What is Viral Hepatitis?

 Viralhepatitis 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.
 Inaddition to the nominal hepatitis viruses, other viruses
that can also cause liver inflammation include Herpes
simplex, Cytomegalovirus, Epstein–Barr virus, or Yellow
fever.
 Clinical Terms
 Hepatitis: inflammation of liver;
 Acute Viral Hepatitis: symptoms last less than 6 months
 Acute Hepatic Failure:is the appearance of severe complications rapidly
after the first signs of liver disease (such as jaundice), and indicates
that the liver has sustained severe damage (loss of function of 80-90%
of liver cells).Massive hepatic necrosis with impaired consciousness
within 8 weeks of onset of illness.
 Chronic Hepatitis: Inflammation of liver for at least 6 months
 Cirrhosis: Replacement of liver tissue fibrosis(scar tissue).These
changes lead to loss of liver function.
 Fulminant Hepatitis: severe impairment of hepatic functions or
severe
necrosis of hepatocytes in the absence of preexisting liver disease.
Viral Hepatitis- Historical Perspective

“Infectious” A Enterically
E
transmitted

Viral hepatitis NANB

Parenterally
“Serum” B D C transmitted
G
 Types Of Viral Hepatitis
Viral Hepatitis A Viral Hepatitis B Viral Hepatitis C Viral Hepatitis D Viral Hepatitis E

Agent Hepatitis A Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus
virus (HAV); (HBV); dsDNA; (HCV); ssRNA; (HDV); ssRNA; (HEV); ssRNA;
ssRNA; envelope envelope envelope from no envelope
No envelope HBV
Route of Fecal-oral Parenteral, Parenteral Parenteral Fecal-oral
Transmissio Vertical, Sexual.
n
Age affected Children Any age Adults Any age Young adults

Carrier state Nil Common Present Nil (only with Nil

HBV)
Incubation period 10-50 days (avg. 50-180 days 40-120 days 2-12 weeks 2-9 weeks
25-30) (avg. 60-90)
Chronic infection No Yes Yes Yes No

Specific Ig and Vaccine Ig and Vaccine Nil HBV vaccine Nil

Prophylaxis
 Hepatitis A
 Hepatitis A (formerly known as ―infectious‖ hepatitis
or epidemic jaundice) is an acute infectious disease
caused by Hepatitis A virus (HAV).
 The disease is heralded by non-specific symptoms
such as fever, chills, headache, fatigue, generalized
weakness and aches and pains, followed by
anorexia, nausea, vomiting, dark urine and jaundice.
 The disease is benign with complete recovery in
several weeks.
 Epidemiological determinants
 Agent factors
a) AGENT: The causative agent, the
hepatitis A virus, is an enterovirus
of the Picornaviridae family. It
multiplies only in hepatocytes.
b) RESISTANCE: The virus is fairly
resistant to heat and chemicals. RNA
-Withstands heating to 600 C for 1 hr.
and is not affected by chlorine in
doses usually employed for Naked RNA virus
chlorination.
-Formalin is stated to be an
effective
disinfectant.
-The virus is inactivated by
ultraviolet rays and by boiling for 5
minutes or autoclaving.
c) RESERVOIR OF INFECTION: The human cases are the only
reservoir of infection.
d) PERIOD OF INFECTIVITY : The risk of transmitting HAV is
greatest from 2 weeks before to 1 week after the
onset of jaundice.
e) INFECTIVE MATERIAL : Mainly man’s faeces.
f) VIRUS EXCRETION: HAV is excreted in the faeces for
about 2 weeks before onset of jaundice and for up to
2 weeks thereafter.
 Host factors

a) AGE: Infection with HAV is more frequent among children than in

adults. However, people from all ages may be infected if
susceptible.
b) SEX: Both sexes are equally susceptible.
c) IMMUNITY: Immunity after attack probably lasts for life.

 Environmental factors

 Cases may occur throughout the year.

 In India the disease tends to be associated with periods of heavy
rainfall.
 Incubation period
10-50 days (usually 25 to 30 days).

 Mode of Transmission

a) FAECAL-ORAL ROUTE: Major route of transmission.

