Flashcards in LMP301 Lecture 16: Viral Hepatitis Deck (111)
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Causes of hepatitis
1. drugs
2. toxins
3. bacteria
4. viruses
5. parasites
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define: hepatitis
inflammation of the liver
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drugs that may cause hepatitis
- anticonvulsants
- corticosteroids
- alcohol
- tylenol/asprin overdose
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toxins that may cause hepatitis
- DDT
- mushrooms
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bacteria that may cause hepatitis
- thyphoid fever
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viruses that may cause hepatitis
- hepatitis A, B, C, D, E, G
- CMV
- EBV
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parasites that may cause hepatitis
tapeworm
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clinical symptoms of viral hepatitis
- enlarged liver
- elevated liver enzymes
- change colour of urine/feces
- accumulation of biliburin (jaundice)
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on a virus particle, what can be used to identify the strain?
- ssDNA or RNA
- surface proteins (HBsAg)
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define: antigen (Ag)
a substance (protein) that prompts the generation of antibodies -> immune response
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define: antibody (Ab/IgG/IgM)
proteins produced by B-cells which play an immunological role; identify & neutralizes foreign particles through antigens
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Which antibody is first released when there is an immune response? Which is released after?
IgM, then IgG
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IgM indicates...
primary immune response
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__ are produced during the primary immune response
memory lymphocytes
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The virus particle is surrounded by...
capsule coat
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The genetic material of virus is in the form of...
DNA or RNA (single or double stranded)
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what is directly inside the capsule coat?
Viral nucleocapsid (HBcAg)
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HBcAg
Viral nucleocapsid
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HBeAg
particles associated with nucleocapsid
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Where are HBeAg found?
inside the viral capsid (HBcAg)
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When does the production change from IgM to IgG?
after mature B cells are formed
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What is it called when IgG production begins and IgM production stops?
class-switching
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class-switching is....
a stable change in the B-cell's genome, and is transmitted to all progeny cells
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Lifecycle of a virus
1. enters hepatocyte (capsule coat removed), viral DNA moves to nucleus of host
2. viral dsDNA -> cccDNA -> template for viral mRNA
3. viral mRNA transcription & assembly of new viral particles
4. viral proteins assemble around DNA core
5. new viral particles released from outer membrane of the host
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dsDNA -[?]-> cccDNA
cellular enzymes
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___ can persist in the hepatocyte during chronic infection
cccDNA
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cccDNA is genetic material of...
virus
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Steps of viral reproduction
1. Uncoating
2. Repair (formation of cccDNA)
3. Transcription
4. Translation
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How does release of viral particles determine host cell health?
If a little bit of the particle is released at a time, host lives
if all released, host dies
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If the host cell dies, what happens to the viral production cycle?
it halts
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Describe the Hep A virus
- small
- ssRNA (single protein core)
- no surface proteins to identify
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how is Hep A virus transmitted?
fecal-oral
- person-to-person contact
- contaminated water
- poor hygiene & sanitation
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Who is at high risk for Hep A?
- children in daycare
- travelers to places where sanitation is bad
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onset of symptoms for Hep A
- very abrupt
- lasts 1 ~ 8 weeks
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what is a common clinical symptom of Hep A? How many adults develop this symptom?
jaundice
70-80%
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What is responsible for causing Hep A?
HAV
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where does HAV replicate?
in liver
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how does HAV leave the body?
through stool
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when is HAV most infectious (found in stool)?
first 2 weeks of contracting disease, a lot of HAV will be found in the stool
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When does [HAV] decline in the stool?
after jaundice appears
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what happens to those people who have Hep A?
will recover, and develop immunity to HAV
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what is a marker used for diagnosing/confirming recent/acute HAV infection?
anti-HAV IgM + ALT (liver enzyme)
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what is a marker that indicates immunity to HAV?
anti-HAV IgG, and the absence of anti-HAV IgM in serum
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clinical symptoms of Hep A appears about...
2 weeks after infection, and lasts until week 8 (duration: 6 weeks)
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What anti-HAV IgG a marker off?
past or present infection; cannot make a definitive diagnosis of a recent infection
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genome of HBV
double stranded circular DNA
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What are the 2 antigens found on HBV?
- Hep B surface antigen (HBsAg)
- Hep B core antigen (HBcAg)
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What is the structure that holds viral DNA?
central core nucleocapsid
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What is the main structural difference between HAV and HBV?
