INTRODUCTIONINTRODUCTION

• High incidence rateHigh incidence rate

• Do not grow in the laboratoryDo not grow in the laboratory

• Discovered in 1964Discovered in 1964

The Hepatitis VirusesThe Hepatitis Viruses

Virus Virus Classification Classification Main rout ofMain rout of transmission transmission

HAVHAV PicornaviridaePicornaviridae EntericEnteric

HEVHEV CaliciviridaeCaliciviridae

HBVHBV HepadnaviridaeHepadnaviridae Parenteral Parenteral

HDVHDV DeltavirusDeltavirus

HCVHCV FlaviviridaeFlaviviridae Parenteral Parenteral

GBV-A,B,CGBV-A,B,C Flavi-like Flavi-like virusesviruses

Viral Hepatitis - OverviewViral Hepatitis - OverviewTypes of Hepatitis

A B C D E

Source of Virus

Feces BloodBloodBlood-Blood-

derived body derived body fluidsfluids

BloodBloodBlood-Blood-

derived body derived body fluidsfluids

BloodBloodBlood-Blood-

derived body derived body fluidsfluids

FecesFeces

Route of Trans-mission

Fecal-Oral PercutaneousPercutaneous

PermucosalPermucosalPercutaneousPercutaneous

PermucosalPermucosalPercutaneouPercutaneouss

PermucosalPermucosalFecal-Fecal-OralOral

Chronic Infection

No YesYes YesYes YesYes NoNo

Primary Prevent-ion

Pre/Post-

ExposureImmunization

Handwashing

Pre/Post-Pre/Post-

ExposureExposure

ImmunizationImmunization

Risk Behavior Risk Behavior ModificationModification

Blood Donor Blood Donor ScreeningScreening

Risk Behavior Risk Behavior ModificationModification

Pre/Post-Pre/Post-Exposure Exposure

ImmunizationImmunization

Risk Behavior Risk Behavior ModificationModification

Ensure safe Ensure safe drinking drinking

waterwater

PROPERTIESPROPERTIESClassificationClassification• HepadnaviridaeHepadnaviridae

• Infect only humanInfect only human

MorphologyMorphology• Icosahedral (Dane + Filaments & Icosahedral (Dane + Filaments &

Sphere particles)Sphere particles)

• EnvelopedEnveloped

*Dane particle:*Dane particle: DNA + Polymerase +DNA + Polymerase +

HBcAg + HBeAg)HBcAg + HBeAg)

Filaments + Spheres particles:Filaments + Spheres particles: HBsAgHBsAg

Hepatitis B Virus

Hepatitis B virus particlesHepatitis B virus particles

ANTIGENS & ANTIBODIESANTIGENS & ANTIBODIES

HBsAg HBsAg HBeAg HBeAg Anti-HBc Anti-HBc Anti-HBeAnti-HBe Anti-Anti-

HBsHBs Symptoms, InfectionSymptoms, Infection Little infection / CompleteLittle infection / Complete

recoveryrecovery

Start of Start of recoveryrecovery

(Convalescence)(Convalescence)

Serological markers of hepatitis B infectionSerological markers of hepatitis B infection

Marker Marker RemarksRemarks Present inPresent in

AntigensAntigensHBsAg HBsAg Surface antigen, not Surface antigen, not

infective infective

Acute and chronicAcute and chronic infection infection

HBeAgHBeAg Core of virion. Core of virion. Indicates infectivity Indicates infectivity

Acute and chronic Acute and chronic hep.hep.

Viral DNA Viral DNA polymerasepolymerase

As for HBeAg, above As for HBeAg, above As for HBeAg, aboveAs for HBeAg, above

Antibodies Antibodies

Anti-HBcAnti-HBc In IgM form; In IgM form; indicates recent indicates recent infection infection

Persists in IgG form Persists in IgG form for life for life

Anti-HBe Anti-HBe Little or no Little or no infectivity infectivity

ConvalescenceConvalescence

Anti –HBs Anti –HBs Complete recoveryComplete recovery Convalescence Convalescence

Postnatal infection:Postnatal infection:

