HEPATITIS VIRUSES

Zeinab Abd Elkhalek

Ass. Prof. of Medical Microbiology & Immunology
Faculty Of Medicine, Cairo University
 Hepatitis Viruses
 There are many different viruses that cause infection of the liver
(liver may be the primary target or secondary target organ).
 Viruses infecting the liver as a primary target include:
 HAV: Picornaviridae (non-enveloped, positive-sense ssRNA)

 HBV: Hepadnaviridae (enveloped, partially dsDNA)

 HCV: Flaviviridae (enveloped, positive-sense ssRNA)

 HDV: Deltaviridae (defective, ssRNA)

 HEV: Calicivirus (non-enveloped, positive-sense ssRNA)

 HGV: Flaviviridae (enveloped, positive-sense ssRNA)

 Viruses infecting the liver as a secondary target include the

yellow fever virus, Epstein-Barr virus (EBV) and cytomegalovirus
(CMV).
HEPATITIS A VIRUS (HAV)
HEPATITIS A VIRUS (HAV)
 HEPATITIS A VIRUS (HAV)
 HAV, originally classified as Enterovirus type 72, is now
considered to be the prototype of Hepatovirus genus in the
Picornaviridae family.
 HAV is a non enveloped virus with a genome composed of
ssRNA, measuring 27 nm in diameter.
 There is only one serotype.
 It is destroyed by boiling for 5 min and by treatment with
chlorine.
 HAV causes hepatitis A (previously called infectious
hepatitis).
 The disease occurs in sporadic or epidemic forms.
Epidemiology
The virus is transmitted mainly by the faeco-oral route affecting children and
young adults. The disease occurs in sporadic or epidemic forms
Clinical Features
Asymptomatic and subclinical infections are common in children. Symptomatic
cases suffer from nausea, vomiting, anorexia, fever, abdominal discomfort
and fatigue. Many cases are “anicteric”, however, when jaundice may
appears. Hepatitis A infection is usually mild and self-limiting.
Laboratory diagnosis
1. Marked elevation of liver transaminases and bilirubin
2. Detection of anti-HAV IgM (by RIA or ELISA) in acute phase.
Prevention and Control
1. Careful disposal of sewage and avoiding contamination of food
2. Pooled human immune serum globulin (ISG) can be protective if
given early after exposure.
3. An inactivated vaccine (Havrix) given intramuscularly (IM) as
one dose followed by a booster dose 6 months later for
individuals above 2 years of age.
HEPATITIS B VIRUS
(HBV)
HEPATITIS B VIRUS (HBV)
 HBV is a DNA virus of Hepadnaviridae family that
causes serum hepatitis.
 The family name comes from the major disease
caused by members of this group (hepatitis) and
the type of nucleic acid found in the virion (DNA).
 These are enveloped viruses with a complex
capsid symmetry. The nucleic acid is circular and
partially double-stranded and encodes four
genes.
HEPATITIS B VIRUS (HBV)
The intact virion, known as the Dane particle, is spherical
with 42 nm diameter, and is composed of:
 An outer shell of lipoprotein containing the
hepatitis B surface antigen (HBsAg): There are two
forms of such particles, 22 nm spherical and 200
nm tubular particles which are non-infectious.
 A core contains the hepatitis B core antigen
(HBcAg), hepatitis B e antigen (HBeAg) and DNA-
dependent DNA polymerase.
 The virus genome is a partially double-stranded
DNA.
Structure of HBV
Electron micrograph of serum
containing HBV
 HBV Transmission
 The highest concentration of the virus occurs
in the blood and serum.

 Lower concentrations are found in semen,

vaginal fluid, and saliva.

 Other body fluids, including tears, sweat,

urine, faeces, breast milk, cerebrospinal fluid,
and synovial fluid may contain HBsAg,
however, these fluids have not been
associated with transmission.
 Modes of HBV Transmission
 Parenteral route: Blood, Blood products, Syringes,
………..
 Sexual contact either heterosexual or homosexual.
 Direct inoculation of HBV by needles especially
among parenteral drug addicts.
 Other percutaneous exposures include tattooing,
ear piercing, and acupuncture, and by needle sticks.
 Perinatally from an infected mother to her infant,
most commonly by contact of maternal blood to the
infant's mucosa at the time of delivery.
 Risk Factors for Hepatitis B
 Sexual partner of a hepatitis patient or
carrier.
 Parenteral drug addicts.
 Infants of infected mothers.
 Household contacts with a hepatitis patient.
 Patients receiving transfusion of blood or
blood products e.g., haemophiliacs.
 Haemodialysis patients and staff.
 Occupational exposure to blood and
infectious body fluids (health care workers).
 Individuals undergoing tattooing.
Pathogenesis and Clinical Presentations
 The incubation period ranges from 6 weeks to 6
months.

 The onset of the disease is gradual.

 The clinical manifestations depend on the age at

infection, level of HBV replication, and host's immune
status:
 Perinatally infected infants generally have no
clinical signs or symptoms, and infection produces
typical illness in only 5-15% of children aged 1-5
years.
 Older children and adults are symptomatic in 33-

50% of infections.

 Constitutional symptoms such as malaise and

anorexia may precede jaundice by 1-2 weeks.
Pathogenesis and Clinical Presentations
 Clinical symptoms and signs include nausea, vomiting,
abdominal pain, and jaundice. Skin rashes, joint pains,
and arthritis may occur. The liver is enlarged and
tender.

 Most patients recover fully and spontaneously within 4-

6 months.

 Fulminant hepatitis occurs in 1-2% of patients with

acute disease. Hepatic failure occurs in approximately
0.1-0.5% of patients.

