Hepatitis Viruses - part 1 Flashcards
HAV, HBV, HEV
Viral hepatitis - types
HAV, HBV, HCV, HDV, HEV
Hepatitis as a complication
- Yellow fever, CMV, EBV, HSV
- Entero, Rubela, Adeno
Hepatitis A common name
Infectious
Naked, RNA, picornavirus is the virus structure of ?
Hepatitis A
Transmission - Hep A
Fecal-oral
Incubation period - Hep A
Short
Usual onset - Hep A
Abrupt
Mild or asymptomatic severity for which virus?
Hep A
Very low mortality rate for which virus?
Hep A
Chronicity/carrier state for Hep A?
None
Hep A has other disease associations (T/F)
False
The common name for Hepatitis B is serum (T/F)
True
Virus structure for Hep B
Envelope, DNA, hepadnavirus
The transmission of Hep B is fecal oral (T/F)
False; parenteral and sexual
Incubation period - Hep B
Long
The usual onset of Hep B is?
Insidious (gradual)
The severity of Hep B is occasionally severe (T/F)
True
Mortality rate - Hep B
Low
Presence of chronicity/Carrier state - Hep B
Yes
Hep B has other disease associations which are?
HCC, Cirrhosis
HCC - explain
Hepatocellular carcinoma - primary liver cancer
In chronic infection for Hepatitis, the virus continues to replicate in liver cells causing continued immune response leading to cell death.
Since the liver regenerates, mitosis occurs consistently.
Also due to cell death, scar tissue forms leading to high chance for cirrhosis.
With higher rates of mitosis, replication must occur more often and this leads to higher chances of mutations = cellular dysplasia (abnormal development of cells+tissues) causing HCC
Hepatitis C common name
Posttransfusion non A, non B
(Hepatitis was found in some persons receiving blood transfusions; HepA is rare to contract from post transfusion and Hep B is usually asymptomatic. Cases of non A, non B Hepatitis is referred to as Hep C)
Incubation period of Hep C is short (T/F)
False; it is long
Usual onset of Hep C is abrupt (T/F)
False; it is insidious
Subclinical - define
relating to or denoting a disease which is not severe enough to present definite or readily observable symptoms.
Severity of Hep C is usually subclinical (T/F)
True
Mortality rate for Hep B and Hep C is low (T/F)
True
Chronicity/carrier states are common in Hep C (T/F)
True
HCC and Cirrhosis are other disease associations of Hep B and Hep C (T/F)
True
Hepatitis D - common name is Delta (T/F)
True
Hep D causes symptoms only in people who also have hepatitis B infection (T/F)
True
Transmission of Hep B,C and D are all parenteral and sexual
True
Incubation period - Hep D
Intermediate
Onset of Hep D is?
Abrupt
Occasionally to often severe - severity of Hep D (T/F)
True
Mild severity but severe in pregnant women is the severity of which Hepatitis virus?
Hepatitis E
Mortality rate of Hep D is?
High to very high
Chronicity/ carrier state for Hep D exists?
Yes
Fulminant hepatitis - define
Severe liver function impairment
Cirrhosis, fulminant hepatitis are the disease associations of which hepatitis virus?
Hepatitis D
Enteric - define
Illness occurring in intestines
Hepatitis E common name
Enteric non A, non B
Envelope RNA, flavivirus - which hep virus structure?
Hep C
Envelope RNA - which hep virus structure?
Hep D
Naked RNA, calici like - which hep virus structure?
Hep E
Hep A and Hep E transmission is by fecal oral route (T/F)
True
Incubation period Hep E
Short
Incubation period for Hep A and Hep E
Short
Usual onset of Hep E
Abrupt
Usual onset of Hep A, Hep D, Hep E
Abrupt
Hepatitis E mortality rate is low except for which demographic?
Pregnant women
There is no carrier state in Hep E (T/F)
True
Hep E - disease associations
None
Icosahedral symmetry, non-enveloped - which virus?
Hep A
How many serotypes of Hep A are there?
