HEPATITIS:

ETIOLOGI dan PATHOGENESIS

NENNY SRI MULYANI
JOGYAKARTA

OUTLINE

Hepatitis and etiology

Focus: Hepatitis B,Why?
HBV structure
HBV replication
HBV clearance
Outcome of infection
Immune= tolerant phase
Phases in natural history
Conclusion

HEPATITIS AND ETIOLOGY

General Concepts
Hepatitis = 'inflammation of the liver'.
Etiology:
1. Viral: hepatotropic, non- hepatotropic
2. Toxin
3. Autoimmune
4. Drugs
5. Systemic

Viral Hepatitis - Historical Perspectives

Infectious
Viral
hepatitis
Serum

Enterically
E
transmitted

A
NANB

B D

Parenterally
C transmitted
F, G, TTV
? other

caSe
14y/o male, presented with
General malaise, poor appetite and abd.
discomfort
Icteric sclera, tea-color urine, ascites,

Past history
Operation, transfusion or systemic disease
Symptom of hepatitis infection

Family history:
Mother (48y/o): HBsAg+,brother: HBsAg+

FOCUS:
HEPATITIS B VIRUS

EPIDEMIOLOGY
VERTICAL TRANSMISSION
HBV : OUTCOME OF INFECTION

caSe
14y/o male, presented with
General malaise, poor appetite and abd.
discomfort
Icteric sclera, tea-color urine, ascites,

Past history
Operation, transfusion or systemic disease
Symptom of hepatitis infection

Family history:
Mother (48y/o): HBsAg+,brother: HBsAg+

HBV STRUCTURE

HBV Structure & Antigens

Dane
particle

HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr,

ayw and ayr)

HBcAg = inner core protein (a single serotype)

HBV : Structure

HBV Structure & Antigens

Dane
particle

HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr,

ayw and ayr)

HBcAg = inner core protein (a single serotype)

Open Reading Frames

There are 4 open reading frames derived from the same strand (the
incomplete + strand)
S - the 3 polypeptides of the surface antigen (preS1, preS2 and
S - produced from alternative translation start sites.
C - the core protein
P - the polymerase
X - a transactivator of viral transcription (and cellular genes?).
HBx is conserved in all mammalian (but not avian)
hepadnaviruses. Though not essential in transfected cells, it is
required for infection in vivo.

HBV REPLICATION

HBsAg

HBV CLEARANCE

Mechanisms of HBV
clearance
Destruction of virus- infected cells: 1.
immune- mediated cell injury, 2. direct
cytotoxicity
Cytotoxic T- lymphocytes: directly inhibit
HBV replication and inactivate HBV without
killing the infected heaptocyte
Expression of a product of HBV genome to
cause cell death
Genetic differences in the host immune
response also may be a factor

OUTCOME OF INFECTION

Outcome of hepatitis B virus

infection

The natural history of HBV infection and

the rate of progression to chirrosis and
HCC is variable
The outcome is dependent on:
Immune factors
The age at infection (the major
determinant of chronicity)
Viral factors: HBV genotype
Host factors/ genetic factors

Outcome of hepatitis B virus

infection
Approximately 10% to 15% of chronic
carriers may spontaneously become
HBsAg- neg, the remainder are at
risk for transmission of HBV. There is
at present no effective way to
neutralize the virus in vivo
(management: close follow- up and
efforts to decrease the risk of
infectivity to other persons)

80

60

40

Chronic Infection

100
80

60

40

Chronic Infection (%)

20

20

Symptomatic Infection (%)

Chronic Infection
(%)

100

Outcome of Hepatitis B Virus

Infection
by Age at Infection

Symptomatic Infection
0
Birth

1-6 months

7-12 months

Age at Infection

1-4 years

0
Older Children
and Adults

Outcome of hepatitis B virus infection

Outcome of symptomatic acute hepatitis B

Spectrum of Chronic Hepatitis B Diseases

1. Chronic Persistent Hepatitis - asymptomatic
2. Chronic Active Hepatitis - symptomatic
exacerbations of hepatitis
3. Cirrhosis of Liver
4. Hepatocellular Carcinoma

IMMUNE- TOLERANT PHASE

 MENGAPA 90% terjadi kronis?

Karena ada fase imuntolerant: Hbe
dan HBc

 Immuntolerance????

PHASES

CONCLUSION

THANK YOU