Download Hepatitis Viruses

Hepatitis viruses
http://zamberi.tripod.com/index
Dr Zamberi Sekawi
BSc (Med), MD (UKM), MPath (Microbiol), AM (M’sia)
Clinical Microbiologist
Faculty of Medicine & Health Sciences
University Putra Malaysia
VIRAL HEPATITIS
Hepatitis
Hepatitis
Hepatitis
Hepatitis
Hepatitis
Hepatitis
A virus
B virus
C virus
D virus
E virus
G virus
Future:
? Hepatitis H virus
? Hepatitis I virus
? Hepatitis J virus
Etc…
HEPATITIS A VIRUS
Picornaviridae
Hepatovirus
Non-envelope, singlestranded RNA,
positive sense.
Only one serotype.
Incubation period:
2 – 6 weeks
Transmission:
• faecal-oral
• food/water
• blood product
Associated with poor personal hygiene and
overcrowding.
More symptomatic in adults.
Symptoms
Constitutional symptoms of anorexia, nausea
and vomiting, fatigue, malaise, arthralgias,
myalgias, headache, photophobia, pharyngitis,
cough, and coryza may precede the onset of
jaundice by 1 to 2 weeks.
Nausea, vomiting, and anorexia are frequently
associated with alterations in olfaction and
taste.
Dark urine and clay-coloured stools may be
present.
Tender hepatomegaly.
Fulminant hepatitis occurs in elderly and patients
with underlying liver disease.
Presentation:
Severe jaundice, neurological changes,
coagulopathy, renal failure, cardiopulmonary
failure.
High mortality rate.
Lab diagnosis
Serology:
IgM positive: recent
hepatitis A
IgG positive:
past hepatitis A
Prevention
Passive immunisation
Anti-HAV preparation.
Used in post-exposure prophylaxis.
Active immunisation
Formalin-inactivated vaccine.
Approved for use in those > 2 years old.
Recommended to selected groups of people, e.g.
travellers, food handlers, laboratory workers, etc.
Adults: 0, 6 - 12 months
Children: 0, 1, 6 – 12 months
HEPATITIS B VIRUS
Hepadnavirus
double-stranded DNA
HBsAg -- Anti-HBs
HBeAg -- Anti-HBe
HBcAg -- Anti-HBc
350 million chronic carriers world-wide.
Malaysia:  5%
Prevalence is highest in China, Africa (Sub-Sahara), South
East Asia and among Eskimos.
Transmission:
1. Blood product
2. Vertical transmission (predominant in endemic areas)
3. Sexual transmission
4. Intravenous drug abuse
Outcome in adult
Acute Hepatitis B
(25%)
Subclinical infection
(65%)
Chronic carriers
(10%)
Outcome in neonates
Acute Hepatitis B and
Subclinical infection
(10%)
Chronic carriers
(90%)
Adults
65%
Subclinical infection
10%
25%
Acute
Chronic Carrier
<1%
Fulminant
Hepatitis
Lifelong
Immunity
Death
Cirrhosis
Hepatocellular
Carcinoma
Acute hepatitis B
(1) Incubation period: 1 – 6 months.
HBsAg and HBeAg start to increase during this period.
Patient is infectious.
(2) Acute symptoms:
Jaundice, fever, nausea, right hypochondriac pain.
ALT reaches high level.
(3) The appearance of anti-HBe and anti-HBc antibodies.
HBeAg disappears.
Symptoms resolving.
(4) Window period
‘Window period’= period between disappearance of detectable
HBsAg and appearance of detectable anti-HBs by standard
laboratory test.
(5) Patient in convalescent state.
Anti-HBs, the protective antibody becomes detectable.
(6) Years later.
IgM anti-HBc disappears in 3 – 12 months.
IgG anti-HBc and persist for life.
Acute Hepatitis B
Chronic Hepatitis B
The presence of HBsAg in serum for 6 months or longer
after initial detection.
High risk groups:
1. Neonates
2. immunocompromised host
Majority is asymptomatic.
Minority experiences only mild and intermittent fatigue.
Chronic Hepatitis B
(1) Immune-tolerant phase
High viral replication.
The host is able to tolerate the presence of the virus.
(2) Immune-clearance phase.
Low viral replication.
Patient will enter this phase when tolerance to HBV break
down (about 15 – 35 years later).
Host actively tries to eradicate virus. Therefore, ALT are
raised.
There were increasing production of anti-HBe.
Most of liver damage happens during this time, leading to
cirrhosis.
The longer the duration of this phase, the greater the liver
damage. Hence the risk of liver cancer is high.
(3) Latent infection phase
Patient enters this phase once HBV-infected cells are
destroyed by the immune system.
Active replication cease and HBeAg disappear.
ALT normal. Anti-HBe positive.
HBsAg is still present. ‘Healthy carrier’.
Anti-HBs is never produced.
Chronic hepatitis B model
Patient will have cirrhosis and eventually die of
hepatocellular carcinoma (HCC).
