Hepatitis A-E VirusesDr F Noordeen

Department of MicrobiologyFaculty of Medicine

PeradeniyaMay 2013

• Modes of transmission and the pathogenesis of viralhepatitis in humans

• Main clinical features of viral hepatitis

• Principles of diagnosis, management and preventionviral hepatitis in humans

Learning outcomes

AA“Infectious”

“Serum”

Viral hepatitis

Entericallytransmitted

Parenterallytransmitted

F, G other?

EE

NANB

BB DD CC

Viral Hepatitis - Historical Perspectives

Source ofvirus

Faeces Blood/blood-derived

body fluids

Blood/blood-derived

body fluids

Blood/blood-derived

body fluids

Faeces

Route oftransmission

Fecal-oral Percutaneouspermucosal

Percutaneouspermucosal

Percutaneouspermucosal

Fecal-oral

Chronicinfection

No Yes Yes Yes No

Prevention Pre/post-exposure

immunization

Pre/post-exposure

immunization

Blood donorscreening;

risk behaviormodification

Pre/post-exposure

immunization;risk behaviormodification

Ensure safedrinking

water

Hepatitis A-E

A B C D E

Hepatitis A virus

Hepatitis A virus Non enveloped RNA virus Related to enteroviruses, formerly known as

enterovirus 72, now put in the family: heptovirus Only one stable serotype 4 genotypes exist but in practice most of them

are group 1

Incubation period: Average 30 daysRange 15-50 days

Jaundice by <6 years, <10%age group: 6-14 years, 40%-50%

>14 years, 70%-80%

Complications: Fulminant hepatitisCholestatic hepatitisRelapsing hepatitis

Chronic sequelae: None

Hepatitis A - Clinical features

FaecalHAV

Symptoms

0 1 2 3 4 5 6 12

24

Hepatitis A infectionHepatitis A infection

Total anti-HAV

Titre ALT

IgM anti-HAV

Months after exposure

Typical Serological Course

Close personal contact(Household contact, sexual contact and child care centers)

Contaminated food and water(Infected food handlers & raw shellfish)

Blood exposure (very rare)(Injecting drug use and transfusion)

Transmission of Hepatitis A

Laboratory diagnosis Acute infection is diagnosed by the detection of

HAV - IgM in serum by ELISA Past Infection i.e. immunity is determined by the

detection of HAV - IgG by ELISA

Direct Detection - EM, RT-PCR of faeces Can detect illness earlier than serology

but rarely performed

Many cases occur in community-wide outbreaks No risk factor identified for most cases Highest attack rates in 5-14 year olds Children serve as reservoir of infection

Persons at increased risk of infection Travelers Homosexual men Injecting drug users

Hepatitis A Vaccination StrategiesEpidemiologic Considerations

Pre-exposure Travelers to intermediate and high

HAV-endemic regions

Post-exposure (within 14 days)Routine Household and other intimate contactsSelected situations Institutions (Day care centers) Common source of exposure (Food prepared

by infected food handler)

Prevention – Immunoglobulin

Hepatitis B Virus Enveloped DNA virus

Core - HBcAg and HBeAg

Coat – HBsAg

HBV - 8 genotypes (A-H)

Incubation period: Average 60-90 days

Clinical illness (jaundice): <5 years, <10%5 years, 30%-50%

Acute case-fatality rate: 0.5%-1%

Chronic infection: <5 years, 30%-90%5 years, 2%-10%

Premature mortality fromchronic liver disease: 15%-25%

Hepatitis B - Clinical features

Chronic Hepatitis B 1. Chronic persistent hepatitis -

asymptomatic

2. Chronic active hepatitis -symptomatic exacerbations

3. Cirrhosis

4. Hepatocellular carcinoma (HCC)

Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc anti-HBsHBsAg

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

Acute Hepatitis B Virus Infection with RecoveryTypical Serologic Course

Weeks after Exposure

Titre

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

Weeks after Exposure

Titre

Progression to Chronic HBV InfectionTypical Serologic Course

High ModerateLow/Not

Detectable

Blood Semen UrineSerum Vaginal fluid Faeces

Wound exudates Saliva SweatTears

Breast milk

Concentration of Hepatitis B Virus in Various Body Fluids

Sexual - Sex workers and homosexuals

Parenteral - IDU and health workers

Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring during deliveryPerinatal transmission is the main means of transmission in high prevalence populations

