1. HEPATITIS C VIRUS Dr. Magdy Muharram

2. What is Hepatitis?  “Hepatitis” means inflammation of the liver  Can be caused by:  Genetic diseases  Medications (including over-the-counter)  Alcohol  HEPATITIS VIRUSES (A,B,C,D,E)

3. Hepatitis A  Spread through contaminated food and water  Vaccine available to prevent hepatitis A

4. Hepatitis B  Spread through blood- blood contact  Also transmitted through sex  Vaccine available to prevent hepatitis B

5. Hepatitis C  Identified in 1989  Blood test became available in 1992  Used to be known as “non-A, non-B” hepatitis  Spread through blood-to- blood contact  No vaccine available to prevent hepatitis C  HCV has rarely been detected in semen and vaginal fluids. However, most studies suggest that the virus is not often found in these body fluids, or that it is present in very low amounts and the virus particles may be noninfectious

6. HCV  Genus Hepacivirus  Family Flaviviridae, with classical flaviviruses and animal pestiviruses  6 genotypes worldwide, many subtypes and isolates based on nucleotide diversity  Quasispecies within individual  Genotype does not influence disease progression but does affect response to antiviral treatment (Genotypes 2 and 3 more responsive to alpha-interferon therapy than Genotype 1).

7. Distribution of Hepatitis C genotypes From Forns and Bukh, 1999.

8. HCV virion structure Hypothesized structure:  Icosahedral lipid membrane with E1/E2 glycoproteins  Icosahedral nucleocapsid

10. HCV Genome  9.6 kb RNA genome  Open reading frame encoding polyprotein of ~3000 amino acids

11. C E1 E2 p7 NS2 NS3 NS4A NS4B NS5A NS5B Core protein (nucleocapsid) Envelope glycoprotein-1 Envelope glycoprotein-2 Viroporin ? Zn-dependent proteinase Zn-dependent proteinase, serine protease, helicase NS3 cofactor ER-derived membranous web formation Unknown function; component of replicase? RNA dependent RNA polymerase HVR-1 HVR-2 5’ UTR 3’ UTR ORF

12. Hepatitis C Life Cycle CD81?

13. Prevalence of HCV by world region HEPATITIS C ESTIMATED WORLD INFECTION PREVALENCE (BY WHO REGION) WHO Region Total Population (Millions) Hepatitis C Prevalence (Rate %) Infected Population (Millions) Number of Countries (by WHO Region) Where Data Unavailable Africa6025.331.912 Americas7851.713.17 Eastern Mediterranean 4664.621.37 Europe8581.038.919 South-East Asia15002.1532.33 Western Pacific16003.962.211 Total58113.1169.759 Data Source: Weekly Epidemiological Record No. 49 / Dec, 1999 / WHO

14. HCV VIRAL LOAD TESTS Viral load tests are blood tests that measure HCV ribonucleic acid (RNA, or genetic material) in the blood. The presence of viral RNA indicates that the virus is actively replicating (reproducing and infecting new cells). A viral load test is usually first done after a person has tested positive for exposure to HCV based on an antibody test. A blood sample is taken and the amount of HCV RNA in a milliliter of blood is measured. Viral load tests confirm whether an individual is actively infected with HCV. Viral load test results were previously measured in number of copies, but are now reported in terms of International Units per milliliter (IU/mL).

15. Types of HCV Viral Load Tests There are two categories of HCV viral load tests: Qualitative viral load tests — These tests determine the presence of HCV RNA in the blood. This type of test is usually used to confirm chronic infection with HCV. If viral RNA is detected, a positive result is reported; if viral RNA is not detected, the test result is negative. Quantitative viral load tests — These tests measure the amount of virus in one milliliter of blood. 1.Polymerase chain reaction (PCR) — PCR tests detect HCV RNA in the blood, which indicates current active infection. This type of quantitative PCR test is very sensitive, and can measure as few as 5-10 IU/mL. 2.Branched-chain DNA (bDNA) — The bDNA method quantitative viral load testing is easier (and cheaper) to use for a large number of samples, but only measures viral loads greater than 615 IU/mL. This means that if a person has a viral load below 615 IU/mL, HCV could be present in the blood but not be detected by the test. However, the test will detect higher viral load ranges so it is useful when beginning HCV therapy.

