Hepatitis Viruses

Dr. Muna. M. A. Yousif

M.D Clinical Microbiology
Overview
 Viral hepatitis is viral infection of liver cells
that causes hepatic inflammation
 Viruses which exclusively infect the liver are

called hepatitis viruses: HAV, HBV, HCV, HDV,

HEV and HGV.
 Other viruses that do not exclusively infect

the liver but infect other sites too include

EBV, CMV, yellow fever virus, RVF and rubella.
Epidemiologic features of viral hepatitis
Hepatitis virus Incubation Clinical Transmission Risk factors
period presentation route

Hepatitis A 2-6 wks Acute Faeco-oral Overcrowding,

poor hygiene
Hepatitis B 2-6 mths Acute and chronic Parenteral i.v drug abuse,
sexual activity,
perinatal
Hepatitis C 2 wks- Acute (fulminant) Parenteral i.v drug abuse,
5mths or chronic blood
transfusion
Hepatitis D 1-4 mths Acute and chronic Parenteral i.v drug abuse
Hepatitis E 2-8 wks Acute Faeco-oral Untreated water

Hepatitis G Unknown Acute Parenteral Same as HCV

Vaccine and type of genome
Virus Classification Nucleic Envelope Diagnosis Vaccine
acid
HAV Picornavirus RNA No IgM HAV Yes
HBV Hepadnavirus DNA Yes HBsAg, Yes
HBsAb,
IgM
HBcAb
HCV Flavivirus RNA Yes HCV Ab No
HDV Deltavirus RNA Yes Ab to No
delta Ag
HEV Calcivirus RNA No None No
HGV Flavivirus RNA Yes HGV Ab, No
HGV RNA
Hepatitis A virus
Hepatitis A virus
 Hepatitis is an enterovirus that belongs to the
picornaviridae.
 Also known as enterovirus 72.
 It is a non- enveloped, SS RNA with an icosahedral
nucleocapsid symmetry.
 Resistant to inactivation by heat at 60⁰C for 1 hr,
is resistant to anionic detergents and remains
infectious in the environment for weeks.
 Inactivated by: boiling for 1 minute, chlorine
treatment of water, formalin and UV radiation.
 Survives prolonged storage at 4⁰C or below.
Transmission
 HAV is transmitted by the faeco-oral route.
The virus is excreted in the stool of patients
2-3 weeks before and 8-10 days after the
appearance of jaundice. Patients are most
infectious before the onset of jaundice.
 HAV is transmitted by food > water
Pathogenesis of HAV
 The virus replicates in the GIT and from there
spreads through the blood to the liver.
 Damage caused to liver cells is due cytotoxic

T cells and NK attacking virally infected cells.

 The virus itself has NO CPE.
 Our immune system clears the infection and

damage to hepatocytes is cleared and no

residual chronic infection occurs.
Clinical disease
 Subclinical infection: the majority of
infections caused by HAV occur in children
and are subclinical with no jaundice
appearing so infections in children is milder.
 Clinical infection: occurs mostly in adults

after an incubation period of 2-6 weeks. The

patient develops non-specific, flu-like illness
with anorexia, nausea, vomiting and malaise
which is later followed by the appearance of
jaundice.
Seqeuence of seroconversion in HAV
Lab diagnosis of HAV
 Diagnosis maybe made clinically
 Lab diagnosis is by:

1. Liver enzymes : AST and ALT

2. Bilirubin
3. IgM antibody
4. A fourfold rise in IgG
5. Viral isolation (first hepatitis virus which was
cultured)
Treatment and prevention of HAV
 There is no specific treatment for acute
infection. Treatment is mainly supportive
 Prevention:

1. Observation of proper hygiene

2. Passive immunization with immunoglobulins
can be given prior to infection or up to 2
weeks after exposure
3. Active immunization by administration of a
killed viral vaccine (2 doses)
Hepatitis E virus
 HEV is a non-enveloped, icosahedral, SS RNA
virus belongs to calciviridae family.
 Is a hepevirus and is the only virus in the

family.
 HEV is similar in epidemiology to HAV.
 Transmission is faeco-oral and is mostly

transmitted in faecally contaminated water

(water >food)
 Has only been cultured recently.
Clinical disease
 Is also similar to HAV infection with a pre-
icteric non-specific phase that is later
followed by an icteric phase.
 Unlike HAV the virus has a high mortality rate

(>30%) in pregnant women, especially in the

third trimester.
 Recovery from HEV infection is usually

complete, no chronic liver disease occurs.

