Hepatitis C: Epidemiology, Transmission, and Screening. Jennifer Price, MD Assistant Professor of Medicine University of California San Francisco

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1 Activity Code FA376

2 Hepatitis C: Epidemiology, Transmission, and Screening Jennifer Price, MD Assistant Professor of Medicine University of California San Francisco

3 Learning Objectives Upon completion of this presentation, learners should be better able to: Recognize trends in the epidemiology of HCV infection Successfully implement HCV screening guidelines

4 Faculty and Planning Committee Disclosures Please consult your program book. There will be no off-label/investigational uses discussed in this presentation.

5 Causes of Death Among HIV+ 40% 35% 30% 25% 20% 15% 10% 5% 0% AIDS Liver Cardiac Cancer Other Causes of death in 33,308 HIV+ adults followed prospectively in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Adapted from D:A:D Study Group.AIDS 2010, 24:

6 Chronic HCV Epidemiology Worldwide: ~3% (170 million) chronically infected Global prevalence varies depending on area Up to 20% in highly endemic areas such as Nile Delta 5 million are HIV-HCV coinfected United States: % ( million) chronically infected with HCV 8% are HIV-infected 25-30% of HIV+ in US are also HCV+: prevalence varies by transmission risk factor WHO: CDC: Lavanchy D. Clin Microbiol Infect. 2011;17: Ghany, et al. Hepatology.2009;49:

7 Global Prevalence of HCV 2.9% % % <1.0% No data

8 Global Prevalence of HCV 1>2,3 1>2>3 1>3>2 2>1 4 3>1,2 1>2>6 2.9% % % <1.0% No data 5 1>3,6>2 1>2,3

9 Which of the following is the most efficient mode of HCV transmission? A. Heterosexual contact B. Injection drug use C. Maternal-child transmission D. Male homosexual contact 25% 25% 25% 25% A. B. C. D. 8

10 Transmission of HCV Mother-child transmission 2-5%; 5 x higher if mother is HIV+ CDC: Yeong et al.. Hepatology. 2001;34(2):223. Mast et al.. J Infect Dis. 2005;192:

11 Anti-HCV+, % Prevalence of HIV-HCV by HIV Risk Factor Injection Drug Use Heterosexual Contact Sulkowski and Thomas. Ann Intern Med. 2003;138: Male Homosexual Contact Entire Cohort

12 HCV Transmission: Serodiscordant heterosexual couples N Incidence (per year) Piazza Italy (1997) 499 1% Kao Taiwan (2000) % Vandelli Italy (2004) 776 0% Tahan Turkey (2005) 216 0% Terrault United States (2013) % Piazza et al Arch Intern Med 1997; 157: ; Kao et al J Gastroenterol Hepatol 2000;15: ; Vandelli et al. Am J Gastroenterol 2004;99: ; Tahan et al. Am J Gastroenterol 2005;100: ; Terrault et al. Hepatology 2013;57:

13 Browne et al. Sex Transm Infect 2004; 80: Gilleece et al. J Acquir Immune Defic Syndr 2005; 40: Gambotti, et al. Euro Surveill 2005; 10: Ghosn, et al. HIV Med 2004; 5: Gotz et al. AIDS 2005; 19: Luetkemeyer et al. J Acquir Immune Defic Syndr 2006; 41: Fierer, et al. J Infect Dis 2008; 198: HCV Transmission: HIV+ MSM 2004/2005: Clusters of acute HCV in HIV+ MSM reported in Northern Europe Ulcerative STI s more common in HCV incident cases Molecular genetics more similar to each other than to IDU-associated HCV isolates Linkages made to high-risk sexual behavior (fisting, group sex, traumatic and receptive intercourse) and recreational (not-injected) drugs

