Hepatitis Viruses

Dr. Pendru Raghunath, Ph.D

 General characteristics
• Five medically important viruses, called hepatitis
viruses because their main site of infection is the
liver
• These are:
• Hepatitis A virus (HAV); a Picornavirus
• Hepatitis B virus (HBV); a Hepadnavirus
• Hepatitis C virus (HCV); a Flavivirus
• Hepatitis D virus (HDV); unclassified
• Hepatitis E virus (HEV); unclassified
• All infect liver as common target but differ in their
morphology, replication pattern and course of
infection
• They also cause distinct clinical pathology
producing characteristic symptoms of jaundice and
production and release of liver enzymes in the
serum
• Most of them spread very fast because infected
individuals are contagious even during incubation
 Hepetitis A Virus (HAV)
• Picornavirus most commonly transmitted by the
fecal oral route

• Relatively short incubation period (3-4 weeks) after

which jaundice starts suddenly

• It does not cause chronic disease or fatal disease

• Only one serotype exist and is not related to other

hepatitis viruses
 Pathogenesis
• Virus multiplies first in gastrointestinal tract and then
spreads to liver

• Infect hepatocytes and cause damage to

hepatocytes by an unknown mechanism

• Cytotoxic T cells appear to cause damage of

hepatocytes; hence once infection is cleared, the cell
damage is repaired and no chronic infection occurs

• Liver pathology not different from that of other HVs

 Clinical syndrome: Acute
hepatitis A
• Fatigue, nausea, vomiting, fever, hepatomegaly, jaundice
and rash are main signs and symptoms

• Condition also associated with passing of dark colored

urine, pale feces and elevated serum transaminase
(SGOT and SGPT)levels

• Self limiting disease (2-4 weeks) conferring life long

immunity without chronic carrier state

• No hepatocellular carcinoma but acute liver failure and

cholestatic hepatitis are rare complications
 Reservoir, source and
transmission
• Humans are reservoir for HAV

• Infected humans are main source of infection as

they contaminate food or water

• Transmission is primarily by fecal-oral route

• Infection is more common in developing countries

in the areas of low socioeconomic status and poor
sanitation
 Laboratory diagnosis
• Specimens: serum for antibody detection test and liver,
bile, stool and blood for HAV antigen

• Direct antigen detection: virus can be detected in stool 2

weeks before jaundice

• Serodiagnosis: ELISA for detection of IgM and IgG in

serum

• Liver function test: ↑alanine aminotransferase (ALT or

SGPT) and aspartate aminotransferase (AST or SGOT)
in serum
Treatment, prevention and
control
• No antiviral available. Treatment is supportive

Prevention
• Vaccines: active immunization with vaccines
containing formalin-inactivated HAV
• Prophylaxis with immune serum globulin
• Measures to prevent fecal oral spread of infection
 Hepatitis B Virus

• It is major cause of infectious hepatitis

• It is a Hepadnavirus with restricted host range and
limited tissue tropism
• The virus is transmitted parenterally by blood and by
sexual contact and perinatally
• Has long incubation period of >3 months
• Usually causes chronic disease and is associated
with hepatocellular carcinoma
 Structure

VIRUS CONSISTS OF
 A core which has icosahedral
symmetry.
 An outer coat or envelope
 Within the core is double
stranded DNA and
DNA polymerase.
 ANTIGENS

 HBs Ag – Surface antigen

 HBc Ag – Core antigen
 HBe Ag – Hidden component of core.
 Reservoir and source of
infection
• Individuals with chronic HBV infection are the major
reservoir

• HBV is present at high level in their serum

• The virions are also present at very low levels in

semen, vaginal mucosa, saliva, and tears and all
are infectious

• The virus is not detected in urine, stool, or sweat,

hence these specimens are not infectious
SOURCE OF INFECTION: Patient or Carrier
MODE OF TRANSMISSION :-
A)Parenteral
 Minute quantities( 0.00001 ml)
is infectious
 Needle stick injury.
 Tattooing, acupuncture
 Multiple blood transfusion
B) Sexual Contact
 Occurs more frequent than for
HCV and HDV.
 Infection is associated with vaginal
intercourse, genital-rectal
intercourse
C) Vertical transmission

 From carrier/infected
mother to newborn.
 Acquired during delivery
 Lead to Carrier for life
 High risk group
 Health care workers
Doctors, dental surgeons, nurses, lab technicians,
blood bank personel.
 Staff of haemodialysis unit.
 Haemodialysis patients
 Haemophiliac
 Intravenous drug abusers
 Homosexuals.
 Prostitutes
 Pathogenesis
• Virus infect hepatocytes with expression of viral
antigens on surface of infected cells

• Cytotoxic T cells recognise these antigens resulting

in an immunological response

• Injury to cells occurs due to CMI and the formation of

immune complexes is responsible for some of the
symptoms such as arthritis seen during the early
stage of disease
• Immune complexes are also responsible for some of
the complications associated with chronic hepatitis
such as glomerulonephritis (serum hepatitis)

• A chronic carrier state sets in when cytotoxic

response is not strong enough to clear the infection

• Hepatocellular carcinoma is a result of persistent

cellular regeneration that tends to replace the dead
hepatocytes
 Clinical syndrome
• It is one of the most important causes of acute and
chronic hepatitis

• Clinical manifestations vary from subclinical hepatitis

to symptomatic and icteric hepatitis

• Incubation period: 6 weeks to 6 months

• Manifestations depend on: age of infection, immune

status of host, level of HBV
 Acute hepatitis
• Prodromal or preicteric phase: anorexia, malaise and
fatigue

• Icteric phase: liver becomes tender, jaundice

• Nausea, vomiting, and pruritis, dark colored urine are

main symptoms noted

• Clinical manifestations are similar to those of hepatitis A

but tend to be more severe and life threatening with HBV
infection
 Chronic HBV infection

• It is one of the major complications of HBV

infection
• The risk of chronic infection is higher in:
• Those infected at birth (90%)
• Patients who are immunocompromised
• Only 5-10% of older children or adults progress to
develop chronic infection
• The following are complications of HBV:
Complications of HBV infection
• Fulminant hepatic failure associated with
coagulopathy, encephalopathy and cerebral edema

• Hepatocellular carcinoma: due to repeated episodes

of chronic inflammation and cellular regeneration

• Liver cirrhosis

• Glomerulonephritis, cardiopulmonary disease, joint

and neurologic manifestations etc (due to immune
complexes)
 Lab diagnosis
• Specimens: Serum is most important because
definitive diagnosis of HBV depends on serological
testing

• Serodiagnosis: Acute hepatitis by detection of

HBsAg and HBeAg to show viral replication
• Anti-HBeAg and HBsAb are also detected later as
well as HBcAb

• Other diagnosis: Elevated ALT and AST in acute

hepatitis while serum bilirubin indicates the
intensity of jaundice
 Treatment
• No specific antivirals recommended for patients
with acute disease and treatment remains
supportive

• Therapy is recommended for patients with chronic

disease

• Interferon and nucleoside analogs such as

lamivudine, adefovir, and telbivudine are the
antivrials mostly used
 Prevention and control

• Prevention by use of either the vaccine or

hyperimmunoglobulin or both

• Vaccine: can be plasma derived or recombinant DNA

HBV vaccine

• Hepatitis B immunoglobulin (HBIg): it is used for

passive immunisation of patients after or just before
the exposure