Hepatitis

1. Hepatitis

2. Hepatitis viruses • At least 6 viruses • HAV • HBV • HCV • HDV • HEV • HGV?

3. Hepatitis Viruses • hepatitis alphabet of viruses includes at least six viruses, A through E, and G • Although the target organ for each of these viruses is the liver, and the basic hepatitis symptoms are similar, they differ greatly in their structure, mode of replication, mode of transmission, and in the time course and sequelae of the disease they cause. : • Hepatitis A virus (HAV) • Hepatitis B virus (HBV) • Hepatitis C virus(HCV) • Hepatitis D virus (HDV • Hepatitis E virus (HEV)

4. Hepatitis viruses /hepatitis • Liver damage • Icteric symptomes • Jaundice • Release of liver enzymes

5. Hepatitis Viruses Hepatitis A, which is sometimes known as infectious hepatitis, • is caused by a picornavirus, a ribonucleic acid (RNA) virus; • is spread by the fecal-oral route; • has an incubation period of approximately 1 month, after which icteric symptoms start abruptly; does not cause chronic liver disease; rarely causes fatal disease.

6. Spread of HAV within the body

7. Hepatitis A virus/Epidemiology Seropositivity rate of adults in various countries: • Sweden 13% • USA 41-44% • Yugoslavia 97% • Taiwan 88% • Turkey 65-above 95%

8. Time course of HAV infection

9. Hepatitis A virus/Laboratory diagnosis • Time course of the clinical symptomes • Identification of a known infected source • Specific serologic tests • anti-HAV IgM by ELISA

10. Hepatitis A virus/Treatment, Prevention & control • Fecal-oral spread • Prophylaxis • Immune serum globulin • Before or early in the incubation period: 80-90% effective in preventing clinical illness • Vaccine: killed HAV vaccine (FDA appr) • For use in children or adults at risk for infection

11. Hepatitis B virus • Hepadnaviruses • Infect : liver, kidneys, pancreas • Only humans and chimpanzees

12. Hepatitis B virus/Structure • Small • Envelopped • DNA genome • Several unusual properties: • Small (3200 bases) -circular-partly double-stranded DNA • Encodes a reverse transcriptase • Replicates through an RNA intermediate

13. Hepatitis B • previously known as serum hepatitis, • (1) is caused by a hepadnavirus with a deoxyribonucleic acid (DNA) genome; • (2) is spread parenterally by blood or needles, by sexual contact, and perinatally; • (3) has a median incubation period of approximately 3 months, after which icteric symptoms start insidiously; • (4) is followed by chronic hepatitis in 5% to 10% of patients; and (5) is causally associated with primary hepatocellular carcinoma (PHC). • More than one third of the world's population has been infected with HBV, resulting in 1 to 2 million deaths per year. • The incidence of HBV is decreasing, however, especially in infants, because of the development and use of the HBV subunit vaccine.

14. Unique Features of Hepadnaviruses • Virus has enveloped virion containing partially double-stranded, circular DNA genome. • Replication is through a circular RNA intermediate. • Virus encodes and carries a reverse transcriptase. • Virus encodes several proteins (HBsAg [L, M, S]; HBe/HBc) that share genetic sequences but with different in-frame start codons. • HBV has a strict tissue tropism to the liver. • HBV-infected cells produce and release large amounts of HBsAg particles lacking DNA. • The HBV genome can integrate into the host chromosome.

15. Hepatitis B virus/Structure • Virion: Dane particule, 42nm in diameter • Unusually stable for an envelopped virus • Resist treatment with : • ether, • a low pH, transmission • Freezing, • Moderate heating

16. Hepatitis B virus/Structure • Virion: Dane particule, 42nm in diameter include: • a polymerase • Reverse transcriptase activity • Ribonuclease activity • HBcAg • HBsAg, 3 forms: • L>M>S glycoproteins, contains “a” determinant (goup- specific), and “d” or “y” and “w” or “r”, type-specific determinants

18. Hepatitis B virus/Replication • “Unique!” • Replicatesthrough an RNA intermediateandproducesandreleasesantigenicdecoyparticules

21. Hepatitis B virus The virus has RNA-dependent DNA polymerase: (Reverse transcriptase)

22. Hepatitis B virus • A circular positive-strand RNA intermediate is first synthesized by: cell’s DNA dependent RNA polymerase RNA-dependent DNA polymerase: a negative strand DNA is formed positive RNA degragated Positive strand DNA is initiated but stops when the genome and the core enveloped RESULT: partially double stranded DNA

23. Hepatitis B virus/Pathogenesis&Immunity • HBV can cause: • Acute or • Chronic, • Symptomatic or, • Asymptomatic disease...