One
Types of cell cultures for Hep A
Human & simian (ape) cell cultures
How to inactivate hep A
Inactivated by boiling in 1 minute, formalin, chlorine
Whole virus particle
Vaccine is made using the entire virus particle, this is usually done by heating
Antibody - anti HAV
Virus shedding of Hep A is done by
Feces
Communicability - Hep A
2 weeks before to 1 week after onset
Risk factors - Hep A
Poor personal hygiene & Overcrowding
Prognosis for Hep A is usually good (T/F)
True
Hepatitis virus pathogenesis
- Entry- mouth
- Viral multiplies in intestinal epithelium
ssRNA - HAV, HCV, HDV, HEV
pdsDNA (partially ds) - HBV - Reaches its destination i.e. liver by haematogenous spread where it multiplies
Enters cell via endocytosis
Synthesize proteins via ribosomes (+)
RNA dep RNA polymerase synthesizes more RNA
HBV
Endocytosis
Uncoating - release envelope + antigens
DNA repair enzymes finish the double strand (e.g. if it’s 75% finished)
mRNA made to make proteins e.g. capsomeres
Pregenomic RNA - Hep B is type of retrovirus
Reverse transcriptase converts RNA -> ssDNA then partial dsDNA forms
– Can potentially become incorporated into genome and viral replication will occur infinitely
Lysis of hepatocyte = cell death - Liver cell death due to immune response
Infecteded cell secreted IFN-gamma which activates macrophages which activates CD8T cells
CTLs recognize antigen on MHC I of nucleated liver cell
Perforins - cause holes to form in liver cells
Granzymes - enter through holes inducing apoptosis/programmed cell death - Brief viremia (presence of virus in blood)
- Fever + malaise presentation
Cytokines produced by damaged liver cells
IL-1, IL-6, TNF-alpha
These cytokines stimulate hypothalmus to cause fever - Nausea + vomiting
Toxins (hepatotoxins) accumulate in blood and go to CNS
Chemotrigger zone sensitive to hepatotoxins
Chemotrigger sends signal to ammetic center
Ammetic centre activates nerves in GIT = retroperistalsis (vomiting/reverse peristalsis)
Can also have diarrhoea
- Low electrolytes , weight loss - Icterus, Jaundice, Dark Urine
Hemoglobin -> Heme -> Biluribin (unconjugated) -UCB
UB taken to liver to be converted to conjugated bilurubin (CB)
Liver cells are lysing so UCB and CB spill out of liver cells and into blood
Bile acids accumulate in blood also due to blockage
Conc’n of UCB, CB, bile acids are high in blood so moves to diff tissues ( Yellow Eye - sclera = icterus, Palms + Soles yellow colour = jaundice )
CB in urine because kidneys filter CB but large increase will cause dark urine - Clay coloured stools - icteric phase
Bile is broken down by bact in gut so decreased bile due to failed liver = decreased bilurubin in gut. Product of broken down bilurubin = brown colour of stools
So stools will be clay coloured instead. - Hepatomegaly - icteric phase
Right upper quadrant abd pain - Virus present in blood and feces 10 -12 days after infection
- Virus excretion in feces-During late Icteric Phase (affected by jaundice) and Preicteric (before jaundice) Phase
For HBV, HCV
— Plasma cells produce antibodies against Hep virus
– Antibodies bind to virus forming a complex which deposits into tissues
E.g. in synovial joints – Arthritis
in BV – vasculitis
In pericardium + myocardium – Myocarditis + pericarditis
In glomurela basement of kidney – glomerulonephritis
What is the most common cause of acute hepatitis in children ?
Hep A
What are the stages of Hep A?
1) Prodromal or Preicteric- flu like symptoms
Onset - Abrupt :- Acute or insidious - fever, malaise, anorexia, nausea, vomiting
2) Icteric - Jaundice, acolic stools, liver tenderness/hepatomegaly
3) Convalescent phase - Acute infection only
- Flu like symptoms going away, not much jaundice, hepatomegaly going away
Recovery time - Hep A
4-6 weeks - slow
Hepatitis A signs and symptoms
Fever, Jaundice (yellow eyes, yellow tinge to skin), pain/tenderness in upper abdomen, urine dark yellow/brown, feces pale
Anti-HAV IgM (IgM antibody to hepatitis A)
Indicates current or recent infection with hepatitis A.
IgM anti-HAV is usually present 5-10 days before symptom onset and declines to undetectable levels within six months of initial infection.
When should someone order the Anti-HAV IgM test?
This is the test that should be ordered for a patient who is suspected of having acute hepatitis A.
Anti-HAV IgG (IgG antibody to hepatitis A) test shows?
