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   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

 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

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

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

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

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

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

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

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

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

 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

 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

 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

 HBsAg negative phase: Phase after loss of AHBsAg

Chronic hepatitis B 1. HBsAg-positive 6 months 2. Serum HBV DNA 20,000 IU/mL (10 5copies/mL), lower values 2, ,000 IU/mL ( 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

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

Serologic markers of HBV

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

Hepatitis D

HDV prevalence in Turkey CHB n = %  %  %  % Cirrhosis n= %  %  %  % (

 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

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

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

HCVFlaviviridae + sense ssRNA About 9000 bp, enveloped

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

 Worldwide 210 million HCV infection  Annual new cases  deaths per year  Anti-HCV seropositivity rate in Turkey 0.5 % %

Anti-HCV seroprevalence by age groups

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

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 (+)