1. Hepatitis B virus Hepatitis viruses: A B formerly serum hepatitis C D non A nonB E G

2. One of the most prevalent infections Worldwide: 2 out of 6 billion encountered with HBV 350–400 million CHB cases - 4 million new cases/year - >1 million deaths/year

3. HBV   Hepadnavirus  semi (relaxed) circular 3.2 kb ds DNA  Encodes 7 polypeptides  Large amounts of of HBs is released from infected cells  HBV genome integrates to host cell chromosome

5.  Proteins: 4 ORF - Two structural proteins: HBs and HBc/HBe - Polymerase - X protein - 3 initiation codons for S: L, M, S - 2 inititions codons for C: HBc+e

6.  S protein contains common antigenic determinan “a”  Phenotypes of HBs: adw, ayw*, adr and ayr – 8 serotypes

7.  In serum with EM: - Spherical particles 22 nm - Tubuler of filamentous 200 nm long - Spherical virions 42 nm (Dane particle)

8. Replication  Attachment and uncoating  cccDNA formation in nucleus  cccDNA  3.5 kb pregenomic RNA  Pregenomic RNA is encapsidated with new HBc and + sense DNA is produced by reverse transcription in Golgi

14.  Transmission: Through blood and body fluids (semen, saliva, milk, vagina, menstruel secretions and amniotic fluids  Vertical transmission  Incubation period min 6 weeks

15. 1/3 of world pop. Has serologic evidence 350 M chronically infected HBV related HCC  >1 M deaths and 5-10 % liver transplantations

20. High-Risk Groups for Hepatitis B Virus  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

30. Chronic hepatitis B 1. HBsAg-positive 6 months 2. Serum HBV DNA 20,000 IU/mL (10 5copies/mL), lower values 2,000- 20,000 IU/mL (10 4-10 5 copies/mL) are often seen in HBeAg-negative chronic hepatitis B 3. Persistent or intermittent elevation in ALT/AST levels 4. Liver biopsy showing chronic hepatitis with moderate or severe necroinflammation

31. Resolved hepatitis B 1. Previous known history of acute or chronic hepatitis B or the presence of anti-HBc anti-HBs 2. HBsAg 3. Undetectable serum HBV DNA* 4. Normal ALT levels *Very low levels may be detectable using sensitive PCR assays

32. Serologic markers of HBV

36.  IFN-alpha  LAmivudin  Entacavir  Adefovir  Tenofovir  Telbivudin

37. Hepatitis D

38. HDV prevalence in Turkey CHB n = 5961 20 %  1980-1990 31 %  1991-2000 19.4 %  2001-2005 11 % Cirrhosis n= 264 32.5 %  1980-1990 43.5 %  1991-2000 26.1 %  2001-2005 24 % (

39.  Viroid  HBV dependent  1700 bp ss RNA  HBsAg envelope  Cellular RNA pol II copies genomik RNA  Ribozyme  cleaves circular RNA into mRNA for small delta ag

40.  Delta ag gene is mutated by celular ds RNA activated adenosine deaminase enzyme which allows large delta ag production.

41.  Percutaneous  Blood and blood product transfusion kan ve faktör  Person-person  Open lesions of the skin

52. HCVFlaviviridae + sense ssRNA About 9000 bp, enveloped

53. Milestones in HCV  1989 cloning of hepatitis C (HCV) genome  1989 developement of HCV antibody test (ELISA)  1990 HCV viral load test (HCV RNA  test)  1998 approval of Interferon + ribavirin combination therapy 2001 FDA approval of pegylated IFN

54.  Worldwide 210 million HCV infection  Annual 35.000 new cases  10000-12000 deaths per year  Anti-HCV seropositivity rate in Turkey 0.5 % - 1.8 %

56. Anti-HCV seroprevalence by age groups

59. Diagnosis  Anti-HCV antibodies ELISA RIBA (recombinant immunoblot assay) HCV RNA

65. Fecal-oral transmission HAV (+++) HEV (+++) Parenteral transmission HBV (+++) HCV (+++) HDV (++) HGV (++) HAV (+) Sexual transmission HBV (+++) HDV (++) HCV (+) Perinatal transmission HBV (+++) HCV (+) HDV (+) Sporadic (unknown) transmission HBV (+) HCV (+)