HEPATITIS VIRUSES

Department of Clinical Microbiology

Medical Faculty
Universitas Brawijaya
HEPATITIS VIRUSES
 HEPATITIS VIRUS ALPHABET
• Members
• Hepatitis A, Hepatitis B,
Hepatitis C, Hepatitis D,
Hepatitis E
• Differences
• Separate virus families -
replication strategies
• Epidemiology
• Incubation period
• Complications
 HEPATITIS VIRUSES

VIRUS TRANSMISSION VACCINE CHRONICITY DNA/RNA

Hep A Fecal/Oral Yes No RNA

Blood, Body
Hep B Yes Yes DNA
fluid

Hep C Blood No Yes RNA

Hep D Blood See Hep B Yes RNA

Hep E Fecal/Oral No No RNA

HEPATITIS A VIRUS
HEPATITIS A VIRUS (HAV)

• Family Picornaviridae
• Genus Hepatovirus
• 27-29 nm, icosahedral symmetry, non-enveloped
• Single stranded RNA, positive sense, 7.5 kb nucleotides
• Six genotype (I-VI, originally VII), divided into subtype A
and B
• Genotype I and III are the most prevalent genotypes
isolated from human. Genotypes IV, V & VI are found in
other primates
• Single serotype
SURVIVAL
• Stable in environment for 1 month
• Enteric virus – withstands stomach acid and bile
• Inactivation
• 37o C for 30 min in 1% sodium dodecyl sulfate

• Destroyed
• Autoclaving (121o C) for 20 min
• Boiling water for 5 min
• Dry heat (180o C) for an hour
• Formaldehyde 1 : 4000 on 37o C for 72 h
• Chlorine 10 – 15 ppm for 30 min

• On human hands, 16-30% of initially detectable virus can

still be detected after 4 h
EPIDEMIOLOGY

• HAV infections occur in all countries, approximately

1.5 million clinical cases occur annually
• Mostly in regions with low standards of hygiene
• In less developed countries
• HAV infection is highly endemic with most infections occur in
early childhood (tend to be asymptomatic) → reported rates of
disease are low, outbreaks are uncommon

• In developing and developed countries

• Infections usually occur in late childhood and adolescence
(symptomatic) → reported rates can be higher than in less developed
countries, outbreaks are common
 Hepatitis A Seroprevalence

Jacobsen , Wiersma . Vaccine. 2010 1.5 million symptomatic cases/year

> 20 million asymptomatic cases/year
ROUTES OF TRANSMISSION
• Fecal-oral is the most common route of transmission
through contaminated food and water
• Secondary infections occur through close contact
• Men who have sex with men
• Injecting drug use
• Travel to endemic countries
• Transfusion - blood or blood products (uncommon)
• Vertical transmission (uncommon)
 LIFE CYCLE
Virions reach portal blood flow
↓
Bind to the receptor on hepatocytes
↓
Taken up by hepatocytes
↓
Replicate
↓
Release

Possible enterohepatic cycling of HAV

(Cuthbert et al 2001 )
HAV REPLICATION
 CLINICAL SIGNIFICANCE
• Generally self limited
• HAV replication causes liver dysfunction → triggers immune responses
→ liver inflammation
• Fulminant hepatitis is uncommon
• Low case fatality rate:
• 0.1% among children <15 years old
• 0.3% for adults aged 15-39
• 2.1% for aged > 40

• Disease may require patient hospitalization - several days to weeks

• Absenteeism from school or place of employment

• Potentially incur high expenses from direct medical cost and losses in
productivity
PREVENTION
• Improvements in living standards
• Better sanitation and environmental conditions
• Adequate supplies of drinking water
• Proper disposal of sewage within community
• Personal hygiene practices

