INFECTIVE VIRAL

HEPATITIS
Sreelakshmi 64
Sreelakshmi M 65
■ Liver may be subjected to a number of different infections.
■ Viral hepatitis must be considered in anyone presenting with hepatitic
liver blood tests(high transaminases).
■ CAUSES OF VIRAL HEPATITIS
1.More common:Hepatitis A,B,C,D and E
2.Less common:Cytomegalovirus and Epstein barrr virus
3.Rare:Herpes simplex and yellow fever.
HEPATITIS A

■ The hepatitis A virus belongs to picorna group of enteroviruses.

■ Highly infectious and is spread by Feco-oral route
■ Risk of infection is associated with a lack of safe water and poor
sanitation.
■ Infection may be asymptomatic or produce symptoms after an
incubation period of 28 days
■ Development of symptom is related to age
■ Infected individuals excrete the virus in faeces or about 2-3 weeks
before the onset of symptoms and then for a further week or so.
INVESTIGATIONS

■ Diagonosis based on Antibody testing.

■ Only one HAV antigen is found and infected people make an antibody
to this antigen(anti-HAV)
■ Anti-HAV immunoglobulin M antibody is detectable in the blood 5-10
days before the onset of symptoms and falls to low levels within 3
months of recovery.SO it is the diagnostic of acute HAV infection.
■ Anti-HAV IgG antibody persists for years after infection,and is a
marker of previous HAV infection.
MANAGEMENT

■ Infection prevented by improving social conditions,especially over

crowding and poor sanitation.
■ Individuals can be protected from infection by active immunisation
with an inactivated virus vaccine.
■ Immunisation should be given to people at high risk like people
travelling to endemic areas,Close contacts of HAV infected patients
etc,those with major liver disease and pregnant women
■ Immediate protection can be provided by immune serum globulin if
this is given soon after exposure to the virus.
■ Intra muscular injection of immune serum globulin is recommended
for close contacts of infected individuals who are less able to respond
to vaccination such as immunocompromised,>60yrs of age.
■ It is also effective in a hepatitis outbreak,in a school or nursery as
injection to those at risk prevents spread to families.
■ NO ROLE FOR ANTIVIRAL DRUGS IN THERAPY OF HEP A INFECTION
HEPATITIS B

■ Conists of a core containing DNA and a DNA polymerase enzyme

needed for virus replication,surrounded by surface protein.
■ The virus and an excess of its surface protein (HBSAg)circulate in the
blood.
■ The virus replicates and assembles with in hepatocytes.but not
cytotoxic.
■ Hepatocyte damage occurs during immune medited clearance of
infected hepatocytes.
■ HBV is one of the most common cause of CLD and hepatocellular
carcinoma worldwide.
■ HEPATITIS B CAUSES ACUTE OR CHRONIC INFECTION
■ Risk of developing chronic HBV infection depends on the source and
timing of exposure.
■ Most common cause of chronic infection:Vertical transmission from
mother to child in perinatal period.
■ Exposure to HBV at older age leads to acute infection.
■ Chronic hepatitis can lead to cirrhosis or hepatocellular carcinoma.
CAUSES
INVESTIGATIONS

■ Assesment of HBV relies on looking at a combination of viral

markers(surface antigen,e antigen and viral load) and liver markers
(ALT and fibrosis markers)to determine stage of the disease.
■ HBV contains several antigen to which the infected person can make
immune response.
■ These antigens and their antibodies are important in identifying the
stage of disease.
■ Direct assessment of viral load by PCR for HBV DNA.
HEPATITIS B SURFACE ANTIGEN

■ Main indicator of active infection

■ Negative test makes infection very unlikely.
■ Antibody to HBSAg(Anti HBs) usually appears after about 3-6 months
and persists for many months and perhaps permanently
■ Anti-HBs implies either a previous infection in which antiHBc also
present or previous vaccination in which case anti-HBC not present.
HEPATITIS B CORE ANTIGEN

■ HBcAg is not found in the blood,but anti body to it (anti-HBc) appears

early in illness rapidly reaches a high titre ,which gradually subside
and then persists.
■ Anti-HBc is initially of igM type ,with IgG antibody appearing later.
HEPATITIS B e ANTIGEN

■ Is a part of the core antigen and is detectable in blood.

