Update on Prevalence,

Diagnosis and Treatment

of Hepatitis B virus
Dr.Hesham Noaman Abdel Raheem Mustafa
M.B.B.CH

 HBV was discovered in 1966 (Wang et

al., 2002a).
HBV the causative agent of B-type
hepatitis in humans is a Hepatotropic
DNA-containing virus that replicates
via reverse transcription (Shen et al.,
2004).
It is the only known DNA virus that
has hepatocytes specificity (Lu et al.,
2004a).

 2 billion people infected worldwide,

and 350 million suffering from chronic
HBV infection (Alter, 2003).
Being the 10th leading cause of death
worldwide, HBV infection results in 0.5
to 1.2 million deaths per year caused
by chronic hepatitis, cirrhosis, and
hepatocellular carcinoma; the last
accounts for 320 000 deaths per year
(Lavanchy, 2004).

Fig. (1): Electron microscopic presentation of HBV

particles. The round 42 nm particles represent infectious
virions (Dane particle). The small empty spheres and the
filaments are non-infectious. The preparation was
enriched in virus particles (Guptan et al., 2002).

Fig. (2): Geographic pattern of Hepatitis B prevalence (CDC,

2003).

Fig.(3):Geographic pattern of Hepatitis B prevalence (WHO,

2004).

Fig. (4): Global status of countries using HepB vaccine in their national
infant immunization system (WHO, 2003).

Fig. (5): Geographic distribution of HBV Genotype (Hayashi and

Furusyo, 2004).

Egypt was reported by Andre (2000) to be an

area of high prevalence for HBV; however,
Poynard (2002) reported it to be an
intermediate area. It was reported that the
carrier rate of HBV is 8% among primary
school children (Esmat, 2005).
The seroprevalence of HBV was ranging
from 24% in the general population to 66%
in persons 40-67 years of age (Abdelaziz et
al., 2000).

HCV 21 %
Median
Age 26

Median
Age 46

All -ve

16 %
HBV

Median
Age 12

Median
Age 34

25%
HAV

Median
Age 44

13 %
1%
Mixed

HEV 24 %

Analysis of 1860
Acute hepatitis
cases

Age distribution of patients with

acute hepatitis B
70
60
50
40
Sedes
1

30
20
10
0
< 14 ys

14-30 ys

31-50 ys

> 50 ys

Graph (1): Age distribution of patients with acute hepatitis

B (Esmat, 2005).

Blood and blood products.

Sexual contact.

Parentral drug abuse.

Peri-natal transmission.

Transmission in high endemic areas.

Exposure of unknown origin.

HBV can present as

Acute infection.

Fulminant hepatic failure (FHF).

Chronic hepatitis.

Extra-hepatic manifestations.

Post hepatitis B cirrhosis.

Combined HBV with HDV or HCV.

Occult HBV infection is characterized

by the presence of HBV infection with
undetectable hepatitis B surface
antigen (HBsAg).

Laboratory Markers of HBV infection:

HBsAg: Present in acute or chronic infection.
HBsAb: Marker of immunity acquired
through natural HBV infection, vaccination or
passive antibody (immune globulin).
HBcAb :
IgM indicate infection in the previous six
months.
IgG indicate more distant HBV infection
that may have been cleared by the immune
system or that may persist.

HBeAg correlates with a high level of viral

replication.
HBeAb: correlates with low rates of viral
replication.
HBV DNA: correlates with active replication;
useful in monitoring response to treatment of
HBV infection, especially in HBeAg ve
mutants.

Diagnostic Criteria for HBV infection :

Chronic disease:
- HBsAg +ve for longer than 6 months.
- Serum HBV DNA > 100.000 copies per ml.
- Persistent or intermittent elevation of transaminases level.
- Liver biopsy showing chronic hepatitis.
Inactive HBsAg carrier:
- HBsAg +ve for longer than 6 months.
- HBeAg ve, HBeAb +ve.
- Serum HBV DNA < 100.000 copies per ml.
- Persisently normal transaminases level.
- Liver biopsy to confirm absence of significant hepatitis.
Resolved disease:
- History of acute or chronic hepatitis B.
- Presence of HBcAb HBsAb.
- HBsAg ve.
- Normal transaminases level.

Goals of Antiviral Treatment of

Chronic Hepatitis B
1. Sustained suppression of HBV replication:

- Decrease in serum HBV DNA to <105 copies/ml.