HBV has a coat over the capsid that contains surface proteins
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transmission of Hep B
exchange of body fluids
- needle
- transplant
- sex
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individuals at risk for Hep B
- injection drug users
- unsafe sex
- occupation working with blood
- institutionalized populations (prisoners)
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incubation period for Hep B
60 - 90 days (2-3 months)
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Onset of Hep B is very...
subtle
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Less / More people develop jaundice when infected with HBV compared to HAV
less (only 30-50%)
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What happens to individuals infected with HBV?
recover within six months and develop immunity
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2-10% of infected individuals with Hep B will progress to...
chronic infection
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15-50% of people with chronic Hep B...
die prematurely as a result of chronic liver disease
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Markers of Hep B
- HBsAg
- HBeAg
- anti-HBc (IgM)
- anti-HBe (IgG)
- anti-HBs (IgG)
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HBsAg
Hep B surface antigen
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HBeAg
Hep B envelope antigen
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What can be used to identify the strain of Hep B?
type of HBsAg and HBeAg that can be found in serum
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Anti-HBc (IgM)
IgM antibody to the core antigen
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Anti-Hbe (IgG)
antibody to HBe antigen
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Anti-Hbs (IgG)
antibody to HBs antigen
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What can be used to identify the stage of hepatitis infection?
see which antibody is secreted by the body (IgM or IgG)
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What is used to follow patient progress throughout hepatitis infection?
serial testing: follow patient's progress using markers (HBsAg, HBeAg, anti-HBe, anti-HBs)
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What markers can be seen for acute hepatitis?
- HBsAg = there are surface antigens
- HBeAg = there are envelop antigens
- anti-HBc (IgM) = there is a core
(the viral parts, mostly)
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duration of an acute Hep B infection
2 weeks - 3 months
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what markers appear during early recovery and recovery phase of Hep B?
anti-HBs & anti-HBe
(the antigens)
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duration of early recovery period for Hep B
3-6 months
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duration of recovery for Hep B
6-12 months / years
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what is the last marker to appear for Hep B?
anti-HBs
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What does the presence of anti-HBs and anti-HBe indicate?
- Hep B is resolving (leaves acute stage)
- establishment of immunity
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individual is considered chronically infected if...
HBsAg is present for more than six months
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what markers can be seen for chronic hep B infection?
- HBsAg and HBeAg are elevated even at later stage
- antibodies to those viral particles are also constantly present
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Hep B: indicator of disease resolution
Anti-HBe
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Hep B: indicator of recovery & immunity
Anti-HBs
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Hep B: indicator of acute infection (unique to this category)
Anti-HBc (IgM)
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genomic material of HCV
ssRNA encased by nucleocapsid (core)
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difference between envelope of HBV and HCV
HCV has an envelope proteins, but they can't be used to identify the strain
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HCV is encased by...
lipid envelope
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size of HCV
< 50 nm
very small
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transmission of HCV
blood
- needle
- transfusion
- perinatal
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individuals at risk for Hep C
- injection drug users
- occupational hazard
- transfusions before 1992
- institutionalized populations (prisoners)
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60-70% of people with Hep C have what symptom?
asymptomatic!
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20-30% of people with acute Hep C have what symptom?
jaundice
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___% of Hep C patients become chronically infected
60-85
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10-20% of people with chronic Hep C develop _____
cirrhosis
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1-5% of people with chronic Hep C develop _____
hepatocellular carcinoma
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hepatocellular carcinoma occurs over...
20-30 years (latent infection)
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HCV is a leading cause of....
liver transplants
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HCV reacts differently depending on...
what other "factors" you have
- alcohol use
- HIV
- drugs
...
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duration of incubation for HCV
2-26 weeks
avg: 6-7 weeks
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when do people infected with HCV develop symptoms?
6-7 weeks
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define: seroconversion
development of antibodies in response to disease states
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how long does it take before seroconversion occurs for Hep C?
8-9 weeks
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What individuals are considered infectious for Hep C?
* positive for HCV antibody
liver enzymes could still be normal
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why might there not be an elevation in liver enzymes for those with Hep C?
slow infection cycle allows liver to slowly adjust to the increasing strain
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how is HCV diagnosed?
1. detecting antibodies specific to HCV (anti-HCV)
2. ruling out HAV or HBV
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symptoms of Hep C appears during...
week 1 - week 5 of infection period
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downside of using anti-HCV as marker for diagnosis
- may not appear if tested early
- can take >2 months to become positive
- does not distinguish between acute & chronic
- can't tell when they got the disease
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what can be found at a constant level for those infected with HCV?
HCV RNA
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what liver enzyme is abnormal in Hep C individuals, and what is the serologic pattern like?
- ALT
- more abundant than normal (peak about week 2-3)
- decreases and goes fluctuates, slightly above normal range later on
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serologic pattern for anti-HCV
increase as duration of Hep C increases (exponential)
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HCV RNA measure...
level of circulating virus = "viral load"
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high viral load means that...
the virus is replicating a lot
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Why is HCV RNA testing used?
- detect HCV before anti-HCV may be formed
- access viral load before and after treatment
- detect HCV infection in cases with ambiguous serology (blood test)
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which viral hepatitis has abrupt onset
Hep A
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which hep virus has the shortest incubation time?
hep A
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which hep virus will most likely cause a chronic infection?
hep C
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