Hepatitis Viruses

HEPATITIS
VIRUSES
Hepatitis A virus (HAV)
◦ single-stranded RNA virus, ic osahedral, naked
◦ genus Hepatovirus
◦ family Pic ornaviridae
◦ it was first provisionally c lassified as enterovirus 72
◦ Average incubation period is 2–6 weeks. (1month)
◦ so c alled epidemic or infec tious hepatitis
◦ Occurrence of virus
◦ Blood: 2 weeks before to ≤1 week after jaundic e
◦ Stool: 2 weeks before to 2 weeks after jaundic e
◦ Urine: Rare
◦ Saliva, semen: Rare
◦ Clinical and laboratory features
◦ Onset: Abrupt (within 24 hours)
◦ Fever >38 °C (100.4 °F)
◦ Duration of aminotransferase elevation: 1–3 weeks
◦ Immunoglobulins (IgM levels): Elevated
◦ Complications: Uncommon, no chronicity
◦ Mortality rate (ic teric c ases): <0.5%
◦ The virus is destroyed by autoc laving (121 °C for 20 minutes), by boiling
in water for 5 minutes, by dry heat (180 °C for 1 hour), by ultraviolet
irradiation (1 minute at 1.1 watts), by treatment with formalin (1:4000 for
3 days at 37 °C), or by treatment with chlorine (10–15 ppm for 30
minutes).
◦ Heating food to >85 °C (185 °F) for 1 minute and disinfecting surfaces
with sodium hypochlorite (1:100 dilution of chlorine bleach) are
nec essary to inac tivate HAV.
Laboratory diagnosis of hepatitis A
◦ C lotted venous blood, 5–10ml
◦ Hepatitis A IgM: Becomes positive 5 days after the onset of symptoms;
positive up to 4–6 months
◦ Hepatitis A IgG: Becomes positive from a week after onset of illness or
receiving hepatitis A vaccination and persists throughout life.
◦ When detected alone, e.g. without IgM, signifies immunity to infection
due to either past infection or vaccination.
◦ Feces
◦ PC R for hepatitis A virus
◦ treatment is supportive
◦ fulminant hepatitis: liver transplantation may be indicated.
◦ Prophylaxis:Pre-exposure
◦ Killed hepatitis A virus vaccine is available. Two doses given one year
apart offer protection for up to 10 years.
◦ A booster may be required at 10 years but recent evidence suggests
that the two doses will give lifelong protec tion.
◦ Post-exposure
◦ Normal human immunoglobulin and/or hepatitis A vac c ine should be
given to household c ontac ts within 14 days of exposure.
◦ Immune (gamma) globulin (IG) :given within 1–2 weeks after exposure
to hepatitis A
Hepatitis C virus (HC V)
◦ Hepatitis C virus is a single-stranded RNA virus
◦ family Flaviviridae
◦ genus Hepac ivirus
◦ The resulting disease was termed non-A, non-B (NANB) hepatitis.
◦ The average incubation period is 2–6 weeks, but may be as long as 3
months
◦ Route of infec tion:Predominantly parenteral
◦ infec tious throughout their lifetime
◦ Route of spread
◦ Blood and blood product transfusion
◦ Intravenous drug use
◦ Iatrogenic (through medic al treatment)
◦ Organ and tissue donation from infected donors
◦ Renal dialysis, if proper precautions are not followed.
◦ Infection can be transmitted after a sharps or needle-stick injury from
an infected source patient to an HCW.
◦ Ear and body pierc ing, tattooing
◦ Sexual and vertic al (from mother to baby) transmission
◦ ac ute infec tions are asymptomatic

◦ malaise, fatigue, nausea and jaundic e
◦ Chronic HCV infection
◦ develop cirrhosis of the liver after 20–30 years, a small proportion of whom
will develop hepatoc ellular c arc inoma.
◦ C irrhosis is a major risk fac tor for hepatoc ellular c arc inoma.
◦ anti-HC V EIA: sc reening
◦ Anti-HC V immunoblot
◦ RT-PCR and quantitative branched chain DNA: viral therapy monitoring
◦ HC V RNA: should be negative after 6 months of therapy
◦ Sc reening for ac ute or c hronic HC V infec tion

◦ 5–10ml of c lotted venous blood
◦ Hepatitis C antibody Positive: indicates infection, initial screen MUST be confirmed by repeat testing.
◦ There is no HCV specific IgM test available to distinguish acute from chronic infection.
◦ For establishing infec tion status of patient

◦ Hepatitis C PC R for HC V RNA.
◦ Mostly quantitative (viral load) assay
◦ Positive result indicates either acute or chronic infection.
◦ Negative result indicates clearance of infection either naturally or post-treatment.
◦ Assessment of infec ted patient for treatment

◦ EIAs that detect serum antibodies to HCV proteins are available as screening tests
◦ Antibodies are directed against core, envelope, and NS3 and NS4 proteins and tend to be
relatively low in titer.
Hepatitis E virus (HEV)
◦ Hepatitis E virus is a small (32 to 34 nm), naked, ssRNA virus
◦ genus Hepevirus
◦ previous c lassific ation: C alic ivirus
◦ family Hepeviridae/Hepadnaviridae
◦ naked, ic osaheral c apsid
◦ genotypes 1 and 2 are limited to humans only
◦ genotype 3 and 4 have animals as their reservoir and therefore are zoonotic
infections
◦ genotype 3:US
◦ Avian HEV:c hic kens

◦ swine: worldwide
◦ wild deer:Japan
◦ Route of spread
◦ Hepatitis E is spread by the faecal–oral route, mostly through drinking water
and probably by eating contaminated food.
◦ waterborne
◦ The average incubation period is 6 weeks
◦ Self limiting viral hepatitis
◦ high fatality rate among pregnant women: 3rd trimester of
pregnanc y: fulminant hepatitis
◦ dark urine, pale fec es, jaundic e

