BY

A,SHAWKY
PROF.OF HEPATOGASROENTEROLOGY
AIN SHAMS SCHOOL OF MEDICINE
 Hepatitis B virus is a member of the Hepadnavirus
family.

The virus particle, called Dane particle (virion),

consists of an outer lipid envelope and
an icosahedral nucleocapsid core composed
of protein.

IT HAS TEN GENOTYPES (A-J). THE GENOTYPE IN

EGYPT IS D

IT CONSISTS OF THR FOLLOWING PROTEINS:

HBcAg (HBeAg is a splice variant)

Hepatitis B virus DNA polymerase

HBx. The function of this protein is not yet well

known,[26] but evidence suggests it plays a part in the
activation of the viral transcription process.
Cure of CHBV INFECTION COULD BE:
1- complete sterilisingcure with undetectable HBsAg in serum and
eradication of HBV DNA including intrahepatic cccDNA and integrated
HBV DNA.

2-functional cure with sustained, undetectable HBsAg and HBV DNA in

serum with or without seroconversion to hepatitis B surface
antibody(anti-HBs) after completion of a finite course of treatment,
resolution of residual liver injury, and a decrease in risk of
hepatocellular carcinoma (HCC) over time (several levels of functional
cure including complete shutdown of cccDNA transcription, elimination
of cccDNA, complete resolution of liver damage, and elimination of risk
of HCC

3-partial cure with detectable HBsAg but persistently undetectable HBV

DNA in serum after completion of a finite course of treatment.
1-Attachment of the virus to the heparan
sulfate proteoglycan which allow binding
to NTCP. Binding inhibitors may be
neutralizing Ab, -Ve chared competitors,or
binder to NTCP eg bile acids and
ezetimib.All are non specific and need
high concentration.
1-Irreversible NTCP inhibitors: myrcludex B
(myristoylated pre-S1 peptide Myrcludex B
is a synthetic N-acylated pre-
S1),cyclosporin A, and derivatives are
allosteric inhibitorsof NTCP. They irreversibly
block receptor function at nonsaturating
concentrations and have long half-time at
the receptor, but they can block transport of
bile salts and other NTCP substrates at
higher concentrations.
 MYRCLUDEX B
 Myrcludex B is a novel drug candidate
for treatment of chronic hepatitis B and
chronic hepatitis delta, as well as
potentially a range of inflammatory and
metabolic diseases. Myrcludex B was
originally developed by Professor
Stephan Urban (University of Heidelberg,
Germany).
 Myrcludex B mechanism of antiviral action is the
highly specific, highly stable binding and
inactivation of the hepatocyte surface
protein NTCP. It is the single representative of a
novel class of anti-HBV molecules, entry
inhibitors. By blocking NTCP, Myrcludex B
misdirects HBV and co-infecting HDV to an
unproductive pathway and thereby prevents an
infection of the cell. This mechanism of action
offers the possibility to address the two most
important medical needs, namely long-term HBV
eradication as well as antiviral activity against
hepatitis delta virus (HDV).
1-Damage :CRISPR-associated (cas) nucleases,
specifically targeting cccDNA are being explored
in experimental animal.
2-Functional silencing : Targeting HBX protein.
3-Viral trnascript by siRNA Preliminary results of a
phase II trial showed that a single dose of ARC-520
in combination with entecavir resulted in a
profound and durable decrease in serum HBV DNA
in both HBeAgpositive and HBeAg-negative
patients and a decrease in HBsAg level in HBeAg-
positive, but not in HBeAg-negative, patients.
Nucleocapsid assembly and pgRNA packaging:
The HBV precore/core protein has recently
emerged as a promising direct antiviral
target. With the knowledge of the three-
dimensional structure of the core protein.
-Several classes of non-nucleoside small
molecules called core protein assembly
modulatorshave been developed, including ph
enylpropenamide and
heteroaryldihydropyrimidine derivatives.
1-immune modulatory therapies

2-Stimulator of IFN gene agonists

3-Checkpoint modulation

4-Theraputic vaccins.