Hepatitis B Virus Infection in

children
Nenny Sri Mulyani

HBV

Hepatitis B virus: partially double

standard DNA virus, enveloped,
hepadnavirus
Several Ag can be found in the blood
at various times during viral infection
HBsAg is an envelope protein
Other antigens: HBcAg, HBeAg, viral
DNA, DNA polymerase, protein kinase

HBV, cont...

Dane particle

Clinical outcome of acute HBV

infection

Resolution
Fulminant hepatitis
HBsAg pos for more than 6 months:
resolution, asymptomatic carrier
state, chronic persistent hepatitis
(extrahepatic disease), chronic active
hepatitis (cirrhosis, HCC, extrahepatic
disease)

Clinical Manifestations

Acute phase: subclinical/ anicteric,

icteric, fulminant
Chronic phase: ansymptomatic carrier
state, chronic hepatitis, cirrhosis,
hepatocelluler ca.
Extrahepatic manifestations: can
occur with both acute and chronic
infection

Acute Hepatitis

Subclinical/ anicteric hepatitis: 70%

Icteric hepatitis: 30%
More severe in patients coinfected
with other hepatitis viruses or within
underlying liver diseases
Fulminant hepatic failure: 0,1- 0,5%

Diagnosis
Initial diagnosis:
Cholestasis
Altered liver enzyme profiles in the blood:
AST, ALT
ALP elevated
Bilirubin elevated
HBsAg and HBeAg pos
HBsAg only: predicts minimal liver damage

Diagnosis, cont...

HBsAg and HBeAg predicts more liver

damage, cirrhosis
IgM anti HBc and HBsAg is usually the
best indication of an acute infection
Convalescence sign: An increase in
Anti- HBs and Anti- HBeAg

Mode of transmission

Vertical: Perinatal transmission

Horizontal

Phases of chronic HBV infection

Generally consists of 2 phases
- Early replicative phase with active
liver disease
- Late or nonreplicative phase with
remission liver disease
- Patients with perinatally acquired HBV
Immun tolerance phase

Replicative phase: Immune

tolerance

High level of HBV replication

No evidence of active liver disease:
lack of symptoms, normal serum ALT,
minimal changes on liver biopsy
Lasts 10- 30 years

Replicative phase: immune

clearance

Spontaneous HBeAg clearance

increases
Not always accompanied by
biochemical exacerbation
Some are acc. By symptoms of acute
hepatitis
May be associated with an elevation
in the IgM anti HBc titer

Replicative, cont...

More commonly observed in men

than women related cirrhosis and
HCC
Hepatic decomp and hepatic failure
( small percentage)
Abortive immune clearance

Low or nonreplication phase

HBeAg neg and anti- HBeAg pos

Some of patients, virus replication
has ceased HBsAg remain pos
Undetectable HBV DNA in serum
(PCR)
Liver disease is remission: normal
ALT
Resolution of necroinflamation (liver
biopsy)

Low, cont....

Clearance of HBsAg does not preclude

the development of cirrhosis or HCC
probably results from its integration
into the genome ( HBV DNA ) pos by
PCR or from coinfection with VHC
or VHD, or undocumented cirrhosis
prior to seroconversion

Low, cont...

Many patients have undetectable HBV

DNA by hybridization assays but
remain pos by PCR
A small proportion of patients maybe
infected with a mixture of the wildtype and HBV variants with a deletion
in the pre- S1 region reduction in
HBsAg synthesis

Low, cont...

Reactivation may occur when the patients

are immunosuppressed vary in severity:
mild and asymptomatic to severe with
possible fulminant hepatic failure
A small precentage of patients: moderate
levels of HBV replication (by hybridization)
and active liver disease may have
residual wild or HBV variants that cannot
produce HBeAg due to precore or promoter
variants

Sequele and Prognosis of chronic

HBV infection

Inactive carrier state

Cirrhosis
Hepatic decompensation
HCC
Extrahepatic manifestations
Death

Prognosis, cont...
The prognosis is not so good:
- Patients from endemic areas
- Patients with chronic hepatitis
The estimated 5 year- rates of
progression are:
- Chronic hepatitis cirrhosis: 12- 20%
- Comp cirrhosis hep. Decomp: 2023%

Prognosis, cont...

Compensated cirrhosis to HCC: 615%

Factors influencing the survival

Patients with prolonged replication

phase worse prognosis
The five- years survival rate was
significantly lower in patients who
were HBeag p[os than HBeAg neg
The risk of HCC is much higher in
patients who are HBeAg pos than
HBsAg pos but HBeAg neg

Factor, cont....

HCC was signif higher in HBsAg and

HBeAg pos compared to those who
are HBsAg pos but HBeAg neg
The effect of HBeAg status remained
an independent factor after adjusting
for important covariates including
HCV status, alcohol intake, and
cigarette smoking

Prevention

Active immunization: HBV vaccine

Passive immunization

Conclusions Hepatitis B Virus:

Magnitude of the problem

Vaccination: problem at birth?
Screening for pregnant women?
Immunoglobuline expensive and
sometimes not available