Hepatitis C Knowledge Network Webinar Series

Hepatitis C Knowledge Network Webinar Series HCV Epidemiology: The Silent Epidemic Presented by: Michael Saag, MD, FIDSA IDSA Hepatitis Task Force Director, Center for AIDS Research University of Alabama at Birmingham June 28, 2013

Disclaimer Any diagnostic or therapeutic recommendations and all opinions expressed during the IDSA Hepatitis C Knowledge Network are those of the presenter only. They do not necessarily represent the views of IDSA. The webinar viewer must use their own independent professional judgment in making clinical decisions. The webinar viewer assumes all risks in using the information provided. IDSA will bear no legal liability for resulting use of the information provided during the webinar. The IDSA Hepatitis C Knowledge Network is in full compliance with HIPPA. 2

Introduction IDSA Hepatitis C Knowledge Network offers a monthly, hour-long webinar to educate IDSA members on the current recommended practices to treat and manage patients infected with the hepatitis C virus (HCV) Provides information on the critical knowledge topics to effectively identify, treat, and manage HCV Opportunity for HCV treaters to engage with HCV experts, discussing issues related to complex patient care and effective treatments To find out more, please visit: www.idsociety.org/hcv_knowledge_network/ (Member Login Required) 3

Outline Epidemiology of Hepatitis C Virus (HCV) Morbidity and mortality of chronic hepatitis C (CHC) Special populations New CDC HCV screening recommendations Improving testing and linkage to care Era of advances in therapy for HCV 4

Large Global Burden of HCV Infection and Disease Global 130-170M chronic infections ~ 2.2 3% world population 27% of cirrhosis and 25% of HCC due to HCV 75% with HIV are co-infected with HCV in some countries (China, Vietnam, Russia) ~ 499,000 HCV-related deaths annually 3 to 4 million new infections with HCV each year Liver International pages 1-3, 8 JUN 2012 Lim SS, Lancet 2012; 3 Perz J Hepatol. 2006; 4 Zhuang X et al. Drug Alcohol Depend 2012; 5 Serano L etal. J Int Assoc Physicians AIDS Care 2012 Jul 24; 6 Pltt L et al. Eur J Public Health 2009.; 7 CDC. MMWR, 2012 5

IOM 2010 Study Report Hepatitis and Liver Cancer: A National Strategy for the Prevention and Control of Hepatitis B and C ~ 5 million Americans chronically infected with HBV or HCV ~ 65 to 75 percent of the 5 million not aware of Dx ~ 150,000 Americans die from liver cancer (HCC) or end-stage liver disease (ESLD) associated HBV or HCV in the next decade The death rate from HCV expected to triple in the next 10 to 20 years Total medical costs for untreated HCV could more than double over the next 20 years from $30 to $80 B/yr 6

Hepatitis C Evolution Association Transfusion With Hepatitis Non-A, Non-B Concept Pegylated Interferon/ Ribavirin DAA Oral HCV (Chiron) Therapies: Protease Inhibitors Recognition Infectious Nature of Hepatitis Discovery of Hepatitis B Interferon Interferon Ribavirin Polymerase Inhibitors More HCV AB Test 1900 1940 1950 1960 1970 1980 1990 2000 Beyond 2011 7

Estimated Incidence of Acute HCV United States,1982-2008 20 18 16 14 12 10 8 6 4 2 0 Surrogate testing of blood donors Decline among transfusion recipients Anti-HCV test (1 st generation) licensed Anti-HCV test (2 nd generation) licensed Decline among injection drug users HIV Epidemic Recognized 1981 HIV Antibody Test licensed Sentinel Counties Study of Viral Hepatitis and State Disease Surveillance, CDC. Year 8

HCV Natural History Acute HCV Infection 75% Resolution ~ 30-40% mild-moderate symptoms Mortality rare from acute HCV Chronic HCV infection Normal ALT 70% Chronic hepatitis ~30% HCC incidence ~1-4% /year Cirrhosis HCC Death ESLD (Liver failure) ~5-7% /year 20 years 30 years 40 years Poynard. Lancet. 1997, Feld & Liang. Hepatology. 2006Santantonio T et al, J Hepatology. 2008;49:625-33. NIH Consensus Conference Statement, June 2002, John-Baptiste A et al, J Hepatology. 2010;53:245-51. Seeff LB, Liver International. 2009;29(suppl 1):89-99., 1 Freeman AJ et al, Hepatology 2001; 2 Norderstedt, et al. Dig Liv Dis 2010; 3 Hassan MM, et al. J.Clin, Gastroenterol 2002; 4 Rein et al, Dig Liver Dis 2011; Am J Epidemiology 2002; 5 Perz et al, J Hepatology 2006; 9

Projected Prevalence of HCV Disease Ever infected Chronic Hepatitis Cirrhosis Acute Hepatitis Davis, G. Gastroenterology 2010;513 10

Hepatocellular Carcinoma in the U.S. Since 1975, HCC incidence has tripled 1 HCC incidence increases 2001-2006 2 Overall 3.5%/year Blacks 4.8% Whites 3.8% Persons 50-59 years 9.1% 50% caused by HCV 3 Primary liver cancer mortality 1 increasing faster than other causes of cancer deaths 3 0 Hepatocellular Carcinoma Incidence: US, 2001-2006 Rate per 100,000 6 5 4 3 2 Male Both Sexes 2001 2002 2003 2004 2005 2006 Year of Diagnosis 1. Altekruse, et al. J Clin Oncol. 2009. 2. MMWR. 2010;59(17):517-520. 3. Eheman, et al. Cancer. 2012. 11

Long-Term US Mortality Trends with Average Annual Percentage Change 2000-2009 By Cancer Site* Males Females Average Annual Percent Change 2000-2009 From The Annual Report to the Nation on the Status of Cancer, J Natl Cancer Inst, Feb 6, 2013 * 10 year AAPC is statistically significant from 0 (p<.05) based on joinpoint model. Incidence data from SEER 13, mortality data from NCHS.

Age-Adjusted Rates of Mortality Associated with HBV, HCV, and HIV 7 United States, 1999 2007 Rate per 100,000 Persons 6 5 4 3 2 1 Hepatitis B Hepatitis C HIV 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year In 2007, >70% of registered deaths in HCV-infected were aged 45-64 yo Ly et al. Ann Int Med. 2012. 13

Cause of Death by Age Group in U.S. Rank 35-44 45-54 55-64 65+ 1 Accidents Malignancies Malignancies Heart 2 Malignancies Heart Heart Malignancies 3 Heart Accidents COPD Cerebrovasc 4 Suicide Cirrhosis/CLD Diabetes COPD 5 HIV Suicide Accidents Alzheimer 6 Homicide Cerebrovasc Cerebrovasc Pneumonia 7 Cirrhosis/CLD HIV Cirrhosis/CLD Diabetes 8 Cerebrovasc. Diabetes Suicide Accidents 9 Diabetes COPD CKD CKD 10 Pneumonia Viral hepatitis Septicemia Septicemia CDC. National Vital Statistics Reports 2009; 58. 14

Monitor Case Reporting and HCV Mortality Years to Death from the Date of HCV Diagnosis Massachusetts: 1992-2009 Number of deaths 1800 1600 1400 1200 1000 800 600 400 200 0 N=8,499 Median interval: 3 years Median age: 53 years <1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Years to death from date of HCV diagnosis A total of 76,122 HCV diagnoses were reported to the MDPH between 1992 and 2009, 8,499 of these reported HCV cases died and are represented in the figure V Lijewski, D Church, MA Dept of Health 15

HCV Testing Recommendations in United States Issued in 1998 CDC recommendations (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 ALT) Infants born to HCV infected mothers HIV infection USPSTF recommendations (2004) Rating I: Screening of high risk persons Rating D: General population screening MMWR. 1998;47 (No. RR-19). 16

Prevalence of HCV by Risks and Demographic Characteristics in the U.S.1999-2002 NHANES Elevated HCV prevalence 57.5% IDU Only 17% reported injection in past year 5.8% Transfusion history 7.5% >20 lifetime sexual partners 3.0% Black 65.6% of those HCV+ born in 1945-1965 Peak prevalence 40-49 years Overall 4.3% Men 6.2% Blacks 9.4% Black men 13.6% Overall U.S. prevalence Prevalence of Anti-HCV 8% 7% 6% 5% 4% 3% 2% 1% 0% Anti-HCV 1.6% (4.1 million) Chronic HCV 1.3% (3.2 million) ALL Men Women 6-19 20-34 35-39 Born ~1945-1965 40-44 Age Group (years) 45-49 50-54 55+ Armstrong et al. Ann Intern Med. 2006. 17

