Research Support) Shashi Kapadia, MD, Gilead Sciences Inc (Grant/Research Support) Kristen Marks, MD, Gilead Sciences (Grant/Research Support)
912. Expansion of Hepatitis C Treatment with New Medicaid Subscription Model in Louisiana
Authors: Richey Lauren E , Bennani Yussef , Frontini Maria 
Published: December 2021

Abstract

Background
It is estimated that nearly 80,000 people with hepatitis C are living in Louisiana, many with Medicaid coverage. Previously, only Medicaid patients free from drugs and alcohol with a fibrosis score of F3 or F4 were eligible for treatment, resulting in few patients receiving treatment. Beginning in July 2019, generic sofosbuvir/velpatasvir was made available through the Medicaid program in a subscription model, allowing unlimited hepatitis C treatment in Louisiana’s Medicaid program for 5 years at a set price to the program. This has dramatically expanded access to Hepatitis C treatment for people with Medicaid in Louisiana.

Methods
Patients with Hepatitis C seen in the Infectious Diseases Center at University Medical Center in New Orleans, in 2020 by the 5 main hepatitis C providers were included. Demographics and laboratory data were collected to determine outcomes.

Results
Most patients with a hepatitis C (HCV) viral load and insurance data had Medicaid (80%, N=275). Twenty-two (8%) were HIV co-infected. Most were men (75%) and African-American (77%). Among the mono-infected patients with Medicaid and an HCV viral load, 216 (85%) had an undetectable viral load by the beginning of June 2021. Of the remaining 37 patients, 30 patients were prescribed treatment; but did not take it (n=4), didn’t follow-up (n=23), or followed-up but never got labs (n=3). One was treated but had a treatment failure (n=1). Six of the 37 were not prescribed medications due to a short life expectancy or significant drug interactions. The percentage of patients with an undetectable viral load was similar by gender and race, however younger age groups had lower viral suppression. In those aged less than 35, only 47% had an undetectable viral load and among those aged 36 to 44, it was 66%. Using the previous criteria of requiring a fibrosis score of F3 or F4, only 20% (n=44) would have been eligible for medicine to treat hepatitis C.

Conclusion
The new hepatitis C treatment subscription model with resultant removal of previous barriers has dramatically expanded treatment for people with Medicaid in Louisiana. More than five times the number of Medicaid patients received treatment in 2020 in our academic medical clinic.

Disclosures
Yussef Bennani, MD, MPH, Gilead Sciences (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator)
914. The Relationship Between Buprenorphine Maintenance Therapy and Hepatitis C Virus Infection, Testing, and Treatment in Southern Appalachian Ohio
Authors: Brook Daniel L , Schalkoff Christine , Piscalko Hannah M , Sibley Adams L , Kline David , Lancaster Kathryn , Go Vivian , Miller William 
Published: December 2021

Abstract

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
916. Finding the Missing Millions and Addressing Health Disparities: Automated Hepatitis B Screening and Linkage to Care
Authors: Xu Binghong , Wang Su , Brogden Ruth P , Yango Jaymie , Adedeji Mary O 
Published: December 2021

Abstract

Background
Globally, HBV is the most common blood-borne infection. An estimated 1.2 million people in the US and 350 million worldwide lived with HBV, a primary driver of liver cancer. It is endemic in many parts of the world and is a major health disparity in immigrant communities, including the US, which has the largest immigrant population in the world. Asian American Pacific Islanders are 5% of the total population in the US, but represent 50% of people living with HBV. In 2016, WHO set a goal of hepatitis elimination by 2030 but with only 10% of those living with HBV diagnosed, screening must be scaled up.

Methods
Modifications were made in the electronic medical record (EMR) to automate screening, with HBV (HBsAg) orders triggered by a patient’s country of birth or race. The began in the Emergency Department and later expanded to the Inpatient setting. Automated notifications are sent to nurse for eligible patients and then to the patient navigator (PN) for positive tests. The PN contacts the patient to provide education and arrange linkage-to-care (LTC) for evaluation and care.

Results
From Mar 2018 to Mar 2021, we conducted 23,883 HBV screenings. The patients originated from 173 countries based on registration; top 5 countries of origin were Haiti, Jamaica, Ecuador, Guyana, and Portugal. We found 228 (1.0%) patients with HBV infection, 101 (47%) were newly diagnosed and 182 (85%) were linked to care. We examined race and insurance status for any association with those previously tested versus newly diagnosed. Blacks were more likely to be newly identified HBV versus Asians (61.6% vs. 28.9%, p&lt; .001), as were self-pay (uninsured) versus insured patients (66.7% vs 47.2%, p=0.043). Compared to the approximately 0.4% HBV prevalence in the US, the HBV prevalence in several towns around our hospital in Essex County is two to four times higher.
Table 1. The HBV Prevalence in Towns of Essex County

Conclusion
Our community is diverse and social determinants of health, like race and insurance status, may contribute to provider behaviors of HBV screening with blacks receiving less screening than Asians. Automated testing programs can address health disparities and scale up screening. Such micro-elimination approaches are important for achieving global hepatitis elimination by 2030.

Disclosures
Su Wang, MD MPH, Gilead Sciences (Grant/Research Support)Gilead Sciences (Grant/Research Support)