Indicates immunity to hepatitis A, either from past infection or vaccination.
Anti-HAV IgG test is not recommended post vaccination, why?
Vaccine generally induces a very good immune response and immunity after vaccination can be assumed.
HAV IgM and IgG; total anti-HAV (IgM and IgG antibody to hepatitis A)
Occasionally, the laboratory reports the IgG and IgM together.
Primarily used to determine exposure to HAV either naturally or due to vaccination.
Anti HAV levels will rise from month of exposure consistently past 12 months
Is the total anti-HAV test informative? Why or why not?
This result is not informative, as it does not allow you to determine if this is an acute infection or if the patient is immune to hepatitis A.
Specimen for hep A
Feces, blood
Visualization of Hep A
IEM ( Immune Electron Microscopy ) , IF ( Immuno Florouscence )
HAV Ag detection
ELISA
HAV serology
IgM anti-HAV Antibodies by ELISA ,
RIA ( appear during acute phase & disappear within 3 – 6 months .
—[ Elevated liver enzymes and serum bilirubin level ].
Pooled human Immunoglobulin (Ig)
Human immunoglobulin preparations are pooled from plasma from normal blood donors.
It contains antibodies to hepatitis A, measles, mumps, varicella, polio .
Live attenuated vaccine
Used to protect people who have been exposed to virus (post-exposure) or otherwise may be exposed to the virus (pre-exposure).
This vaccine works by exposing you to a small dose of the virus, which causes the body to develop immunity to the disease.
Inactive vs Live vaccines
Inactivated vaccine (or killed vaccine) - consists of virus particles grown in culture and killed to destroy disease producing capacity.
Live vaccines - use pathogens that are still alive (but are almost always attenuated/ weakened)
Why are some vaccines inactivated?
Pathogens are grown under controlled conditions and are killed to:
- prevent infection from the vaccine
Classification of inactivated vaccines by method of inactivation
Whole virus vaccines - use the entire virus particle, fully destroyed using heat, chemicals, or radiation.
Split virus vaccines - using a detergent to disrupt the virus.
Subunit vaccines - produced by purifying antigens that best stimulate the immune system to mount a response to the virus, while removing other components necessary for the virus to replicate or survive or that can cause adverse reactions
Why are booster shots necessary for inactivated vaccines?
Inactivated viruses produce a weaker response by the immune system than live viruses
Multiple “booster” injections provide an effective immune response against the pathogen
Which demographic may be more suitable for inactivated vaccines?
Some people cannot take attenuated vaccines because the pathogen poses too much risk for them
E.g. elderly people or people with immunodeficiency
Prevention - HAV
Improved sanitary practices
Prevention of fecal contamination of food and water
Passive –pooled normal human Ig IM
Formaldehyde inactivated vaccine – prepared from human fetal lung fibroblast cell lines –IM.
Live attenuated vaccine –prepared from human diploid cell line ( China ).
HAV vaccines - list
Formalin inactivated whole virus
HAVRIX (GlaxoSmithKline)
(Two I.M. injections)
Protection from 4 weeks, upto 20 yrs
Immunogenic - define
Producing long lasting immunity
Hepatitis E Virus genome
ss+ve RNA genome
Labile - define
Easily broken down/displaced
HEV is mainly transmitted via water contamination with feces with minimal person-person transmission (T/F)
True
HEV epidemics reported in
India , Asia , Africa & Central America
Serology sequence in HEV
- After an incubation period ranging from 15 to 60 days, HEV-infected patients develop symptoms of hepatitis with appearance of anti-HEV IgM antibody in serum
(Viral shedding in stool from weeks 3-8) - This is followed by detectable anti-HEV IgG within a few days.
- Anti-HEV IgM may remain detectable up to 6 months after onset of symptoms, while anti-HEV IgG usually persists for many years after infection.
- Anti-HEV IgM is the serologic marker of choice for diagnosis of acute HEV infection.
HEV visualization
Electron Microscopy-
Specimen
Feces & bile in Icteric Phase or Acute phase of illness.
Molecular testing - HEV
HEV RNA ( by reverse transcriptase PCR ) in stool and serum of infected patients
HEV serology
Anti-HEV antibody : IgM & IgG ( Serum antibody detection by ELISA ).
HEV - prevention
Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit / vegetables not peeled or prepared by traveler.