14 Browne et al. Sex Transm Infect 2004; 80: Gilleece et al. J Acquir Immune Defic Syndr 2005; 40: Gambotti, et al. Euro Surveill 2005; 10: Ghosn, et al. HIV Med 2004; 5: Gotz et al. AIDS 2005; 19: Luetkemeyer et al. J Acquir Immune Defic Syndr 2006; 41: Fierer, et al. J Infect Dis 2008; 198: HCV Transmission: HIV+ MSM Clusters of acute HCV among HIV+ MSM reported in both US and Australia Northern Europe cohort studies suggests increased HCV incidence since 2000 Short time frame (<2 years) between HIV diagnosis and HCV seroconversion

15 Hepatitis C History 1973: Non-A non-b viral hepatitis described HBV discovered 1965 HAV blood testing developed : HCV genome cloned 1989: HCV antibody test commercially available in US 1990: HCV PCR test developed

16 Estimated Incidence of Acute HCV in US, 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 Source: CDC

17 Incidence of Acute HCV in US, , by Age Group Source: National Notifiable Diseases Surveillance System (NNDSS)

18 HIV impacts which of the following among HCV-infected individuals? A. Clearance of acute HCV infection B. Progression to cirrhosis C. Survival after development of cirrhosis D. Graft and patient survival after liver transplant E. All of the above 20% 20% 20% 20% 20% A. B. C. D. E. 8

19 Natural History of HCV Acute HCV Resolved 15-40% Chronic HCV 60-85% Stable 85-90% Cirrhosis 10-15% Slowly progressive 75% HCC Liver failure 25% (2-4%) NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002.

20 Complications of Cirrhosis Ascites Variceal bleed Hepatic encephalopathy Grade I: Changes in behavior, mild confusion, disoriented sleep Grade II: Lethargy, moderate confusion Grade III: Stupor, incoherent speech Grade IV: Coma, unresponsive to pain Hepatocellular carcinoma

21 Natural History of HIV/HCV Lower rates of spontaneous clearance Resolved 15-40% Acute HCV Chronic HCV 60-85% Stable 85-90% Cirrhosis 10-15% Slowly progressive 75% HCC Liver failure 25% (2-4%) NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002.

22 Natural History of HIV/HCV Acute HCV Resolved 15-40% Chronic HCV 60-85% Accelerated fibrosis progression Stable 85-90% Cirrhosis 10-15% Slowly progressive 75% HCC Liver failure 25% (2-4%) NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002.

23 Natural History of HIV/HCV Acute HCV Resolved 15-40% Chronic HCV 60-85% Stable 85-90% Cirrhosis 10-15% Increased risk of decompensation Slowly progressive 75% HCC Liver failure 25% (2-4%) NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002.

24 Natural History of HIV/HCV Acute HCV Resolved 15-40% Chronic HCV 60-85% Stable 85-90% Cirrhosis 10-15% Slowly progressive 75% HCC Liver failure 25% (2-4%) Liver Transplant Death Shorter survival after decompensation

25 Natural History of HIV/HCV Acute HCV Resolved 15-40% Chronic HCV 60-85% Stable 85-90% Cirrhosis 10-15% Slowly progressive 75% HCC Liver failure 25% (2-4%) Liver Transplant Poorer outcomes after liver transplant Death

26 Burden of Chronic HCV in the US 193,000 HCV deaths next 10 yrs 1.83 million person-years of life lost $11 billion in direct medical care costs $21.3 and $54 billion societal costs from premature disability & mortality million 1.1 million 800, million Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: The National Academies Press; 2010; Wong Am J Pub Health 2000

27 Annual Age-Adjusted Death Rate Due to HCV is Higher than HIV 0.21 per 100, per 100, per 100, Underlying/contributing cause Total Deaths Age-adjusted/100,000 HCV 15, ( HIV 12, ( ) HBV 1, ( ) Ly et al. Ann Intern Med 2012;156:271-8

28 Which of the following is a true statement regarding HCV screening? A. Over 50% of individuals with chronic HCV in the US are undiagnosed B. All pregnant women should be screened for HCV C. Screening is not recommended for patients who only used injection drugs once D. All patients meeting HCV screening criteria should undergo HCV nucleic acid testing 25% 25% 25% 25% A. B. C. D. 8

29 The Problem of Undiagnosed Infection million 45-85% undiagnosed 1.1 million 21% undiagnosed 800, million 65% undiagnosed Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: The National Academies Press; 2010.