-By contaminated water, food or milk.
b) PARENTERAL ROUTE (Rarely):
-By blood and blood products or by skin penetration through
contaminated needles.
c) SEXUAL TRANSMISSION:
-May occur mainly among homosexual men because of oral-anal
contact.
Diagnosis

1. Demonstration of Virus in feces, blood, bile:

By: Immunoelectron microscopy
2. Virus Isolation:
3. Detection of Antibody :By ELISA
4. Biochemical tests:
i) Alanine aminotransferase (ALT)
ii) Bilirubin
iii) Protein
5. Molecular Diagnosis : RT PCR of feces
 Prevention:-
-hygienic measures and sanitation
-passive immunization(Human Immunoglobulin
Gamma globulin given before exposure to virus
or early during the incubation period, will
prevent or attenuate a clinical illness.
-active immunization
Several inactivated or live attenuated vaccines
against hepatitis A have been developed.
 Treatment:
-nospecific, dietary food and long rest
Hepatitis B
 Hepatitis B (formerly known as ―serum‖ hepatitis)
is an acute systemic infection with major pathology
in the liver, caused by hepatitis B virus.
 Transmitted by the Parenteral route.
 The acute illness causes liver inflammation, vomiting,
jaundice, and, rarely, death. Chronic hepatitis B may
eventually cause cirrhosis and liver cancer.
 Hepatitis B is endemic throughout the
world, especially in tropical & developing
countries.
Epidemiology Determinants
 Agent factor

a) AGENT: Hepatitis B Virus (HBV)

-It is a complex, 42 nm double-shelled DNA virus originally known

as ―Dane Particle‖.
-It replicates in liver cell.

HBV occurs in 3 morphology form in serum:

i. Small spherical particles with an average Diameter of 22nm.
ii. Filamentous or Tubules of varying length & of 22 nm diameter.
iii. Dane particle.
Out of 3 morphology forms, only the Dane particle is considered infectious, other
circulating morphology forms are not infectious.
HBV : Structure
Dane particle
b) RESERVOIR OF INFECTION:
-Men is the only reservoir of infection which can be spread either from
carriers or from cases.
c) Infective material:
-Contaminated blood is the main source,
-Virus has been found in body secretion such as saliva, vaginal secretion &
Semen in infected material.
d) Resistance:
-Readily destroyed by sodium hypochlorite, as is by heat sterilization in
an autoclave for 30-60 min.

 Host factor
a) AGE:
-Acute hepatitis B -Chronic hepatitis B
90% resolve by themselves; <1% develop 2-10% progress to chronic state.
fulminant hepatic failure. -occur in approx.
-occurs in approx.: Perinatal -95%
Perinatal -1% Childhood -80%
Childhood -10%(1-5 yr. age) After 5 yr. of age -5-10%
Late infection -30%(>5 yr. age)
b) High Risk Group:

 People from endemic regions

 Babies of mothers with chronic HBV
 Intravenous drug abusers
 People with multiple sex partners
 Hemophiliacs and other patients requiting blood and
blood product treatments
 Health care personnel who have contact with blood
 Patients who are immunocompromised.
c) Humoral and cellular response:

-HBV has 3 distinct antigen:

i. HBsAg, also known as ―Australian antigen,
ii. HBcAg antigen (core antigen)
iii. HBeAg envelope antigen
They stimulate production of corresponding antibody.

 Incubation Period

45-180 days (usually 60-90 days)

 Mode of Transmission

 Parenteral- IV drug abusers, health workers

are at
increased risk.
 Sexual- sex workers and homosexuals are particular at
risk.
 Perinatal (Vertical) – mother (HBeAg+) →infant. Mothers
who are HBeAg positive are much more likely to transmit
to their offspring than those who are not. Perinatal
transmission is the main means of transmission in high
prevalence populations.
Diagnosis
 Serology
 Liver Chemistry tests
AST, ALT, ALP, and total Bilirubin
 Histology--Immunoperoxidase staining
 HBV Viral DNA--Most accurate marker of viral
DNA and detected by PCR
 Liver Biopsy--to determine grade(Inflammation)
and stage(Fibrosis) in chronic Hepatitis
 Serologic Events
1) HBsAg :- It is the first marker to appear in blood after infection.
2) Anti-HBs(HBsAb) :-Disappearance of HBsAg and the appearance of anti-
HBs signals recovery from HBV infection, non-infectivity.
3) Anti-HBc :- IgM anti-HBc appears shortly after HBsAg is detect (HBcAg
alone
dose not appear in serum)
IgM-HBc may also or can persist for 3-6 months or longer.
IgG-HBc also appear during acute hepatitis B but persist indefinitely.
4) HBeAg :-
HBeAg appear in blood concurrently with HBsAg, or soon afterwards.
HBeAg is a soluble protein found only in HBeAg positive serum.
HBeAg indicate viral replication and infectivity.
Persistence of HBeAg in serum beyond 3 month indicate an increased like
hood of chronic hepatitis B.
 Symptoms
ALT

concentration

Anti-HBc
HBsAg

Anti-HBs

Anti-HBc Anti-HBe
HBeAg IgM

8 12 16 20 28 32 36 44 52
24
40
Weeks post infection
 Interpretation of common serological patterns in HBV infection

