Between the hepatocyte plates are liver sinusoids, which are enlarged capillaries through which blood from the hepatic portal vein and hepatic artery enters via the portal triads, then drains to the central vein.
Viral hepatitis A
RAJALEKSHMY. P. R
DEPT OF SWASTHAVRITTA
AMRITA SCHOOL OF AYURVEDA 1
• It is the largest gland of the body.
• Located behind the ribs in the right upper quadrant,
from 5th-12th rib.
• It weighs 1800gms in men and 1400gms in women.
• It is divided into 4 lobes and multiple lobules.
• It is connected to two large blood vessels,
the hepatic artery and the portal vein.
• These blood vessels subdivide into small
capillaries known as liver sinusoids, which
then lead to a lobule.
LIVER: A GLANCE.....
• The lobules are roughly hexagonal, and consist of plates of
hepatocytes radiating from a central vein.
• The central vein joins to the hepatic vein to carry blood out from
• A distinctive component of a lobule is the portal triad, which can
be found running along each of the lobule's corners.
• Branch of the hepatic artery
• branch of the hepatic portal vein
• Bile duct
• The hepatic portal vein delivers approximately 75% of the liver's
blood supply, and carries venous blood drained from
the spleen, gastrointestinal tract, and its associated organs.
• The hepatic arteries supply arterial blood to the liver, accounting
for the remaining quarter of its blood flow.
• Blood flows through the liver sinusoids and empties into the
central vein of each lobule.
• Central vein hepatic vein inferior vena cava
• Glucose metabolism
• Protein metabolism
• Fat metabolism
• Vitamin and iron storage
• Drug metabolism
• Bile formation
• Bilirubin excretion
• Inflammation of the liver.
• Hepatitis is acute when it lasts less than six months and chronic when it
• Acute hepatitis can be self-limiting can progress to chronic hepatitis, or,
rarely, can cause acute liver failure.
• Chronic hepatitis may have no symptoms, or may progress over time
to fibrosis (scarring of the liver) and cirrhosis (chronic liver failure).
• Cirrhosis of the liver increases the risk of developing hepatocellular
Heavy alcohol use
Bacterial and viral infections
Viral hepatitis is a systemic disease
with primary inflammation of the
liver by any one of a heterogeneous
group of hepatotropic viruses.
•The most common causes of viral hepatitis are the five
unrelated hepatotropic viruses - Hepatitis A, Hepatitis
B, Hepatitis C, Hepatitis D, and Hepatitis E.
•In addition to the nominal hepatitis viruses, other viruses
that can also cause liver inflammation include Herpes
simplex, Cytomegalovirus, Epstein–Barr virus, Yellow
fever or Rubella virus. 11
Agent Hepatitis A
Parenteral Parenteral Fecal-oral
Age affected Children Any age Adults Any age Young adults
Carrier state Nil Common Present Nil (only with
40-120 days 2-12 weeks 2-9 weeks
Chronic infection No Yes Yes Yes No
Specific Ig and Ig and Nil HBV vaccine Nil
• Hepatitis A refers to liver inflammation caused by infection with the hepatitis
• HAV has been known as infectious jaundice since 1912.
• Acc. To WHO, HAV had many names in the past:
• Epidemic hepatitis
• Epidemic jaundice
• Infectious hepatitis
• Catarrhal jaundice
• HA and type A hepatitis
• HAV is referred to as one of the oldest diseases known to mankind
by the WHO.
• It was recognized as a separate entity from other types of hepatitis
during world war II.
• It was discovered in1973 by Steven. M. Feinstone as a non
enveloped, spherical, positive stranded RNA virus.
• HAV was an unidentified viral disease prior to this discovery.
• Globally, symptomatic HAV infections are believed to occur in around 1.5 million
people a year.
• In 2010, acute hepatitis A resulted in 102,000 deaths, which is slightly up from
99,000 in 1990.
• Hepatitis A is much more common in countries with underdeveloped sanitation
systems and, thus, is a risk in most of the world.
• HAV is a common infection in developing nations of Africa, Asia, and Central and South
• Largest outbreak occurred in Delhi in 1955-56, when
more than 40000 people were affected, because of the
contamination of river Yamuna with the sewage.
• Even though, mortality is very low, incapacitation is very
high resulting in great loss of human resource.
