Clinical Manifestations of

HBV Infection
n Only 30-50% of adult infections are
symptomatic
n Need diagnostic tests to distinguish
n Incubation period - 45 to 180 days
(average = 60-90 days)

1
<2% = low

2% – 7% = intermediate

≥8% = high 2
Indonesia High Prevalence of Hepatitis
B&C
Reported : around 30 million people suffer from the
diseases.
50 % (15.000.000) chronic liver disease

10 % menjadi liver fibrosis, liver cancer

1.500.000 people have a risk for liver cancer

13 out of 33 provinces in Indonesia are of high prevalence of

hepatitis; Central Sulawesi and East Nusa Tenggara being
on top of the list.
3
 Disease Progression
Chronic HCC
hepatitis
10-20%

Cirrhosis

Liver
15-40%
Failure
Death or
20% OLTx

Age 40 50 60 Years

EASL Consensus Guidelines. J Hepatol 2003

4
Lok et al, Hepatology42004
Natural history of HBV
 Perjalanan Penyakit
• Respon imun minimal
Fase • Virus aktif bereplikasi
Imunotolerans • 2-4 minggu pada anak
• > 10 tahun pada dewasa

• Reskonstruksi imun
Fase • Proses inflamasi
Imunoreaktif • Destruksi hepatosit

• Sistim imun tubuh berhasil melawan VHB

Fase karier • Replikasi minimal
inaktif • Serokonversi HBeAg

• Gambaran inflamasi aktif

Fase • Derajat kerusakan hati
reaktivasi fluktuatif
 Diagnosis Hepatitis B
Hepatitis B kronik asimptomatik, maka diperlukan
pemeriksaan laboratorium:
• Status infeksi VHB :
• Antigen dan antibodi
• Viral load

• Derajat kerusakan hepatosit

• Serum ALT
• Pemeriksaan histologis
Diagnosis
A battery of serological tests are used for the diagnosis of acute and chronic
hepatitis B infection.
nHBsAg - used as a general marker of infection.

nHBsAb - used to document recovery and/or immunity to HBV infection.

nanti-HBc IgM - marker of acute infection.

nanti-HBcIgG - past or chronic infection.

nHBeAg - indicates active replication of virus and therefore infectiveness.

nAnti-Hbe - virus no longer replicating. However, the patient can still be positive
for HBsAg which is made by integrated HBV.
nHBV-DNA - indicates active replication of virus, more accurate than HBeAg
especially in cases of escape mutants. Used mainly for monitoring response to
therapy.
 Hepatitis B Lab Markers
Marker
Hepatitis B surface antigen
M class immunoglobulin
antibody to hepatitis B core
antigen
Antibody to hepatitis B core
antigen
Antibody to Hepatitis B surface
antibody
Hepatitis B e antigen
Antibody to Hepatitis B e antigen
Abbreviation Use
HBsAg Detection of acutely or chronically
infected persons; antigen used in
hepatitis B vaccine
IgM Anti-HBc Identification of acute or recent HBV
Anti-HBc, IgM infections (including those in HBsAg-
negative persons during the “window”
HBcAb, IgM
phase of infection)
Anti-HBc Identification of persons with acute,
HBcAb resolved, or chronic HBV infection
(not present after vaccination)
Anti-HBs Identification of persons who have
HBsAb resolved infection with HBV;
determination of immunity after
immunization
HBeAg Identification of infected persons at
increased risk for transmitting HBV
Anti-HBe Identification of infected person with
HBeAb lower risk for transmitting HBV
 Serologic Diagnosis of Hepatitis A and C
Interpretation IgM Anti HBsAg Anti HBeAg Anti IgM HBV
Anti HCV HBs HBe Anti DNA
HAV HBc

Recent HAV + - - - - - - -
infection
HCV - + - - - - - -
infection
 Interpretation : Hepatitis B Viral Markers
Phase HBsAg Anti-HBs HBeAg Anti-HBe Anti-HBc Anti-HBc HBV DNA
IgM IgG
Acute infection