■ Indicator of viral replication
■ Loss of HBeAg and development of anti Hbe antibody indicates a
partial immune control over the virus and is associated with a
signicant drop in viral load.
■ Occurs 10-30 years later in perinatally acquired infections but within
3-6 months in adult acquired acute infections.
PHASES OF CHRONIC HBV
INFECTION
INTERPRETATION OF
SEROLOGICAL TEST
MANAGEMENT

■ Management of acute hepatitis

■ Full spontaneous recovery occurs in more than 95% of adults
following acute HBV infection.
■ Fulminant liver failure occurs in less than 1 %of cases but can be life
threatening and requires liver transplantation.
■ Antiviral therapy is considered only in those with severe liver injury or
a course with persistent symptom for>4 weeks.
■ Recovery occurs with in 6 months and is characterised by the
appearance of antibody to viral antigens.
■ MANAGEMENT OF CHRONIC HEPATITIS B
■ Treatment aimed at supressing viral replication to prevent disease
progression to cirrhosis and hepatocellular carcinoma.
■ Goals include HBeAg seroconversion,reduction in HBV-DNA and
normalisation of the LFT.
■ Two different type drugs are used to treat hepatitis B.:direct acting
nucleoside/nucleotide analogues and pegylated interferon-alfa.
DIRECT ACTING
NUCLEOSIDE/NUCLEOTIDE ANALOGUES

■ Main stay of therapy

■ Orally administered.
■ They inhibit the reverse transcription of pre genomic RNA to HBV DNA by
DNA polymerase
■ DRUGS:Lamivudine,entecavir,tenofovir.
LAMIVUDINE

■ Long term therapy is complicated by development of HBV DNA

polymerase mutants which leads to viral resistance.
■ This agent is not commonly used now a days but may be used
prevent reactivation in patients with past HBV infection.
Entecavir and tenofovir

■ More effective than lamivudine

■ Antiviral resistance mutations occur very rarely
■ Both drugs have action against HIV virus ,so their use as monotherapy
is contraindicated in HIV positive patients as it may lead to HIV
antiviral drug resistance
Other management methods

■ Pegylated interferon α
Pegylated interferon α acts by augmenting the host immune response.
This is most effective in patients with a pre-treatment low viral load and
serum transaminases greater than twice the upper limit of normal.

liver transplantation:Done in patients with advanced liver disease or

HCC
PREVENTION

■ A recombinant hepatitis B vaccine containing HBsAg is

available(Engerix) and is capable of producing active immunisation in
95% of normal individuals.
■ The vaccine should be offered to those at increased risk of infection
who are not already immune, as evidenced by anti-HBs in the blood.
■ The vaccine is ineffective in those already infected by HBV.
■ Following known exposure, infection can also be prevented or
minimised by the intramuscular injection of specific hepatitis B
immunoglobulin (HBIg) prepared from blood containing anti-HBs.
■ This should be given within 48 hours, or at most a week, of exposure to
infected blood.
■ Neonates born to hepatitis B-infected mothers should be immunised at
birth and given immunoglobulin. Hepatitis B serology should then be
checked at 12 months of age.
Hepatitis C , D& E
Hepatitis C

■ Small, enveloped, single-stranded RNA virus belonging

to the family Flaviviridae.
■ Most individuals are unaware of when they became
infected and are identified only when they develop
chronic liver disease.
■ Because of genomic instability and antigenic
variability, producing an effective HCV vaccine is
difficult.
HCV has six genotypes and in India, most prevalent is
HCV3.
■ If hepatitis C infection is left untreated, progression
from chronic hepatitis to cirrhosis occurs over 20–40
years.

Risk factors for Progression

■ Male gender,
■ Immunosuppression (such as co-infection with HIV),
■ Prothrombotic states
■ Heavy alcohol misuse

Complications
 Hepatocellular carcinoma.
 Ascites
Incubation period: 2-26 Weeks
Viral particles are 30-38 nm in diameter.

Nearly 80% infected individuals develop chronic hepatitis.

Mode of spread:
■ Mainly transmitted by the parenteral route (transfusion of blood and
blood products, and in drug addicts) as a blood borne infection.
■ Sexual contact (low chances of transmission).
■ Perinatal/vertical transmission.
■ HCV is not transmitted by breastfeeding.
 Investigations

Serology
■ It take 6–12 weeks for antibodies to appear in the blood following
acute infection , such as a needle stick injury.

■ Active infection is confirmed by the presence of serum hepatitis

C RNA in anyone who is antibody-positive.

