Hepatitis A-E Viruses

An Overview
 Viral Hepatitis - Historical Perspectives

“Infectious” A Enterically
E
transmitted

Viral hepatitis NANB

Parenterally
“Serum” B D C transmitted

F, G, TTV
? other
 Acute viral hepatitis
Introduction
 Systemic viral infection predominantly affecting the
liver
 Common causes - Hepatitis A,B,C,D,E
viruses
 Other viruses – CMV, herpes simplex etc.
 Type of Hepatitis
A B C D E

Source of feces blood/ blood/ blood/ feces

virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
 ABC of ABCDE
 Hepatitis-A – self limiting, 1% fatality
 Hepatitis-E - self limiting, 1 – 3% fatality
- pregnancy, 25% fatality
 Hepatitis- B - self limiting in 95% of adults
- chronicity more in children
 Hepatitis-C – self limiting in 20 – 50%
- >90% if treated with IFN
 Hepatitis –D – Super infection of Hep-B
 Acute viral hepatitis
Symptoms & signs

 Jaundice  Fatigue
 Anorexia  Abdominal pain
 Nausea  Hepatomegaly
 Ascites(sub acute
 Fever
phase)
 Acute viral hepatitis
Investigations

 Bilirubin, SGPT
 Alkaline phosphatase
 Hypoalbuminaemia - Sub acute hepatitis
- Chronic liver disease
- to assess hepatic function
 Prothrombin time – to assess hepatic function
 Haemoglobin, Creatinine
 Acute viral hepatitis
Immunology

 Acute Hepatitis-A - IgM anti-HAV+

 Acute Hepatitis-B - HBsAg+,anti HBcIgM+
 Acute Hepatitis-C - HCV RNA+
 Acute Hepatitis-E - Anti HEV IgM
 Acute viral hepatitis
Imaging

 Ultrasound scan
- Size, surface and density of liver
- To rule out chronic liver disease
- To rule out biliary obstruction
- To diagnose ascites
 CT & MRI rarely necessary
 Acute viral hepatitis
Management
 Mainly supportive care
 Rest – but not absolute bed rest
 No hospitalisation unless high risk for FHF
 Mixed diet with no exceptions
 Vitamin supplements - ? placebo value
 Hygiene is very important
 Acute viral hepatitis
Management

 Immunisation of close family (HAV & HBV)

 Follow up until HBsAg is negative
 Follow up until LFTs are normal
 Weekly monitoring of total bilirubin and PT
 Acute viral hepatitis
Management

 No hepato supportive medicines

 No herbal medicines
 No anti virals (but for HCV)
 No branding
 No alcohol
 No pill & no HRT
 Acute viral hepatitis - C
Management

 HCV RNA for early detection

 Treatment with alpha Interferon useful
 Indication – HCV RNA +ve
 Reduces risk of chronicity from 80% to10%
 No pre exposure prophylaxis
 Acute Viral Hepatitis
Indicators of poor prognosis

 Prolonged jaundice
 Altered sensorium
 Ascites
 Oliguria
 Prolonged prothrombin time(>3 secs)
 Impaired renal function
Hepatitis A Virus
 Hepatitis A - Clinical
Features
 Incubation period: Average 30 days
Range 15-
50 days
 Jaundice by <6 yrs, <10%
age group: 6-14 yrs, 40%-
50%
>14 yrs,
70%-80%
 Complications: Fulminant
hepatitis

Cholestatic hepatitis
 Hepatitis A Infection
Typical Serological Course
Symptoms Total anti-
HAV

Titre ALT

Fecal
HAV
IgM anti-HAV

0 1 2 3 4 5 6 12 24
Months after exposure
 Hepatitis A Virus Transmission
 Close personal contact
(e.g., household contact, sex contact,
child day care centers)
 Contaminated food, water
(e.g., infected food handlers, raw
shellfish)
 Blood exposure (rare)
(e.g., injecting drug use, transfusion)
 Laboratory Diagnosis
 Acute infection is diagnosed by the
detection of HAV-IgM in serum by EIA.
 Past Infection i.e. immunity is determined
by the detection of HAV-IgG by EIA.
 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

 Hepatitis A Prevention - Immune
Globulin
 Pre-exposure
 travelers to intermediate and high
HAV-endemic regions
 Post-exposure (within 14 days)
Routine
 household and other intimate contacts

Selected situations
 institutions (e.g., day care centers)

 common source exposure (e.g., food prepared by

infected food handler)

Hepatitis B Virus
 Hepatitis B - Clinical Features

 Incubation period: Average 60-90 days

Range 45-180
days
 Clinical illness (jaundice): <5 yrs, <10%
5 yrs, 30%-50%
 Acute case-fatality rate: 0.5%-1%
 Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10%
 Premature mortality from
chronic liver disease: 15%-25%
Hepatitis B - Virus
 Hepa DNA virus
- HBsAg(surface antigen)
- HBeAg
- HBcAg
- HBVDNA
-HBVDNA polymerase
 Concentration of Hepatitis B
Virus in Various Body Fluids

