- HBV is a major global health problem, infecting over 2 billion people worldwide and causing over 500,000 deaths annually. - Egypt has intermediate prevalence of HBV infection, with carrier rates of 8% reported among children. - Chronic HBV infection can lead to serious complications like cirrhosis and liver cancer if left untreated. - Current antiviral treatments aim to suppress viral replication and reduce liver damage, but drug resistance remains a challenge.

1. ‫الرحيم‬‫الرحمن‬‫هللا‬‫بسم‬
‫ا‬
‫قليل‬‫إال‬ ‫العلم‬ ‫من‬‫أوتيتم‬ ‫وما‬
‫العظيم‬ ‫هللا‬ ‫صدق‬

2. Update on Prevalence,
Diagnosis and Treatment
of Hepatitis B virus
Dr.Hesham Noaman Abdel Raheem Mustafa
M.B.B.CH

3. • 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).

4. • 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).

5. 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).

6. Fig. (2): Geographic pattern of Hepatitis B prevalence (CDC,
2003).

7. Fig.(3):Geographic pattern of Hepatitis B prevalence (WHO,
2004).

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

9. Fig. (5): Geographic distribution of HBV Genotype (Hayashi and
Furusyo, 2004).

10.  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).

11. All -ve
13
16 %
24 %
1 %
%
21 %
25%
HBV
HAV
HEV
Mixed
HCV
Median
Age 26
Median
Age 12
Median
Age 44
Median
Age 46
Median
Age 34
Analysis of 1860
Acute hepatitis
cases

12. Age distribution of patients with
acute hepatitis B
0
10
20
30
40
50
60
70
< 14 ys 14-30 ys 31-50 ys > 50 ys
Sedes
1
Graph (1): Age distribution of patients with acute hepatitis
B (Esmat, 2005).

13.  Blood and blood products.
 Sexual contact.
 Parentral drug abuse.
 Peri-natal transmission.
 Transmission in high endemic areas.
 Exposure of unknown origin.

14. 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.

15.  Occult HBV infection is characterized
by the presence of HBV infection with
undetectable hepatitis B surface
antigen (HBsAg).

16. 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.

17.  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.

18. 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.

19. 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.

20. Table (1) : FDA-Approved Therapies for HBV Infection
Drug 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
*Dose for HBeAg +ve (duration 16 weeks)
Dose for HBeAg -ve (duration 12 months)

21. 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 µg/kg/week
subcutaneously for
1 year.

22. 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
Route Subcutaneous Oral Oral
Side Effects
Many e.g.: depression,
hair loss, diarrhea and
fatigue
Negligible
Potential
nephrotoxicity
Drug Resistance - 0%, year 1 None, year 1
70%, year 5 3%, year 2
Cost High Low Intermediate
Table (3): Comparison of Three Approved Treatments of
Chronic Hepatitis B (Shen et al., 2004).

23. Incidence of Lamivudine Resistance
During Monotherapy
20%
49%
67%
38%
0%
20%
40%
60%
80%
1 2 3 4
Chang, 2000
Percent
Lamivudine
Resistant
Resistance = HBeAg loss
Years of Lamivudine

24.  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 afford-
able are still lacking

25.  The hepatitis B virus is a DNA virus and
has the propensity to integrate (i.e.,
insert) parts of itself to the human host’s
DNA.
 The virus can hide inside the nucleus of
the host’s liver cells in the form of ccc
DNA (covalently closed circular DNA).

26.  This can be achieved by the
combination of Lamivudine therapy
pre- and post- transplantation with
HBIG post transplantation.

27. Recommendations

28.  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.

29.  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.

30.  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.

31. Thank you