- HBeAg to HBeAb seroconversion.
- HBsAg to HBsAb seroconversion.

2. Remission of liver disease:

- Normalization of serum ALT levels.
- Decreased necroinflammation in liver.
3. Improvement in clinical outcome:
- Decreased risks of developing cirrhosis, liver
failure and HCC.
- Increased survival.

Table (1) : FDA-Approved Therapies for HBV Infection

Approval

Dose in HBV-Infected
Patients

Interferon-alpha-2b

1991

*5 million units daily

for 16 weeks

Peginterferon-alpha 2a

2005

180 ug once weekly for

48 weeks subcutaneous

Lamivudine

1998

150 mg PO daily at least 1

or 2 years.

Adefovir

2002

10 mg PO daily for 1 year.

Entecavir

2005

0.5-1.0 mg PO once daily

Drug

*Dose for HBeAg +ve (duration 16 weeks)

Dose for HBeAg -ve (duration 12 months)

Table (2): Non Yet FDA-Approved

Therapies for HBV

Drug

Status

Dose

Tenofovir

300 mg PO daily

Emtricitabine

200 mg PO daily

Peginterferon alpha 2b

1.0 g/kg/week
subcutaneously for
1 year.

Table (3): Comparison of Three Approved Treatments of

Chronic Hepatitis B (Shen et al., 2004).
Indications

Interferon

Lamivudine

Adefovir

HBeAg+ve, normal
ALT

Not indicated

Not
indicated

Not indicated

HBeAg+ve chronic
Hepatitis

Indicated

Indicated

Indicated

HBeAg-ve chronic
Hepatitis

Indicated

Indicated

Indicated

HBeAg+ve chronic
hepatitis

Duration: 4-6 months

1 year

1 year

HBeAg-ve chronic
hepatitis

Duration : 1 year

>1 year

>1 year

Subcutaneous

Oral

Oral

Many e.g.: depression,

hair loss, diarrhea and
fatigue

Negligible

Potential
nephrotoxicity

0%, year 1

None, year 1

70%, year 5

3%, year 2

Low

Intermediate

Route
Side Effects
Drug Resistance

Cost

High

Incidence of Lamivudine Resistance

During Monotherapy
80%

Resistance = HBeAg loss

Percent
60%
Lamivudine
Resistant 40%

49%

67%

38%
20%

20%
0%
1

Years of Lamivudine
Chang, 2000

 Currently available monotherapies have

limited long-term efficacy

Treatments need to affect a broader range

of patients (e.g., normal/near normal ALT)
Treatments that are both safe (e.g., no
withdrawal flares) and more easily affordable are still lacking

The hepatitis B virus is a DNA virus and

has the propensity to integrate (i.e.,
insert) parts of itself to the human hosts
DNA.

The virus can hide inside the nucleus of

the hosts liver cells in the form of ccc
DNA (covalently closed circular DNA).

This

can

be

combination of

achieved

by

the

Lamivudine therapy

pre- and post- transplantation with

HBIG post transplantation.

Recommendations

Hepatitis B vaccination is the best

protection as it provides protection against
hepatitis B for 15 years and possibly much
longer. It is recommended that all infants,
health care workers and persons at risk of
exposure e.g. sexual partners of chronically
infected persons; should be vaccinated.
Hepatitis B Immune globulin is
recommended for accidentally exposed
persons, ideally within 24 hours of
exposure and no later than 7 days. A
repeated dose is necessary 28 - 30 days
later.

 Newborns of HBV infected mother

should receive HBIG plus the hepatitis
B vaccine within l2 hours of birth and
two additional doses of vaccine at one
and six to twelve months of age.
Strict governmental instructions for
hygiene and sterilization should be
followed particularly in risky procedures
e.g. surgical intervention, dental
procedures, endoscopies and blood or
body fluids sampling.

 Strict observation of blood donors, the presence of

normal ALT, AST are not sufficient. Evaluation for
occult HBV infection by determination of HBV
DNA in serum or tissues should be considered in the
context of the prevalence of HBV infection in this
geographical area and the type of population.
In order to prevent HBV reinfection after liver
transplantation, it is recommended to combine
Lamivudine therapy pre- and post-transplantation
with HBIG post-transplantation. This regimen has
become the standard of care for most liver transplant
programs.

Thank you