■ Anti-HCV antibodies persist in serum even after viral clearance,

whether spontaneous or post-treatment.
Molecular analysis

■ There are six common viral genotypes. Genotype has no effect on

progression of liver disease but does affect response to treatment.
■ Knowledge of viral genotype still remains relevant in guiding selection
of drugs to treat HCV.
Liver function tests
■ LFTs may be normal or show fluctuating serum transaminases
between 50 and 200 U/L.
■ Jaundice is rare and only usually appears in end-stage cirrhosis.
 Management
Till 2011, treatment of choice was Dual therapy with
Pegylated Interferon-alfa (weekly subcutaneous injection )
Ribavirin (Oral)
■ Treatment was long – up to 12 months for genotype 1 infection.
Side-effects
■ Ribavirin : Haemolytic anaemia , teratogenicity
■ Interferon Alpha : Influenza-like symptoms, irritability and
depression.
■ Efficacy of these agents was poor .
Now classes of Direct-Acting Antiviral agents (DAAs) are used .
These compounds are targeted to specific steps in the hepatitis C viral life cycle to
disrupt viral replication .
Initially, DAAs were added to interferon / ribavirin-based regimens; more recently,
however, combinations of DAAs have increasingly been used in ‘interferon-free’
regimens.

■ This maximises treatment efficacy by directly interfering with replication at

multiple points in the viral life cycle without exposing patients to the side-effect
of interferon-alfa therapy.

■ For example, 12 weeks of treatment with

Oral (sofosbuvir + ledipasvir ) + Ribavirin
Achieve a 99% SVR in treatment of-naive genotype 1 patients.
(SVR =Sustained Virological Response )

Liver transplantation should be considered when complications of cirrhosis

occur, such as diuretic-resistant ascites .
 Hepatitis D

■ Hepatitis D virus (HDV or delta virus), which is a

defective/incomplete RNA virus and belongs to the
Deltaviridae family.

■ The RNA genome is covered by an outer coat/shell of

HBSAg.

■ It has no independent existence and requires HBV for

its replication and expression.

■ Because HDV is dependent on HBV, the duration of

HDV infection is determined by the duration of HBV
Incubation period: 6-9 Weeks
Viral particles are 35 nm in diameter.

It has two clinical patterns.

i. Acute coinfection: It develops when individual is exposed simultaneously

to serum, containing both HDV and HBV. The HBV infection first becomes
established and the HBsAg is necessary for development of complete HDV
virions

ii. Superinfection: It occurs when an individual is already infected with HBV

(chronic carrier of HBV) is exposed to anew dose HDV.
Mode of spread : Parenteral route and
sexual contact.
 Investigation

■ HDV contains a single antigen to which infected

individuals make
■ an antibody (anti-HDV).
■ Delta antigen appears in the blood only transiently, and in
practice diagnosis depends on detecting anti-HDV.

■ Simultaneous infection with HBV and HDV, followed

by full recovery, is associated with the appearance of low
titres of anti-HDV of IgM type within a few days of the onset
of the illness.
• Super-infection of patients with chronic HBV infection
leads to the production of high titres of anti-HDV, initially IgM and later IgG.

Such patients may then develop chronic infection with both viruses, in which case anti-HDV titres
plateau at high levels.

■ Management
■ Effective management of hepatitis B prevents
hepatitis D.
Hepatitis E

■ HEV is an non enveloped, single-stranded RNA virus

■ Belongs to the family Caliciviridae.

Source of infection:
■ HEV is a zoonotic disease with animal reservoirs, such
as monkeys, cats, pigs, rodents, and dogs.
■ Virions are shed in stool during the acute illness.
Mode of transmission:
■ Enterically (faecal–oral ) transmitted, water or food
borne infection. It is common after contamination of
water supplies such as after monsoon flooding.
■ Incubation period: 3-8 Weeks
■ Viral particles are 27 nm in diameter.

Outcome of Infection
■ HEV infection is responsible for more than 30-60% of cases
of sporadic acute hepatitis (clinically very similar to
hepatitis A) in India.
■ It produces self-limiting acute hepatitis. It does not cause
chronic liver disease.
■ High mortality rate (about 20%) among pregnant women.
■ In acute infection, IgM antibodies to hepatitis E virus (HEV)
are positive.
Management : Similar to that of hepatitis A

Prevention and Control

■ Good sanitation and hygiene similar to hepatitis A
■ Vaccine has been developed and used successfully in China.
Thank You