• Another epidemic in Delhi in 1970 due to contamination
of Okhla water supply.
Areas with high levels of infection
• In developing countries with poor
sanitation and hygiene, children are
infected before age of 10 yrs.
• Symptomatic disease rates are low.
• Outbreaks are rare.
Areas with intermediate levels of infection
• In developing countries, countries with
transitional economies and regions where
sanitary conditions are variable, children escape
infection in childhood.
• Higher susceptibility in old age groups.
• Higher disease rates
• Large outbreaks can occur.
Area with low levels of infection
• In developed countries with good sanitary and hygienic condns:
infection rates are low.
• Disease may occur among adolescents and adults in high risk groups
such as injecting drug users, homo sexual men, people travelling to
areas of high endemicity and in isolated population such as closed
HEPATITIS A VIRUS
• Naked RNA virus
• Previously known as enterovirus(type 72).
• One stable serotype only.
• 7 genotypes exist(four human & three simian)
• Difficult to grow in cell culture.
• Human and vertebrates serve as natural hosts.
• Replication in hepatocytes.
• Fairly resistant to low pH, heat and chemicals.
• Survives more than 10 weeks in well water.
• Resistant to heat at 60 degree Celsius for 1 hr.
• Not affected by chlorination.
• Formalin-effective disinfectant.
• Virus inactivated by UV rays, boiling(5 mts) or autoclaving.
• Viral particles first demonstrated in liver cells by workers in
Phoenix laboratory in Arizona- hence called phoenix antigen.
•Human reservoir(active clinical case or sub clinical case
or a carrier-healthy/incubatory).
•Subclinical cases and carriers are responsible for the
endemicity of the disease in community.
•No evidence of chronic carrier state.
•Asymptomatic infections are common in children. 27
PERIOD OF INFECTIVITY
• Risk of transmitting HAV is greatest from 2 weeks before to 1
week after the onset of jaundice.
• Infectivity falls rapidly with the onset of jaundice.
• Mainly man’s faeces
• Blood, serum and other fluids(during stage of viraemia)
• HAV is excreted in faeces for about 2 weeks before onset of
jaundice and for upto 2 weeks thereafter.
• Also excreted in urine.
Frequent among children than adults.
People from all ages get infected (if susceptible).
Severity increases with age.
Anicteric : icteric
Both sex are equally susceptible.
Acquired after an infection.
Immunity after attack lasts for life.
Second attack reported in about 5% patients.
VHA during pregnancy carries a high
No transplacental transmission
• Can occur throughout the year
• In India, associated with heavy rainfall.
• Poor sanitation and over crowding favours spread of infection.
• Faecal oral route
• Direct contact(person to person)
• Indirect- contaminated water, food or milk
• In developed countries, foodborne outbreaks are frequent.
• Eg. Consumption of salads, vegetables and raw or inadequately cooked
shellfish cultivated in sewage polluted water.
• Parenteral route
• Occur during the stage of viremia
• Rare; mode is of minor importance.
• Eg. By blood or blood products or skin penetration through contaminated
• Sexual transmission
• Occurs in homo sexual men
• Oral anal contact
• 10-50 days( usually 14-28 days).
• Length of incubation period proportional to dose of virus ingested.
•After ingestion, the HAV survives in gastric acid, moves
to the small intestine and reaches the liver via the portal
•Replicates in hepatocyte cytoplasm.
•Degeneration and necrosis of hepatocytes.
•Affects liver functions- hyperbilirubinaemia-jaundice
•Inflammation of liver-hepatomegaly-pressure effects on
• Sudden onset of fever, chills, fatigue,
malaise, head ache and body ache
• Within a day or two, develops gastro
• High coloured urine, light coloured
stools lasting for about of 3 to 5 days.
• Onset of jaundice
• With onset of jaundice, fever subsides.
• Sclera looks yellow and skin looks
• Nausea and vomiting decreases.
• High coloured urine continues for
• Jaundice usually reaches maximum by 2
weeks and decreases steadily thereafter.
• Stage lasts for 4 to 6 weeks.
• After about 6 to 8 weeks, inflammatory
process comes down, there is regeneration
• Appetite improves
• Icterus disappears
• Urine and stools become normal
• Stage lasts for 2 to 6 weeks.
• Resolves in 98% cases but relapse of symptoms noted in 3-20% cases.
