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Hepatitis B virus

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

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Hepatitis B virus

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  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

  4. 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

  5. S protein contains common antigenic determinan “a” • Phenotypes of HBs: 4 major serotypes adw, ayw*, adr and ayr – 9 subtypes • Genotypes A-H

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

  7. 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

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

  9. 1/3 of world pop. Has serologic evidence350 M chronically infectedHBV related HCC >1 M deaths and 5-10 % liver transplantations

  10. 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

  11. 95% of neonates 30% of children under 6 years of age less than 5% of adults become chronic carriers

  12. 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

  13. 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

  14. 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

  15. 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

  16. HBsAg negative phase: Phase after loss of AHBsAg

  17. 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

  18. 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

  19. Serologic markers of HBV

  20. IFN-alpha • LAmivudin • Entacavir • Adefovir • Tenofovir • Telbivudin

  21. Hepatitis D

  22. 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 % (

  23. 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

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

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

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