Acute hepatitis:Acute hepatitis: Rash Rash Jaundice Jaundice

- 90% recovery- 90% recovery

- 10 % chronic or - 10 % chronic or deathdeath

Chronic antigenaemia: Chronic antigenaemia:

- Dealy Anti-HBe- Dealy Anti-HBe

- No Anti-HBs- No Anti-HBs

Chronic aggressive (Active) Chronic aggressive (Active) hepatitis:hepatitis: - No - No Anti-HBe Anti-HBe

- No Anti-HBs- No Anti-HBs

Hepatocellular carcinoma:Hepatocellular carcinoma:

Integration of viral genome Integration of viral genome in thein the

DNA of hepatocytes DNA of hepatocytes Death Death

Perinatal infectionsPerinatal infections

• Infected mother Infected mother Baby: Baby:

- Uterus- Uterus

- During delivery- During delivery

- Close contact- Close contact

* Cirrhosis or liver cancer * Cirrhosis or liver cancer Death Death

EPIDEMIOLOGYEPIDEMIOLOGY

Mode of transmission:Mode of transmission:

• BloodBlood

• Body fluid (Cervical secretion, Body fluid (Cervical secretion, semen, milk)semen, milk)

• High – risk groupHigh – risk group

Concentration of Hepatitis B Virus

in Various Body Fluids

High ModerateLow/Not

Detectable

blood semen urineserum vaginal fluid feces

wound exudates saliva sweat

tearsBreast milk

Acute Viral HepatitisAcute Viral Hepatitis

Died of HepatomaDied of Hepatoma

IMMUNE RESPONSEIMMUNE RESPONSE

• Anti-HBs :Anti-HBs : (Complete (Complete recovery)recovery)

• Cytotoxic T cells:Cytotoxic T cells:

(Much of liver damage is (Much of liver damage is due to it)due to it)

Acute Hepatitis B Virus Infection with RecoveryTypical Serologic Course

Weeks after Exposure

Titer

Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc anti-HBsHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Progression to Chronic Hepatitis B Virus Infection

Typical Serologic Course

Weeks after Exposure

Titer

IgM anti-HBc

Total anti-HBc

HBsAg

Acute(6 months)

HBeAg

Chronic(Years)

anti-HBe

0 4 8 12 16 20 24 28 32 36 52 Years

LABORATORY DIAGNOSISLABORATORY DIAGNOSIS

• Non-specific tests:Non-specific tests: Test for Test for liver enzymesliver enzymes

• Specific tests: Specific tests:

- Serology: - Serology:

. ELISA:. ELISA:

HBsAg, HBeAg, Anti-HBc, Anti-HBsAg, HBeAg, Anti-HBc, Anti-HBeAg, Anti-HBsAgHBeAg, Anti-HBsAg

HBsAgHBsAg-ve-ve +ve +ve

No diseaseNo disease Confirmation test Confirmation test

-ve-ve +ve +ve

Profile tests:Profile tests:

. . Anti-HBc Anti-HBc (IgG,IgM.Total)(IgG,IgM.Total)

. HBeAg . HBeAg

. Anti-HBe. Anti-HBe

. Anti-HBs. Anti-HBs

. . Reverse passive Reverse passive hemagglutinationhemagglutination

. Latex test. Latex test

• EMEM

• DNA polymeraseDNA polymerase

ControlControl• Specific treatment:Specific treatment:

- IFN-Alpha for 6 months (For - IFN-Alpha for 6 months (For HBeAg HBeAg +ve, acute case, no +ve, acute case, no need for treatment)need for treatment)

* Do not work in infancy infection* Do not work in infancy infection

- DNA polymerase inhibitors- DNA polymerase inhibitors

ImmunizationImmunization• Recombinant vaccine (HBsAg)Recombinant vaccine (HBsAg)

• IgGIgG

Current Treatment Options Current Treatment Options for HBVfor HBV

• Interferon alpha 2b (Intron A): Interferon alpha 2b (Intron A): GeneralGeneral

• Lamivudine (Epivir HBV):Lamivudine (Epivir HBV): RT RT inhibitorinhibitor

• Hepsera (Adefovir dipivoxil): Hepsera (Adefovir dipivoxil): RT RT inhibitorinhibitor