Hepatitis C Screening Opportunities & Challenges for U.S. Emergency Departments

1. Hepatitis C ScreeningOpportunities & Challenges for U.S. Emergency Departments Richard Rothman, MD, PhD • Professor Emergency Medicine, The Johns Hopkins University Yu-Hsiang Hsieh, PhD • Associate Professor Emergency Medicine, The Johns Hopkins University James Galbraith, MD • Associate Professor Emergency Medicine, University of Alabama at Birmingham Douglas White, MD • Associate Clinical Professor Emergency Medicine, Alameda County Medical Center-Highland, University of California San Francisco http://www.al.com/business/index.ssf/2014/01/which_hospital_in_your_city_ha.html

2. Overview • Background and Rationale • Who to Test? Recent data from the ED setting • Universal Screening: Findings from the front lines • Real-world Challenges: Lessons from the ED • Q and A

3. Background /Rationale I. Hepatitis C: • What it is? • Contagious infectious disease caused by an RNA virus How is it acquired/transmitted? • Most commonly by direct contact with blood from an infected person • Pre ~1990s: Primarily via blood transfusions or organ transplantation • Currently: Primarily via sharing needles/equipment (intravenous drug users) • Other routes (less common): Sexual contacts, Maternal-fetal, Sharing personal items (e.g. razor blades), Tattooing http://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/natural-history/core-concept/all http://www.mobieg.co.za/articles/stds/hepatits

4. Hepatitis C (what happens?) • Acute Hepatitis C Virus infection: • Short-term illness < 6 months of exposure • Acute leads to chronic infection for most people • Chronic Hepatitis C virus infection: • Long-term illness which can last a lifetime • Potential for serious liver problems, including cirrhosis (scarring of the liver) liver cancer and death Time…. 20 – 30 years http://www.mobieg.co.za/articles/stds/hepatits http://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/natural-history/core-concept/all

5. HCV – Disease burden Worldwide • 130–150 million chronic HCV • ~350,000 HCV related deaths/year United States • 3.5 million with chronic HCV • ~15,000+ HCV related deaths/year • Significant reduction (screening blood supply) • Emerging epidemic (IDUs) • Epidemiology not fully characterized • ~50% remain unaware of their infection http://aidafoundation.com/hepatitis-c-info https://www.cdc.gov/hepatitis/statistics/ http://www.hepatitisc.uw.edu/pdf/screening-diagnosis/epidemiology-us/core-concept/all

6. HCV: Disease Burden in US The number of deaths due to hepatitis C is at an all-time high in the US and exceeds those attributable to 60 other infectious diseases including HIV and tuberculosis Ly KN, et al. Rising Mortality Associated With Hepatitis C Virus in the United States, 2003-2013. Clinical Infectious Diseases. 2016;62(10):1287-1288.

7. What’s possible regarding control and treatment? • The good news • Antiviral medicines can CURE approximately 90% of persons with hepatitis C reducing risk of death from liver cancer and cirrhosis • The challenge • Typically indolent (clinically silent) • Optimal systems for screening, linkage to care and treatment remain under development • Resource constraints

8. Who should be screened for Hepatitis C Virus? 2012 CDC Screening Recommendations AUGMENTED prior targeted screening recommendations • IVDU • Recipients of clotting factors*, solid organ transplant • Hemodialysis patients • HIV • Persons with signs/symptoms of liver disease** • Children born to HCV positive mothers Addition of ‘birth cohort’: • Adults born between 1945-1965 (75% of those infected with HCV fall in this cohort) *before 1987; before 1992’; **e.g. elevated AST

9. Why EMERGENCY DEPARTMENTS? • Front Door Health System • Open 24/7 • Critical component of the public health infra-structure • > 140 million visits/year • ~50% US population use ED at least one visit /year • EDs have track record experience /success public health interventions* • Challenged by increasing demands http://www.acepnow.com/wp-content/ *Woollard, et al AEM  2009 Nov;16(11):1138-42.