Outcome Children Adults
Sub clinical infection 80-95% 10-25%
Icteric disease 5-20% 75-90%
Complete recovery > 98% > 98%
Chronic disease None None
Mortality rate 0.1% 0.1% 40
0 1 2 3 4 5 6 7 8 9 10 11 12 13
HAV in stool
EVENTS IN HEPATITIS A VIRUS INFECTION
CONCENTRATION OF HEPATITIS A VIRUS IN VARIOUS BODY FLUIDS
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890
100 102 104 106 108 1010
Infectious Doses per mL
• Fulminant hepatitis A/acute liver failure is a rare but devastating
complication of HAV infection.
• HAV liver parenchymal cells release of toxins
• The cell then produces new viral components that are released into the bile
capillaries hepatic necrosis.
• The fulminant form of hepatitis occurs when this necrotic process kills so
many liver cells.
• Fulminant hepatic failure can also lead to encephalopathy and cerebral
• Demonstration of HAV particles in the faeces, bile or blood.
• HAV is detected in the stool from about 2 weeks prior to the onset of jaundice
and 2 weeks thereafter.
• Anti HAV appears in IgM fraction during acute phase.
• Anti HAV IgM usually declines to non detectable level within 3-6 months.
• Anti HAV IgG appears more slowly and persist for decades.
• Acute infection is diagnosed by the detection of HAV-IgM in serum by
• Past Infection i.e. immunity is determined by the detection of HAV-IgG by
• Detection of Antibody: By ELISA
• Biochemical tests:
• i) Alanine aminotransferase (ALT)
• ii) Bilirubin
• Demonstration of viral particles in the stools by electron
Control of reservoir
• Complete bed rest
• Disinfection of
faeces and fomite
Control of transmission
• Promote simple measures of personal and
• Eg. Hand washing before and after toilet
• Sanitary disposal of excreta
• Purification of community water supply
Control of susceptible population
Passive immunization-human normal immunoglobulin
Prepared from pooled plasma of multiple donors.
Agent/condition Target population Preparation Dose
Hepatitis A Family contacts
IG 0.02 ml/kg of body
weight(3.2 mg/kg of
Travellers exposed to
conditions in tropical
IG 0.02-0.05 ml/kg of
mg/kg of body
Once in 4 months
• Formaldehyde inactivated vaccine
• Live attenuated vaccines
Produced in several
World wide used
Available in several
• Cell cultured liquid vaccine
• Hepatitis virus of HM-175 strain( F strain) is propagated on
human diploid cells, purified by ultra filtration technique and
inactivated by formaldehyde and adsorbed on aluminium
• Dose: adults-1 ml; children-0.5ml given IM in deltoid region.
• Licensed for use in children above 12 months of age.
• Interval between the first and second booster dose: 6-12 months
• Immunity lasts for 15-20 yrs.
• Marketed as HAVRIX.
• Storage temp: 2-8˚ C
• A combination vaccine containing inactivated Hepatitis A and
Hepatitis B vaccine has been licensed since 1966 for children in
• Schedule of combined vaccine is 0, 1 and 6 months.
• Combination of hepatitis A and B, hepatitis A and typhoid vaccine
are developed for travellers.
• Live attenuated freeze dried vaccine containing H2 strain of hepatitis A virus.
• Single dose of 0.5ml is administered subcutaneously in deltoid region for all
above one year of age.
• Safe, immunogenic with good tolerability
• No booster dose required.
• Storage temp: 2-8˚C.
• Recommended for both pre exposure prophylaxis of high risk individuals and
post exposure prophylaxis.
• Marketed as Biovac-A.
WHO SHOULD BE VACCINATED?
• All children at age 1 year (i.e., 12–23 months)
• Children and adolescents ages 2–18 who live in states or communities where
routine Hepatitis A vaccination has been implemented because of high
• Persons traveling to or working in countries that have high or intermediate
rates of Hepatitis A.
• Homo sexuals
• Users of illegal injection
• Persons who have occupational risk for infection
• Persons who have chronic liver disease.
VACCINES IN INDIA
No Brand Name Manufacturers Type
1 Avaxim Aventis Pasteur India Ltd Injection
2 Avaxim 80U Paediatric Aventis Pasteur India Ltd Injection
4 Havrix (360)
5 Havrix (720)