Flashcards in L11: Viral Hepatitis Deck (46):
1
What major organ experiences complications as a result of hepatitis infections?
The Liver :D
2
Which system is the liver primarily a part of?
Biliary system - creates bile and filters harmful substances from the blood
3
Certain enzymes can assess liver function. WIll higher or lower levels of these enzymes (ALT, AST and GGTP) indicate acute liver injury?
Higher
4
What is hepatitis typically characterised by?
- Jaundice
- Fever
- Liver enlargement
- Abdo pain
5
What is cirrhosis?
When scar tissue replaces healthy tissue of the liver and blocks blood flow through the organ --> no functioning hepatocytes (increases risk of hepatocellular carcinoma)
6
What is Hepatocellular carcinoma (HCC)?
A primary malignancy of the liver. Most cases are secondary to Hep B or C infection or cirrhosis most commonly due to alcoholism.
7
What are Kuppfer cells?
Specialised macrophages in the liver that remove foreign particles and destroy RBCs (usually big, white, nucleated cells on histopath.)
8
What makes severe hepatits different from mild hepatitis?
Severe hepatitis commonly manifests with fluid retention, altered mental status and bleeding in addition to symptoms of mild hepatits (malaise, jaundice and abdo pain)
9
What is the difference between acute and chronic hepatitis?
Acute = quick disease progression, symptoms last < 6 months
Chronic = slow progression, symptoms last > 6 months (especially in B and C)
10
What causes jaundice?
Build up of bilirubin in the blood (produced when old cells break down) as a result of the body no longer being able to process it.
11
Hepatitis A - source, mode of transmission, chronic (Y/N), how is it prevented?
Source = faeces
Transmission = feacal-oral
Chronic? = No
Prevention = Pre/post exposure immunisation
12
Hepatitis B - source, mode of transmission, chronic (Y/N), how is it prevented?
Source = blood/body-derived fluids
Transmission = percutaneous, permucosal
Chronic? = Yes
Prevention = pre/post-exposure immunisation
13
Hepatitis C - source, mode of transmission, chronic (Y/N), how is it prevented?
Source = blood/body-derived fluids
Transmission = percutaneous, permucosal
Chronic? = Yes
Prevention = blood donor screening, risk factor modification (don't share needles, etc.)
14
Hepatitis D - source, mode of transmission, chronic (Y/N), how is it prevented?
Source = blood/body-derived fluids
Transmission = percutaneous, permucosal
Chronic? = Yes
Prevention = pre/post-exposure immunisation, risk factor modification
15
Hepatitis E - source, mode of transmission, chronic (Y/N), how is it prevented?
Source = Faeces
Transmission = faecal-oral
Chronic? = No
Prevention = ensure drinking water is safe
16
How is Hep A similar to poliovirus?
- Humans are the only natural host
- Naked
- Both belong to Picornaviridae (different genera though)
- Vaccines are available for both
17
How does Hep A replication work?
gains entry via RM endocytosis, RNA uncoating occurs, 1 ORF, translated into a polyprotein and then self-cleaved by viral protease, (RNA replication occurs in viroplasms), packaged and exits via cell lysis **UTRs increase transmissability
18
What factors contribute most to HAV pathogenesis?
Resistant to low pH and heat because it is a non-enveloped virus
19
Why is ALT important in HAV infection?
It is a surrogate for liver damage
20
How is HAV diagnosed?
ELISA:
- anti-HAV IgM
- anti-HAV IgG (also good for detecting past infection)
Direct detection
- EM
- RT-PCR
21
Is there a HAV vaccine? If so, what type of vaccine is it?
Yes! It is inactivated with Al(OH)3 adjuvant and 1x booster between 6 and 18 months depending on brand
***China uses a live attenuated vaccine (single dose)
22
Hep B fun facts:
- Family
- sense & type of nucleic acid
- Hosts
- Main cellular target
- Number of serotypes
- Any cool features?
- Family = Hepadnaviridae
- sense & type of nucleic acid = dsDNA (+ve strand incomplete)
- Hosts = humans and chimps
- Main cellular target = hepatocytes
- Number of serotypes = 8
- Any cool features? = involves RT (may be a protein primer for synthesis???)
23
How is HBV transmitted?
- blood
- bodily fluids
24
Name three risk factors for HBV.
