hepatitis profile [الأرشيف] - مختبرات العرب

كروموسومة

23-07-2008, 07:05 PM

Hepatitis B Virus
Hepatitis B Virus (HBV)
Family Hepadnaviridae
Morphology
A small, enveloped DNA virus (42nm)
Icosahedral nucleocapsid
Small, circular partially double-stranded DNA genome
Within the core, there is DNA- dependent DNA polymerase
HBV antigens:
HBsAg, located in the envelope
HBcAg, located in the core
HBeAg, located in the core

Hepatitis B Virus (HBV)
Electron microscopy of a patient’s serum reveals 3 different types of particles:
A few 42nm virions
Many 22nm spheres and long filaments 22nm wide, both are composed of surface Ag
These spheres and filaments are the immunogens in one form of the vaccine (the inactivated vaccine)

Different particles in patient’s serum

HBV : Epidemiology
Routes of Transmission
Contaminated blood and blood components
Transfusion,
Needle sharing, acupuncture
Ear piercing,or tattooing
Very close personal contact involving exchange of
saliva, semen & vaginal secretions (sexual contact)
During childbirth from mother to child
Have 90% chance of acquiring hepatitis B infection
HBV : Epidemiology
Seroprevalance
Worldwide in distribution
Is highly endemic in the Far East, sub-Saharan Africa, the Middle East and parts of South America
In Saudi Arabia the seropositivity rate varies with an average of 8.7%

HBV : Epidemiology
High risk groups
Persons from endemic regions
Babies of mothers with chronic HBV infection
I.V drug abusers
Persons with multiple sex partners
Hemophiliacs
Hemodialysis patients
Health care personnel who are in contact with blood

HBV : Clinical Features
Incubation period
The mean incubation period is 10-12 weeks
Acute infection:
Prodromal Phase
Fever, malaise, and anorexia with nausea, vomiting, abdominal discomfort
Classic Icteric Phase
Has symptoms of liver damage:
Jaundice
Dark urine
Pale stools
Most patients (90%) who develop acute infection recover completely

HBV : Clinical Features
Fulminant Hepatitis
In approximately 1% of patients & may be fatal
Chronic Hepatitis
Occurs in 5-10% of infected patients
May be detected only by finding elevated liver
enzymes on routine examination
Is characterised by the presence of HBsAg in
the blood for more than 6 months.
HBV : Clinical Features
Chronic Hepatitis : 4 Groups
1. Resolution of Infection
in 50% of patients
2. Asymptomatic Carrier State
Is associated with normal liver functions
Are sero-negative for HBeAg, HBV-DNA.
Only HBsAg is present in circulation
HBV : Clinical Features
3. Chronic Persistent Hepatitis
Is characterised by mild symptoms like fatigue & discomfort over the liver region
Liver enzymes >5 times upper limit
4. Chronic Active Hepatitis
Persistent elevation of serum aminotransferases
May develop cirrhosis and liver failure
Complication of HBV infection
Primary Hepatocellular Carcinoma (PHC)
80% of all cases of PHC is due to chronic HBV infections

HBV : Infection Markers
1. HBsAg
Usually detectable 2-6 weeks prior to clinical and biochemical evidence of hepatitis and persists throughout the clinical course of the disease (6-12 weeks), typically disappears by the sixth month after exposure
If >6 months = chronic infection
serum, saliva, tears, breast milk, bile duct and urine
All HBsAg-positive materials are potentially infectious for HBV, unless treated.

HBV : Infection Markers
2. HBeAg
The second antigen that appears in circulation
Arise during the incubation period and is present during the prodrome and early acute disease
There is a high correlation between HBeAg and infectivity
Specimens positive for HBeAg are considered to be highly infectious i,e., they contain high concentrations of HBV
Infectivity is reduced, but probably not eliminated, in specimens containing anti- HBe
Persistent positivity for HBeAg, in the absence of anti- HBe, correlates with chronic liver infection
HBV : Infection Markers
3. Anti-HBc
Anti- HBc IgM is detected approximately 2-4 weeks after HBsAg appears.
Because this Ab is directed against the internal core component of HBV, its appearance in serum indicates viral replication
High titers of IgM-anti-HBc are detected in acute hepatitis B
In early convalescence, HBsAg may be undetectable in serum, in that case, the IgM-anti-HBc will establish the diagnosis
Anti- HBc of the IgG class remains detectable long after exposure to infection
HBV : Infection Markers
4. Anti-HBe
Usually appears after the disappearance of HBeAg
Its presence indicates low infectivity
5. Anti-HBs
Generally appears within a few weeks after HBsAg
is cleared from circulation
Once produced, anti-HBs persists for years
Is the only marker for immunity against HBV infection