Virus/Antibody markers
Interpretation
HBsAg HBeAg Anti-HBc Anti-HBs Anti-HBe

Acute HBV infection; highly infectious

+ + IgM - -

Late/Chronic HBV infection or carrier

+ + IgG - - state; highly infectivity

Late/Chronic HBV infection or carrier

+ - IgG - +/- state; low infectivity

Seen rarely in early acute HBV

- +/- IgM - +/- infection; infectious

Remote HBV infection; infectivity nil

- - IgG +/- +/- or very low
Immunity following HBV vaccine
- - - + -
 Prevention

 Vaccination
- highly effective recombinant vaccines
 Hepatitis B Immunoglobulin (HBIG)
-exposed within 48 hours of the incident/ neonates
whose mothers are HBsAg and HBeAg positive.
 Other measures
-screening of blood donors, blood and
body fluid precautions.
National Immunization Schedule

Vaccin When to Give Dose Route Site

e
Hepatitis B At birth or as 0.5 ml IM Antero lateral
soon as side of mid
possible with thigh
in 24 hours.

Hepatitis B At 6, 10, 14 0.5 ml IM Antero lateral

1,2,3 weeks side of mid
thigh
 Treatmen
t
 Interferon Alfa (Intron A)
Response rate is 30 to 40%.
 Lamivudine (Epivir HBV)
(relapse ,drug resistance)
 Adefovir dipivoxil
(Hepsera)
 Hepatitis C

 Hepatitis C is an infectious disease affecting primarily

the liver, caused by the hepatitis C virus (HCV).
 The infection is often asymptomatic, but chronic infection
can lead to scarring of the liver and ultimately to cirrhosis,
which is generally apparent after many years.
 It is estimated that 150–200 million people, or ~3% of the
world's population, are living with chronic hepatitis C.
 HCV infection is prevalent in India too, with an
estimated
12.5 million cases.
 Overt jaundice is seen in about 5 % of patients only.
 The important part in type C hepatitis is the chronic
illness.
 About 50 to 80 % of patients progress to chronic
 Hepatitis C Virus
 HCV is a 50-60 nm virus with a linear,
single stranded RNA genome,
enclosed with in a core and
surrounded by an envelope, carrying
glycoprotein spikes.
 It is a member of
the Hepacivirus genus in the
family Flaviviridae.
 The half life of the virus particles in
the serum is around 3 hours and may
be as short as 45 minutes.
 In addition to replicating in the
liver
the virus can multiply in
lymphocytes.
 Incubation Period
40-120 days

 Mode of Transmission
 Intravenous Drug Use
 Healthcare Exposure: Blood Transfusion, transfusion of Blood products,
Organ Transplant without HCV screening carry significant risk of infection.
 Hemodialysis
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-positive contact
 Multiple sex partners
 Vertical Transmission: Vertical transmission of hepatitis C from an infected
mother to her child
 Hepatitis C Virus Infection
Typical Serologic Course
anti-
HCV
Symptoms

Titre

AL
T

Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure
Diagnosis
• HCV antibody – ELISA used to diagnose hepatitis C infection.
Not useful in the acute phase as it takes at least 4 weeks
after infection before antibody appears.

• HCV-RNA - various techniques are available e.g. PCR and

branched DNA. May be used to diagnose HCV infection in
the acute phase. However, its main use is in monitoring the
response to antiviral therapy.

• HCV-antigen - an EIA for HCV antigen is available. It is used

in the same capacity as HCV-RNA tests but is much easier to
carry out.
 Prevention
 Only General Prophylaxis, such as blood, tissue, organ screening, is possible.
 No specific active or passive immunizing agent is available.

 Treatment
Interferon - may be considered for patients with chronic active hepatitis.
The response rate is around 50% but 50% of responders will relapse upon
withdrawal of treatment.
Ribavirin - there is less experience with ribavirin than interferon.
However, recent studies suggest that a combination of interferon and
ribavirin is more effective than interferon alone.
 Hepatitis D

 Hepatitis D, also referred to as hepatitis D virus (HDV)

and classified as Hepatitis delta virus, is
a disease caused by a small circular enveloped RNA
virus.
 HDV is considered to be a subviral satellite because it
can
propagate only in the presence of the hepatitis B
virus (HBV).
 Hepatitis D virus

VIRION: spherical, 36-38

nm particle with an outer
coat composed of the
HBsAg surrounding ssRNA
genome.

