1. Hepatitis C virus epidemiology Varsha Shete varshas@eden.rutgers.edu Jeni gemini_breeze@hotmail.com

2. Discovery Hepatitis C was discovered in the 1988 Original name was non-A, non-B Hepatitis virus Hepatitis C antibody test made available in 1990 1995 marked first sight under electron microscopy

3. Basics Flaviviridae Linear + Sense SS RNA Genome around10,000 bases Enveloped Spherical 40-50 nm Replicates in cytoplasm

4. HCV IRES  Secondary structure: stem-loop structure  No cap  5’ untranslated region of HCV shown here  AUG start codon shown here

5. Distribution  Deaths due to associated cirrhosis in the United States 10-20K  4% develop chronic hepatitis C  Only 20% of infected people develop symptoms

6. Prevalence Found to be prevalent in incarcerated adults (as high as 80%) More common in developing nations Shepard et al Country Estimated 2004 total population (millions) Estimated HCV seroprevalence (%) Population studied China13003·2 Nationally representative sample (n=68 000) India10870·9 Community-based, West Bengal (n=3579) USA2941·8 Nationally representative sample (n=21 214) Indonesia2192·1 Volunteer blood donors (n=7572) Brazil1791·1 Volunteer blood donors (n=66 414) Pakistan1594·0 Volunteer blood donors (n=103 858)

7. Transmission Blood and body fluids Intravenous drug users Blood or organ donation before1992 or clotting factors before 1987 Unsterile body art / modification Sexual promiscuity Mother to child

8. Other Factors Other cofactors are:  male sex  older age at acquisition of HCV infection  HIV co-infection  hepatitis B virus (HBV) co-infection  alcohol consumption HIV and HCV co-infection causes severe liver damage and further lowers the chances of survival

9. Symptoms and Duration Major cause of liver failure Fever Loss of appetite Nausea Abdominal pain Dark colored urine Clay-colored bowel Joint pain Jaundice Fatigue  10 yrs Chronic hepatitis  20 yrs Cirrhosis  30 yrs Hepatocellular carcinoma

10. Healthy to Hepatitis C Liver Healthy LiverLiver damaged due to HCV

11. Incidents and trends of infection (Epidemics) Impractical to measure infection incidents Center for Disease Control and Prevention (CDC) in USA uses mathematical model for estimation of trends of infection Age-specific reported cases of acute disease and data from a cross- sectional national survey done from 1988 to 1994 was used by CDC The general observation was steady rise in the cases of HCV infection since the 1980’s

12. Incidents and trends of infection (continued)… USA: steady and sharp drop through 1990’s France: death rates from hepatocellular carcinoma was used as a model and similar trend was observed Australia: steady increase from 1961 through 2001 Italy: decline in 1990’s Russia: dramatic increase since 1994 England: clear decline after reduction of use of syringes and alternative drug therapy

13. Treatment No vaccine and no completely effective treatment! But pharmaceutical and medical research companies are working on a variety of possible new treatments Belgian biotech firm Innogenetics is developing a hepatitis C vaccine that may be able to halt or reverse liver damage in people infected with the disease, BBC News reported on 11/04/02

14. Treatment (continued)… Interferon α Patients inject interferon 2-3 times a week 25% of patients have good results with interferon Doctors will discontinue after 3 months if there isn’t a change with interferon and use the Rebetron. Infergen (derivative of Interferon α) Rebetron (Interferon + ribavirin)

15. References “Global epidemiology of hepatitis C virus infection”, Shepard W, Finelli L, Alter M, The Lancet infectious diseases, Vol 5 (9) September 2005, 558-567 “Seroprevalence of hepatitis C among a juvenile detention population”, Feldman G, Sorvillo F, Cole B, Lawrence W, Mares R, Journal of Adolescent health Vol 35 (6), December 2004, 505-508 “Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection epidemiology in Moscow region during 1995–1999” Isakov V, Tsodikov G, Ivanikov I, Kaira A, Seliverstova A, Shakhovski Y Journal of Hepatology, Vol 34 (11), April 2001, 191 www.who.org http://www.ncbi.nlm.nih.gov/ICTVdb http://virology-online.com/viruses/HepatitisC.htmhttp://virology-online.com/viruses/HepatitisC.htm http://www.virology.net/Big_Virology/BVRNAflavi.html http://www.hepnet.com/hepc.html#history http://www.aafp.org/fpr/20031100/27.htmlhttp://www.aafp.org/fpr/20031100/27.html http://www.cnn.com/HEALTH/9703/26/nfm/hepatitis.c/index.html

16. Thank You! Questions and Comments?