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HEPATITIS VIRUSES  By Dr.D.W.Deshkar  30-07-2009
What is Viral Hepatitis ? ,[object Object]
HEPATITIS VIRUSES ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Viral Hepatitis - Historical Perspectives ,[object Object],A Viral hepatitis NA:NB E Enterically transmitted “ Serum” B D C Parenterally transmitted F- Mutant Of B G
Type of Hepatitis Ensure Safe  Drinking water Pre  Post Exposure Immunization Blood donor  screening Pre  Post Exposure Immunization Blood donor  screening Pre  Post Exposure Immunization Prevention No Yes Yes Yes No Chronic Infection Feco-oral Percutaneous Permucosal Percutaneous Permucosal Percutaneous Permucosal Feco-oral Route of Transmission Feces Blood Blood derived  Body fluids Blood Blood derived  Body fluids Blood Blood derived  Body fluids Feces Source of virus E D C B A
HAV
Hepatitis A Virus Naked RNA virus Related to enteroviruses, formerly known as Enterovirus 72, now put in its own family: heptoviridae  One stable serotype only Difficult to grow in cell culture: primary marmoset cell culture and also in vivo in chimpanzees and marmosets  4 genotypes exist, but in practice most of them are group 1 RNA
RESISTANCE ( HAV) ,[object Object],[object Object],[object Object],[object Object]
Hepatitis A Virus Transmission ,[object Object],[object Object],[object Object]
Prodromal or Preicteric phase : (symptoms: fatigue, joint- and abdominal pain, malaise, vomiting, lack of appetite, hepatomegaly)  Icteric phase: Icterus: jaundice (skin, sclera, mucous membranes, cause: elevated bilirubin level, bilirubinuria: dark urine, pale stool)
PATHOGENESIS - HAV ,[object Object],[object Object],[object Object],[object Object]
PATHOGENESIS – HAV   contd-- ,[object Object],[object Object],[object Object],[object Object]
LAB.DIAGNOSIS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Fecal HAV Symptoms 0 1 2 3 4 5 6 12 24 Hepatitis A Infection IgG anti-HAV Titre ALT IgM anti-HAV Months after exposure Typical Serological Course
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Hepatitis A Vaccination Strategies Epidemiologic Considerations
Hepatitis B Virus
Hepatitis  B  Virus
1 、 Properties of HBV ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
HBV   : Structure
HBV   : Structure ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
HBV Structure & Antigens   Dane particle HBsAg  = surface (coat) protein  (  4 phenotypes : adw, adr, ayw and ayr) HBcAg  = inner core protein ( a single serotype)   HBeAg  = secreted protein; function unknown
decoy particles ,[object Object],[object Object],[object Object]
GENOME
[object Object],[object Object],[object Object],[object Object],[object Object],Open Reading Frames
HBx activates the Ras-Raf-MAPK cascade: Influence on cell proliferation? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
2 、 HBV: Replication   ,[object Object],[object Object],[object Object]
Replication  of  HBV
[object Object],[object Object],[object Object],3 、 HBV:  Modes of Transmission
4 、 Epidemiology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
High Moderate Low/Not Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears Breast milk Concentration of Hepatitis B Virus in Various Body Fluids 伤口渗出液 唾液 精液 阴道分泌液
High-risk groups for HBV infection ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Symptoms HBe Ag anti- HBe Total anti- HBc IgM anti- HBc anti- HBs HBs Ag 0 4 8 12 16 20 24 28 32 36 52 100 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Weeks after Exposure Titre
5 、 Pathogenesis  & Immunity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
6 、 Clinical Features ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Possible Outcomes of HBV Infection Acute   hepatitis B infection Chronic HBV infection 3-5% of adult-acquired   infections 95% of infant-acquired infections Cirrhosis   Chronic hepatitis   12-25% in 5 years Liver failure   Hepatocellular   carcinoma Liver transplant   6-15% in 5 years 20-23% in 5 years Death Death
