HEPATITIS WEB STUDY Hepatitis C Screening An Urgent

HEPATITIS WEB STUDY Hepatitis C Screening: An Urgent Priority H. Nina Kim, MD MSc Assistant Professor of Medicine Division of Allergy & Infectious Diseases University of Washington April 24, 2012 No financial conflicts of interest Hepatitis web study

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Burden of Chronic Hepatitis C • Most common bloodborne chronic viral infection. - Chronic viral hepatitis is 3 -5 X more frequent than HIV • No vaccine for hepatitis C. • - Up to 4 million* Americans live with HCV infection - 80% of these have chronic persistent infection - Highest HCV prevalence: • • Aged 40 -59 Blacks, Hispanics Poverty level or below Incarcerated, homeless, immigrant, active IDUs Armstrong, Annals Intern Med 2006; 144: 705. www. cdc. gov/hepatitis/HCV Hepatitis web study

Subgroups with High HCV Seroprevalence Armstrong, Annals Intern Med 2006; 144: 705. Dominitz, Hepatology. 2005; 41(1): 88 -96. Weinbaum, MMWR. 2003 Jan 24; 52(RR-1): 1 -36. Hepatitis web study

HCV Seroprevalence by Age group NHANES Armstrong, Ann Intern Med. 2006; 144(10): 705 -14. Hepatitis web study

Natural History of Hepatitis C Exposure (Acute phase) 5 -25% symptoms Accelerants: HIV & Alcohol 80% Resolved Chronic Stable * in 20 -30 yrs ** per year 5 -20%* Cirrhosis Slowly Progressive 1 -5%** ESLD, HCC Transplant Death Hepatitis web study

Silent Nature of Chronic Hepatitis C • Majority of those infected not yet diagnosed - Asymptomatic – many unaware they are infected with HCV until they have symptoms of cirrhosis or liver cancer - Screening not being done • Only a small minority (0. 5 million) in US have been treated • HCV is leading indication for liver transplantation in U. S. - $30 billion health costs per year • HCV is leading cause of death from liver disease in U. S. - Now up to 12, 000 deaths annually Institute of Medicine Report 2010 on Chronic Viral Hepatitis. www. cdc. gov/hepatitis/HCV Hepatitis web study

Trends in Health Care Resources for HCV in US Grant, et. al. Hepatology 2005; 42(6): 1406 -1413. Hepatitis web study

HCV Disease Progression in an Aging Population Davis, Gastroenterology. 2010; 138(2): 513 -21. Hepatitis web study

Mortality for HCV now exceeds that of HIV US, 1999 -2007 Ly et. al. Annals of Intern Med 2012; 156: 271 -278. Hepatitis web study

So how did we get here? Hepatitis web study

Gaps in Awareness & Understanding among those at highest risk • Drug User Intervention Trial enrolled 3, 004 young injection drug users (IDUs) in 5 U. S. cities – 34% found to be HCV-positive - 72% of HCV-positive not aware of their status or thought they were negative - More likely to be aware if hx drug treatment or needle exchange • Among 150 patients seeking substance-use treatment at VA medical center - 90% of those HCV-infected were not aware of their status - 41% IDUs did not know or were unsure of how HCV was spread or what complications can develop • Australian study: 42% of IDUs believed being antibody positive for HCV meant you were immune Hagan, Public Health Reports 2006; 121(6): 713 -19. Dhopesh, Am J Drug Alc Abuse 2000; 26: 703. O’Brien, Addictive Behav 2008; 33(12): 1602 -05. Hepatitis web study

Lack of Public Awareness Lack of Provider Awareness Lack of Public Resource Allocation • • • At-risk people do not know that they’re at risk or how to prevent getting infected At-risk people may not have access to preventive services Chronically infected people do not know that they are infected Many medical providers do not screen or know how to manage those infected Infected people often have inadequate access to testing & medical care Inadequate disease-surveillance systems both underreport acute/chronic HCV Improved Provider & Community Education Integration & Enhancement of Viral Hepatitis Services Institute of Medicine Report 2010 on Chronic Viral Hepatitis. Improved Disease Surveillance Hepatitis web study

Goals for Healthy People 2020: q Reduce by 25% number of new hep C cases q Increase awareness of hep C infection from 45% to 66% among those infected http: //www. hhs. gov/ash/initiatives/hepatitis/ Hepatitis web study