No Vaccine is available for prevention of HEV
Hepatitis E Virus ( Non A non B enteric transmitted hepatitis ) infection responds well to treatment with immunoglobulin (T/F)
False. Hepatitis E Virus ( Non A non B enteric transmitted hepatitis ) infection responds poorly to treatment with immunoglobulin .
HBV - features
DNA virus, icosahedral symmetry, core circular (HBc = core protein), enveloped, surface protein (HBs)
HBV - morphological forms
Three morphological forms-
1) 22 nm size Spherical forms
2) 22 nm size Filamentous forms
3) 42 nm size Dane particle forms
HBV serotypes seen in which countries?
ADW serotype - Europe , Australia & America
ADR , AYW ,AYR - Asian countries
Inner nucleocapsid consists of which antigen?
HBcAg-Antigen expressed on the core ( Core antigen )
Capsid vs nucleocapsid
Capsid - protein coat surrounding nucleic acid of the virus particle
Nucleocapsid - capsid together with the nucleic acids of a virus
HBeAg in HBV
Soluble nonparticulate nucleocapsid protein ( Hepatitis B e antigen )
Serologic tests were developed in 1980s (T/F)
False. Serologic tests were developed in 1970s
Humans are the only known host of HBV (T/F)
True
Risk factors -HBV
Multiple partners (23%)
Injection Drug Use (20%)
Men who have sex with men (17%)
Household (3%)
HBV - complications
Fulminant hepatitis -1 %, Cirrhosis
Extra hepatic complications – arthralgia (joint pain), urticarial (hives), rarely polyarteritis (BV inflammation damaging organs), glomerulonephritis (filtering sys of kidney - glomeruli damaged).
Hepatocellular carcinoma (primary liver cancer)
Carrier stage -Two types
1) Super carriers - high HBsAg (10^13/ ml of blood), positive HBeAg, DNA polymerase, HBV (10^8/ml) in circulation
2) Simple carriers - low HBsAg, negative HBeAg, DNA polymerase, HBV
HBV has higher risk of carrier in neonate (T/F)
True
Specimen HBV
Serum, Liver biopsy
HBV visualization
EM, IEM
HBV Serological markers
Antigens: HBsAg
HBeAg
Antibodies: Anti-HBc- IgM & IgG
Anti-HBs
Anti-HBe
HBsAg or Surface antigen (hepatitis B surface antigen):
what does this test indicate?
Indicates either acute hepatitis B infection or, more often, a carrier of hepatitis B. These individuals are infectious to others.
Patients who are HBsAg positive require follow-up testing, which includes IgM anti-HBc, HBeAg, anti-HBe and serum transaminases, to determine appropriate clinical management.
What demographic should HBsAg test be conducted for?
This is the test that should be ordered for prenatal screening.
If a mother is HBsAg positive, what action should be taken with regards to the baby?
Babies born to mothers who are HBsAg positive require - hepatitis B Immune Globulin (HBIG) and
- hepatitis B vaccine series beginning at birth
Anti-HBs or HBsAb or surface antibody (antibody to hepatitis B surface antigen):
What does this test indicate?
Indicates immunity to hepatitis B, from either exposure to the virus or from vaccination.
Anti-HBs are always present with HBsAg (T/F)
False; Anti-HBs will usually not be present with HBsAg.
Anti-HBs is the test that should be ordered to assess whether the vaccine has been effective (T/F)
True
What measurement of titre indicates protection against HBV?
A titre of greater than or equal to 10 IU/L indicates protection against hepatitis B.
Anti-HBc or IgG anti-HBc or HBcAb or Core antibody
(IgG antibody to hepatitis B core antigen):
What does this test indicate?
Indicates that the person either has or had hepatitis B.
Anti-HBc does not tell you whether the patient is still infectious (HBsAg positive) or whether they have developed immunity to the virus (anti-HBs positive) since anti-HBc will be present in both conditions.
When does the Core antibody/Anti-HBc develop?
- Develops after exposure to the hepatitis B virus and persists for many years.
Anti-HBc does not develop after immunization with hepatitis B vaccine (T/F)
True
What does HBsAg positive test result mean?
Patient is infectious
What does anti-HBs positive test result mean?
Patient has immunity to virus
Anti-HBc does not tell you whether the patient is still infectious or whether they have developed immunity to the virus, why is that?