24. HepatitisB virus/Pathogenesis&Immunity “It’s determined by the person’s immune response to the infection”

26. HepatitisB virus/Pathogenesis&Immunity • HBsAg and HBeAg in the blood : ongoing active infection • The major source of infectious virus is blood • Semen • Saliva • Milk • Vaginal & menstrual secretions • Amniotic fluid

28. HepatitisB virus/Pathogenesis&Immunity • Infants & young childrens are less able to resolve the infection • ~90% infected perinatally become chronic carriers

30. HepatitisB virus/Epidemiology • asymptomatic carriers foster the spread of the virus • Routes of spread: sexual, parenteral, and perinatal

31. Hepatitis B virus/Epidemiology • Transmission: • Contaminated blood, blood components • Needle sharing • Acupuncture • Ear piercing • Tattooing • Very close personel contact • The exchange of semen, saliva, vaginal secretions (e.g., sex, childbirth)

32. High-Risk Groups for Hepatitis B Virus Infection • People from endemic regions (i.e., China, parts of Africa, Alaska, Pacific Islands) • Babies of mothers with chronic hepatitis B virus • Intravenous drug abusers • People with multiple sex partners, homosexual and heterosexual • Hemophiliacs and other patients requiring blood and blood product treatments • Health care personnel who have contact with blood • Residents and staff members of institutions for the mentally retarded • Hemodialysis patients and blood and organ recipients

33. HepatitisB virus/Clinicalsyndronnes • Chronic infection • 5-10% of people with HBV infections

37. Hepatitis B virus/Clinical syndronnes • Primary hepatocellular carcinoma • 80% of all cases of chronic HBV inf. • One of the three most common cause of cancer mortality in the world • May become the first vaccine-preventable human cancer • Latency period: 9 to 35 years

38. Hepatitis B virus/Laboratory diagnosisInterpretation of serologic markers of hepatitis B virus infection

39. HBeAg • Secretory form of HBcAg • Indicates viral replication and infectivity • In some chronic infections • HBV DNA is high • No HBeAg • Because of a mutation in core promoter or precore region which encodes HBcAg • +mutations in core region enhances severity , increase risk of cirrhosis

40. Acute infection • HBsAg • AntiHBc-IgM • Immunity: • Anti-HBs ≥10IU/ml

41. HBV infection: NAT 1-HBV DNA PCR (real-time PCR: quantitation:IU/ml) -staging the disease -prognosis detection -monitoring therapy 2-HBV Genotyping: Antiviral Resistance detection

42. Hepatitis B virus/Prevention&Control • Screening donated blood • HBsAg, anti-HBc • Avoiding intimate personal contact with HBsAg (+)’s • Avoiding the lifestyles that facilitate the spread of the virus • (High risk groups • Vaccination

43. Hepatitis B virus/Prevention&Control • Universal blood and body fluid precautions (refer to HIV and retroviruses lesson)

44. Prevention, and Control • Transmission of HBV in blood or blood products has been greatly reduced by screening donated blood for the presence of HBsAg and anti-HBc. • Additional efforts to prevent transmission of HBV consist of avoiding sex with a carrier of HBV and avoiding the lifestyles that facilitate spread of the virus. • Household contacts and sexual partners of HBV carriers are at increased risk, as are patients undergoing hemodialysis, recipients of pooled plasma products, health care workers exposed to blood, and babies born of HBV-carrier mothers.

45. Prevention, and Control • Vaccination is recommended for infants, children, and especially people in high-risk groups • For newborns of HBsAg-positive mothers and people accidentally exposed either percutaneously or permucosally to blood or secretions from an HBsAg-positive person, vaccination is useful even after exposure. Immunization of mothers should decrease the incidence of transmission to babies and older children, also reducing the number of chronic HBV carriers. Prevention of chronic HBV will reduce the incidence of PHC. is not readily inactivated by detergents.

46. The HBV vaccines • subunit vaccines. • The initial HBV vaccine was derived from the 22-nm HBsAg particles in human plasma obtained from chronically infected people. • The current vaccine was genetically engineered and is produced by the insertion of a plasmid containing the S gene for HBsAg into a yeast, Saccharomyces cerevisiae. The protein self-assembles into particles, which enhances its immunogenicity.

47. The HBV vaccines • The vaccine must be given in a series of three injections, with the second and third given 1 and 6 months after the first. • More than 95% of individuals receiving the full three-dose course will develop protective antibody. • The single serotype and limited host range (humans) help ensure the success of an immunization program.

48. Universal blood and body fluid precautions • are used to limit exposure to HBV. • It is assumed that all patients are infected. • Gloves are required for handling blood and body fluids; wearing protective clothing and eye protection may also be necessary. • Special care should be taken with needles and sharp instruments. • HBV-contaminated materials can be disinfected with 10% bleach solutions

49. Hepatitis C and G viruses • HCV • was identified by molecular biologic means in 1989 • Predominant cause of NANBH virus infections • Major cause of post-transfusion hepatitis (before routine screening of the blood supply for HCV)

50. Hepatitis C virus • HCV • > 170 000 000 (17x 107) carriers in theworld • Transmissionsimilarto HBV but “Greaterpotentialforestablishingpersistent, chronichepatitis” Cirrhosis HCC