Satellite virus : replicates

only in the presence of
HBV
 Incubation Period

2-12 weeks

 Mode of Transmission

The primary route of Transmission are believed to be

similar to those of HBV, though HDV does not appear to
be sexually transmitted disease.
 Clinical Features

 Infection is dependent on HBV replication, as HBV provides an HBsAg

envelop for HDV.
Two types of infection are recognisesd, coinfection and superinfection.
In Coinfection, delta and HBV are transmitted together at the same time.
In Superinfection, delta infection occurs in a person already harbouring
HBV.
 Diagnosis
 Delta antigen is primarily expressed in liver cell nuclei, where it can
be demonstrated by immunofluorescence.
 Anti-delta antibodies appear in serum and can be identified by
ELISA.
IgM antibody appears 2-3 weeks after infection and is soon replaced
by the IgG antibody in acute delta infection.
 HBV - HDV
Coinfection
Typical Serologic Course
Symptoms

ALT Elevated

Titre
anti-HBs
IgM anti-HDV

HDV RNA

HBsAg
Total anti-HDV

Time after Exposure

 HBV – HDV Superinfection
Typical Serologic Course
Jaundice

Symptoms

Total anti-HDV
AL
Titre T

HDV RNA
HBsAg

IgM anti-HDV

Time after Exposure

 Prevention

 HBV-HDV Coinfection
Pre or post exposure prophylaxis to prevent
HBV infection. Screening of blood donor for
HBsAg.

 HBV-HDV Superinfection
Education to reduce risk behaviors among persons with
chronic HBV infection.
 Hepatitis E
 Hepatitis E is a viral hepatitis (liver inflammation) caused by infection with
a virus called hepatitis E virus (HEV).
 Although Hepatitis E often causes an acute and self-limiting infection (in
that it usually goes away by itself and the patient recovers) with low
mortality rates.
 It bears a high risk of developing chronic hepatitis in immunocompromised
patients with substantial mortality rates.
 Hepatitis E occasionally develops into an acute, severe liver disease,
and is fatal in about 2% of all cases.
 In pregnant women the disease is more often severe and is associated with
a clinical syndrome called fulminant hepatic failure.
 Signs and Symptoms

Acute Infections:
The incubation period of hepatitis E varies from 3 to 8 weeks.
After a short prodromal phase symptoms lasting from days to
weeks follow. They may include jaundice, fatigue and nausea.
Viral RNA becomes detectable in stool and blood serum during
incubation period.
Serum IgM and IgG antibodies against HEV appear just
before
onset of clinical symptoms.
Recovery leads to virus clearance from the blood, while the virus
may persist in stool for much longer.
Recovery is also marked by disappearance of IgM antibodies and
increase of levels of IgG antibodies.
Chronic Infections:
While usually an acute disease, in immunocompromised subjects—
particularly in solid organ transplanted patients—hepatitis E may
cause a chronic infection.
Occasionally this may cause liver fibrosis and cirrhosis.
 Hepatitis E virus

 HEV is spherical nonenveloped virus, 29-nm to 32 nm

in diameter, with a ssRNA genome.
 The surface of the virion shows indentation and
spikes.
 The Virus is very labile.
 II has been classified in the genus Herpes virus under
the family Caliciviridae.

 Animal Reservoir: Pigs

 Incubation Period
2-9 weeks
 Mode of Transmission

It is spread mainly by the fecal-oral route due to

fecal contamination of water supplies or food;
person-to-person transmission is uncommon.
 Hepatitis E Virus Infection
Typical Serologic Course
Symptoms

AL IgG anti-HEV
T

Titer IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Weeks after Exposure 52

 Diagnosis
ELISA kits are available for IgG and IgM antibodies, using
recombinant and synthetic peptide antigens.

 Prevention
Sanitation:
Avoid drinking water of unknown purity, uncooked shellfish,
and uncooked fruit/vegetables not peeled or prepared by
traveler.
Hepatitis G
 GB virus C (GBV-C), formerly known as hepatitis G
virus (HGV) and also known as HPgV is a virus in
the Flaviviridae family and a member of the Pegivirus
genus, is known to infect humans, but is not known
to cause human disease.

 HGV RNA has been found in patients with acute, chronic

and fulminant hepatitis, hemophiliacs, patients with
multiple transfusions and hemodialysis, intravenous drug
addicts and blood donors.
Thank You