Anti-HBc is present in both conditions
IgM anti-HBc or anti-HBc IgM
(IgM antibody to hepatitis B core antigen):
What does this test indicate?
Indicates acute or recent infection with hepatitis B.
When should an IgM anti-HBc test be ordered? And should any additional tests be ordered as well?
This is the test that should be ordered (along with HBsAg) when acute hepatitis B is suspected.
This marker usually disappears within 3 weeks of initial infection (T/F)
False; This marker usually disappears within six months of initial infection.
HBeAg (Hepatitis B e antigen):
What does this test indicate?
HBeAg indicates a person who is highly infectious to others.
HbeAg will only be present in a person who is also HBsAg positive (T/F)
True
When does HbeAg appear in patients and how long does it persist?
HBeAg appears in the acute stage of infection and in some patients will persist for decades.
Anti-HBe (Antibody to hepatitis B e antigen):
What does this test indicate?
Indicates a person who was HBeAg positive but has developed immunity to this antigen.
If a person is HBsAg positive, what does this mean in terms of infectivity to others compared with being HbeAg positive?
If they are still HBsAg positive then they are still infectious to others but less infectious than when they were also HBeAg positive.
What is an immunoglobulin test?
- measures the level of types of antibodies in the blood.
The body makes different antibodies, or immunoglobulins, to fight different things (T/F)
True. For example, the antibody for chickenpox isn’t the same as the antibody for mononucleosis.
Types of antibodies - list
Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Immunoglobulin E, Immunoglobulin D
IgA - is found where?
It’s found in the linings of the respiratory tract and digestive system, as well as in saliva (spit), tears, and breast milk.
IgG is the most common antibody (T/F)
True
IgG is found where? When does IgG form in terms of immune response?
It’s in blood and other body fluids.
IgG can take time to form after an infection or immunization.
Where is IgM found and when does it appear in immune response?
Found mainly in blood and lymph fluid
First antibody to appear in the response to initial exposure to an antigen.
Where is IgE found normally in small amounts?
In what scenario would there be high amounts of IgE?
Normally found in small amounts in the blood.
Higher amounts when the body overreacts to allergens or is fighting an infection from a parasite.
IgD is found where?
Only small amounts in the blood.
What is the interpretation of the foll results?
HBsAg HBeAg Anti-HBc Anti-HBs Anti-HBe
+ + IgM - -
Acute HBV infection ; highly infectious
What is the interpretation of the foll results?
HBsAg HBeAg Anti-HBc Anti-HBs Anti-HBe
+ + IgG - -
Late / chronic inf. or carrier ; highly infectious
What is the interpretation of the foll results?
HBsAg HBeAg Anti-HBc Anti-HBs Anti-HBe
+ - IgG - +/-
Late/chronic inf. or carrier ; low infectivity
What is the interpretation of the foll results?
HBsAg HBeAg Anti-HBc Anti-HBs Anti-HBe
- +/- IgM - +/-
Rarely in early Acute inf. ; infectious
What is the interpretation of the foll results?
HBsAg HBeAg Anti-HBc Anti-HBs Anti-HBe
- - IgG +/- +/-
Remote inf. ; infectivity nil / very low
Remote infection - define
Infection that still carries some risk of reactivation
What is the interpretation of the foll results?
HBsAg HBeAg Anti-HBc Anti-HBs Anti-HBe
- - - + -
Vaccination
Treatment options for HBV for chronic, carrier and general
No specific antiviral treatment
Chronic hepatitis - Interferon alpha
Lamivudine
Famcyclovir Carrier state - no specific treatment
Prevention of HBV
Prevent perinatal HBV transmission
Routine vaccination of all infants
Vaccination of children in high-risk groups
Vaccination of adolescents
Vaccination of adults in high-risk groups
Composition of HBV vaccine is?
Recombinant HBsAg
Efficacy of HBV vaccine
95% (Range :- 80% -100%)
Duration of immunity in HBV vaccine
> 15 years
Schedule for HBV vaccine
3 Doses IM (intramuscular) - 0,1 & 6 months
Booster doses not routinely recommended for HBV vaccine (T/F)
True
Recipients for HBV vaccine
Persons diagnosed with an STD
Injection drug users
Inmates of long-term correctional facilities
Persons receiving hemodialysis
Healthcare workers
Persons travelling to areas of high endemicity
Recipients of certain blood products