 Chronic infection can lead to long term complications:

- Chronic active hepatitis and cirrhosis that end in liver
failure and death especially among infents .
- Hepatocellular carcinoma.
 Laboratory diagnosis
A. Hepatitis B virus markers 1
(HBV antigens and antibodies)
1. HBsAg: can be detected in the blood during the
incubation period and active disease. It usually
declines within a period of 12 weeks. Its
persistence for more than 6 months indicates a
chronic carrier state.

2. Anti-HBs: appears late, with the disappearance of

HBsAg, and denotes immunity.

3. HBcAg: is present only in the liver cells, and can

not be detected in blood.
 Laboratory diagnosis
A. Hepatitis B virus markers 2
4. Anti-HBc: It is the antibody to the HBcAg. Its two
immunoglobulin classes IgM and IgG plays a key role in
diagnosis of the different events of HBV infection. IgM anti-
HBc is detectable at the time of clinical onset and declines
within 6 months, thus it is a valuable diagnostic test for
recent HBV infection when other markers are negative.
 There is a period designated the window phase during
which HBsAg has disappeared while anti-HBs is not yet
detectable. During this phase, IgM anti-HBc is always
positive and diagnostic.
 IgG anti-HBc persists indefinitely as a marker of past
infection.
 Laboratory diagnosis
A. Hepatitis B virus markers 3
5. HBeAg: It can be detected in the serum in the
late incubation period and during the acute
illness. Its presence is associated with high
infectivity of the patient. Its disappearance is a
good prognostic sign.

6. Anti-HBe: Its detection is a strong evidence of

recovery. Persistent HBeAg and absence of
HBeAb is an indication for treatment, as such a
patient is developing chronic active hepatitis.
 Laboratory diagnosis

B. DNA polymerase activity: This can be

demonstrated during viraemic stage of HBV
infection.
C. Viral DNA: can be detected by probe or PCR. It is
indicative of viral replication and is important in
diagnosis of chronic infection.
D. Liver function tests, e.g. serum alanine
aminotransferase (ALT) and bilirubin, supplement
the diagnosis. Liver biopsy permits a tissue
diagnosis of hepatitis.
 Treatment

 No specific
treatment is
available for acute
illness.
 Antiviral drugs are
approved for the
treatment of
chronic hepatitis B.
 Prevention and control
1. General measures

 Screening of blood before transfusion.

 Use of disposable syringes, tattoo
needles … etc. Avoid recapping of the
used needles.
 Standard precautions.
 Prevention and control
2. Specific prophylaxis
Hepatitis B vaccines
 Plasma-derived vaccines: containing purified
HBsAg obtained from serum of HBsAg carriers

 Recombinant vaccines:
These vaccines are produced by using HBsAg
synthesized by yeast, into which a plasmid
containing the gene for HBsAg has been
inserted.
 Prevention and control
2. Specific prophylaxis
 The vaccine is given in series of three
intramuscular doses at 0, 1, 6 months.
The series of three doses induces a
protective antibody response.

 The vaccine should be administered

only in the deltoid muscle of adults and
children or in the anterolateral thigh
muscle of neonates and infants.
 Prevention and control
Passive immunization
Hepatitis B immunoglobulin (HBIG)
together with vaccination are given as
post-exposure prophylaxis to:

 Neonates born to HBsAg positive

mothers.
 Those already exposed to HBV.
HEPATITIS C VIRUS (HCV)
 HCV
 HCV is a member of the
Hepacivirus genus in
Flaviviridae family that
causes over 90% of NANB
(non-A, non-B) transfusion-
transmitted hepatitis.
 HCV has a small single
stranded RNA genome
(+ssRNA). There are 6
genotypes.
 Epidemiology
 HCV has a worldwide distribution and is
particularly prevalent in the Middle East.
 Similar to HBV, HCV is transmitted mainly
parenterally through skin and mucous
membranes. Also there is perinatal
transmission.
 Still 40% of cases show no definable source
or route of infection.
 50% of HCV infections are associated with
development of chronic active hepatitis that
ends in cirrhosis or hepatocellular
carcinoma.
 Laboratory Diagnosis
 Detection of anti-HCV antibodies by ELISA, or the
more specific RIBA test (recombinant immunoblotting
assay). Seroconversion may take up to 6 months.
 PCR for detection of viral RNA in blood. This is useful
in:
 Diagnosis of early cases before seroconversion.
 Serologically confirmed cases to demonstrate active viral
replication and, thus, the need for therapy.
 Follow up the response to treatment.
 Genotyping of HCV.
 Control & Treatment

 Control: No specific vaccine is available.

Prevention is mainly directed at minimizing
exposure as that of preventing HBV infection.

 Treatment: A combination of alpha-interferon

and antiviral chemotherapy (ribavirin).
HEPATITIS DELTA VIRUS (HDV)
 HEPATITIS DELTA VIRUS (HDV)
 The hepatitis delta virus is a unique defective
spherical 36 nm virus that can only replicate in
patients with HBV infection.
 Infection is either a coinfection where the patient
acquires both viruses at the same time or a
superinfection, i.e. on top of a chronic HBV infection
where it may lead to an acute exacerbation.
 As HDV is dependent on HBV it follows a similar
epidemiology. It can be controlled through control of
hepatitis B infection.
 Diagnosis: By detection of anti HDV antibodies
 HEPATITIS E VIRUS (HEV)
 It is a distinctive form of NANB hepatitis, characterized
by faeco-oral transmission and a short incubation period
of about 6 weeks.

 Disease is of self limited nature occurring either

sporadic or in the form of epidemics. It affects mainly
young adults.

 There is little risk of development of chronic hepatitis,

but there is a high mortality rate due to disseminated
intravascular coagulation especially in pregnant females.

Diagnosis
 PCR is used to detect viral RNA in stools.
 Detection of anti-hepatitis E virus IgM and IgG by ELISA.