1. Hepatitis B virus Hepatitis viruses: A B formerly serum hepatitis 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: 4 major serotypes adw, ayw*, adr and ayr – 9 subtypes  Genotypes A-H

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

21. 95% of neonates 30% of children under 6 years of age less than 5% of adults become chronic carriers

27. 5 phases of chronic HBV infections  Immune tolerant phase: HBeAg +, high replication, normal ALT,AST levels, mild- no necroinflammation, no or slow progression to fibrosis Spontaneous HBeAg loss is very low. More frequent more prolonged among subjects infected vertically or in the first year of life Highly contagious

28.  Immune reactive phase: HBeAg +, lower replication, more fluctuations in ALT, AST levels, Moderate-severe necroinlammation, more rapid progression of fibrosis May take from several weeks to several years Spontan HBeAg loss is more frequent More frequent among subjects infected during adulthood

29.  Inactive HBV carrier state: HBeAg+  AntiHBe  Low or undetectable HBV levels  ALT, AST normal, low fibrosis or HCC risk  HBsAG+  Anti-HBs 1-2% per year

30.  HBeAg negative CHB: A later phase in the natural course of CHB following the HBeAg +  Anti-HBe cenversion  Periodic reactivation  HBV variants with alterations in precore and/or basal core promoter regions

31.  HBsAg negative phase: Phase after loss of AHBsAg

35. 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

36. 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

37. Serologic markers of HBV

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

42. Hepatitis D

43. 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 % (

44.  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

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

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

58. HCVFlaviviridae + sense ssRNA About 9000 bp, enveloped

59. 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

60.  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 %

62. Anti-HCV seroprevalence by age groups

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

71. 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 (+)