HEPATITIS VIRUS

Ridha Wahyutomo, dr
Dept. Clinical Microbiology
 What Is Hepatitis?

• The word "hepatitis" means inflammation of the

liver. Toxins, certain drugs, some diseases, heavy
alcohol use, bacterial and viral infections can all
cause hepatitis. Hepatitis is also the name of a
family of viral infections that affect the liver; the
most common types in the United States are
hepatitis A, hepatitis B, and hepatitis C.
 Hepatitis
• Hepatitis (plural hepatitides) implies
injury to the liver characterized by the
presence of inflammatory cells in the
tissue of the organ. The name is from
ancient Greek hepar or hepato, meaning
liver, and suffix -itis, meaning
"inflammation"
 Viral Hepatitis
• A group of viruses known as the hepatitis
viruses cause most cases of liver damage
worldwide. Hepatitis can also be due to toxins
(notably alcohol), other infections.
• Common viruses cause hepatitis include
A,B,C,D,E. G ……….
• Acute hepatitis
• Viral Hepatitis: Hepatitis A through E (more than
95% of viral cause), Herpes simplex,
Cytomegalovirus, Epstein-Barr, yellow fever
virus, adenoviruses.
 Viral Hepatitis - Historical Perspectives

“Infectious” A Enterically
E
transmitted

Viral hepatitis NANB

Parenteraly
“Serum” B D C transmitted

F, G, TTV
? other
 Type of Hepatitis
A B C D E

Source of feces blood/ blood/ blood/ feces

virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
Hepatitis A Virus
 Hepatitis A
• Hepatitis A is an acute liver disease
caused by the hepatitis A virus (HAV),
lasting from a few weeks to several
months. It does not lead to chronic
infection.
 Hepatitis A Virus
• Naked RNA virus
• Related to enteroviruses, formerly known as
enterovirus 72, now put in its own family:
heptovirus
• Picornavirus
• One stable serotype only
• Difficult to grow in cell culture: primary
marmoset cell culture and also in vivo in
chimpanzees and marmosets
 Nature of HAV virus
• HAV is a 27 – 30 nm
spherical particle with
cubic symmetry
• Contain linear single
stranded RNA
genome with size of
7.5 kb.
• Only one serotype
Pathogenesis and immune
reaction to HAV

HAV is ingested and probably enters the bloodstream through the

oropharynx or the epithelial lining of the intestines to reach its target, the
parenchymal cells of the liver.
Replicates in hepatocytes and Kupffer's cells, then released into the bile

and from there into the stool. Virus is shed in large quantity into the stool
10 days before symptoms of jaundice appear or antibody can be detected.
 Hepatitis A Virus….
• Survives well in the general environment
• Somewhat resistant to heat and freezing
• Remain active on the hands for several
hours or in food kept at room
temperature.
Hepatitis A can be transmitted:
• Through fecal-oral route
– by infected food handlers
– in locations/sites with poor sanitation and hygiene
(e.g., in developing countries)
– by poor hygiene standards
– after natural disasters, such as floods, when
drinking water can become contaminated with
sewage
• during sex, particularly oral/anal sex
 Infective dose ….
• Infective dose not known

• But since hepatitis A is transmitted so

easily through person to person contact, it
is thought to be a small amount
 Anti-HAV-IgM Anti-HAV-IgG

Acute infection + -

Old infection - +
(immune to HAV)

Incubation or no - -
infection
 Clinical features
• Malaise
• Anorexia
• Nausea, omitting liver tenderness
• Onset of Jaundice
• Recovery in 4-6 weeks
• Mortality 0.1 – 1 %
 Hepatitis A Prevention
To avoid transmission of hepatitis A, always
wash hands thoroughly:

• after going to the toilet

• before preparing food
• after handling nappies and condoms
 Hepatitis A Prevention
• Avoid sharing food, cutlery, crockery,
cigarettes and drinks with other people.

• In a natural disaster, listen to warnings

about contaminated drinking water and
follow any instructions issued by the
relevant authorities.
 Hepatitis B

• Hepatitis B is a liver disease caused by the

hepatitis B virus (HBV). It ranges in
severity from a mild illness, lasting a few
weeks (acute), to a serious long-term
(chronic) illness that can lead to liver
disease or liver cancer.
Hepatitis B Virus
 Hepatitis B Virus - Virology
• ds DNA
• Complete Dane particle 42 nm ( the virus)
• 28 nm electron dense core ( include the HBcAg
and HBeAg
• coat and the 22 nm free particles contain HBsAg
• At least 4 phenotypes of HBsAg are recognized;
adw, adr, ayw and ayr.
• The HBcAg is of a single serotype
Enveloped, circular dsDNA genome. Member of the hepadnaviruses.

The virions are unusually stable for an enveloped virus. They resist treatment with ether,
low pH, freezing, and moderate heating. These characteristics assist transmission from
one person to another.

Virus carries a reverse transcriptase (RT).

Encodes several proteins (HBsAg, HBe, HBc).