HB Serological Markers
HBV : Laboratory diagnosis
Both ELISA and RIA assays are available
The most important laboratory test to detect early HBV infection is the immunoassay for HBsAg.
HBsAg appears during the incubation period and is detectable in most patients during the prodrome and acute disease. It falls to undetectable levels during convalescence. Its prolonged presence indicates carrier state
There is a period of several weeks when HBsAg has disappeared but HBsAb is not yet detectable, this is the “window phase” at which the HBcAb is always positive and can be used to make the diagnosis
The test for HBcAg is not readily available

HBV : Treatment & Prevention
IFN-alpha is currently used to treat chronic HBV infection
Hepatitis B immune globulin (HBIG) :
Contains a high titer of HBsAb
Provides immediate passive protection to
Persons exposed to HBsAg positive blood within a week of exposure, e.g, after an accidental needle- stick &
To newborn infants of HBsAg-positive mother
Screening donated blood for HBsAg and IgM anti-HBc
Transmission of HBV by blood or blood products has
been greatly reduced
Avoiding intimate personal contact with a HBV carrier
General hygienic measures: the use of gloves when blood or other samples are collected and the use of disposable needles and syringes.
HBV : Treatment & Prevention
Recommendation for neonates born to
HBsAg & HBeAg-positive mother
1. Hepatitis B Immunoglobulin at birth
2. Vaccination
The vaccine contains HBsAg produced in yeasts by genetic engineering technique
Is administered intramuscular in 3 doses at 0, 1, and 6 months, booster is recommended every 5 years
Prior to the advent of this vaccine, an inactivated vaccine consisting of HBsAg prepared from spherical particles purified from the serum of infected individuals was used
Both vaccines are highly effective in preventing hepatitis B and have few side effects

Hepatitis B vaccine produced using cloned genes
HBsAg gene can be cloned into plasmids
The cloned DNA can then be expressed in prokaryotic (bacteria) or eukaryotic (yeast) cells which produce the antigen in sufficient quantity
The produced antigen is then purified giving a vaccine which contains only the immunizing protein antigen

HBV vaccine
The vaccine is indicated for people who are frequently exposed to blood or blood products, such as:
Certain health care personnel e.g, laboratory personnel, medical students, surgeons, dentists
Patients receiving multiple transfusions or dialysis
IV drug abusers
HB vaccine is given to all infants in Saudi Arabia
HDV (delta agent) : Transmission & Pathogenesis
HDV is an enveloped virus with circular ssRNA genome, the internal core protein is called delta antigen
HDV is a defective virus, it can not replicate by itself, because it does not have the genes for its protein coat
HDV can replicate only in cells also infected with HBV, because HDV uses the surface antigen of HBV (HBsAg) as its coat

HDV is transmitted along with HBV
Either at the time of first infection (co-infection) OR
During chronic HBV infection (super-infection)
HDV is transmitted by the same means like HBV
More rapid & severe progression in
super-infection than in co-infection

HDV : Clinical syndromes
Incubation period : 3-7 weeks
Increases the severity of HBV infections
Is responsible for 40% of fulminant hepatitis
Can result in massive liver necrosis & hepatic encephalopathy

Laboratory diagnosis, treatment and prevention of HDV
The diagnosis is made by detecting either delta antigen or IgM antibody to delta antigen in the patient’s serum
Alpha interferon can diminish some of the effects of the chronic hepatitis caused by HDV but does not eradicate the chronic carrier state
There is no specific antiviral therapy against HDV
There is no vaccine against HDV, but a person immunized against HBV will not be infected by HDV