Knowledge of HCV Status Participants in NHANES, 2001-2008 170 anti-hcv+ persons interviewed 86 (51%) unaware of their infection prior to being tested in this survey 84 (49%) already knew their HCV status Reasons for previous testing (n=84) for anti-hcv included 46% routine physical/blood test 16% symptoms of hepatitis 10% blood donations 4% tested because of risk Denniston M, et al Hepatology 2012 18

Best-C: A Retrospective Study of HCV Testing and Linkage to Care in 4 Primary Care Centers* Number with risk factors in medical record (2.6% patients)* (N=209,076) Percent tested Ever IDU n= 2,992 34% Hemophilia n= 1,241 24% HIV+ n= 1,240 62% 10.6% patients had elevated ALT or AST and no other risk indication 23.7% of these were tested for HCV antibody *Henry Ford Detroit;Mt Sinai, NYC; UAB, Birmingham; UT, Houston 19

HCV Test, Care, and Cure Continuum 120% 100% ~ 3 million persons living with HCV 80% 60% 40% 20% 0% 1.6 M (50%) 1.2 M (38%) 750,000 (23%) 360,000 (11%) 200,000 (6%) Holmberg S, et al, NEJM, 2013)

Limited Effectiveness of Risk-based HCV Testing Strategies: Missed Opportunities CDC 1998 risk-based recommendations include Injection drug use Blood transfusion before 1992 and other blood exposures HIV Barriers to HCV testing Provider knowledge and experience Providers may be reluctant to ask about risks Provider time constraints Patient may be reluctant to disclose or may not recall of long-past risk behavior Concerns of stigma 45-85% are unaware of their HCV infection Shehab TM. J Viral Hepat, 2001. Shehab TM, et al. Am J Gastroenterol, 2003. Serrante JM, et al. Fam Med, 2008. Shehab TM, et al. Hepatology, 1999. Roblin, et al. Am J Man Care 2011. Spradling, et al., Hepatology, 2012. Zapata et al, Ann Hepatology, 2010; Napper et al, AIDS Behav, 2010; Haley et al, Preven Med, 2002; Torrone et al, AIDS Pat Care, 2010; Volk et al, 2009 21

Consideration for a Prevalence-Based Strategy To Focus Testing on Persons Born 1945-1965 1 Prevalence 5.3 times higher than other ages (3.29% vs 0.55%) 1 Represents 81% of all adult chronic HCV infections 67% have medical insurance Infected population has modifiable disease co-factors ~ 50% consume 2 alcoholic drinks/day 80% lack Hep A/B vaccination 2 Represents 73% of all HCVassociated mortality 3 1945 1965 1. Armstrong, et al. Ann Int Med. 2006. 2. Kramer, et al. Hepatol. 2011.34. Ly, et al. Ann Int Med. 2012. 22

Harms CDC Consultation August 2011 Evidence Based Review of the Recommendation Non-response to treatment (Failure to achieve SVR) Serious Adverse Events- significant but reversible Benefits Effect of Treatment-related clearance of HCV Reduces risk of HCC by 70% Reduces risk of all-cause mortality by 50% Effect of clinician-directed intervention on alcohol use Decline of alcohol use >38% for >1 year follow-up

Future Burden of Hepatitis C Related Morbidity and Mortality in U.S. Markov model of health outcomes Of 2.7 M HCV infected persons in primary care 1.47 M will develop cirrhosis 350,000 will develop liver cancer 897,000 will die from HCV-related complications Number 40000 35000 30000 25000 20000 15000 10000 5000 0 2010 2012 2014 2016 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2038 2040 2042 2044 2046 2048 2050 2052 2054 2056 2058 2060 Deaths DCC HCC Transplants Rein et al. Dig Liver Dis. 2010. Year 24

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CDC Recommendations for Prevention and Control of HCV infection and Chronic Diseases* Adults born during 1945 1965 HIV-infected patients Persons who ever injected illegal drugs Persons who were ever on chronic (long-term) hemodialysis Persons who received clotting factor concentrates produced before 1987 Prior recipients of transfusions or organ transplants, before July 1992 Persons with persistently abnormal alanine aminotransferase levels Health care, emergency medical, and public safety workers after needle sticks, sharps, or mucosal exposures to HCV-positive blood Children born to HCV-positive women *17, 2012, MMWR 26