 Hepatitis B Virus
Modes of Transmission

 Sexual - sex workers and homosexuals are

particular at risk.
 Parenteral - IVDA, Health Workers are at
increased risk.
 Perinatal - Mothers who are HBeAg positive
are much more likely to transmit to their
offspring than those who are not. Perinatal
transmission is the main means of
transmission in high prevalence populations.
 Transmission…
– sharing toothbrushes or razors
– unsterilised tattooing and body piercing
equipment
– needle –stick injury

Unprotected Sex
• Hepatitis B is found in body fluids
including blood, saliva, semen, mucus,
vaginal fluid and breast milk.
 Concentration of Hepatitis B
Virus in Various Body Fluids

Low/Not
High Moderate Detectable

blood semen urine

serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
 Replication
• The RNA dependent DNA synthesis takes
place within the newly assembled Virion
core in the cytoplasam.
• Hepadnaviruses the only virus that
produce genome DNA by reverse
transcription with mRNA as the
template
What are the clinical symptoms
of Hepatitis B??
 HBsAg AHBsAg HBeAg AHBe AHBc

Acute HBV + - + - IgM

Chronic + - + - IgG
HBV high
infectivity
Chronic + - - + IgG
HBV low
infectivity
Recovery - + - + IgG

Immunized - + - - -
 Treatment
• Interferon - for HBeAg +ve carriers with chronic active hepatitis.
Response rate is 30 to 40%.
– alpha-interferon 2b (original)
– alpha-interferon 2a (newer, claims to be more efficacious and
efficient)
• Lamivudine - a nucleoside analogue reverse transcriptase
inhibitor. Well tolerated, most patients will respond favorably.
However, tendency to relapse on cessation of treatment. Another
problem is the rapid emergence of drug resistance.
 Treatment…..
• Adefovir – less likely to develop resistance than
Lamivudine and may be used to treat Lamivudine
resistance HBV. However more expensive and toxic
• Entecavir – most powerful antiviral known, similar to
Adefovir
• Successful response to treatment will result in the
disappearance of HBsAg, HBV-DNA, and
seroconversion to HBeAg.
 Prevention of Hepatitis B.. Ways to
reduce transmission

• wash hands after touching blood or body fluids

• wear disposable gloves if giving someone first
aid or cleaning up blood or body fluids
• avoid sharing toothbrushes, razors, needles,
syringes, personal hygiene items and grooming
aids or any object that may come into contact
with blood or body fluids
• use new and sterile injecting equipment for each
injection
 Prevention of Hepatitis B.. Ways to
reduce transmission…
• cover all cuts and open sores with a bandage
• wipe up any blood spills and then clean the area
with household bleach
• throw away personal items such as tissues,
menstrual pads, tampons and bandages in a
sealed plastic bag
• practice safe sex
 What is Hepatitis C Virus
• Hepatitis C virus also known as Non A or
Non B virus found while doing experiments
on Chimpanzees.
• HCV infections are seen only in humans
• The epidemiology is like HBV infection.
 HCV Virology
• The virus is not been
grown in culture
• The virus is 50- 60 nm
with linear single
stranded RNA genome
surrounded by an
enveloped carrying
glycoprotein spikes
• Now classified as
Hepacivirus in the
family of Flaviviridae
• Six genotypes are
identified, with high
mutability
 Clinical features
• Overt Jaundice is seen in 5% of patients
• About 50 – 80% patients progress to
chronic hepatitis
• May progress to Cirrhosis, or
Hepatocellular carcinoma
 Risk Factors Associated with
Transmission of HCV

 Transfusion or transplant from infected donor

 Injecting drug use
 Hemodialysis (yrs on treatment)
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-
positive contact
 Multiple sex partners
 Birth to HCV-infected mother
 Prevention of Hepatitis C

 Screening of blood, organ, tissue

donors

 High-risk behavior modification

 Blood and body fluid precautions

• Hepatitis D, also called delta virus, is a
virus that is only found in people who
are already infected with hepatitis B.
 Hepatitis D (Delta) Virus
 antigen HBsAg

RNA
 Hepatitis D Virus

• The delta agent is a defective virus which

shows similarities with the viroids in plants.
• It is a particle 35 nm in diameter
– with delta antigen surrounded by an outer coat of
HBsAg.
• The genome of the virus is very small and consists
of a single-stranded RNA
• Same way as hepatitis B
– through blood and infected blood products
– through sexual intercourse
– small risk of perinatal (maternal to infant)
transmission, but this is rare.
• inject drugs
Those most at risk include people with
• practice unsafehepatitis
sex B who:
 have unsafe tattooing or body piercing
 Hepatitis D Virus ,
Summary Modes of
Transmission

 Percutanous exposures
 injecting drug use
 Permucosal exposures
 sex contact
The symptoms for hepatitis D are similar to
hepatitis B, such as:
– fatigue
– abdominal pain
– loss of appetite
– nausea and vomiting
– fever
– joint aches
– Jaundice
 Hepatitis D - Clinical Features

• A person can be co-infected with hepatitis

D and hepatitis B at the same time.
– severe acute disease.
– low risk of chronic infection
 Hepatitis D - Clinical Features

– A person who is infected with hepatitis D

after becoming infected with hepatitis B is
said to have a super-infection.

 usually develop chronic HDV infection.

 high risk of severe chronic liver disease.
 may present as an acute hepatitis.
• There is no specific treatment for hepatitis
D.