10. Rationale for ED HIV/HCV Screening Populations Known to Be Disparate Users of U.S. ED Services: Uninsured, Medicaid Recipients, Non-Whites, Persons Living Below U.S. Poverty Level Known to Be Disproportionately Affected with HIV / HCV Infection & Often Lack Access to Primary Care-Based Preventative Screening Communities in Crisis: Is There a Generalized HIV Epidemic in Impoverished Urban Areas of the United States, CDC 2012 http://www.cdc.gov/hiv/pdf/statistics_poverty_poster.pdf

11. Can EDs be part of the solution?Building on models of success…. ~1 decade experience in ED based integrated testing at the Johns Hopkins Emergency Department • Process/Models • Regulatory/Ethical • Impact/Outcomes • Numerous examples of success and evolution towards unified and streamlined models Fig. 2 . Proportion of HIV-positive individuals virally suppressed and HIV incidence estimates (2001-2013).The grey triangles denote the proportion of HIV-positive patients with an HIV viral load <400 copies/ml in each identity-unlinked serosurvey. The black circles represent cross-sectional HIV incidence estimates determined by a validated multiassay algorithm with a window period of 101 days and a 0% false recent misclassification rate. Vertical lines indicate 95% confidence intervals. AIDS. 30(1):113-120, January 2, 2016

12. Similarities Between HIV and HCV • Silent, indolent • Under-recognized by providers • Stigmatized: Association with stigmatizing behavior • High morbidity and mortality if left unrecognized • Screening, diagnosis, LTC has a significant impact

13. ED Screening for HIV: Lessons learned and evolving paradigm with HCV HIV* • Large numbers of patients can be effectively screened • Processes established for streamlining screening, LTC and treatment • Systems for reimbursement and sustainability have been achieved HCV* • Ongoing research required to better understand epidemiology • Diagnostic algorithms are distinct/ evolving and can be complex • Pilot programs and implementation science required • Policy changes and longitudinal sustained partnerships required *Tie-in with clinical mission

14. Who to Test: Recent Data from the ED Setting II. Evaluation of CDC Recommendations for HCV Testing in an Urban Emergency Department Yu-Hsiang Hsieh, PhD Associate Professor Richard Rothman1,2, Oliver Laeyendecker3, Gabor Kelen1, Ama Avornu1, Eshan Patel3, Jim Kim1, Risha Irvin2, David Thomas2 and Thomas Quinn3 1Dept. of Emergency Medicine, 2Div. of Infectious Diseases, Dept. of Medicine, Johns Hopkins University, and 3National Institute of Allergy and Infectious Diseases, NIH This work was supported by NIH grants K01AI100681 and R37013806 and the Division of Intramural Research, NIAID, NIH

15. Background • One-time baby boomer birth cohort screening is added in the 2012 CDC revised HCV screening recommendations. In 2013, USPSTF recommends HCV screening for adults at high risk (including birth cohort screening) at Grade B. • EDs are considered a key venue for HCV testing because of their history of success in HIV screening given the populations they serve. • High Seroprevalence of HCV infections (chronic or ever) in ED patients. • Risk-based targeted plus birth cohort screening would miss 50%. (Merchant, 2013)

16. Objectives • To determine the overall burden of undocumented HCV infection in an urban ED • To evaluate CDC recommendations for one-time HCV testing in “baby boomers” in an urban ED

17. Methods • Setting: • An urban adult ED with 66,000 annual census; high HCV seroprevalence • Study Period: • 8 weeks (24h/d), 06/2013–08/2013 • Design: • Cross-sectional identity-unlinked seroprevalence study methodology • Sociodemo/HCV information from the administrative and EMR database • Waste blood samples were tested for HIV and HCV infection (HCV EIA) • “Undocumented HCV infection” was operationally defined as presence of anti-HCV Ab in the absence of evidence of HCV infection in EMR.

18. Prevalence of Anti-HCV Ab in 4,713 ED Patients by Known Status

19. Prevalence of Anti-HCV Ab by Age, Sex, and Race

20. Prevalence of Anti-HCV Ab by Selected Groups under CDC Recommendations

21. Proportion of Undocumented HCV Infection by Baby Boomer Birth Cohort

22. Prevalence of Undocumented HCV Infection by Age, Race and Sex

23. Distribution of 204 Undocumented HCV Infection by Baby Boomer, HIV, and IDU

24. Conclusions • High seroprevalence of HCV infection in our ED, indicating that urban EDs could be a valuable venue for HCV testing. • Birth cohort testing would augment identification of undocumented HCV infections two fold. • However, 25% would still remain undiagnosed, suggesting the need to consider modification of the CDC recommendations in ED settings.