7 、 Laboratory  Diagnosis
Diagnosis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
、 Current Treatment Options   ,[object Object],[object Object],[object Object],[object Object]
Treatment ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
、 Prevention ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Prevention ,[object Object],[object Object],[object Object]
Hepatitis B Vaccine   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
HEPATITIS C VIRION: spherical, icosahedral, NUCLEIC ACID: ss (+) RNA
hypervariable region capsid envelope protein protease/ helicase RNA-dependent RNA polymerase c22 5’ core E1 E2 NS2 NS3 33c NS4 c-100 NS5 3’ Hepatitis C Virus
Hepatitis C Virus ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
HCV replicates exclusively in the cytoplasm via an RNA intermediate Nucleus Viral entry & uncoating Translation & processing (+) (+) (-) (+) HCV RNA replication Virus particle assembly Replicative intermediate
Incubation period: Average 6-7 wks Range 2-26 wks Clinical illness (jaundice): 30-40% (20-30%) Chronic hepatitis: 70% Persistent infection: 85-100% Immunity: No protective  antibody response  identified Hepatitis C - Clinical Features
Chronic Hepatitis C Infection ,[object Object],[object Object]
Symptoms anti-HCV ALT Normal 0 1 2 3 4 5 6 1 2 3 4 Hepatitis C Virus Infection Typical Serologic Course Titre Months Years Time after Exposure
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Risk Factors Associated with Transmission of HCV
Laboratory Diagnosis ,[object Object],[object Object],[object Object]
HCV RNA (PCR testing) 􀂄  Virus load 􀂄  Lower detection limit can be 10-615 IU/ml 􀂄  NOT a predictor of disease severity: a high viral load does not mean the liver disease is more severe, and a low viral load does not mean the patient is ok and does not need therapy! 􀂄  Helps predict response rate to treatment (lower means a higher chance of cure with therapy) 􀂄  Used to monitor response during treatment
Prognostic Tests ,[object Object],[object Object],[object Object],[object Object]
Treatment ,[object Object],[object Object]
OUTCOMES of HCV hepatitis
[object Object],[object Object],[object Object],Prevention of Hepatitis C
HBsAg RNA    antigen Hepatitis D (Delta) Virus
Hepatitis Delta Virion From Murray et. al., Medical Microbiology 5 th  edition, 2005, Chapter 66, published by Mosby Philadelphia,,  Figure 66-14
HEPATITIS D VIRUS (HDV, DELTA AGENT) VIRION: spherical, 36-38 nm, HBV capsid, HDV nucleoprotein NUCLEIC ACID: (-) ss RNA, circular Satellite virus : replicates only in the presence of HBV
Hepatitis D Virus ,[object Object],[object Object],[object Object]
The HDV genome Figure 88-4  Structure of the HDV RNA Genome. The single-stranded circular RNA genome is indicated by the  heavy black continuous line.  The genome has the ability to form an unbranched rod structure, in which approximately 70% of the bases are engaged in Watson-Crick pairs with counterparts from the opposite side of the circular RNA. In this unbranched rod structure, the region encoding HDAg (nt 1598-957) is on one side. The RNA editing site is at position 1012 in the antigenome. The region on the right-hand side contains the autocatalytic cleavage sites (ribozymes), one in the genome (nt 686) and the other in the antigenome (nt 900). The genome binds HDAg and is transcribed by a host DNA–dependent RNA polymerase.  Fields Virology 4 th  edition, 2002, Chapter 88, Lippincott, Williams and Wilkins, 2002 Fig. 88-4
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Hepatitis D - Clinical Features
Consequences of hepatitis B and delta virus infection   Figure 66-15.  Consequences of deltavirus infection. Deltavirus (d) requires the presence of hepatitis B virus (HBV) infection. Superinfection of a person already infected with HBV (carrier) causes more rapid, severe progression than co-infection ( shorter arrow ).  From Murray et. al., Medical Microbiology 5 th  edition, 2005, Chapter 66, published by Mosby Philadelphia.
