9. Hepatitis

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Hepatitis Viruses


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AInfectious

Serum

Viral hepatitis

Enterically

transmitted

Parenterally

transmitted

F, G,

? other

E

NANB

B D C

Viral Hepatitis - Historical Perspectives


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Hepatitis A Virus


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Hepatitis A Virus Type A hepatitis is previously called infectious

hepatitis

Picornaviridae family

Naked RNA virus

Related to enteroviruses, formerly known as

enterovirus 72, now put in its own family: heptovirus One stable serotype only


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Hepatitis A Virus contd.. Difficult to grow in cell culture

Can be grown with difficulty in monkey kidney and

human diploid cells

Replication occurs in cytoplasm of host cells

Four genotypes exist, but in practice most of them aregroup 1


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Pathogenesis and pathology Virus replicates in hepatocytes

Then passes through bile duct to intestine and shed in

large quantities in faeces

There is necrosis of hepatocytes which leads to damage toliver function

It is indicated by elevated liver enzymes in blood

There is no chronicity, carrier state, cirrhosis ormalignancy


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Clinical Features Incubation period is 2-6 weeks

Many infections are silent in young children

Illness starts with malaise, loss of appetite, abdominaldiscomfort and fever

Urine becomes darkand feces pale


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Clinical Features contd. Jaundice by age group:


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FecalHAV

Symptoms

0 1 2 3 4 5 6 1

2

2

4

Hepatitis A Infection

Total anti-

HAV

Titre

ALT

IgM anti-HAV

Months after exposure

Typical Serological Course

(Alanine aminotransferase)


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Transmission

By faecaloral route, Contaminated food, water

HAV survives for long periods in water and wet environment

Large quantities of virions are excreted in faeces for several

days before and after onset of jaundice

During viremic phase

Other routes of transmission may be byblood transfusion, sharing of

needles by drug abusers and sexually (homosexual)

Widespread in countries where sewage treatment and

hygiene are inadequate

Epidemiology


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Epidemiology contd It may occur as endemic and epidemic forms

It may occur as water borne as well as food borneoutbreaks


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EndemicityDisease

RatePeak Age

of Infection Transmission Patterns

High Low to

High

Early

childhood

Person to person;

outbreaks uncommon

Moderate High Latechildhood/

young adults

Person to person;food and waterborneoutbreaks

Low Low Young adults Person to person;food and waterborneoutbreaks

Very low Very low Adults Travelers; outbreaksuncommon

Global Patterns of

Hepatitis A Virus Transmission


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Laboratory Diagnosis Acute infection is diagnosed by the detection of HAV-IgM in

serum by EIA

Lack of hepatitis A antibodies at the onset of clinical manifestationsexcludes hepatitis A.

Past Infection i.e. immunity is determined by the detection ofHAV-IgG by EIA.

Cell culture difficult and take up to 4 weeks, not routinelyperformed

Direct DetectionEM, RT-PCR of faeces

Can detect illness earlier than serology but rarely performed.


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Hepatitis B Virus - Virology Some structures are spherical or tubules with 20-

22 nm in diameter.

Spherical and tubular structures contain only hepatitisB surface antigen (HBsAg)

Replication involves a reverse transcriptase


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Hepatitis B VirusVirology contd.. At least 4 phenotypes of HBsAg are recognized;

adw, adr, ayw and ayr.

The HBcAg is of a single serotype

Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H).

Genotypes A and C predominate in the US. However, genotypes B and Dare also present in the US.

Genotype F predominates in South America and in Alaska

A, D and E predominate in Africa

Genotype D predominates in Russia and in all its prior dominions

In Asia, genotypes B and C predominate


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Antigens and antibodiesHBV markers

Main antigens HBsAg (originally called Australia antigen)

HBcAg and HBeAg can induce specific antibodies HBsAg, HBeAg, viral DNA polymerase, Anti HBs, Anti HBe

and Anti HBc are called markers

Because their presence and absence indicates the course of the

disease Gives idea of infectivity to others

Person who has HBeAg in his blood is highly

infectious


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Incubation period: Average 60-90 days

Range 45-180 days

Clinical illness (jaundice):


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Clinical features contd.Postnatal infections contd

In others it may proceed to fulminant hepatitis leading to

death due to hepatic coma

Before appearance of jaundice, there is a rise in serumtransaminases and HBsAg is detectable in serum

This is followed by HBeAg and DNA polymerase

Anti-HBc is the first antibody to appear

Next is anti-HBe with disappearance of HBeAg (loss ofinfectivity


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Clinical features contd.Postnatal infections contd. Chronic infection may lead to

Chronic antigenaemia, chronic aggressive hepatitis andhepatocellular carcinoma (HCC)

In chronic antigenaemia, patient fails to form anti-HBsand formation of anti-HBe is delayed

HBsAg persists for many years but liver function isnormal

In chronic aggressive hepatitis, patients fail to produceeither anti-HBs or anti-HBe


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Clinical features contd.Postnatal infections contd.

Carry HBsAg, HBeAg and infectious virions in their blood,

they are infectious to others The patients are called as super carriers

There is significant damage to liver parenchyma

These patients are liable to repeated episodes of hepatitis and may

develop cirrhosis

Hepatocellular carcinoma (HCC) may result from integrationof viral genome into the DNA of hepatocytes

It arises after chronic infection for at least 2 years


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Clinical features contd.Perinatal infections

Infants born to mother with acute hepatitis B may become

acutely infected

HBV is also transmitted from contact with blood and bodyfluids at birth or after by close contact

Sometimes infection acquired early in life does not presentas an acute infection with jaundice.


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Diagnosis contd.. HBeAg - indicates active replication of virus and therefore

infectiveness.

Anti-HBe - virus no longer replicating. However, the patient canstill be positive for HBsAg which is made by integrated HBV

HBV-DNA - indicates active replication of virus, more accuratethan HBeAg especially in cases of escape mutants

These markers used mainly for monitoring response to therapy


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Pathogenesis and pathology Along with HBV, HDV multiplies only in

hepatocytes

Pathological changes in liver are similar to HBV.


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9. Hepatitis

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