• Vaccination
• Available worldwide since 1992
• Highly immunogenic, current scientific evidence showed
that protection is considered lifelong after completing two
scheduled dose
• There are 2 design of HAV vaccination program (depends
on each country policy)
• Universal vaccination program → cover infants or adolescents or
both
• Selective vaccination program → only vaccinate selected
populations or high risk groups
PRECAUTIONARY STANDARDS
• Health workers should receive proper training about HAV
transmission and how to treat HAV patients properly
• Vaccination for health workers who treat HAV patients
• Wear gloves and gown while treating a patient and wash
hands after having contact with patients or contaminated
materials
• Proper disposal of contaminated and infectious material or
put in a plastic bag with infectious label on it for
decontamination and further process
• Isolate HAV patients with low standards of personal
hygiene
• Diaper-changing personnel in day care should wash their
hands after changing diaper and before handling food
• HAV infected food-handler is not allowed to handle food
in 3 – 6 months
HEPATITIS B VIRUS
HEPATITIS B VIRUS (HBV)

• Causes hepatitis B infection

• Family Hepadnaviridae
• Genus Orthohepadnavirus
• Enveloped, partially double-stranded, circular
DNA virus
• HBV particles
• Virion (Dane particle) consist of
nucleocapsid, surrounded by envelope
• Subviral particles comprise of the HBV
envelope only
 HEPATITIS B VIRUS (HBV)
Virion (Dane particle), 42 nm,
consists of
• 27 nm icosahedral
nucleocapsid (“core”)
• Hepatitis core antigen
(HBcAg)
• DNA polymerase
• HBV genome → 3.2 kb
circular double-standed DNA
with incomplete positive
strand → 15 – 50% single-
stranded
• Envelope comprises of lipid
and the Hepatitis B surface
antigen (HbsAg)
 HEPATITIS B VIRUS (HBV)
Subviral particles
• Non infectious
• Outnumber the complete virions by as much as 1000:1
• There are two different shapes
• Spheres, 22 nm
• Tubules, 20 x 20 – 200 nm
EPIDEMIOLOGY

CDC, 2012
 EPIDEMIOLOGY
Genotypes
• 8 genotypes
• Major genotypes A – D →
worldwide
• Genotype B, C → predominantly Asia
and Oceania
• Genotype E → restricted to Central and
West Africa
• Genotype F → Alaska, Central America
and Polynesia
• Genotype G → limited to small number
of people in Europe and US
• Genotype H → largely confined to
Central and South America
Bowden, 2010 Mutimer, 2011
ROUTES OF TRANSMISSION

• Perenteral and mucosal exposure to HBsAg-

positive body fluid
• Vertical transmission (infected mother to her
baby)
• Sexual contact
• Injecting drug use
• Transfusion of blood or blood product
HBV REPLICATION
• Replicates via reverse transcription of a
pregenomic RNA
RISK FACTORS

• Infant born from HBV infected mother

• Shared injecting drug use
• Sexual partner of HBV infected person
• Health workers who exposed to HBV
contaminated blood
• Hemodialysis patients
CLINICAL SIGNIFICANCE

• May develop to chronic infection and the

most common cause of liver infection
• Children < 6 years most likely to develop
chronic infection
• Infants infected during the first year → 80 – 90%
develop chronic infections
• Children infected before 6 years → 30 – 50%
develop chronic infections
• Among adults
• Healthy persons infected as adults → <5% develop
chronic infection
• Adults chronically infected → 20 – 30% develop
cirrhosis and/or liver cancer
PREVENTION
• Vaccination →
Universal vaccination
program covers all
infants
• Routine screening for
pregnant mother
• Safe sex
PRECAUTIONARY STANDARDS
• Blood, body fluids and blood or body fluid
contaminated materials are considered infectious and
contaminated by HBV or other bloodborne pathogen
• Wear gloves and gown while treating a patient and
discard them before leaving the infectious area
• Wear mask and safety glasses if there is a risk of
infectious material splashes
• Use disposable needle
• Decontaminate working area with chlorine
• Mouth pipetting, eat, drink and smoking in the
laboratory are prohibited
• Sterilize instruments using autoclave or ethylene oxide
gas
HEPATITIS C VIRUS
 HEPATITIS C VIRUS (HCV)

