1. HEPATITIS VIRUSES By Dr.D.W.Deshkar 30-07-2009

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

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)

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

16. Hepatitis B Virus

17. Hepatitis B Virus

19. HBV : Structure

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

23. GENOME

27. Replication of HBV

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

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

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

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

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

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

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

55. OUTCOMES of HCV hepatitis

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

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

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.

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

68. Hepatitis E Virus

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

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

75. THANK YOU