HEPATITIS VIRUSES

The term viral hepatitis is usually used to

describe infections caused by agents whose primary
tissue tropism is the liver. At least five hepatitis
viruses have been recognized, and these have been
named: Hepatitis A, B, C, D and E. Each of the
hepatitis viruses infects and damages the liver,
causing the classic icteric symptoms of jaundice and
the release of liver enzymes. However, they differ
greatly in their structure, mode of replication, and
mode of transmission and in the course of the
disease they cause.
Hepatitis A, which is sometimes known as
infectious hepatitis
(1) is caused by a picornavirus, an RNA virus;

(2) is spread by the fecal-oral route;

(3) has an incubation period of approximately
1 month, after which icteric symptoms start
abruptly;
(4) does not cause chronic liver disease;
(5) rarely causes fatal disease.
Hepatitis B, previously known as serum hepatitis,
(1) is caused by a hepadnavirus with a DNA genome;
(2) is spread parenterally;
(3) has a median incubation period of approximately
3 months, after which icteric symptoms start
insidiously;
(4) is followed by chronic hepatitis in 5% to 10% of
patients; and
(5) is causally associated with primary hepatocellular
carcinoma (PHC). More than one third of the world's
population has been infected with HBV, resulting in 1
to 2 million deaths per year.
Hepatitis C virus is also widely prevalent,
with more than 170 million carriers of the
disease. HCV is spread by the same routes
as HBV but usually causes chronic disease.
HCV is a flavivirus with an RNA genome.
Hepatitis E virus (HEV) is a calicivirus , and
its disease resembles HAV.
 Hepatitis D, or delta hepatitis, is unique in
that it requires actively replicating HBV as a
"helper virus" and occurs only in patients who
have active HBV infection. HBV provides an
envelope for HDV RNA and its antigen or
antigens. Delta agent exacerbatesthe
symptoms caused by HBV.
Hepatitis A virus ， HAV
 Biological Properties

 picornavirus, +ssRNA
genome
 27 nm in diameter ,non-
enveloped icosahedral particle

Feinstone
（ 1973 ）
 Stronger than enterovirus, resistant to
detergents, acid (pH 1.0 for 2h), 60℃ for 1h ，
survive for months in fresh water and salt water
Pathogenesis 致病性
 spread via the fecal-oral route
 Source of infection: patient, inapparent
infection
 Viral shedding in the stool precedes the onset
of symptoms by 14d but stops before the
cessation of symptoms
 Symptoms
 Initial symptoms: fever, fatigue, nausea, loss of
appetite, abdominal pain
 Jaundice
 Asymptomatic infections are very common.
As already noted, disease in children is
generally milder than that in adults and is
usually asymptomatic
 No a chronic infection and carrier,not
associated with hepatic cancer.
 Complete recovery:99%
 Fulminant hepatitis: 1~3 / 1000, 80% mortality
rate
 Pregnant women may develop more severe
disease.
 Treatment and Prevention

 Control the source of infection

 Cut down the route of transmission

 Passive immunization - Normal immunoglobulin

 Active immunizations
 A killed HAV vaccine
 a live attenuated HAV vaccine
hepatitis B virus, HBV
 SHAPE AND STRUCTURE

There are 3 particles in patient’s blood

 Dane particle
 small spherical particle

 tubulose particle
Dane particle
Complete particle, infective HBV
spherical ， double capsid 。
outer capsid=envelope
inner capsid=protein coat
internal ：
DNA--- circular, double- stranded
DNA polymerase
small spherical particle

containing particles
tubulose particle
 Antigen of HBV
Antigen of outer capsid
 hepatitis B surface antigenHBsAg
 indicates that virus replication is occurring
in the liver
 four phenotypes ： adr,adw,ayr,ayw
 anti － HBs:neutralization antibody
Antigens of inner capsid

 hepatitis B core antigen HBcAg

 not found in blood
 anti － HBc non － neutralization antibody
 Core IgM indicates recent infection.
 Core IgG indicates exposure to HBV
 hepatitis B e antigen HBeAg
 the best correlate to the presence of infectious virus.
anti-HBe indicates low infectivity in a carrier
resistance
strong
resistance to cool,dry, ultraviolet, alcohol
inactivate: 100℃ 10min
Pathogenesis

 source of infection
patients or carriers
 route of transmission
 sexual routes
 parenteral routes
 injection of the virus into the blood stream
 contaminated blood and blood components by
transfusion, needle sharing, acupuncture, ear piercing, or
tattooing
 perinatal routes
 contact with the mother’s blood at birth and in mother’
milk
 Clinical Findings
 Acute infection
 Fulminant hepatitis

 Chronic infection

 Primary hepatocellular carcinoma

（ PHC ）
 Acute infection
a long incubation period and an insidious
onset
 prodromal period :fever, malaise, anorexia,
nausea, vomiting, abdominal discomfort,
chills
 classic icteric symptoms of liver damage

 Recovery
 Fulminant hepatitis

 occurs in approximately 1% of icteric

patients and may be fatal
1%
 severe liver damage, such as ascites and
bleeding
 Chronic infection
 elevated liver enzyme levels
 10% of patients with chronic hepatitis may
develop cirrhosis and liver failure
10%
 major source for spread of the virus
 at risk for fulminant disease if they become
co-infected with HDV
 Primary hepatocellular carcinoma
（ PHC ）

 promoting continued liver repair and cell

growth in response to tissue damage
 integrating into the host chromosome and
stimulating cell growth directly
 Treatment and Prevention
 Control the source of infection
 Cut down the route of transmission

 Passive immunization - Hepatitis B immune

globulin （ HBIg ）
 Active immunizations

 HBsAg vaccine
 No specific treatment
 hepatitis C virus,HCV

predominant cause of non A non B hepatitis

 Biological properties

 40 ～ 60nm,spherical
 an enveloped virion

 Genome: (+)ss RNA

 Pathogenesis
 six genotypes ：Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ、Ⅵ
 transmitted by means similar to HBV
in infected blood
Intravenous drug abusers
transfusion
organrecipients
hemophiliacs receiving factors Ⅷ or Ⅸ

 sexually
 Pathogenesis

persistent, chronic hepatitis →cirrhosis ，

hepatocellular carcinoma

 acute hepatitis 15%

 chronic persistent infection 70%
 severe rapid progression to cirrhosis
15 ％
 Laboratory diagnosis
 ELISA recognition of antibody
 genetic techniques to detect HCV RNA

Treatment
 No vaccine
 Recombinant IFN-αalone or with ribavirin
 hepatitis D virus ， HDV

 a defective virus that acquires

an HBsAg coat for
transmission ，
 Pathogenesis
 spread by the same routes as HBV: blood,
semen, and vaginal secretions
 increases the severity of HBV infections:

Fulminant hepatitis
Coinfection
Superinfection
 Treatment and prevention

 no known specific treatment

 prevention of infection with HBV prevents HDV
infection.
 hepatitis E virus ， HEV

 spherical, non-enveloped, and 27-34 nm

 a positive-sense, single-strand RNA
genome
 spread by the fecal-oral route
 symptoms and course of HEV disease are
similar to those of HAV disease
 Acute hepatitis ， mortality rate : 1% to
2%
 especially serious in pregnant women
(mortality rate of approximately 20%)