◦ inc rerased liver enzymes
◦ Acute hepatitis
◦ C lotted venous blood, 5–10ml
◦ Hepatitis E IgM: Bec omes positive within first week of ac ute
hepatitis and remains positive for up to 3 months. Signifies ac ute
infection.
◦ Hepatitis E IgG: Becomes positive from 1 to 2 weeks after onset

of illness. When detected alone, e.g. without IgM, signifies
immunity to infection due to past infection.
◦ Treatment is supportive.
◦ fulminant hepatitis: liver transplantation may be indicated.
◦ There is no vaccine or passive prophylaxis available
Hepatitis B and D viruses (HBV and HDV)
• Hepatitis B virus (HBV) is a member of the Hepadnaviridae family of

viruses, and has a double-stranded circular DNA and a DNA polymerase
enzyme.
• It has two major proteins:
• hepatitis B surface antigen (HBs Ag), which is an outer protein

expressed in excess when the virus replicates in the liver; and
• hepatitis B core antigen, an inner protein, which is expressed only within
hepatocytes in the liver.
• hepatitis B e antigen (HBe Ag), is also shed in the blood when the virus
replicates, and its presence is associated with high infectivity.
• Hepatitis D virus (HDV) is a defective DNA virus, which cannot
replicate in humans in the absence of HBV. Patients can be co-
infected with HBV and HDV, or HBV infected patients can be
super-infected with HDV
• Route of spread
• parenteral (blood exposure)
• sexual
• vertical (from mother to baby).
• Incubation period
• Infection can develop from 6 weeks to 6 months after
exposure to the virus.
• Acute hepatitis B
• Acute infection is accompanied with a rise in ALT of >500 IU/L
and jaundice.
• Fulminant hepatitis and death
• Ninety-five per cent of adults clear the virus within 6 months
after an acute infection
• Chronic hepatitis B
• persistence of hepatitis B infection beyond a period of 6
months subsequent to acute infection.
• Failure to clear the virus may lead (over a period of several
years) to progressive liver damage with persistent hepatitis,
chronic hepatitis, cirrhosis, hepato-cellular carcinoma.
• Treatment
• Acute hepatitis B
• Acute infection is self-limiting and 95% of immunocompetent
adults clear the virus within 6 months of onset of acute
hepatitis.
• Fulminant hepatitis may occur in <1% and may require a liver
transplant.
• Chronic infection
• A small number of patients will spontaneously clear the virus,
with 10–15% of HBe Ag positive patients per year
seroconverting to anti-HBe positive status and then over a
period of time clearing the virus altogether.
• Newer aminoglycoside analogue drugs, such as lamivudine,
adefovir, tenofovir and entecavir are more effective either on
their own or in combination with interferon, but resistance is a
problem especially with lamivudine.
• Liver transplantation may be the last resort in case of liver
failure.
• Pre-exposure prophylaxis
• Three doses are given, with the first two at an interval of one
month and the third 6 months after the first (0, 1 and 6
months)
• a booster dose is recommended once after 5 years of primary
immunization and provides long-term protection against the
disease
•
• Post-exposure prophylaxis
• For accidental and sexual exposure
• Vaccination: Due to the long incubation period of hepatitis B the

vaccine has a high effectiveness for post-exposure prophylaxis; a
rapid schedule of three doses at 0, 1 and 2 months with a booster
at 12 months is recommended.
• Immunoglobulin: Hepatitis B specific immunoglobulin should also

be considered for accidental and sexual exposure to hepatitis B. To
be effective it should be given within a week of exposure and
preferably within 48 hours.
• Neonates
• vaccinated and given hepatitis B specific immunoglobulin.
• Babies born to mothers who are anti-HBe positive do not require
immunoglobulin but should receive hepatitis B vaccination.
Hepatitis D (Hepatitis delta)
• Hepatitis D or delta is a defective DNA virus and requires the
hepatitis B surface antigen (which it uses as its outer protein coat)
so it can enter the cells to infect and replicate.
• Two types of infection are described:
• Co-infection: Where a person who is susceptible to HBV is

exposed to someone who is co-infected with HBV and delta virus,
this results in acute co-infection with both the viruses at the same
time.
• Super-infection: When an HBV carrier is exposed to infected

blood from co-infected patients then the exposure results in
super-infection of the existing HBV infection with delta virus; this
may result in development of acute hepatitis (due to delta virus) in
an HBV chronic carrier.
• Infection is diagnosed by screening blood for delta virus IgG;
although delta virus IgM is not always present in acute
infection a positive result is useful in confirming acute delta
virus infection.

Hepatitis Viruses

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HEPATITIS

◦ ac ute infec tions are asymptomatic

◦ Sc reening for ac ute or c hronic HC V infec tion

◦ For establishing infec tion status of patient

◦ Assessment of infec ted patient for treatment

◦ Avian HEV:c hic kens

◦ dark urine, pale fec es, jaundic e

◦ Hepatitis E IgG: Becomes positive from 1 to 2 weeks after onset

• Hepatitis B virus (HBV) is a member of the Hepadnaviridae family of

• It has two major proteins:

• hepatitis B surface antigen (HBs Ag), which is an outer protein

• For accidental and sexual exposure

• Vaccination: Due to the long incubation period of hepatitis B the

• Immunoglobulin: Hepatitis B specific immunoglobulin should also

• Two types of infection are described:

• Co-infection: Where a person who is susceptible to HBV is

• Super-infection: When an HBV carrier is exposed to infected

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