Version 2 displaying better characters of this module on definitions, transmission and immunological aspects of hepatitis B

2. Outcomes
HBV
str
Serology
Acute
vs
Patterns
Interpretn
Phases
General Points on
Hepatitis B Virus
Infection

3. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Serology
Acute
vs
Patterns
Interpretn
Phases
Learning Outcomes
At the end of this module, participants are
expected to:
• Be able to define the common terminologies
used regarding hepatitis B virus and outcome of
infection
• Differentiate acute from chronic infection
• Explain the clinical significance of the
serological markers of hepatitis B virus

4. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Image from Microbiology Info.com
• HBsAg, HBV surface antigen is on surface of virus.
• There is nucleocapsid core within the viral particle.
• HBcAg, HBV core antigen is on surface of nucleocapsid
• HBV DNA is in the inside of nucleocapsid
• HBeAg, HBV envelope antigen, is located between HBV
surface and core
• DNA Polymerase – enzyme that helps in the replication
of the HBV
Structure of Hepatitis B virus
Serology
Acute
vs
Patterns
Interpretn
Phases

5. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Serology
HBV DNA (Viral load) | Quantitative or qualitative
Antigens Antibodies
HBsAg Hepatitis B surface Antigen Anti-HBs
HBcAg Hepatitis B core Antigen
(absent in blood)
IgM anti-HBc
IgG anti-HBc
HBeAg Hepatitis B e Antigen Anti-HBe
Types of Serological Markers for HBV
Acute
vs
Patterns
Interpretn
Phases

6. Outcomes
HBV
str
Serology
Acute
vs
Patterns
Interpretn
Phases
*Breakwell et al, 2017
Marker Clinical significance
HBsAg Appears in blood in acute stage of infection and
persists in chronic infection
– Its an alternative to HBV DNA to monitor response
to treatment
IgM Anti-HBc IgM subclass of anti-HBc – this is a serological marker
of acute
infection.
Disappears in chronic infection (in the presence of
HBsAg)
HBeAg Indicates high viral load as well as high infectivity
(HBV patients in Africa have low prevalence of this
antigen*)
Anti-HBe Indicates decreasing viral load.
But may be absent in some mutant forms of HBV
infection
Anti-HBs Indicates recovery from hepatitis B infection
(in the presence of Anti-HBc IgG) or immunity from
vaccination
Clinical Significance of Serological Markers
for HBV

7. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Serology
Acute
vs
Acute
6 months
Chronic
Acute versus chronic HBV
• The terms, acute and chronic as it refers to HBV
infection refers to a timeline rather than severity
• Acute means infection lasting less than 6 months
• Chronic means infection lasting beyond 6 months
Patterns
Interpretn
Phases

8. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Serology
Acute
vs
Patterns
Pattern of serological markers
in acute HBV infection
Patterns
Pattern of serological markers
in acute HBV infection
Interpretn
Phases
• The 1st serological marker to appear in blood is
HBsAg, followed by HBeAg and then anti-HB core
• Anti-HB core is like a scar that does not disappear,
even when one achieves HBsAg clearance

9. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Serology
Acute
vs
Patterns
Pattern of serological markers in
chronic HBV infection
Interpretn
Phases

10. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Serology
Acute
vs
Patterns
Interpretn
Phases Interpretation of serological markers in
HBV infection
HBsAg Anti-HBc IgG Anti-HBc IgM Anti-HBs Interpretation
- - - - Never exposed
(susceptible)
- + - + Past infection, cleared;
natural
immunity acquired
- + - - Past infection, cleared;
natural
immunity has waned over
time
- - - + Immunity due to
vaccination
- - + + Recent infection,
recovered;
immunity achieved
+ - + - Acute ongoing infection
+ + - - Chronic ongoing infection

11. Introduction and
generalities on viral
hepatitis
Outcomes
HBV
str
Serology
Acute
vs
Patterns
Interpretn
Phases
Phases of HBV infection by immune
response

12. Phases of HBV infection by
immune response
• These phases provide a summary of the
natural course of HBV infection
• The phases are not necessarily
sequential
• Strictly, there are 4 phases
• Next, we shall describe the events of
the phases in terms of clinical and
laboratory parameters
1
e tolerance
otolerant
stently normal
ve | HBeAb –ve
ry high
mal or mild
2
ance
se
ermittently
ve
an in immune
lammatory
3
rrier state
mal
+ve
(but upto
d
4
ns
5
e