[object Object],[object Object],[object Object],[object Object],Hepatitis D Virus Modes of Transmission
anti-HBs Symptoms ALT Elevated Total anti-HDV IgM anti-HDV HDV  RNA HBsAg HBV - HDV  Coinfection Typical Serologic Course Time after Exposure Titre
Jaundice Symptoms ALT Total anti-HDV IgM anti-HDV HDV RNA HBsAg HBV – HDV  Superinfection Typical Serologic Course Time after Exposure Titre
[object Object],[object Object],[object Object],[object Object],Hepatitis D - Prevention
Hepatitis E Virus
Hepatitis E Virus ,[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],Hepatitis E - Clinical Features
Symptoms ALT IgG anti-HEV IgM anti-HEV Virus in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Hepatitis E Virus Infection Typical Serologic Course Titer Weeks after Exposure
[object Object],[object Object],[object Object],[object Object],Hepatitis E -  Epidemiologic Features
[object Object],[object Object],[object Object],[object Object],Prevention and Control Measures for Travelers to HEV-Endemic Regions
HEPATITIS G VÍRUS FLAVIRUS: similar morphology and genome ◊  in risk groups: acute, chronic and fulminant  hepatitis ◊  transmission: blood (mother- newborn babies) ◊  prevalence is higher in HCV infected people
THANK YOU

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Hepatitis ppt final

  • 1. HEPATITIS VIRUSES By Dr.D.W.Deshkar 30-07-2009
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  • 5. Type of Hepatitis Ensure Safe Drinking water Pre Post Exposure Immunization Blood donor screening Pre Post Exposure Immunization Blood donor screening Pre Post Exposure Immunization Prevention No Yes Yes Yes No Chronic Infection Feco-oral Percutaneous Permucosal Percutaneous Permucosal Percutaneous Permucosal Feco-oral Route of Transmission Feces Blood Blood derived Body fluids Blood Blood derived Body fluids Blood Blood derived Body fluids Feces Source of virus E D C B A
  • 6. HAV
  • 7. Hepatitis A Virus Naked RNA virus Related to enteroviruses, formerly known as Enterovirus 72, now put in its own family: heptoviridae One stable serotype only Difficult to grow in cell culture: primary marmoset cell culture and also in vivo in chimpanzees and marmosets 4 genotypes exist, but in practice most of them are group 1 RNA
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  • 10. Prodromal or Preicteric phase : (symptoms: fatigue, joint- and abdominal pain, malaise, vomiting, lack of appetite, hepatomegaly) Icteric phase: Icterus: jaundice (skin, sclera, mucous membranes, cause: elevated bilirubin level, bilirubinuria: dark urine, pale stool)
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  • 14. Fecal HAV Symptoms 0 1 2 3 4 5 6 12 24 Hepatitis A Infection IgG anti-HAV Titre ALT IgM anti-HAV Months after exposure Typical Serological Course
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  • 17. Hepatitis B Virus
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  • 19. HBV : Structure
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  • 21. HBV Structure & Antigens Dane particle HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr) HBcAg = inner core protein ( a single serotype) HBeAg = secreted protein; function unknown
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  • 30. High Moderate Low/Not Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears Breast milk Concentration of Hepatitis B Virus in Various Body Fluids 伤口渗出液 唾液 精液 阴道分泌液
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  • 32. Symptoms HBe Ag anti- HBe Total anti- HBc IgM anti- HBc anti- HBs HBs Ag 0 4 8 12 16 20 24 28 32 36 52 100 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Weeks after Exposure Titre
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  • 35. Possible Outcomes of HBV Infection Acute hepatitis B infection Chronic HBV infection 3-5% of adult-acquired infections 95% of infant-acquired infections Cirrhosis Chronic hepatitis 12-25% in 5 years Liver failure Hepatocellular carcinoma Liver transplant 6-15% in 5 years 20-23% in 5 years Death Death
  • 36. 7 、 Laboratory Diagnosis
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  • 43. HEPATITIS C VIRION: spherical, icosahedral, NUCLEIC ACID: ss (+) RNA
  • 44. hypervariable region capsid envelope protein protease/ helicase RNA-dependent RNA polymerase c22 5’ core E1 E2 NS2 NS3 33c NS4 c-100 NS5 3’ Hepatitis C Virus
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  • 46. HCV replicates exclusively in the cytoplasm via an RNA intermediate Nucleus Viral entry & uncoating Translation & processing (+) (+) (-) (+) HCV RNA replication Virus particle assembly Replicative intermediate
  • 47. Incubation period: Average 6-7 wks Range 2-26 wks Clinical illness (jaundice): 30-40% (20-30%) Chronic hepatitis: 70% Persistent infection: 85-100% Immunity: No protective antibody response identified Hepatitis C - Clinical Features
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  • 49. Symptoms anti-HCV ALT Normal 0 1 2 3 4 5 6 1 2 3 4 Hepatitis C Virus Infection Typical Serologic Course Titre Months Years Time after Exposure
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  • 52. HCV RNA (PCR testing) 􀂄 Virus load 􀂄 Lower detection limit can be 10-615 IU/ml 􀂄 NOT a predictor of disease severity: a high viral load does not mean the liver disease is more severe, and a low viral load does not mean the patient is ok and does not need therapy! 􀂄 Helps predict response rate to treatment (lower means a higher chance of cure with therapy) 􀂄 Used to monitor response during treatment
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  • 55. OUTCOMES of HCV hepatitis
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  • 57. HBsAg RNA  antigen Hepatitis D (Delta) Virus
  • 58. Hepatitis Delta Virion From Murray et. al., Medical Microbiology 5 th edition, 2005, Chapter 66, published by Mosby Philadelphia,, Figure 66-14
  • 59. HEPATITIS D VIRUS (HDV, DELTA AGENT) VIRION: spherical, 36-38 nm, HBV capsid, HDV nucleoprotein NUCLEIC ACID: (-) ss RNA, circular Satellite virus : replicates only in the presence of HBV
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  • 61. The HDV genome Figure 88-4 Structure of the HDV RNA Genome. The single-stranded circular RNA genome is indicated by the heavy black continuous line. The genome has the ability to form an unbranched rod structure, in which approximately 70% of the bases are engaged in Watson-Crick pairs with counterparts from the opposite side of the circular RNA. In this unbranched rod structure, the region encoding HDAg (nt 1598-957) is on one side. The RNA editing site is at position 1012 in the antigenome. The region on the right-hand side contains the autocatalytic cleavage sites (ribozymes), one in the genome (nt 686) and the other in the antigenome (nt 900). The genome binds HDAg and is transcribed by a host DNA–dependent RNA polymerase. Fields Virology 4 th edition, 2002, Chapter 88, Lippincott, Williams and Wilkins, 2002 Fig. 88-4
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  • 63. Consequences of hepatitis B and delta virus infection Figure 66-15. Consequences of deltavirus infection. Deltavirus (d) requires the presence of hepatitis B virus (HBV) infection. Superinfection of a person already infected with HBV (carrier) causes more rapid, severe progression than co-infection ( shorter arrow ). From Murray et. al., Medical Microbiology 5 th edition, 2005, Chapter 66, published by Mosby Philadelphia.
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  • 65. anti-HBs Symptoms ALT Elevated Total anti-HDV IgM anti-HDV HDV RNA HBsAg HBV - HDV Coinfection Typical Serologic Course Time after Exposure Titre
  • 66. Jaundice Symptoms ALT Total anti-HDV IgM anti-HDV HDV RNA HBsAg HBV – HDV Superinfection Typical Serologic Course Time after Exposure Titre
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  • 71. Symptoms ALT IgG anti-HEV IgM anti-HEV Virus in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Hepatitis E Virus Infection Typical Serologic Course Titer Weeks after Exposure
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  • 74. HEPATITIS G VÍRUS FLAVIRUS: similar morphology and genome ◊ in risk groups: acute, chronic and fulminant hepatitis ◊ transmission: blood (mother- newborn babies) ◊ prevalence is higher in HCV infected people

Editor's Notes

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