• There is some indication that antiviral

medication, such as interferon or
lamivudine, used to treat hepatitis B, will
also treat hepatitis D.
 Hepatitis D -
Prevention
 HBV-HDV Coinfection
Pre or postexposure prophylaxis to
prevent HBV infection.
 HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection.
• Hepatitis E is a contagious viral infection
which causes acute hepatitis but does not
lead to chronic hepatitis.

• Hepatitis E is found mostly in developing

countries, especially in India, Asia, Africa
and Central America.
 Hepatitis E Virus
• Calicivirus-like viruses
• unenveloped RNA virus, 32-34nm in
diameter
• +ve stranded RNA genome, 7.6 kb in size.
• very labile and sensitive
• Can be grown in cellculture
Hepatitis E Virus
• By ingestion of contaminated water

• Easily transmitted by person to person

contact where household and personal
hygiene is poor
 Transmission..

• Hepatitis E is most often spread through

fecal-oral route

• NO evidence of transmission through

needles, blood, body fluids or through
sexual contact
• Symptoms of hepatitis E are very similar to
those of hepatitis A:
• fever
• weakness
• fatigue
• loss of appetite
• nausea
• vomiting
• The majority of people with hepatitis E recover
with no lasting immunity
• 1-2% chance of developing sudden and
severe liver disease
• Hep E in pregnant women :with greater risk
of acute illness and liver failure, and
occasionally death.
– occurs mainly in developing countries
where hepatitis E is endemic, and where
there is limited ante-natal care and
maternal health is poor.
• There is no medical treatment for hepatitis
E.
• The aim of treatment : to alleviate
symptoms through:
– bed rest
– fluid replacement
 Prevention and Control Measures
for Travelers to HEV-Endemic
Regions
 Avoid drinking water (and beverages with ice)
of unknown purity, uncooked shellfish, and
uncooked fruit/vegetables not peeled or
prepared by traveler.
 IG prepared from donors in Western countries
does not prevent infection.
 Unknown efficacy of IG prepared from donors
in endemic areas.
 Vaccine?
• The hepatitis G virus is an RNA virus
(ribonucleic acid) similar to, but
distinct from, the hepatitis C virus.
•Hepatitis G virus: newly identified virus.
• Found among people who had blood transfusion --
developed post transfusion hepatitis which could not
be
identified as any known virus.
•Infection with the hepatitis G virus can lead to
persistent
infection in 15 - 30% of adults.
• Long term outcomes of the infection are not yet
known.
• People with hepatitis A, B, or C can be co- or super-
infected with hepatitis G.
•There is no vaccination available for hepatitis G.
The transmission route known is through infected
blood products. This means that those at risk of
infection may include people who:
– inject drugs
– receive blood transfusions, haemodialysis,
tissue and organ transplants
– have being unsafely tattooed and/or body
pierced.
• Can cause persistent viremia lasting for
several years.

• Means ‘presence of virus in the blood’ and

may not mean the person is sick.

• Like any viral infection, a person with

hepatitis G may experience some flu-like
symptoms.
• To date: no links established between infection
with hepatitis G virus and chronic liver disease.

• People with hepatitis G who also have hepatitis

A, B or C do not appear to have worse health
outcomes because of the co-infection.
• There is no treatment currently available
for hepatitis G.
Hepatitis TT
 History and characteristics

• In 1997, a novel DNA virus was isolated from the

serum of a patient with post-transfusion hepatitis
of unknown etiology in Japan

• It was named TT virus (TTV) after the initials of

the index patient.

• TTV is a nonenveloped, single-stranded and

circular DNA virus, and its entire sequence of
~3.9 kb has been determined.
 Transmission
• Recent reports indicate that TTV can be
transmitted via blood/blood products

• In another study, a high rate of cervical

carriage (66%) of TTV DNA was found by
PCR, which suggests that perinatal and
sexual transmission is possible.
 Hepatitis F
• Hepatitis F is a hypothetical virus linked to
hepatitis.

• Several hepatitis F candidates emerged in

the 1990s; none of these reports have
been substantiated
 Karakteristik Virus Penyebab Hepatitis

Sifat VHA VHB VHC VHD VHE VHG VTT

Masa 15-45 40-80 5-12 mg 4-20 15-40 ? ?
tunas hari hari hari/ hari
3-6 mg
Penularan Fekal- Parenter Parenter Parenter Fekal- Parenter Parenter
oral al al al oral al al,fekal-
oral
Kronitas Tidak Ya Ya Ya Tidak Ya Ya
Carrier Tidak Ya Ya Ya Tidak Ya Ya

Penyebab Picorna Virus Flavi- Defectiv Calici Flavi DNA

Virus Hepadna virus e virus virus Virus
(RNA) (DNA) virus diliputi (RNA) (RNA)
(RNA) HBsAg
(RNA)

Soewignjo Soemohardjo, 1999

End of lecture, thank you!