13. Phases of HBV infection by immune
response
• These phases provide a summary of the
natural course of HBV infection
• The phases are not necessarily
sequential
• Strictly, there are 4 phases
• Next, we shall describe the events of the
phases in terms of clinical and
laboratory parameters
1
Phase 1: Immune tolerance
• Alternative term is immunotolerant
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is very high
• Liver histology – either normal or mild
inflammatory changes
2
ance
se
ermittently
ve
an in immune
lammatory
3
rrier state
mal
+ve
(but upto
d
4
ns
5
e

14. Phases of HBV infection by immune
response
• These phases provide a summary of the
natural course of HBV infection
• The phases are not necessarily
sequential
• Strictly, there are 4 phases
• Next, we shall describe the events of the
phases in terms of clinical and
laboratory parameters
1
Phase 1: Immune tolerance
• Alternative term is immunotolerant
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is very high
• Liver histology – either normal or mild
inflammatory changes
2
Phase 2: Immune clearance
• Alternative term is immune reactive phase
• Liver enzyme, ALT is persistently or
intermittently abnormal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is high, but less than in
immune tolerant phase
• Liver histology – moderate or severe
inflammatory changes
3
rrier state
mal
+ve
(but upto
d
4
ns
5
e

15. Phases of HBV infection by immune
response
• These phases provide a summary of the
natural course of HBV infection
• The phases are not necessarily
sequential
• Strictly, there are 4 phases
• Next, we shall describe the events of the
phases in terms of clinical and
laboratory parameters
1
Phase 1: Immune tolerance
• Alternative term is immunotolerant
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is very high
• Liver histology – either normal or mild
inflammatory changes
2
Phase 2: Immune clearance
• Alternative term is immune reactive phase
• Liver enzyme, ALT is persistently or intermittently
abnormal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is high, but less than in immune
tolerant phase
• Liver histology – moderate or severe inflammatory
changes
3
Phase 3: Immune control
• Alternative term is inactive HBsAg carrier state
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg -ve | HBeAb +ve
• HBV DNA (viral load) is <2,000 IU/mL (but
upto 20,000 IU/mL)
• Liver histology – either normal or mild
inflammatory changes
4
ns
5
e

16. Phases of HBV infection by immune
response
• These phases provide a summary of the
natural course of HBV infection
• The phases are not necessarily
sequential
• Strictly, there are 4 phases
• Next, we shall describe the events of the
phases in terms of clinical and
laboratory parameters
1
Phase 1: Immune tolerance
• Alternative term is immunotolerant
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is very high
• Liver histology – either normal or mild
inflammatory changes
2
Phase 2: Immune clearance
• Alternative term is immune reactive phase
• Liver enzyme, ALT is persistently or intermittently
abnormal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is high, but less than in immune
tolerant phase
• Liver histology – moderate or severe inflammatory
changes
3
Phase 3: Immune control
• Alternative term is inactive HBsAg carrier state
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg -ve | HBeAb +ve
• HBV DNA (viral load) is <2000IU/mL (but upto
20000IU/mL)
• Liver histology – either normal or mild
inflammatory changes
4
Phase 4: Immune escape
• Alternative term is HBeAg negative chronic
hepatitis B or reactivation (relapse)
• Liver enzyme, ALT is persistently or
intermittently abnormal
• Serology shows HBeAg -ve | HBeAb +ve
• HBV DNA (viral load) is >2,000 IU/mL
(fluctuates)
• Liver histology – Moderate to severe
inflammation and fibrosis +/- cirrhosis
• Predominance of HBV with precure mutations
5
e

17. Phases of HBV infection by immune
response
• These phases provide a summary of the
natural course of HBV infection
• The phases are not necessarily
sequential
• Strictly, there are 4 phases
• Next, we shall describe the events of the
phases in terms of clinical and
laboratory parameters
1
Phase 1: Immune tolerance
• Alternative term is immunotolerant
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is very high
• Liver histology – either normal or mild
inflammatory changes
2
Phase 2: Immune clearance
• Alternative term is immune reactive phase
• Liver enzyme, ALT is persistently or intermittently
abnormal
• Serology shows HBeAg +ve | HBeAb –ve
• HBV DNA (viral load) is high, but less than in immune
tolerant phase
• Liver histology – moderate or severe inflammatory
changes
3
Phase 3: Immune control
• Alternative term is inactive HBsAg carrier state
• Liver enzyme, ALT is persistently normal
• Serology shows HBeAg -ve | HBeAb +ve
• HBV DNA (viral load) is <2000IU/mL (but upto
20000IU/mL)
• Liver histology – either normal or mild
inflammatory changes
4
Phase 4: Immune escape
• Alternative term is HBeAg negative chronic
hepatitis B or reactivation (relapse)
• Liver enzyme, ALT is persistently or
intermittently abnormal
• Serology shows HBeAg -ve | HBeAb +ve
• HBV DNA (viral load) is
>2000IU/mL(fluctuates)
• Liver histology – Moderate to severe
inflammation and fibrosis +/- cirrhosis
• Predominance of HBV with precure mutations
5
Additional Phase: HBsAg
negative phase
• Alternative name is resolved hepatitis B
• Loss of HBsAg
• HBV DNA may remain detectable in the liver,
but not in the serum
• Some patients with HBsAg loss may still have
detectable HBV DNA in the serum (occult
HBV)
• The latter are vulnerable to HBV reactivation
following immunosuppression