16. Transmission sources

17. HCV research  Unknowns  No cell culture system  No small animal model

18. Who Should Be Tested for HCV Past or present injection drug use Blood transfusion prior to 1992 Persons with hemophilia Long-term hemodialysis Born to an HCV-infected mother Intranasal drug use Receiving an unregulated tattoo Occupational percutaneous exposure Surgery 18

19. Lower Risk: High Risk: How Do People Become Infected With Hepatitis C?  HCV is a blood-borne disease, that is, it is transmitted by blood-to-blood contact. Any activity that lets one person's blood or body fluids to come into contact with another person's blood or mucous membranes can potentially transmit HCV.  HCV can be transmitted by sharing equipment for injection and non-injection drugs (for example, needles, cookers, cocaine straws, and crack pipes).  Needles used for tattooing, body piercing, and acupuncture may also spread HCV. Sharing personal items like razors, toothbrushes, or nail files is a less likely – but still possible – transmission route.  In the past, many people contracted HCV through blood transfusions, but since 1992 there has been a reliable HCV blood test and today donated blood is safe.  Today the likelihood of contracting HCV through infected blood is less than.001%

20. Hepatitis C is NOT Spread By:  Sneezing  Coughing  Food or water  Sharing drinking glasses or eating utensils  Handshakes  Holding hands  Hugging  Playing with children  Donating blood

21. How Can You Prevent the Spread of Hepatitis C?  Cover open wounds  Tell people not to touch your blood  Clean blood spills yourself or inform others to use latex gloves  Dispose of needles/materials properly  Do not inject drugs

22. How Can You Prevent the Spread of Hepatitis C?  Avoid sharing contaminated articles  Razors, toothbrushes, or other personal care items  Inform healthcare professionals/others  Do not donate blood, body organs, tissues

23. How is Hepatitis C Diagnosed?  Blood testing 1.Hepatitis C antibody test 2.Hepatitis C PCR test to find virus in blood  Liver function tests

24. Why Should You Be Concerned About Hepatitis C?  Hepatitis C causes serious problems in some patients  Fibrosis  Cirrhosis  Advanced liver disease  Hepatocellular carcinoma (liver cancer)

25. How Will You Know if You Have Problems from Hepatitis C?  Blood tests  Can be normal even with liver damage  Liver biopsy  Only way to determine the amount of scarring  Small risk of complications and very few side effects  Should be free of alcohol and street drugs

26. Hepatitis C & HIV Co-Infection HIV  Spread through blood and sexual contact  Over time makes it hard for your body to fight off dangerous infections  Can be treated BUT there is no cure Hepatitis C  Spread through blood only  Over time can cause cirrhosis and liver cancer  There is a cure BUT it’s not effective in all patients These viruses are spread in similar ways but are very different diseases All patients with hepatitis C should be tested for HIV

27. What Treatment is Available?  Interferon  Given by shot, usually 3 times a week  Pegylated interferon  Long-acting, taken once a week  Combination therapy  Interferon (standard or pegylated) taken with ribavirin  Ribavirin is a pill taken twice daily

28. Does Treatment Work?  Interferon alone:  10 – 15% chance of clearing the virus from the blood  Interferon & ribavirin:  Up to 40% chance of clearing the virus  Pegylated interferon alone:  About the same as interferon & ribavirin 40%  Pegylated interferon & ribavirin:  Up to 50% chance of clearing the virus

29. During Treatment  Medications taken for either 6 or 12 months  Blood testing required 2 to 3 times the first month, then every 4 weeks  Clinic visits every 1 month  Interferon must be refrigerated

30. Thank You