Hepatitis B &C research

By Eman Said Issa

To Dr May Ramadan
Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus
.(HBV)

It is a major global health problem. It can cause chronic infection and puts people at high risk
. of death from cirrhosis and liver cancer

Transmission

hepatitis B is most commonly spread from mother to child at birth (perinatal transmission),
or through horizontal transmission (exposure to infected blood), especially from an infected
child to an uninfected child during the first 5 years of life. The development of chronic
.infection is very common in infants infected from their mothers or before the age of 5 years

Hepatitis B is also spread by needle stick injury, tattooing, piercing and exposure to infected
blood and body fluids, such as saliva and, menstrual, vaginal, and seminal fluids. Sexual
transmission of hepatitis B may occur, particularly in unvaccinated men who have sex with
.men and heterosexual persons with multiple sex partners or contact with sex workers

Infection in adulthood leads to chronic hepatitis in less than 5% of cases, whereas infection
in infancy and early childhood leads to chronic hepatitis in about 95% of cases. Transmission
of the virus may also occur through the reuse of needles and syringes either in health-care
settings or among persons who inject drugs. In addition, infection can occur during medical,
surgical and dental procedures, through tattooing, or through the use of razors and similar
.objects that are contaminated with infected blood

The hepatitis B virus can survive outside the body for at least 7 days. During this time, the
virus can still cause infection if it enters the body of a person who is not protected by the
vaccine. The incubation period of the

hepatitis B virus is 75 days on average, but can vary from 30 to 180 days. The virus may be
detected within 30 to 60 days after infection and can persist and develop into chronic
.hepatitis B
Life cycle

The life cycle of Hepatitis B virus is complex. Hepatitis B is one of a few known non-retroviral
.viruses which use reverse transcription as a part of its replication process

Attachment

The virus gains entry into the cell by binding to receptors on the surface of the cell and
entering it by endocytosis mediated by either clathrin or caveolin-1. HBV initially binds to
heparin sulfate proteoglycan. The pre-S1 segment of the HBV L protein then binds tightly to
the cell surface receptor sodium taurocolate cotransporting polypeptide (NTCP), encoded by
the SLC10A1gene. NTCP is mostly found in the sinusoidal membrane of liver cells. The
.presence of NTCP in liver cells correlates with the tissue specificity of HBV infection

Penetration

Following endocytosis, the virus membrane fuses with the host cell's membrane, releasing
.the nucleocapsid into the cytoplasm

Uncoating

Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to
be transferred to the cell nucleus. It is thought the capsid is transported on the microtubules
to the nuclear pore. The core proteins dissociate from the partially double stranded viral
DNA, which is then made fully double stranded (by host DNA polymerases) and transformed
into covalently closed circular DNA (cccDNA) that serves as a template for transcription of
.four viral mRNAs

Replication

The largest mRNA, (which is longer than the viral genome), is used to make the new copies
of the genome and to make the capsid core protein and the viral RNA-dependent-DNA-
.polymerase

Assembly

These four viral transcripts undergo additional processing and go on to form progeny virions
which are released from the cell or returned to the nucleus and re-cycled to produce even
.more copies

Release

The long mRNA is then transported back to the cytoplasm where the virion P protein
.synthesizes DNA via its reverse transcriptase activity

Treatment

Acute hepatitis B treatment

over-the-counter painkillers, such as paracetamol or ibuprofen, for tummy pain oral antiviral
agents

metoclopramide, to stop feeling sick, and chlorphenamine to reduce itching

Chronic hepatitis B treatment

Oral antiviral drugs

Tenofovir disoproxil

Entecavir

Hepatitis C

Life cycle

Stage 1

HCV makes itself at home in a liver cell. The virus is covered with a coating that contains
specific proteins. These proteins locate and attach to an element on the surface of your liver
.cell called a receptor. The receptor receives signals for your liver cell

Stage 2

The virus enters your liver cell’s outer barrier. The barrier then surrounds the virus, swallows
.it up, and brings it into the cell

Stage 3
The virus coating breaks down. Viral RNA carrying genetic information is released into your
liver cell. This may happen when the virus penetrates the outer barrier. It could also be due
.to liver enzymes dissolving the cell

Stage 4

The viral RNA prepares to reproduce. It mimics your liver cell’s RNA and begins producing its
RNA materials. It may also prevent your liver cell from functioning properly. Sometimes, the
.viral RNA causes your liver cell to reproduce, too

Stage 5

Things amp up as the viral RNA constructs a template for replicating itself. The replication
process of the virus isn’t completely understood. The viral RNA is cloned over and over to
.create new viruses

Stage 6

The virus’s coating is made of different protein-based coverings. These are developed by
.ribosomes, or cell protein builders, during this stage and released

Stage 7

Protein units called capsomeres come together and form new particles around the viral RNA.
These make a covering shaped like a sphere, known as a capsid. The capsid protects the
.virus’s genetic material

Stage 8

In the final stage, the new virus creates a bud with itself inside. A protective coating
surrounds the bud. It’s released through the barrier of your liver cell, ready to infect another
.of your liver cells. This process continues until the infected liver cell dies

Treatment

Hepatitis C treated by direct acting antiviral

Simeprevir second generation HCV protease inhibitor

Sofosbuvir oral nucleoside analogue and potent inhibitor of the hepatitis C virus (HCV) RNA
.polymerase that is used in combination with other antiviral agents to treat chronic hepatitis
Ledipasvir is a potent inhibitor of HCV NS5A, a viral phosphoprotein that plays an important
.role in viral replication, assembly, and secretion

Ombitasvir is classified as a direct acting antiviral and acts against HCV to inhibit viral
replication

Velpatasvir is an NS5A inhibitor (by Gilead) which is used together with sofosbuvir in the
.treatment of hepatitis C infection of all six major genotypes

Glecaprevir is an inhibitor of the HCV NS3/4A protease, which is a viral enzyme necessary for
the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS3,
NS4A, NS4B, NS5A, and NS5B proteins , which is essential for viral replication