• Causes Hepatitis C infection

• Family Falviviridae
• Genus Hepacivirus
• An enveloped, 55 – 65 nm RNA virus
• RNA virus with positive single stranded RNA
• It’s genome consists of 9.4 kb nucelotides
• Has enormous genetic diversity in infected host →
quasipecies
• Evade host immune response, antiviral drugs
• Difficult to develop an effective vaccine
EPIDEMIOLOGY
• 150 million infected worldwide
• 40% (estimated 8,000-10,000 deaths) of chronic liver
disease is HCV-related
• 6 major genotypes with 50 subtypes
• Subtypes do not differ significantly in their virulence
• Genotype had major impact on treatment
responsiveness → genotypes 2 and 3 respond best to
interferon-containing treatment
• Genotypes 1 and 3 are predominant in UK and also
found in US
• Genotype 4 mostly found in Africa, while genotype 6 in
Asia
EPIDEMIOLOGY
HCV GENOTYPE DISTRIBUTION

• Genotype 1 → the most prevalent (42.2%)

• Genotype 3 → 30.1%
• Genotype 2, 4, and 6 → 22.8%
• Genotype 5 → < 1% Hepatology. 2015 Jan; 61(1): 77–87.
 ROUTES OF TRANSMISSION

• Parenteral
• Injecting drug use
• Tattoo needle → rare, except
in prison
• Transfusion of blood or blood
product and organ transplant
→ rare, regarding current
standard screening
• Vertical transmission, but
not as often as HBV (5%)
• Sexual transmission → low (1
– 5%) among monogamous Adapted from Robotin et al Journal of
Gastroenterology and Hepatology 2004
sexual partnership, but
higher among multiple sex
partners
RISK FACTORS

• Sharing syringe/needle
• Clotting factor products therapy among
hemophiliacs before 1987
• Blood donor recipient who receive blood from
HCV positive person
• Chronic hemodialysis patients
• Sexual partner of a HCV positive person
• Medical worker(s) who exposed by the blood
of Hep C patient
HCV REPLICATION
 CLINICAL SIGNIFICANCE
• Most acute hep C infections asymptomatic → unrecognized
• 55 – 85% acute infections will progress to chronic disease
• Chronic HCV infection potentially lead to cirrhosis, end-stage
liver disease and hepatocellular carcinoma
• HCV is the leading indicator for liver transplant in Western
countries and expected to increase 5 – 10 fold in 10 years
• Commonly found as co-infection with HIV due to the similar
route of transmission
• 20 – 30% of the world’s individuals with HIV are co-infected with
HCV
• HCV-related liver disease has become a leading cause of
morbidity and death among in patient with HIV
• Chronic HCV development is more common in HIV patients
and associated with higher HCV viral load
PREVENTION

• Use disposable syringe/needle

• Work according to precautionary standard
• Dispose needle into safety container box
• Sterilize instrument(s) which exposed to blood
• Do not share toiletries (i.e. toothbrush, nail
clipper, hair clipper or scissor)
• Vaccine is still unavailable due to the
variability in HCV RNA
PRECAUTIONARY STANDARDS

• Basically similar like HBV

• Blood, body fluids and blood or body fluid
contaminated materials are considered infectious and
contaminated by HBV or other bloodborne pathogen
• Wear gloves and gown while treating a patient and
discard them before leaving the infectious area
• Wear mask and safety glasses if there is a risk of
infectious material splashes
• Use disposable needle
• Decontaminate working area with chlorine
• Mouth pipetting, eat, drink and smoking in the
laboratory are prohibited
• Sterilize instruments using autoclave or ethylene oxide
gas
THANK YOU
TERIMA KASIH