Low/Not
High Moderate Detectable

blood semen urine

serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
 Hepatitis B Virus
Modes of Transmission
 Sexual - sex workers and homosexuals are
particular at risk.
 Parenteral - IVDA, Health Workers are at
increased risk.
 Perinatal - Mothers who are HBeAg positive are
much more likely to transmit to their offspring
than those who are not. Perinatal transmission is
the main means of transmission in high
prevalence populations.
Hepatitis B
Mode of transmission
 Vertical – mother to child
 Blood transfusions
 Sexual transmission
 Needle stick injuries
 Tattooing
 Ear & nose piercing
 Diagnosis
 A battery of serological tests are used for the diagnosis of
acute and chronic hepatitis B infection.
 HBsAg - used as a general marker of infection.
 HBsAb - 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 and therefore
infectiveness.
 Anti-Hbe - virus no longer replicating. However, the patient
can still be positive for HBsAg which is made by integrated
HBV.
 Acute Hepatitis B Virus Infection with
Recovery Typical Serologic Course
Symptoms
HBeAg anti-HBe

Total anti-HBc
Titre

HBsAg IgM anti-HBc anti-HBs

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

Weeks after Exposure

Progression to Chronic Hepatitis B Virus Infection:
Typical Serologic Course
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
 Outcome of Hepatitis B Virus Infection
100 by Age at Infection 100

80
80

Symptomatic Infection (%)

(%)
Chronic Infection

60 60
Chronic Infection

40 Chronic Infection (%) 40

20 20

Symptomatic Infection
0 0
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
Age at Infection
 Serological markers made easy

 HBsAg  Acute / chronic infection

 Anti HBcIgM  Recent infection

 HBeAg  High infectivity
 Anti HBe  Low infectivity
 Anti HBs  Immunity (vaccinated)
 Anti HBcIgG & HBsAg  Chronic infection
 Anti HBcIgG & anti HBs  Resolved infection
 Prevention

 Vaccination - highly effective recombinant vaccines are now

available. Vaccine can be given to those who are at increased risk
of HBV infection such as health care workers. It is also given
routinely to neonates as universal vaccination in many countries.
 Hepatitis B Immunoglobulin - HBIG may be used to protect
persons who are exposed to hepatitis B. It is particular efficacious
within 48 hours of the incident. It may also be given to neonates
who are at increased risk of contracting hepatitis B i.e. whose
mothers are HBsAg and HBeAg positive.
 Other measures - screening of blood donors, blood and body fluid
precautions.
 Hepatitis-B – Prevention

 Proper screening for blood transfusion

 Proper disposal of needles
 Immunisation of high risk groups
 Immunisation of babies born to HBsAg positive mothers
 Hepatitis B - Vaccines

 Engerix B etc.,
 Recombinant vaccines
 Produced by yeast cells
 Protective efficacy more than 90%
 Reduces carrier pool significantly
 Immunogenicity-
Hep-B Vaccine
 Protective response = anti HBs > 10mIU/ml
(>90% adults, >95% children)
 Reduced immunogenicity
- Older age, male sex, smoking, obesity etc
- Immunosupression
- Chronic medical illness
 Who should be vaccinated?
 All infants
 Children and adolescents
 Children born to HBsAg +ve mums
 Contacts of carriers
 Haemodialysis patients
 Haemophiliacs
 Health care workers
 Dosage Recommendations

 Children < 10 yrs - 0.5ml – 0,1 & 6m

 Adults - 1.0ml - 0,1 & 6m
 Haemodialysis pts - 2.0ml- 0,1 & 6m
 Non responders - Additional schedule
 Other approved schedule –0,1,2 & 12m
 Hepatitis – B
Post exposure – prophylaxis

 Needle stick or sexual exposure

 HBIg 0.04 to 0.07ml/kg or 1000 to 2000IU IM
 Given as soon as possible after exposure
 Immunisation, initiated at the same time
 Definition:chronic hepatitis B

 Chronic necroinflammatory disease of liver

caused by persistent HBV infection.
Spectrum of Chronic Hepatitis B Diseases

1. Chronic Persistent Hepatitis -

asymptomatic
2. Chronic Active Hepatitis -
symptomatic exacerbations of hepatitis
3. Cirrhosis of Liver
4. Hepatocellular Carcinoma
 Diagnostic Criteria
 Chronic hepatitis B
- HBsAg +ve >6 months
- Serum HBV DNA >105copies/ML
- Persistent or intermittent elevation of
ALT/AST levels
- Liver biopsy showing chronic hepatitis
 Therapeutic Agents for Hepatitis B
Nucleoside analog
Immune Modulators
 Lamivudine
 Interferon
 Adefovir
 Thymosin
 Entecavir
 Therapeutic vaccines
 Clevudine