18. Transmission of Hepatitis B Virus
Horizontal transmission
This by far the commonest mode of transmission in Africa
Occurs in family members and between child to child
Unsafe Blood transfusion
This was particularly the case before screening for
Infections prior to transfusion was commenced
Vertical transmission
From mother to child at:
Time of delivery (labour or shortly after- perinatal)
Or
Rarely in 2nd or third trimester of pregnancy

19. Transmission of Hepatitis B Virus
Blood and blood products contact
This includes needle stick injuries and contacts with blood
spills
Unhealthy medical practice
Razors, inadequate sterilization, dental and
surgical procedures
Intravenous drug use
This is not very commonly reported in Africans,
but may be contributing to adult acute infection cases

20. Transmission of Hepatitis B Virus
Non medical risks
Manicures, tattoos, sharing toothbrushes, traditional surgical
-scarification practice
-hair and barbing salons
Unprotected sexual contact
Most infections in Africans occur in childhood
For most adults with infections, only a small
proportion may have acquired HBV via hetero or
homo sexual routes

21. Groups at high risk
of Hepatitis B
Virus infection
Listen to this video first!
YouTube Video on Routes of transmission of HBV
Opens a new window!

22. Birth before 1985
(people who have ever received
unsafe blood or blood product)
Children born to HBV positive
mothers
These are less likely to clear the virus and thus become
chronic carriers – hence birth dose HBV vaccine is
paramount for prevention

23. Pregnant women Health care workers exposed
to biological fluids
Especially if they are engaged in exposure-prone
procedures
Risk to baby if mum has high HBV DNA, or is HBeAg +ve

24. Individuals infected with HIV
or HCV
Inmates of correctional
facilities – (prisoners)
Due to weakened immune systems
These tend to have risky behaviours and or live in
suboptimal conditions

25. Persons who have ever
injected drugs
Persons requiring
immunosuppressive therapy
These persons tend to share
needles in an unsafe way and thus
promote transmission of HBV
Immune systems are weakened and
chance of reversion of occult HBV is
high

26. Sex workers
Men having sex with men
History of multiple sexual
partners or STIs
Patients undergoing renal
dialysis
These individuals are dependent on
blood and blood products and
hence prone to infection

27. Cirrhosis
• Defined as an advanced stage of
liver disease characterized by
o extensive liver fibrosis
o nodularity of the liver
o alteration of liver architecture
o disrupted blood flow to the liver

28. Decompensated
cirrhosis
o Clinical complications of
cirrhosis including:
o Jaundice
• Ascites
• spontaneous bacterial peritonitis
• oesophageal varices
• hepatic encephalopathy
• sepsis and renal failure

29. More definitions
• Persistently abnormal LFTs
• Three ALT determinations above the upper limit of normal, made
at unspecified intervals during 6 to 12-month period or
predetermined intervals during a 12-month period
• HBeAg seroconversion: Loss of HBeAg and seroconversion to anti-HBe
• HBsAg seroconversion: Loss of HBsAg and development of anti-HBs
• HBeAg reversion: Reappearance of HBeAg in a person who was
previously HBeAg negative
• Presence of anti-HBc indicates:
• If HBsAg –ve: prior exposure to HBV
• If HBsAg +ve: current HBV infection

30. What you have learned in this module
• Commonly used terminologies about hepatitis B, including serology and phases of
infection
• Structure of hepatitis B virus and explanations about the various proteins
• Although described in phases, the course of hepatitis B infection is non-linear
• Patients fluctuate between immune tolerant phases through to immune clearance and
reversal
• Modes of transmission of HBV and groups at high risk were also defined
• Transmission of HBV in African is often horizontal, meaning that most infections occur
before the age of 5.
• Unsafe blood transfusion and use of unsterile equipment are also important
• HBV infection can lead to cirrhosis and its decompensation

31. General Points on Hepatitis B Virus
Infection
This ends the trial modules – Consider purchasing the
Liver Course for a complete set of modules
You have done well to have completed this
module: