التهاب الكبد

1. Hepatitis B
Virus (HBV)
Saleh Bahaj
Prof. of Medical
Microbiology/Immunology
Lecture 11

3. Hepatitis B virus

4. Egypt Objectives
V) Test yourself
III) Lab. diagnosis
IV) Treatment & Prevention
II) Pathogenesis
I) Definition
&Structure
By the end of this lecture, all students
should be able to Understanding:-

5. I) Def. of HBV
HBV

6. I) Def. of HBV
Cirrhosis & HCC
It is Hepdnaviridae
dsDNA, enveloped,
Icosahedral
Attacks the liver
(Acute &Chronic)

7. II) Structure
of HBV
HBV

8. II) Structure of HBV
Partial
dsDNA
DNA
polymerase
HBeAg
HBcAg
HBsAg
RT
Dane particle
Core

9. II) Structure of HBV
HBsAg
(Non-infectious)
Tubular
Spherical

10. II) Structure of HBV
HBsAg
(Non-infectious) Dane particle
(Infectious)
HBsAg

11. III)
Pathogenesi
s
HBV
(Mode of
transmission)

12. III) Mode of
transmission
1) Parenteral
2) Sexually
3)Perinatal

13. III) Mode of
transmission
1) Parenteral transmission
 Introduced
through break
in the skin
(Blood borne infection)

14.  Blood
transfusion
1) Parenteral transmission
 1010 copies/mL

15.  Needle-stick
injury
1) Parenteral transmission
 1010 copies/mL

16.  Ear
piercing
1) Parenteral transmission

17.  Dental
clinics
1) Parenteral transmission

18.  Tattoo
1) Parenteral transmission

19.  Razors
1) Parenteral transmission

20. 1) Parenteral transmission

21. 2) Sexually
III) Mode of
transmission

22. III) Mode of
transmission
3) Perinatal transmission
(Pre/natal)

23. 3) Perinatal
3) Perinatal transmission

24. III) Pathogenesis
 NO CPE
How liver cell is
destroyed?
Hepatocyte
 hepatotropic

25. III) Pathogenesis
HBV in blood
Ag display on the cell
surface with MHCI

26. III) Pathogenesis
Cytotoxic T
cells

27. III)
Pathogenesi
s
HBV
Clinical
manifestation

28. III) Pathogenesis
 Acute HB
 90% cure
(Immunity)
 10% Chronic
Chronic Active
Chronic carrier

29. III) Pathogenesis
Cirrhosis
&HCC
HHC may start
without cirrhosis
Chronic

30. III) Pathogenesis
Newborn
 Infants
90%
chronic
No manifestations !!

31. III) Pathogenesis
Give reason
Extrahepatic manifestation in
Hepatitis B infection

32. III) Pathogenesis
Extra hepatic
manifestation
Y
Formation of I.C

33. III) Pathogenesis
Glomerulo-
nephritis
Type III

34. III) Pathogenesis
Arthritis
Y
Type III
Vasculitis
Skin rash

35. IV) Lab.
diagnosis of
HBV
HBV

36. IV) Lab. diagnosis of HBV
I) Liver
Function test
III) Molecular
diagnostic
II) Serological
Assay

37. IV) Lab. diagnosis of HBV
I) Liver
Function test ALT

38. IV) Lab. diagnosis of
HBV
1) HBsAg
3 3
2) HBeAg
3) HBcAg
1) Anti-HBs
2) Anti-HBe
3) Anti-HBc
II) Serological Assay (Markers)

39. IV) Lab. diagnosis of
HBV
Antibodies
for diagnosis
Anti-HAV
Anti-HEV
Anti-HDV
Anti-HCV

40. IV) Lab. diagnosis of
HBV
In HBV
Antigen for
diagnosis
Not Aby ??!!

41. IV) Lab. diagnosis of
HBV
1)HBsAg & 1)Anti-HBs

42. IV) Lab. diagnosis of
HBV
Pre S1
Pre S2
Pre S
Pre-core
& core
Pol
HBX
HBsAg
HBsAg
Dane
particle
Excess

43. HBsAg
Three
morphological
forms
Spherical
Tubular
Dane particle
(Infectious)
Non
infectious
1

44. HBsAg
The first Ag
identified
2

45. HBsAg
Infection
Acute
Chronic
(> 6 months)
3

46. HBsAg
Infection
False negative
 Incubation
period (I.P)
Infection
2-6 months
I.P HBsAg
HBV
DNA
3

47. Anti-HBs
Immunity
Natural
infection
Vaccination
1
Y Y
Y
Y

48. Anti-HBs
Weeks after exposure
Anti-HBs
W
HBV
Titer
HBsAg
Detected after
disappearance of HBsAg
2

49. Anti-HBs

50. 2)HBcAg & 2)Anti-HBc
IV) Lab. diagnosis of
HBV

51. HBcAg

52. HBcAg

53. HBcAg

54. Anti-HBc
No role in
protection
1

55. Anti-HBc
Exposure
2

56. Anti-HBc IgM
Acute infection
HBsAg
Anti-HBc IgM
Weeks after exposure
Titre
year
3

57. Anti-HBc IgM
Window period
HBsAg
Anti-HBc IgM
Weeks after exposure
Titre
4
year

58. Anti-HBc IgG
Anti-HBc IgG
+
HBsAg
Chronic infection
HBsAg
Anti-HBc IgG
Titre
Weeks after exposure
5
year

59. Anti-HBc IgG
year
Anti-HBc IgG
+
Anti-HBs
Immunity
HBsAg
Anti-HBc IgG
Titre
Weeks after exposure
Anti-HBs
6

60. IV) Lab. diagnosis of
HBV
3) HBeAg & 3) Anti-HBe

61. HBeAg
Replication
Excess
1

62. HBeAg
Replication
1
N

63. HBeAg
Replication
HBVDNA
1

64. HBeAg
Replication
(Pre-c mutant)
HBVDNA
(HBeAg –ve)
1

65. HBeAg
Infectivity
 Vertical transmission
(20-90% !!!!)
2

66. Anti-HBe
Good
prognosis

67. Anti-HBe

68. Think & Answer
Does the presence of anti-Hbe
Play a role in prevent infection?

69. Summary
HBsAg Infection
Acute Chronic
HBsAg
Immune
Anti-HBs
IgM IgG IgG
Anti-HBc
HBsAg

70. III) Pathogenesis
Chronic
Carrier Active
-HBeAg +HBeAg
HBsAg +ve

71. IV) Lab. diagnosis of
HBV
Molecular test
DNA by Real
time PCR
Why?

72. Occult HBV infection
 NO HBsAg
BUT
presence of
HBV-DNA

73. V) Prevention
& Treatment
HBV

74. V) Prevention &
Treatment
1) General measures
2) Active
Immunization
3) Passive Immunization

75. 1) General measures
A) Educational
program

76. 1) General measures
B) Proper screening of blood donors

77. 1) General measures
C) Avoid sharing
of needles,
toothbrushes &
Razors

78. 1) General measures
D) Proper
sterilization

79. 1) General measures
D) Avoid injury
with sharp
instrument

80. 2) Active Immunization
 Recombinant
HBV vaccine

81. Adult shots for hepatitis B (20µg)
0 1 6
2) Active Immunization

82. VI) Prevention
1) General measures
2) Active
Immunization
3) Passive Immunization

83. Exposed to HBV
3) Passive Immunization

84. V) Prevention
Exposed to HBV
after 24 hours
HBIG
HB vaccine
After 1 month After 6 months
HB
vaccine

85. Neonates born to HBsAg positive mother
Baby shots for hepatitis B (10µg)
3) Passive Immunization

86. Neonates born to HBsAg positive mother
At birth (after 12
hours
After 1-2
months
After 6 months
HBIG
HB
vaccine
HB vaccine
3) Passive Immunization

87. V) Treatment
HBV

88. V) Treatment
Challenges in treat HBV
 DNA
(inside nucleus)
 Integration with
Host DNA

89. V) Treatment
DNA > 2000 U/mL
 Normal ALT
No
Treatment

90. V) Treatment
DNA <2000 U/mL
 ALT
 RT inhibitor
(Prevent replication)
Interferon +
1998

91. V) Treatment
DNA <2000 U/mL
 ALT
Vemlidy
November 2016
 RT inhibitor
(Prevent replication)

92. V) Treatment
DNA = Undetected
(negative)
Drugs prevent the
replication
Stop drug Replication
Duration of uses

93. Exercise
Case study-
3&4

94. Case study
A nurse stick herself with a needle for a patient with
hepatitis B virus, after 6 months she made some
serological tests to assure her heath. Serologic tests
for HBsAg, Antibodies to HBsAg are all negative.
However, she is positive for Anti-HBc-IgM
Questions
Q1) What is your comment?
Q2) What is the indication for HBsAg?
Q4) What is the indication for Anti-HBsAg and it is
present with HBsAg?
Q5) What is the indication for Anti-HBc-IgM?