Diagnosis and treatment
 Diagnosis: Is usually clinical, supported by
changes in liver enzymes and exclusion of
other hepatitis viral infections.

Treatment:
 Is mainly supportive
 No vaccine is available
Hepatitis B virus
HBV
 HBV is a member of the hepadnaviridae family, is an
enveloped virus with an icosahedral nucleocapsid and a
partially DS DNA genome.
 There infectious form(virion) is called the Dane particle.
 The Dane particle is 42nm and contains 3 important
antigens:
1. Hepatitis B surface antigen (HBsAg) is found in the
envelope
2. Hepatitis B core antigen (HBcAg) is found in the
nucleocapsid ‘core’
3. Hepatitis e antigen (HBeAg) is secreted from infected
cells in to the blood
Virus structure
Virus structure cont.’d
 2 other forms that are 22nm in diameter.
exist (sphere and filaments)
 These forms have no DNA and so are not

infectious. They are composed of surface

antigens. In serum they outnumber the actual
virions.
Transmission
 HBV is transmitted parenterally (i.v drug
abuse, by infected blood and blood
products), sexually and perinatally.
 Individuals susceptible to get the infection

are:
1. Healthcare workers
2. Intravenous drug users
3. Haemophiliacs
4. Renal dialysis patients
5. Infants born to HBsAg +ve mothers
Transmission of HBV cont.’d
Clinical presentation
 I.P is 2-6 months
 Many patients develop subclinical infections

which can be detected by elevated liver

enzymes or performing HBsAg.
 Patients who develop symptoms may present

with a picture similar to HAV infection but it

presents in a more severe form.
Outcome
 Most infected individuals (90-95%) will
overcome the infection
 Around 5% of adult patients will develop

chronic hepatitis B infection (HBsAg persists

in blood > 6 months) and many patients
develop complications (liver cirrhosis and
hepatocellular carcinoma)
 95% of infant acquired infections will

progress to chronic infection

Outcome of HBV cont.’d
Lab diagnosis
 Detection of HBsAg using ELISA or rapid tests.
 HBsAg is detected during the incubation period
and prodromal period but during convalescence
is replaced by the appearance of HBsAb.
 Persistence of HBsAg >6 months indicates
chronic infection.
 Window period: is a period when HBsAg has
disappeared from blood but HbsAb is not yet
detectable. Infection during the window period is
detected using HBcAb.
La diagnosis cont.’d
 HBcAb is present in those with acute infections and
chronic infections and in patients who have recovered.
 To distinguish between acute and chronic infections

IgM cAb and IgG cAb are used.

 HBeAg arises during the incubation period and

prodromal period and sometimes during chronic

cases. It indicates a high likelihood of transmissibility
of infection.
 HBeAb indicates a lower likelihood of transmissibility
 HB viral DNA can be detected using PCR in serum of

patients
Serological results in different stages of HBV
infection
Test Acute Window Complete Chronic
disease phase recovery carrier state
HBsAg Positive Negative Negative Positive
HBsAb Negative Negative Positive Positive
HBc-Ab Positive Positive Positive Positive
Treatment
 No drugs cure HBV. Drugs used only reduce
hepatic inflammation and lower the levels of
hepatitis virus in chronic active hepatitis. Once
the drugs are stopped viral replication resumes.
 Pegylated alpha interferon (Pegasys) can be
used to treat chronic infections.
 Other drugs used include lamivudine, adefovir,
entecavir and telbivudine.
Prevention
 Prevention is by the use of vaccines or
immunoglobulins (antibodies).
1. Vaccine contains HBsAg. Dose of vaccine: 0,1,6
months, given intramuscularly.
2. HB immunoglobulin contains a high titer of
HBsAb and is prepared from the sera of
patients who have recovered from infection. It
provides immediate, passive protection and is
given to individuals with accidental needle stick
injury and to infants born to HBV infected
mothers.
Hepatitis D
 Is an enveloped, SS RNA genome.
 Also known as delta agent.
 Is a defective virus (doesn’t have the gene

which encodes its envelope)

 Can only replicate in the presence of HBV

infection because it uses the HBsAg as its

envelope.
 HDV is transmitted sexually, by blood and
perinatally.
 Clinically it presents as either co-infection

with HBV or as superinfection.

