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Harrison’s Hour

Acute Viral Hepatitis


Part 1
1 2 3
Causative Agents
Virology, characteristics, Epidemiology, Routes of
incubation period, Transmission

4 5
Serologic and viral
Serologic patterns of
markers
HBV infection and
interpretation
Acute Viral Hepatitis

● Systemic infection affecting the liver predominantly


● Caused by:

○ Hepatitis A virus (HAV)

○ Hepatitis B virus (HBV)

○ Hepatitis C virus (HCV)

○ Hepatitis D virus (HDV)

○ Hepatitis E virus (HEV)


Hepatitis A
● Non-enveloped 27 nm single stranded positive-sense RNA
virus
● Genus: Hepatovirus; Family: Picornavirus

● Inactivation of viral activity can be achieved by

○ Boiling for 1 min

○ Contact with formaldehyde and chlorine

○ Ultraviolet radiation

● Incubation period of 3-4weeks


● Replication is limited to the liver

○ But the virus is present in the liver, bile, stools and


blood during the late incubation period and acute
preicteric/presymptomatic phase of illness

● Despite slight longer persistence of virus in the the liver,


fecal shedding, viremia and infectivity diminish rapidly once
jaundice becomes apparent
● anti-HAV can be detected

○ serum aminotransferase activity is


elevated

○ fecal HAV shedding is still occurring

Hepatitis A diagnosis = IgM anti HAV


● Transmitted almost exclusively by: fecal-oral route

● Person-to-person spread is enhanced by poor personal


hygiene and overcrowding
Hepatitis B

● DNA virus

● classified as Hepadnavirus type 1


-represent excess viral
envelope protein

-represent intact hepatitis virion


 product of S gene
● HBsAg

○ first virologic marker detectable in


serum within 1-12weeks

○ preceded elevation of serum


aminotransferase activity and clinical
symptoms by 2-6weeks

○ remains detectable during the entire


icteric or symptomatic phase

● Anti- HBS

○ Detectable after HBsAg disappears


● HBcAg

○ intracellular and, naked

○ not detectable routinely

● Anti-HBc

○ demonstrable in serum beginning


within the first 1-2 weeks after the
appearance of HBsAg
● HBeAg

○ coincides temporally with high levels of virus


replication

○ presence of circulating intact virions and


detectable HBV DNA

○ undetectable shortly after peak elevations in


amino transferase activity, before the
disappearance of HBsAg

● Anti HBe

○ period of relatively lower infectivity


● Percutaneous inoculation has long been recognized as a major route
● HBsAg has been identified in almost every body fluid, most notably are
infectious

○ Semen and saliva


● By contrast, 2 non percutaneous routes considered to have greatest impact
are:

○ Intimate (especially sexual) contact

○ Perinatal transmission
Hepatitis D

● The only member of the genus Delta virus


● Defective RNA virus that co-infects with and require the
helper function of HBV for its replication and expression
● Formalin-sensitive, 35 to 37 nm virus with hybrid structure
● HDAg bears no antigenic
homology with HBV antigens

● HDV core is “encapsidated” by an


outer envelope of HBsAg
● HDV can either:

○ Co-infection

■ infect a person simultaneously with HBV

○ Superinfection

■ Superinfect a person already infected with HBV


● 2 epidemiologic patterns that exist:

○ Endemic areas

■ Nonpercutaneous means especially close


personal contact

○ Nonendemic areas

■ Blood and blood products, primarily injection


drug users and hemophiliacs
Hepatitis C

● Linear, single strand, positive sense RNA virus

● Only member of the genus Hepacivirus in the


family Flaviviridae
● HCV does not integrate into the
host genome

● It circulate in low titer, thus


visualization is difficult

● Replication rate: 1012 virions per


day

● half life is 2.7h


● HCV RNA

○ Most sensitive indicator of HCV


infection

○ Detected within few days of


exposure and persist for the
duration of infection
● Transmission:

○ Transfusion

○ Injection drug use


Hepatitis E

● epidemic or enterically transmitted non-A, non-B hepatitis

● Resembles hepatitis A

● 27 to 34 nm, non enveloped, heat stable


VIRAL REPLICASE: Nucleocapsid protein
Protease
Polymerase
Helicase
Small structural phosphoprotein involved in virus particle secretion
● detected in stool, bile, and liver
● excreted in the stool during the late
incubation period

● Both IgM anti-HEV during early


acute infection and IgG anti-HEV
predominating after the first 3 months
can be detected

● HEV RNA in serum and stool


accompanies acute infection
● Primarily enteric mode of spread

● Contamination of water supplies (eg


Monsoon flooding)

● Unique: Rare secondary person-to-person


spread

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