Hepatitis B Virus Modes of Transmission

Diagnosis An array of serological tests are used for the diagnosis of

acute and chronic HBV infection HBsAg - Used as a general marker of infection Anti-HBs - Used to document recovery and/or immunity to

HBV infection anti-HBc IgM - Marker of acute infection anti-HBcIgG - Past or chronic infection HBeAg - Indicates active replication of virus/infectiveness Anti-HBe - Virus no longer replicating

The patient can still be positive for HBsAg HBV-DNA - Indicates active replication of virus, more

accurate than HBeAg Used mainly for monitoring response to therapy

Treatment Interferon alpha Lamivudine Adefovir Entecavir

Prevention Vaccination - Highly effective recombinant vaccines

Vaccinate those at increased risk of HBV infection (healthcare workers)Given routinely to neonates as universal vaccination

Hepatitis B Immunoglobulin - HBIG may be used toprotect persons who are exposed to hepatitis BIt is particular efficacious within 48 h of the incidentGiven to neonates who are at increased risk ofcontracting hepatitis – mothers HBsAg + HBeAg positive

Other measures - Screening of blood donors, blood andbody fluid precautions (ABC)

Hepatitis C virus (HCV) A flavivirus of RNA genome

HCV has a total of six genotypes (type 1 to 6)

Genotype 1 and 4 has a poorer prognosis and response to interferon therapy

Incubation period: Average 6-7 wks

Clinical illness (jaundice): 30-40% (20-30%)

Chronic hepatitis: 70%

Persistent infection: 85-100%

Immunity: No protective antibodyresponse identified

Hepatitis C - Clinical features

Chronic hepatitis C infection

The spectrum of chronic HCV infection is essentially the same as chronic HBV infection

All the manifestations of chronic HBV infection may be seen, with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis and HCC

Symptoms

anti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4

Hepatitis C Virus InfectionTypical Serologic Course

Titre

Months YearsTime after Exposure

Transfusion or transplant from infected donor

Injecting drug use (IDU) Hemodialysis (years on treatment) Accidental injuries with needles/sharps Sexual/household exposure to HCV RNA

positive contact Multiple sex partners Birth to HCV-infected mother

Risk factors associated with transmission of HCV

Laboratory diagnosis HCV antibody - Used to diagnose HCV infection

Not useful in the acute phase as it takes at least 4 weeks for the antibody to appear

HCV RNA - Various techniques are available e.g. PCR and qPCR used to diagnose HCV infection in the acute phase and in monitoring the response to antiviral therapy

HCV antigen - An ELISA for HCV antigen is available It is used in the same capacity as HCV RNA tests but is much easier to carry out

Treatment Interferon and Ribavirin in combination

Screening of blood, organ and tissue donors

High-risk behavior modification

Blood and body fluid precautions (ABC)

Prevention of Hepatitis C

HBsAg

RNA

antigen

Hepatitis D (Delta) Virus

Hepatitis D virus (HDV) The delta agent is a defective virus

The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg

The genome of the virus is very small and consists of RNA

Co-infection– Severe acute disease– Low risk of chronic infection

Superinfection– Usually develop chronic HDV infection– High risk of severe chronic liver disease– May present as an acute hepatitis

Hepatitis D - Clinical features

Hepatitis E virus

• Non enveloped RNA virus• Very labile and sensitive

Incubation period: Average 40 days

Case-fatality rate: Overall, 1%-3%Pregnant women, 15%-25%

Disease severity: Increased with age

Chronic sequelae: None identified

Hepatitis E - Clinical features

Outbreaks: Faecally contaminated drinking water

Large epidemics have occurred in the Indian subcontinent, China, Africa and Mexico

Hepatitis E -Epidemiologic features

Prevention and Control Avoid drinking water of unknown purity,

uncooked shellfish & uncooked fruits/vegetables Vaccine?

Following serological data for a 42 year old male that had a history of unprotected sexual encounter during his travel 5 weeks ago to China presented with fever, jaundice and malaise.

Laboratory findings

HBsAg - positive IgG anti-HBc - positive IgM anti-HBc - positive Anti-HBsAg - negative

Your diagnosis based on these findings is?

A. acute HBV infection B. acute HCV infection C. vaccinated against HBV D. super infection with HDVE. chronic HBV infection