USPSTF Recommendations for HCV Testing June 2013 USPSTF recommends screening for HCV infection in adults at high risk including those with any history of intravenous drug use or blood transfusions prior to 1992 - Grade B (moderate certainty that the net benefit is moderate to substantial) USPSTF recommends that clinicians consider offering screening for HCV infection in adults born between 1945 and 1965 - Grade C (HCV screening has at least a small net benefit) Grade A/B no-copay preventive service, a priority for performance measurement 27

HCV Infection, Past or Present Case Definitions 2012 Clinical Presentation No symptoms are required Laboratory Criteria Anti-HCV positive (repeatedly reactive) by EIA (enzyme immunosorbant assay) verified by at least one additional more specific assay, OR Positive HCV RIBA (Recombinant ImmunoBlot Assay), OR Positive HCV NAT (nucleic acid test, RNA or genotype) OR Anti-HCV positive with predictive s/co 28

Hepatitis C Virus (HCV) Infection Testing Algorithm Simplified to Detect Current Disease* ANTI-HCV Point-of-care immunoassay (Rapid Test) or Bench immunoassay (EIA, CIA, MEIA, CMIA) REACTIVE (+) NEGATIVE (-)* NAT for HCV RNA NEGATIVE (-)** STOP POSITIVE (+) Active / Current HCV infection Refer to Care and Treatment # If immunocompromized status or acute infection is suspected, then test for HCV RNA. # # If ongoing risk factors (e.g.. injecting drug use or other recent exposures) repeat anti-hcv testing >6 months after most recent exposure *CDC, 2012, Published Vital Signs, MMWR, 5.7.13 29

Cost of HCV Diagnostic Tests Interpretation Anti-HCV (EIA) HCV RNA HCV Genotype Hepatitis C + + + Resolved/ False positive + - NA McGarry et al $30 $83 NA Eckman et al $20 $50-60 $360 McGarry. Hepatology 2012; 1344, Eckman Clinical Inf Dis 2013, in press 30

Eradication of HCV Is Durable and Reduces Liver Failure, HCC, and Death Van der Meer JAMA 2012; Backus Clin Gastro 2011; Imazeki Hepatology 2003; Shiratori Ann Intern Med 2005; Veldt et al Ann Intern Med 2007; Berenguer Hepatology 2009; 31

Eradication of HCV Is Durable and Reduces Liver Failure, HCC, and Death Van der Meer JAMA 2012; Backus Clin Gastro 2011; Imazeki Hepatology 2003; Shiratori Ann Intern Med 2005; Veldt et al Ann Intern Med 2007; Berenguer Hepatology 2009; 32

Efficacy of HCV Treatment on Viral Eradication 100 90 80 70 Average Sustained Viral Response (SVR) Rates from Clinical Trials 1991 2013+ % SVR 60 50 40 30 20 10 0 IFN 6m IFN 12m I/R 6m Modified from Strader. Hepatology 2004;39:1147 I/R 12m p-ifn 12m p-ifn/r 12m PI/I/R 6-12m Perfectovir DAAs/PI/R or 33 All Oral DAA combos

Potential Impact on Future Burden of Hepatitis C Related Mortality in the US 40000 35000 30000 25000 20000 15000 10000 5000 HCV deaths prevented 143,000 238,000 476,00 714,000 No Testing treat 15% treat 25% treat 50% treat 75% 0 2010 2020 2030 2040 2050 2060 2070 2080 Rein,D., HCV Payer Panel 2013

Summary The prevalence of chronic hepatitis C is large Many, if not most, persons living with chronic hepatitis C remain undiagnosed Screening and linkage to care, evaulation, and treatment must improve to realize health gains anticipated from new therapies The burden of HCV-related morbidity and mortality is large, growing, and associated with health disparities A one-time HCV test for persons born 1945-1965 is a cost-effective approach to reduce HCV morbidity and mortality HCV care and treatment can cure infection and prevent adverse health outcomes Collaboration among public health, clinical care providers, laboratories and payers is essential to improve HCV testing and linkage to care and treatment We can control and eventually eliminate HCV transmission and disease

Acknowledgements CDC John Ward, MD Bryce Smith, PhD Cynthia Jorgenson, DrPH Scott Holmberg, MD Bernie Branson, MD Amy Remick, MBA David Rein, NORC Carol Brosgart, MD Quest Rick Pesano, MD AASLD and IDSA Ira Jacobson, MD Don Jensen, MD Maribel Rodriguez-Torres, MD Ray Kim, MD Anna Lok, MD David Thomas, MD Mark Sulkowski, MD 36