Early acute HBV + - + - + + or - High

Convalescent Window - - - + + + or - Low

Acute HBV
Immune due to - + or - - + - + Absent
resolution of infection
Immune due to - + - - - - Negative
vaccination
Chronic Infection

HBeAg positive CHB + - + - - + High

HBeAg negative CHB + - - + - + Moderate

Inactive carrier + - - + - + Low

Absent
Patterns of Viral and Biochemical Markers in
Patients with Resolved versus Chronic Hepatitis
B
A Acute self-limiting HBV infection

HBV DNA
Antigen or Antibody Level

HBeAg
Anti-HBs
HBsAg
Anti-HBc
Anti-HBe
ALT

0 5 10 15 20 48 2 4 6 8 >10

Weeks since exposure Years since exposure

B Chronic HBV infection

Antigen or Antibody Level

HBV DNA
HBeAg
Anti-HBs
HBsAg
Anti-HBc
Anti-HBe

0 5 10 15 20 48 2 4 6 8 >10 ALT

Weeks since exposure Years since exposure

Based on Ganem & Prince. N Engl J Med 2004

 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Titer

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

13 13
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Titer

HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

14 14
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

HBeAg

Titer

HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

15 15
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

HBeAg anti-HBe

Titer

HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

16 16
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe

Titer

HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

17 17
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe

Titer
IgM anti-HBc
HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

18 18
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA

HBsAg

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

19 19
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA

HBsAg anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

20 20
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe
Total anti-HBc
Titer
IgM anti-HBc
HBV DNA

HBsAg anti-HBs

Window
Period

0 4 8 12 16 20 24 28 32 36 52 100
Weeks after Exposure

21 21
 Fase Infeksi Hepatitis Kronis
Immune Immune Low Replicative Reactivation
Tolerance Clearance Phase Phase
HBeAg+ HBeAg-/anti-HBe+ (precore/core promoter variants)
< >< >
> 2000 IU/mL
HBV DNA < 2000 IU/mL
2 x 108 -
2 x 1011 IU/mL 200,000 - 2 x 109 IU/mL

ALT

Normal/mild Moderate/severe CH Normal/mild CH Moderate/severe CH

CH
Cirrhosis Inactive cirrhosis Cirrhosis

HBeAg+ Inactive-carrier state HBeAg-

chronic hepatitis chronic hepatitis

Slide courtesy of A. S. F. Lok, MD.

 CHB Is A Dynamic Disease!

HBeAg
Treatment
Anti-HBe
Treatment
HBV DNA

ALT

Immune Immune Inactive HBeAg-

tolerant active carrier state negativeCHB

Normal or minimal Chronic Normal or Progressive Cirrhosis

hepatitis hepatitis inactive hepatitis fibrosis HCC
CHB is a dynamic disease and patients can transition backwards and forwards between stages

23
23
Adapted from Yim & Lok, Hepatology 2006; 43: S173
 Interpretation of Serological Tests
Test Results Interpretation
HBsAg Negative Susceptible
anti-HBc Negative (Never infected or vaccinated)
anti-HBs Negative
HBsAg Negative Immune
anti-HBc Negative (Due to vaccine)
anti-HBs Positive
HBsAg Negative Immune
anti-HBc Positive (Resolved Infection)
anti-HBs Positive
HBsAg Positive Acutely Infected
anti-HBc Positive
IgM anti-HBc Positive
anti-HBs Negative
HBsAg Positive Chronically Infected
anti-HBc Positive
anti-HBs Negative
IgM anti-HBc Negative
HBsAg Negative Four Possible Interpretations
anti-HBc Positive
anti-HBs Negative

24 24
Four Possible Interpretations
n May be recovering from acute HBV infection
n May be distantly immune and test not sensitive
enough to detect very low level of anti-HBs in serum
n May be susceptible with a false positive anti-HBc
n May be undetectable level of HBsAg present in the
serum and the person is actually a carrier

25 25
26