This alarming trend in hep C can be reversed… We know HCV treatment can save lives and permanently clear HCV virus… Hepatitis web study

Sustained Virologic Response (SVR) Goal of HCV Treatment Sustained Virologic Response (SVR) HCV RNA Log 10 IU/ml 7 HCV RNA negative 24 weeks after cessation of treatment 6 Sustained Virologic Response (SVR) 5 4 End of Treatment 3 24 Weeks 2 1 0 Undetectable -8 -4 -2 0 4 8 12 16 20 24 32 40 48 52 60 72 Weeks After Start of Therapy Modified From: Ghany MG, et. al. Hepatology. 2009; 49: 1335 -74. Hepatitis web study www. hepwebstudy. org

HCV Patients with Advanced Fibrosis: SVR Reduces Mortality & Morbidity Liver Failure 50 50 40 40 Liver Failure (%) Liver-Related Death 30 20 10 0 0 1 2 3 4 5 Year 6 7 8 5 -yr occurrence SVR: 4. 4% (CI: 0% to 12. 9%) No SVR: 12. 9% (CI: 7. 7% to 18. 0%) P =. 024 (log likelihood) Veldt BJ, et al. Ann Intern Med. 2007; 147: 677 -684. 30 20 10 0 0 1 2 3 4 5 Year 6 7 8 5 -yr occurrence SVR: 0% No SVR: 13. 3% (CI: 8. 4% to 18. 2%) P =. 001 (log likelihood) Hepatitis web study

Sustained Virologic Response Clinical Outcomes in HIV-HCV Patients Incidence per 100 person-yrs 5 4 Hepatic decompensation 3 2 1 0 Liver-related Death Non-SVR Hepatic decompensation SVR Berengeur et. al. Hepatology 2009; 50: 407 -413. Hepatitis web study

Therapy for Hepatitis C: Historical Milestones Timeline 1986 Source: Ghany MG, et. al. Hepatology. 2009; 49: 1335 -74. 1998 2001 2002 Hepatitis web study

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Therapy for Hepatitis C: Historical Milestones Timeline 1986 1998 2001 2002 2011 70 Hepatitis web study

Direct-Acting Antivirals A New Era of HCV Therapy • New standard of care for HCV genotype 1 infection - HCV protease inhibitor + peg. IFN / ribavirin “triple therapy” - Higher SVR rates observed across all patient groups including “difficult to treat” groups (prior tx failures, AA, cirrhotics). • Challenges remain: - Access & tolerability still limited by Peg-IFN + RBV - Pill burden, q 8 h dosing + meal - Additional side effects - Drug interactions - Resistance? - Cost! • IFN-free era in horizon? Hepatitis web study

Hepatitis C Virus Classes of Direct-Acting Antivirals NS 3/4 A protease inhibitor Hepatitis C Proteins Structural Proteins C E 1 Nucleocapsid Envelope Glycoprotein Nonstructural (NS) Proteins E 2 p 7 Envelope Glycoprotein NS 2 Cysteine Protease Vioporin NS 3 NS 4 A NS 4 B Serine Protease Cofactors Serine RNA Protease Helicase NS 5 A NS 5 B RNA binding and assembly recognition complex Membranous Web Induction RNA-Dependent RNA Polymerase NS 5 A polymerase inhibitor NS 5 B polymerase inhibitors - Nucleoside analogues - Non-nucleoside inhibitors Hepatitis web study

Hep C Screening is the First Step… Cure Assessment Testing Treatment Counseling Screening Hepatitis web study

Comprehensive Strategy to Prevent & Control HCV Primary Prevention • • • Screen & test blood, plasma, organ, tissue donors Sterilize plasma-derived products Infection control practices Risk reduction & counseling services Drug treatment & safe syringe/needle access Secondary Prevention • Identify, counsel & test persons at risk • Medical management of infected persons Hepatitis web study

What is Recommended for Hep C Screening? Centers for Disease Control, 1998: Yes: “Testing should be offered routinely to persons most likely to be infected with HCV… and be accompanied by appropriate counseling & medical follow-up. ” American Association for Study of Liver Diseases, 2009: Yes: “as part of a comprehensive health evaluation, all persons should be screened for behaviors that place them at high risk for HCV infection. ” US Preventive Services Task Force, 2004: Not really: “USPSTF found insufficient evidence to recommend for or against routine screening for HCV infection in adults at high risk for infection. ” Hepatitis web study