95. Case study
Q1) What is your comment?
Expose to infection

96. Case study
Q2) What is the indication for HBsAg?
Infection

97. Case study
Q4) What is the indication for Anti-
HBsAg and it is present with HBsAg?
Immunity
No

98. Case study
Q5) What is the indication for Anti-
HBc-IgM?
Acute
IgM alone road of cure
+ HBsAg

99. Case study
Ahmed Jamal is a GP doctor, his supervisor has asked him
take part in an abdominal operation only as observer, in
order to encourage him, the surgeon asked Ahmed to stitch
skin incision, during suturing he pricked his finger by the
needle, the patient infected with hepatitis B virus. After 6
months Ahmed made serological test to ensure his heath,
the serological tests appeared as follow
*HBsAg= positive *Anti-HBc IgM = positive *HBeAg = positive
The medical council prevent Ahmed from entry any
surgical operation. Ahmed blames himself why he did
not take a vaccine

100. Case study
Q1) What is your comment?
Acute hepatitis B
infection

101. Case study
Q2) Interpret each marker?
HBsAg= positive Infection
Anti-HBc IgM =
positive Acute
HBeAg = positive Replication

102. Case study
Q3) What is your expectation the results
of Anti-HBsAg & Anti-HBe?
Definitely Negative

103. Case study
Q5) Can we prevent this infection after he
pricked his finger?
after 24 hours
HBIG
HB vaccine
After 1 month After 6 months
HB
vaccine

104. Exercise
 Predict

105. Predict
Q1) Predict the results of tests that reflect the
following cases
 Chronic active hepatitis B infection
 Chronic carrier hepatitis B
 Acute hepatitis B infection
 Immune due to natural infection
 Vaccinated person

106. Predict
Q1) Predict the results of tests that reflect the
following cases
 Chronic active hepatitis B infection
HBsAg +ve
Anti-HBc IgG +ve
Anti-HBs -ve
HBeAg +ve

107. Predict
Q1) Predict the results of tests that reflect the
following cases
 Chronic carrier hepatitis B
HBsAg +ve
Anti-HBc IgG +ve
Anti-HBs -ve
HBeAg -ve

108. Predict
Q1) Predict the results of tests that reflect the
following cases
 Immune due to natural infection
HBsAg -ve
Anti-HBc IgG +ve
Anti-HBs +ve
HBeAg -ve

109. Predict
Q1) Predict the results of tests that reflect the
following cases
 Vaccinated person
HBsAg -ve
Anti-HBc IgG -ve
Anti-HBs +ve
HBeAg -ve

110. III) Test yourself

111. III) Test yourself

112. Case 1
Acute hepatitis
Chronic carrier hepatitis
Chronic Active hepatitis
HBsAg +ve Anti-HBc IgM +ve
Anti-HBs -ve
HBeAg +ve

113. Case 2
Acute hepatitis
Chronic carrier hepatitis
Chronic Active hepatitis
HBsAg +ve Anti-HBc IgG +ve
Anti-HBs -ve
HBeAg +ve

114. Case 3
Acute hepatitis
Chronic carrier hepatitis
Chronic Active hepatitis
HBsAg +ve Anti-HBc IgG +ve
Anti-HBs -ve
Anti-HBeAg +ve

115. Case 4
Past Infection
Susceptible
Vaccination
HBsAg -ve
Anti-HBc IgG -ve
Anti-HBs -ve

116. Case 5
Immune due to infection
Susceptible
Immune due to vaccine
HBsAg -ve
Anti-HBc IgG +ve
Anti-HBs +ve

117. Case 6
Immune due to infection
Susceptible
Immune due to vaccine
HBsAg -ve
Anti-HBc IgG -ve
Anti-HBs +ve

118. Case 7
Immune due to infection
Window period
Immune due to vaccination
HBsAg -ve
Anti-HBc IgM +ve
Anti-HBs -ve

119. Case 8
Failure vaccination
Incomplete vaccination
Taken vaccine after infection
HBsAg
+ve
Anti-HBc IgG +ve
Anti-HBs -ve
Vaccinated
person

120. Case 9
HBsAg +ve Anti-HBc IgG +ve
HBV DNA high
HBeAg -ve
LFT Fibrosis
Acute hepatitis
Chronic carrier hepatitis
Chronic Active hepatitis

121. I) Def. of HDV
HDV

122. II) Structure of HDV
RNA
Defective virus
Lacks gene code
for envelope

123. I) Def. HDV
It is a defective
RNA virus
Replicates only in
the presence of HBsAg
(uses as its envelope)

124. III) Co-infection
 IgM HDV
 Anti-HBc-IgM
(for HBV)

125. III) Super-infection
 IgG HDV
Super-infection is more
than co-infection

126. IV) Lab. diagnosis
 Detection
of
Anti-HDV IgM

127. IV) Lab. diagnosis
 Detection
HDV Ag
HDV
Ag

128. IV) Lab. diagnosis
RT-PCR
RNA

129. V) Prevention
 Control HBV, it
will control
the HDV