 Co-infection occurs when the patient is

infected by both HBV and HDV at the same

time
 Superinfection occurs when the patient is

previously infected with HBV and then

becomes infected with HDV.
Lab diagnosis of HDV
1. Co-infection:
 Anti-HDV antibodies and antiHB core IgM

antibodies are positive

2. Superinfection:
 Anti-HDV abs are positive, antiHB core IgM

antibodies are negative.

Treatment
 Alpha interferon (doesn’t eradicate chronic
carrier state)
 No vaccine against HDV
 A person immune to HBV will be also immune

to HDV.
HCV
 Non-A, non-B hepatitis
 Is a flavivirus
 The virus is enveloped, contains a SS RNA genome.
 Based on differences in the genes that code for its

envelope glycoproteins, HCV has been divided into 6

genotypes.
 Genotype 1, 2, 3 are found world-wide
 Genotype 4 is found in N. Africa and the Middle East
 Genotype 5 is found in S. Africa
 Genotype 6 is found in S. E Asia
Epidemiology
 HCV was the major cause of post-transfusion
hepatitis, but now the most common route of
transmission is via intravenous drug abuse.
 Vertical and sexual transmission may also

occur but are less common modes of

transmission of HCV.
Pathogenesis of HCV
 Infected liver cells show no cytopathic effect.
 Death in infected liver cells is caused by cytotoxic T
cells and NK cells attacking infected hepatocytes.
 HCV predisposes to liver cirrhosis and hepatocellular
carcinoma.
 Hepatocellular carcinoma is thought to result from
prolonged liver damage with consequent liver
regeneration.
 Any factor which increasing liver damage may
enhance the rate of development of hepatocellular
carcinoma in patients with HCV infection
(alcoholism!!!!)
Clinical presentation
 Incubation period is 8 weeks
 Acute infection with HCV is mostly subclinical

with fever, anorexia, nausea and jaundice.

 80% of patients become chronic carriers,

most of which are asymptomatic until the

sequelae of chronic hepatitis appear
(cirrhosis and hepatocellular carcinoma)
 In these infection can be detected by

serology.
Clinical presentation of HCV cont.’d
 People with HCV infection present with
extrahepatic manifestations:
vasculitis
arthralgia
purpura
membranoprilferative GN
Essential mixed cryblobulinaemia
Lab diagnosis of HCV
 Liver enzymes
 ELISA detects Abs to HCV.
 Test does not differentiate between acute and

chronic infection and has a high false positive rate.

 RIBA (recombinant immunoblot assay) is used to

confirm infection by HCV.

 PCR is done in individuals with a positive RIBA to

detect viral RNA

 Chronic infection is diagnosed if there are elevated

liver enzymes, positive RIBA and positive viral RNA

after 6 months.
Treatment of HCV
 Alpha interferon is used to treat acute infection
 Pegasys and ribavirin are used to treat chronic
HCV infection
 Duration and response to treatment depends
on the genotype.
 Genotype 1 is less responsive to interferon and
ribavirin than genotypes 2 and 3.
 Patients infected with genotype 1 are treated
for 48 weeks, whereas those infected with
genotypes 2 and 3 are treated for 24 weeks.
Prevention of HCV infection
 Proper screening of blood and discarding any
infected blood or blood products.
 Avoiding i.v drug abuse
 People infected with HCV should avoid

alcohol consumption
 Chronic hepatitis C infected patients and

those with liver cirrhosis should be monitored

regularly for the development of
hepatocellular carcinoma
 No vaccine exists
Hepatitis G
 Was discovered in 1996 in patients with post-
transfusion hepatitis.
 Resembles HCV in that it is a flavivirus.
 Not associated with chronic hepatitis or

hepatocellular carcinoma
 Transmitted by sexual contact and blood
 Patients co-infected with HIV and HGV have a

lower mortality rate and a less HIV viral load

in their blood.
 ?? It may interfere with HIV replication
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