Who Should be Screened for Hepatitis C? CDC Guidelines, 1998 • Ever injected illegal drugs • Received clotting factors made before 1987 • Received blood/organs before July 1992 • Ever on chronic hemodialysis • Evidence of liver disease (elevated liver enzymes) • Infants born to HCV-infected mothers • HIV infection • After HCV exposure (needlestick injury) Hepatitis web study

Where Should Screening for Hepatitis C Take Place? CDC Guidelines, 1998 Screen at these venues: ü Correctional institutions ü HIV counseling & testing sites ü Drug treatment facilities ü STD treatment programs Screening must include: ü Counseling on o What results mean o Whether further testing needs to be done ü Referral/linkage to medical care Hepatitis web study

Targeted Risk-Based Screening Only as good as the asking… • 4, 000 primary care physicians mailed survey; 1, 412 responded • Most clinicians lack familiarity with HCV: - 73% had < 5 hep C patients in the preceding year - 44% had no experience with treatment of HCV • Only 59% said they asked all patients about hep C risk factors Mc. Ginn, Arch Intern Med 2008; 168(18): 2009 -2013. Hepatitis web study

Risk-based Screening Limitations • Patients uncertain of past exposure history • Reticence to disclose sensitive risk behaviors • Providers reluctant to ask about sensitive risk behaviors • Inconsistent system-wide implementation • Ultimately it has failed… - 40 -85% of HCV-infected still undiagnosed Mc. Ginn, Arch Intern Med 2008; 168(18): 2009 -2013. Shehab, J Viral Hepat 2001; 8(5): 377 -83. Serrante, Fam Med 2008; 40(5): 345 -51. Hepatitis web study

Birth Cohort Screening CDC, 2012 -2013 • We need enhanced easy-to-implement screening guidance that works • Remember: 80% HCV-infected persons born 1945 -1965 • Birth cohort screening shown by modeling to be more costeffective than risk-based screening: - Would identify additional 808, 580 HCV cases & prevent 82, 000 HCV-related deaths at a cost of $2874 per new case identified • $15, 700 per QALY saved assuming standard treatment and $35, 700 per QALY saved assuming addition of new antivirals. • Revised CDC guidelines coming… stay tuned. Rein, Annals of Intern Med 2012; 156: 263 -270. Hepatitis web study

HCV Diagnostic Algorithm Antibody Test EIA for anti-HCV Negative for HCV Infection Additional Testing Recommended if: • Acute HCV suspected • Hemodialysis • Immunocompromised HCV RNA Active HCV Infection Medical Evaluation RIBA Resolved HCV Infection CDC Guidelines on Hep C Dx, MMWR 2003; 52(RR 03): 1 -16. False-Reactive EIA Hepatitis web study

Counseling the HCV-positive Patient www. cdc. gov/hepatitis/HCV Hepatitis web study

Rapid Testing for HCV FDA approved, June 2010 • Approved for whole blood, fingerstick • Oral swab testing not yet approved • Antibody test, similar to HIV rapid test • Point-of-care – results x 20 min • Preliminary “positive” – needs confirmatory testing - Sensitivity 79 -99% - Specificity 80 -100% • Increased feasibility of testing in outreach settings (needle exchange, STD clinics, methadone programs) Smith BD, J Infect Dis. 2011; 204(6): 825 -31. Hepatitis web study

May 19 National Hepatitis Testing Day • Opportunity to remind health care providers and the public who should be tested for chronic viral hepatitis. • Build collective voice around this urgent issue. http: //www. cdc. gov/hepatitis/Know. More. Hepatitis. htm Hepatitis web study

Meeting the Challenges of HCV Parallels with HIV • Both infections can carry stigma - Disproportionate burden among marginalized • Many undiagnosed & untreated • Risk-based screening has proven inadequate in identifying infected persons promptly • Barriers to new life-saving treatments - Increasing complexity of management - Shortage of skilled clinicians - Concerns re cost & reimbursement • But HCV treatment is of limited duration & achieves a cure • Like HIV, we can gain ground with advocacy & education Hepatitis web study

www. hepwebstudy. org Hepatitis web study

Questions? Hepatitis web study