Risk of acquiring HCC from chronic hepatitis B is 98 times
of the normal population.
Lab investigations
Serology:
1. HBsAg:
Presence of virus (acute or chronic)
2. HBeAg:
Active replication of HBV.
3. Anti-HBs: Immunity to HBV either by natural infection
or vaccination.
4. Anti-HBe: Low viral replication.
5. Anti-HBc: Ongoing or previous HBV infection
depending on IgM or IgG.
HBsAg
HBeAg
Anti-HBe
Anti-HBc IgM
Anti-HBc IgG
Anti-HBs
Acute
+
+
+
+
-
Conva
+
+
+
Chr Post-vac
+
+/-/+
+
+
Treatment
Acute hepatitis
Supportive.
Chronic hepatitis
Aim: to help the body to eradicate the virus. (during the
second phase).
Recommended for patients with:
• persistent levels of ALT in serum
• detectable levels of HBsAg, HBeAg and HBV DNA in
serum
• liver biopsy suggesting chronic hepatitis and
compensated liver disease.
Presence of anti-HBe and normal ALT (third phase) will
indicate the treatment is effective.
1.
2.
3.
4.
5.
 interferon
Pegylated  interferon
Lamivudine
Adefovir
Entecavir
Prevention
Three main strategies:
1. behaviour modification
2. active immunoprophylaxis
3. passive immunoprophylaxis
Active immunisation has been very successful.
Standard regimen: 0, 1 and 6 months
Highly efficacious (85 to 95% seroconversion).
Immunocompromised patients respond poorly to the
vaccine.
Passive immunoprophylaxis is used in:
1. neonates born to HBsAg-positive mothers.
Anti-HBs immunoglobulins should be given immediately
after delivery together with the recombinant HBV
vaccine. (90% protected)
2. after needlestick exposure.
3. after sexual exposure.
4. after liver transplantations in patients who are HBsAgpositive pretransplantation.
HEPATITIS C VIRUS
Flavivirus
single-stranded RNA, positive sense
6 genotypes (1 through 6).
Hepatitis C virus mutates very rapidly. Therefore, the
production of protective antibody is short-lived.
Vaccine production is very difficult.
Worldwide incidence: 1 – 2%
Higher rates in Eastern Europe and Africa (especially
Egypt).
Genotypes
1a :North and South America, Australia
1b:North America, Europe, Japan
2 :North America, West and Southern Europe
3 :Australia, Southern Asia
4 :Egypt, Central Africa
6 :Asia
Transmission:
1. Blood borne (especially blood transfusion)
2. Injection-drug abuse
3. Vertical transmission (uncommon)
4. Multiple sexual partners
Incubation period: 2 weeks
Associated with extrahepatic manifestation.
E.g. mixed cryoglobulinaemia and
membranoproliferative glomerulonephritis.
Primary
Hepatitis C
5 – 20%
Clearance
80 - 95%
Persistance infection
(Chronic Hepatitis C)
Cirrhosis
20 years
DEATH
Hepatocellular
carcinoma
Laboratory diagnosis
1. Screening: Serology. e.g. ELISA.
2. Confirmation:
Immunoblot assay e.g. RIBA, LIA
Genome detection. e.g. PCR.
Treatment and prevention
Treatment:
a) IFN  monotherapy
Sustained response rate for:
6-month therapy = 10 – 20%
12 – 18-month therapy = 15 – 30%
b) Combination IFN  and ribavirin
Sustained response rate:  40%
(Sustained response: normal ALT  undetectable HCV RNA
6 months after completion of therapy)
Interferon therapy is indicated in patients who are at the
greatest risk for progression to cirrhosis:
1. Persistently elevated ALT > 6 months.
2. Detectable serum HCV RNA by a qualitative or
quantitative assay.
3. Liver biopsy = grade 2 or 3 fibrosis.
4. Moderate degrees of liver inflammation and necrosis.
No vaccine is available.
HEPATITIS D VIRUS
a.k.a. delta hepatitis
agent.
Defective RNA virus,
requires HBV for its
replication.
Worldwide distribution with endemicity in the
Mediterranean countries.
HDV can either:
 infect a person simultaneously with HBV (coinfection) or
 superinfect a person already infected with HBV
(superinfection).
Duration of HDV infection is determined by duration of
HBV infection.
Serology
No specific treatment.
Prevention by giving HBV vaccine.
HEPATITIS E VIRUS
Non-envelope, single-stranded RNA, positive sense.
World wide distribution.
Causes acute hepatitis. High mortality among pregnant
women.
HEPATITIS G VIRUS
Also known as GBV-C.
Genome: single-stranded RNA, positive sense.
25% similar to hepatitis C.
Transmission:
1.
Blood transfusion
2.
Injecting drug users
Hepatic damage appears to be mild or absent.
Role as a causative agent is still questionable.
Enquiries:
03 – 8946 8459
[email protected]
[email protected]
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