30 Risk-based Screening Unsuccessful Among high-risk populations for whom routine HCV testing is recommended, prevalence of testing = 17-87% Why? Limited access to care, patients uncomfortable with disclosing risk behaviors, poor recall of remote events Time constraints on physicians, reluctance to ask questions about risky behaviors, lack of knowledge Smith B, et al. MMWR. 2012; 61(RR04);1-18.

31 CDC Releases Birth Cohort Screening Guidelines Adults born during should receive one-time testing for HCV without prior ascertainment of HCV risk All persons identified with HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services Smith BD, et al. MMWR Recomm Rep. 2012;61(RR-4):1-32.

32 Prevalence of HCV By Year of Birth NHANES Data, and Anti-HCV prevalence among persons born during : 3.25% 5 x higher than among adults born in other years Armstrong GL, et al. Ann Internal Med. 2006;144: Smith BD, et al. AASLD 2011.

33 US Birth Cohort With HCV Generating the Greatest Demand for LT Biggins SW, et al. Liver Transpl. 2012;18:

34 HCV Screening Guidelines Anyone born between 1945 and 1965 HIV-infected History of illicit injection drug use or intranasal cocaine use, even if only used once Received clotting factors made before 1987 Ever on chronic hemodialysis Persistently elevated ALT level Informed that they received blood from a donor who later tested positive for HCV Received blood/organs before July 1992 Children born to HCV-infected mothers. Needle stick injury or mucosal exposure to HCV+ blood Smith, et al. MMWR Recomm Rep 2012; 61:1-32.

35 Projected Health Impact of Birth Cohort Recommendations Outcome Birth Cohort Testing With Therapy PR PR + DAA Additional cases identified 808, ,580 Cirrhosis cases averted 138, ,000 Decomp. cirrhosis cases averted 50,000 74,000 HCC cases averted 32,000 47,000 Liver transplants averted 11,000 15,000 Deaths from HCV averted 82, ,000 Medical costs averted $1.5 billion $2.5 billion Cost/QALY gained $15,700 $35,700 DAA, direct-acting antiviral; PR, peginterferon/ribavirin Rein DB, et al. Ann Intern Med. 2012;156:

36 HCV Screening Among HIV+ All patients should be screened for HCV at least once Annual HCV testing recommended for*: Injection drug users HIV+ men who have unprotected sex with men *European AIDS Clinical Society recommends annual HCV screening in all HIV+ persons IDSA Primary Care Guidelines for Management of Persons Infected with HIV: 2013 Update AASLD/IDSA Recommendations for Testing, Managing, and Treating Hepatitis C: 2014

37 anti-hcv antibody HCV Screening If positive HCV RNA confirmatory testing HCV RNA testing anti-hcv positive anti-hcv negative but suspect acute HCV anti-hcv negative but severely immunocompromised

38 HCV Linkage to Care Falck-Ytter, et al. Ann Intern Med. 2002;136: Grebely, et al J Viral Hepat. 2009;16: Mehta SH, et al. AIDS. 2006;20: Mehta SH, et al. J Community Health. 2008;33: Hallinan, et al. Drug Alcohol Depend. 2007;88:49-53.

39 Key Points HCV Epidemiology and Screening HCV incidence peaked in US in 1980 s Long-term sequelae occur decades after infection Majority of chronically infected are undiagnosed One-time screening recommended for all baby boomers and all HIV+ Challenges Implementation of screening recommendations Identifying those with advanced fibrosis/cirrhosis Linkage to care

40 Activity Code FA376

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