25. Universal Screening: Findings from the Front Lines III. Outcomes of HCV Testing in Urban Emergency Departments James Galbraith, MD Associate Professor of Emergency Medicine University of Alabama at Birmingham

26. Targeted HCV Testing in US EDs Galbraith JW. Hepatitis C Virus Screening: An Important Public Health Opportunity for United States Emergency Departments. Annals of Emergency Medicine. 2016;67(1):129-130.

27. ED “Integrated” HCV Testing

28. UAB Targeted HCV Testing (Birmingham, AL) Baby Boomer AB+ Prevalence 11.6% Galbraith JW, Franco RA, Donnelly JP, et al. Unrecognized chronic hepatitis C virus infection among baby boomers in the emergency department. Hepatology. 2014: Sep 1. doi: 10.1002/hep.27410. [Epub ahead of print]

29. Highland Hospital Targeted HCV Testing(Oakland, CA) White DAE, Anderson ES, Pfeil SK, Trivedi TK, Alter HJ. Results of a Rapid Hepatitis C Virus Screening and Diagnostic Testing Program in an Urban Emergency Department. Annals of Emergency Medicine. 2016;67(1):119-128.

30. Pragmatic Targeted Screening Missed the Mark Identifying non-baby boomer targets (IDUs) is challenging • 85% of persons tested were baby boomers or older at UAB • UAB tests for IDU risk accounted for <5% of all test orders • Incidental (non-risk based) tests of persons born after 1965 revealed 10% HCV-Ab prevalence at UAB Stigma barriers • Provider - not asking IDU questions • Patient – recall bias, privacy

31. Universal HCV Testing Eligibility • Born after 1944* • Age >13 - 18 years* • Medically stable for HCV questionnaire • Self-reports no prior HCV diagnosis • No prior test result in the EHR *Eligibility slightly differs by ED site

32. UAB Universal Testing Data 9/3/13 to 1/19/16 Daily Testing Rates Universal screening implemented Sept 15, 2015 2013 2016

33. Combined Site Universal Testing Outcomes

34. Universal ED HCV Testing –Birth Cohort by Race *Hopkins non-black male and female results shown

35. Implications of Universal Testing Outcomes – Heroin Epidemic & HCV Eradication 1st Wave “Baby Boomers” 2nd Wave Predominantly IDU Centers for Disease Control and Prevention (CDC). (2011). Hepatitis C virus infection among adolescents and young adults: Massachusetts, 2002-2009. MMWR. Morbidity and Mortality Weekly Report, 60(17), 537–541.

36. Implications of Universal Testing Outcomes - Surveillance • High volume of unique visitors • Well-positioned to identify IDU • Wide geographic reach • Sizable HCV yield that allows for identification of high prevalence geographic clusters Donnelly JP, Franco RA, Wang HE, Galbraith JW. Emergency Department Screening for Hepatitis C Virus: Geographic Reach and Spatial Clustering in Central Alabama. Clinical Infectious Diseases. 2015;62(5):613-616. doi:10.1093/cid/civ984.

37. IV. Real-World Challenges:HCV Testing Lessons Learned from the Emergency Department Doug White, MD Associate Clinical Professor of Emergency Medicine Alameda County Medical Center-Highland University of California San Francisco

38. Challenges (and Solutions) • Continuum of care completion • Cost • “Best” screening model

39. HCV Screening Continuum of Care

40. HCV Continuum of Care: UAB and HH

41. Time from HCV positive ab test to stages of the ED HCV Continuum of Care* Time (days)

42. Challenge – Test Algorithm Completion

43. Challenge – Test Algorithm Completion X

44. Solution - Test Algorithm Completion Screening packets EMR Prompts Precautions

45. Solution - Test Algorithm Completion Reflex Viral Load Testing • Challenges • Specimen handling requirements • 1 vs 2 tube • Cross contamination

46. Challenge - Linkage • Predicated on completion of test algorithm • High numbers positives + limited capacity • High-no show rates • Uninsured • Homeless, phoneless • Drugs, alcohol, psychiatric illness

47. Solution - Linkage • Linkage coordinator • Insurance enrollment • Case management • Test algorithm completion • Centralized treatment referral • Community partnerships • Primary care treatment

48. Alameda County HCV Linkage Map Alameda Health Consortium Alameda Health System Other • Referral network expansion • Beyond specialists • FQHC / primary care treaters

49. Challenge – Cost • Screening • Programmatic • Treatment

50. Challenge - Screening Costs • Prior to 2013, access to screening limited • Grade B Recommendation • Baby Boomers (1-time screen) • Risk