 Famciclovir
 Goals of Treatment
 Prevent long-term clinical outcomes
- Cirrhosis, Hepato cellular carcinoma, mortality
- By durable suppression of HBV DNA
 Treatment end points
- Normalize ALT
- HBV DNA
- Induce HBeAg loss
- Histological improvement
 Hepatitis C Virus

capsid envelope protease/helicase RNA-dependentRNA polymerase

protein

c22 33c c-100

5’ 3’

core E1 E2 NS2 NS3 NS4 NS5

hypervariable
region
 Hepatitis C - Clinical Features

Incubation period: Average 6-7

wks
Range
2-26 wks
Clinical illness (jaundice): 30-40% (20-30%)
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective

antibody
 Chronic Hepatitis C Infection
 The spectrum of chronic hepatitis C infection is
essentially the same as chronic hepatitis B
infection.
 All the manifestations of chronic hepatitis B
infection may be seen, albeit with a lower
frequency i.e. chronic persistent hepatitis, chronic
active hepatitis, cirrhosis, and hepatocellular
carcinoma.
Natural history of HCV

Acute Hepatitis C

Chronic Hepatitis
50 – 85% 10 – 30
years

Cirrhosis
20 – 30%

Decompensation Hepatocellular Carcinoma

6 - 10% 5 - 10%

Death
5 - 10%
 Hepatitis C Virus Infection
Typical Serologic Course
anti-
HCV
Symptoms

Titre

ALT

Normal
0 1 2 3 4 5 6 1 2 3 4
Month Years
s Time after Exposure
 Risk Factors Associated with
Transmission of HCV

 Transfusion or transplant from infected donor

 Injecting drug use
 Hemodialysis (yrs on treatment)
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-positive
contact
 Multiple sex partners
 Birth to HCV-infected mother
 Laboratory Diagnosis
 HCV antibody - generally used to diagnose hepatitis C
infection. Not useful in the acute phase as it takes at least 4
weeks after infection before antibody appears.
 HCV-RNA - various techniques are available e.g. PCR and
branched DNA. May be used to diagnose HCV infection in
the acute phase. However, its main use is in monitoring the
response to antiviral therapy.
 HCV-antigen - an EIA for HCV antigen is available. It is
used in the same capacity as HCV-RNA tests but is much
easier to carry out.
Candidates for Therapy

 Acute Hepatitis C

 Chronic Hepatitis C
Non cirrhotic
Compensated cirrhosis
HAI
ALT
 Treatment
 Interferon - may be considered for patients with
chronic active hepatitis. The response rate is around
50% but 50% of responders will relapse upon
withdrawal of treatment.
 Ribavirin - there is less experience with ribavirin than
interferon. However, recent studies suggest that a
combination of interferon and ribavirin is more
effective than interferon alone.
 Prevention of Hepatitis C

 Screening of blood, organ, tissue donors

 High-risk behavior modification
 Blood and body fluid precautions
 Hepatitis D (Delta) Virus
 antigen HBsAg

RNA
 Hepatitis D - Clinical Features

 Coinfection
– 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 Virus Modes
of Transmission

 Percutanous exposures
 injecting drug use
 Permucosal exposures
 sex contact
 HBV - HDV Coinfection
Typical Serologic Course
Symptoms

ALT Elevated

Titre
anti-HBs
IgM anti-HDV

HDV RNA

HBsAg
Total anti-HDV

Time after Exposure

 HBV - HDV Superinfection
Typical Serologic Course
Jaundice

Symptoms

Total anti-HDV
ALT
Titre

HDV RNA
HBsAg

IgM anti-HDV

Time after Exposure

 Hepatitis D - Prevention
 HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent
HBV infection.
 HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection.
Hepatitis E Virus
 Hepatitis E - Clinical Features

 Incubation period: Average 40 days

Range 15-
60 days
 Case-fatality rate: Overall, 1%-3%
Pregnant
women,
15%-25%
 Illness severity: Increased with
age
 Hepatitis E Virus: Typical Serologic Co
Infection
Symptoms

ALT IgG anti-HEV

Titer IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 1 11 1 1
0 2 3
Weeks after Exposure
 Hepatitis E -
Epidemiologic Features
 Most outbreaks associated with faecally contaminated
drinking water.
 Several other large epidemics have occurred since in
the Indian subcontinent and the USSR, China, Africa
and Mexico.
 In the United States and other nonendemic areas,
where outbreaks of hepatitis E have not been
documented to occur, a low prevalence of anti-HEV
(<2%) has been found in healthy populations. The
source of infection for these persons is unknown.
 Minimal person-to-person transmission.
 Prevention and Control Measures for
Travelers to HEV-Endemic Regions

 Avoid drinking water (and beverages with ice) of

unknown purity, uncooked shellfish, and uncooked
fruit/vegetables not peeled or prepared by traveler.
 IG prepared from donors in Western countries
does not prevent infection.
 Unknown efficacy of IG prepared from donors in
endemic areas.
 Vaccine?