Hepatitis A-E Viruses

Dr F Noordeen Department of Microbiology Faculty of Medicine Peradeniya May 2013

Learning outcomes
Modes of transmission and the pathogenesis of viral hepatitis in humans Main clinical features of viral hepatitis Principles of diagnosis, management and prevention viral hepatitis in humans

Viral Hepatitis - Historical Perspectives

Infectious Viral hepatitis

A
NANB

Enterically E transmitted

Serum

B D

Parenterally C transmitted F, G other?

Hepatitis A-E
A
Source of virus Faeces

E
Faeces

Blood/ Blood/ Blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids Percutaneous Percutaneous Percutaneous permucosal permucosal permucosal Yes Yes Yes

Route of transmission Chronic infection Prevention

Fecal-oral

Fecal-oral

No

No

Pre/postPre/postBlood donor Pre/postEnsure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification

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

Hepatitis A - Clinical features

Incubation period:

Average 30 days Range 15-50 days <6 years, <10% 6-14 years, 40%-50% >14 years, 70%-80% Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis None

Jaundice by age group:

Complications:

Chronic sequelae:

Hepatitis A infection
Typical Serological Course
Symptoms

Total anti-HAV

Titre
Faecal HAV

ALT

IgM anti-HAV

Months after exposure

1 2

2 4

Transmission of Hepatitis A

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)

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

Hepatitis A Vaccination Strategies Epidemiologic Considerations

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

Prevention Immunoglobulin

Pre-exposure

Travelers to intermediate and high HAV-endemic regions

Post-exposure (within 14 days)

Routine Household and other intimate contacts Selected situations Institutions (Day care centers) Common source of exposure (Food prepared by infected food handler)

Hepatitis B Virus

Enveloped DNA virus Core - HBcAg and HBeAg Coat HBsAg HBV - 8 genotypes (A-H)

Hepatitis B - Clinical features

Incubation period: Clinical illness (jaundice): Average 60-90 days <5 years, <10% 5 years, 30%-50% 0.5%-1% <5 years, 30%-90% 5 years, 2%-10%

Acute case-fatality rate: Chronic infection:

Premature mortality from chronic liver disease:

15%-25%

Chronic Hepatitis B
1. Chronic persistent hepatitis asymptomatic 2. Chronic active hepatitis symptomatic exacerbations 3. Cirrhosis 4. Hepatocellular carcinoma (HCC)

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course

Symptoms HBeAg anti-HBe

Total anti-HBc

Titre
HBsAg IgM anti-HBc anti-HBs

12 16 20 24 28 32 36

52

100

Weeks after Exposure

Progression to Chronic HBV Infection Typical Serologic Course

Acute (6 months) HBeAg HBsAg Total anti-HBc Chronic (Years) anti-HBe

Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36

52

Years

Weeks after Exposure

Concentration of Hepatitis B Virus in Various Body Fluids

High Moderate Low/Not Detectable Urine Faeces Sweat Tears Breast milk

Blood Semen Serum Vaginal fluid Wound exudates Saliva

Hepatitis B Virus Modes of Transmission

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 delivery Perinatal transmission is the main means of transmission in high prevalence populations

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 (health care workers) Given routinely to neonates as universal vaccination Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B It is particular efficacious within 48 h of the incident Given to neonates who are at increased risk of contracting hepatitis mothers HBsAg + HBeAg positive

Other measures - Screening of blood donors, blood and body 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

Hepatitis C - Clinical features

Incubation period: Clinical illness (jaundice): Chronic hepatitis: Persistent infection: Immunity: Average 6-7 wks 30-40% (20-30%) 70% 85-100% No protective antibody response identified

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

Hepatitis C Virus Infection

Typical Serologic Course
Symptoms

antiHCV

Titre

ALT

Normal 0 1 2 3 4 Months 5 6 1 2 3 Years 4

Time after Exposure

Risk factors associated with transmission of HCV

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

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

Prevention of Hepatitis C
Screening of blood, organ and tissue donors High-risk behavior modification Blood and body fluid precautions (ABC)

Hepatitis D (Delta) Virus

antigen HBsAg

RNA

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

Hepatitis D - Clinical features

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 E virus

Non enveloped RNA virus Very labile and sensitive

Hepatitis E - Clinical features

Incubation period: Case-fatality rate:

Average 40 days Overall, 1%-3% Pregnant women, 15%-25% Increased with age None identified

Disease severity: Chronic sequelae:

Hepatitis E Epidemiologic features

Outbreaks: Faecally contaminated drinking water Large epidemics have occurred in the Indian subcontinent, China, Africa and Mexico

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

Your diagnosis based on these findings is? A. acute HBV infection B. acute HCV infection C. vaccinated against HBV D. super infection with HDV E. chronic HBV infection