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Epidemiologic Update: Hepatitis C Miriam J. Alter, Ph.D. Division of Viral Hepatitis Centers for Disease Control and Prevention Hepatitis C Virus Infection Clinical entity (non-A, non-B hepatitis) in transfused patients reported late 1960s RNA Flavivirus (Hepacivirus) – Discovered using recombinant DNA technology 1989 Bloodborne (primarily) and sexually-transmitted Vaccine difficult to develop – Mutations occur during viral replication – Substantial heterogeneity (quasispecies) selects for neutralization escape variants HCV Accomplishments During Past 15 Years Determined burden of infection and morbidity in the general population Eliminated transfusion-associated infections Characterized the epidemiology Documented >80% decline in incidence Implemented community-based prevention – Slowed rates of infection in new IDUs Vaccine developed that may prevent chronic infection (subtype specific) Tissue culture systems effective for growing infectious virus – May speed development of new antivirals Hepatitis C Virus Infection, United States New infections per year 1985-89 2003 242,000 30,000 Persons ever infected (1.6%) 4.1 million (3.4-4.9)* Persons with chronic infection 3.1 million (2.5-3.7)* HCV-positives tested 40% Persons with HIV co-infection 225,000 * 95% confidence interval (data from NHANES 1999-2002 New Infections/100,000 Estimated Incidence of Acute HCV, U.S. 140 N~240,000/yr 120 100 Decline in injection drug users 80 60 40 20 0 N~30,000 Decline in transfusion recipients ≠ 1960 1970 1980 1989 1991 1993 1995 1997 1999 2001 2003 Year Source: Armstrong GL. Hepatology 2000;31:777-82; Alter MJ. Hepatology 1997;26:62S-65S; CDC, unpublished data Percent Anti-HCV Positive Prevalence of HCV Infection in the General Population by Age, U.S., 1988-2002 6 Total 88-94 Total 99-02 5 4 3 2 1 0 6-11 12-19 20-29 30-39 40-49 Age in Years Source: NHANES: Alter MJ, NEJM 1999;341:556-562; Armstrong GL, Ann Intern Med 2006, in press 50-59 60-69 70+ Distribution of HCV Genotypes in the US General Population, NHANES, 1988-1994 80 Percentage positive 70 60 50 40 30 20 10 0 Genotype 1 Genotype 2 Genotype 3 Nainan et al. Gastroenterology 2006, in press Others Risk Factors Associated With Acquiring HCV Infection Transfusion, transplant from infectious donor Injecting drug use Occupational blood exposure (needle sticks) Birth to an infected mother Infected sex partner Multiple heterosexual partners Outbreaks of HCV Infections Clustered in Time and Place Health-care related transmission – In- and outpatient care, long-term dialysis – Most due to unsafe injection practices • Finger stick devices, multi-dose medication vials, reuse of syringes/needles for anesthesia, pain management, saline flushes Sexual transmission among HIV-pos. MSM – Reported from France and UK Relative Efficiency of HBV, HCV, HIV Transmission by Type of Exposure Type of exposure to infected source Transfusion Injecting drug use Unsafe injections Needlestick Sexual Perinatal Non-intact skin Intact skin Efficiency of transmission HBV HCV HIV ++++ ++++ +++ +++ +++ ++++ ++ - ++++ ++++ +++ + + ++ +/- ++++ ++++ + <+ +++ +++ +/- Relative Infectivity of HBV, HCV, HIV HBV HCV HIV Copies/mL 108-9 105 103 Environmental stability Infectious after drying at room temperature ++++ ++ - >7 days >16 h 0 Sources: Bond Lancet 1981; Krawczynski Hepatology 2003 Effect of Environmental Stability on Transmission of HCV and HBV More rapid acquisition among IDUs – Associated with sharing drug preparation equipment (i.e., cookers and cotton) – Clean needles and syringes insufficient to interrupt transmission Facilitates iatrogenic transmission – Patient-to-patient from contaminated multi-dose vials, reused needles and syringes Prevalence of Chronic HBV and HCV in HIV Positives by HIV Risk Group Average percentage positive 90 80 Anti-HCV HBsAg 70 60 50 40 30 20 10 0 Total IDU Hemophilia HIV risk group Heterosexual Homosexual Denis F, Pathol Biol 1997; Thio CL, Lancet 2002; Sherman K, CID 2002, Kellerman S JID 2003; Konopnicki D, AIDS 2005 Exposures Not Associated With Acquiring HCV Case Control Studies of Acute Hepatitis C, U.S., 1979-85 Exposure (prior 6 months) Cases n=148 Controls n=200 Medical care procedures Dental work Health care work (no blood contact) Ear piercing Tattooing Acupuncture 30.4% 24.3% 4.1% 2.7% 0.7% 0 29.5% 23.5% 5.0% 3.0% 0.5% 1.0% Sources: JID 1982;145:886-93; JAMA 1989;262:1201-5. Presence of a Risk Factor Does Not Necessarily Equate With “Increased Risk” HCV Prevalence by Selected Groups United States Hemophilia Injecting drug users Hemodialysis STD clients Gen population adults Surgeons, Nurses, PSWs Pregnant women Military personnel 0 10 20 30 40 50 60 70 Average Percent Anti-HCV Positive 80 90 HCV Prevalence in Selected Groups of Adults United States General population Prevalence of Group in Population Males Females (17%) (<1%) ( 9%) STD clients First responders Surgeons, nurses Snorted cocaine Tattooed (10%) Body pierced (20%) (20%) 0 0.5 1 1.5 2 2.5 3 3.5 4 Average Percent Anti-HCV Positive 4.5 5 HCV Prevalence in Selected Groups of Adults by History of Injection Drug Use, United States No IDU General population IDU Males Females STD clients First responders Surgeons, nurses Snorted cocaine Tattooed Body pierced 0 0.5 1 1.5 2 2.5 3 3.5 4 Average Percent Anti-HCV Positive 4.5 5 Screening for IDU Efficiently Identifies Most HCV-Positives Setting and Criteria Screened HCV Pos STD clients IDU, transfusion <1992 Incoming prison inmates IDU IDU, hx liver disease General population 20-59 years old IDU, transfusion <1992 IDU, transfusion <1992, abnl ALT 3356 12% 1148 11% 13% 165 (5%) 70% 152 (13%) 61% 70% 7% 18% Source: Gunn RA, Sex Transm Dis 2003; D Burnett, Wisconsin; Armstrong GL, Annals 2006. 53% 85% Progress in HCV Prevention and Control Among Injecting Drug Users Cumulative infection rates have slowed – 30% prevalence after 2-3 years Harm reduction messages more HCV-specific – All drug paraphernalia, not just needles/syringes Incidence still remains high – 15% annual rate – Accounts for 60-70% of all new infections