Any of:
- children of mothers with HBV
- people who live in the same house as someone with HBV
- blood donation recipients
- IV drug use
- Unprotected sex
- people whose occupation involves handling blood
25
Hep B symptoms (7) and associated diseases (4)?
Symptoms:
- Jaundice
- Fatigue
- Dark urine
- nausea/vomiting
- abdo pain
- fever
- appetite loss
Associated diseases:
- Asymptomatic carrier
- Hepatocellular carcinoma (HCC)
- cirrhosis
- Hepatitis
26
Is Hep B the end of the world if you get it?
Probably not - 90-95% of cases are resolved within 6 months with lifelong immunity. It's usually people with limited CM-IR who develop acute and chronic HBV infection.
27
Why is chronicity more likely in regions where endemicity it high?
People are exposed to the virus much earlier in life (usually birth or early childhood) and so a kickass CM-IR can't be generated as well as it would in adulthood. As a result, infection is more likely to persist and cause some problems like HCC and cirrhosis
28
How is HBV diagnosed?
Serological tests (Y)
- Anti-HBs Ab = indicates recovery and/or immunity (against surface S protein)
- Anti-HBc IgM = marker of acute infection
- Anti-HBc IgG = marker of past or chronic infection (c = core protein)
- Anti-HBe = indicates persistent infection
- HBsAg = general infection marker
- HBeAg = marker for active virus replication
- HBV-DNA = also indicates active virus replication. This one is more accurate as it includes escape mutants!
29
Why is ALT important in HBV infection?
- high levels of ALT indicate hepatocyte destruction
30
Is there a treatment for HBV? If so, what does it involve?
Kind of yes.. it's very limited. Can use interferon (30-40% response rate), nuceloside analogues (RT inhibitors, guanine analogue) or liver transplant
31
What does the HBV vaccine(s) involve?
Plasma derived vaccine:
- from HBsAg positive donors and inactivated HBV virion
- discontinued in 1989
Recombinant vaccine
- S gene cloned in yeast
- safe since no nucleic acid
32
What makes Hepatitis D weird?
It relies on co-infection with HBV
33
What happens if you are coinfected with HBV and HDV compared to just HBV alone?
Symptoms are worse
Complications are more severe
- inc likelihood of liver failure in sever infection
- faster progression of cirrhosis
- inc chance of liver cancer in chronic infn
34
How is HDV transmitted?
- percutaneously (IV drug use)
- permucosally (unprotected sexy times)
- vertical transmission, although much less common than in HBV alone
35
What is the difference between superinfection and coinfection of HBV and HDV?
Co-infection = getting both at the same time
Superinfection = already having chronic HBV then getting D which results in significantly faster progression to cirrhosis/HCC/etc.
36
Does HDV carry RdRp?
Nope! Host genome sees it as DNA because it has similar rod structure so can't get host to do it either and so cellular enzymes within the cell are used
37
HCV fun facts:
- Family
- Risk factors
- Sense and strand type(s)
- Enveloped?
- Grows in cell culture?
- Vaccine?
- Family = Flaviviridae
- Risk factors = infected blood or organ donor, improper care with needles, IV drug use, HCV mother, sexual/household interactions with infected individuals
- Sense and strand type(s) = +ssRNA
- Enveloped? = sure is
- Grows in cell culture? = No
- Vaccine? = Nope :(
38
What steps are involved in the development of HCV-induced hepatocarcinogenes?
1. HCV infection
2. +metabolic or genetic predisposition = oxidative stress
3. oxidative stress accumulates
4. inc fibrosis, genome instability, DNA damage
5. Cirrhosis
6. Liver cancer :(
Takes 30-50 years
39
How is HCV diagnosed? (3)
- HCV Ab = not useful for acute phase - usually takes 4ish weeks to appear
- RT PCR of HCV RNA = more accurate, cheaper although mainly used in monitoring anti-viral treatment progress
- Immunoassay for HCV Ag
40
What factors effect prognosis (2) and what is typically used to treat (2) of HCV infections?
- Genotype = subtype 1 and 4 are worse and respond poorly to IFN therapy
- Viral load = high usually means poor prognosis
- IFN = 50/50 response rate, used in patients with chronic active HCV
- Ribavirin = not a lot known but this + IFN seems to be more effective than IFN alone
41
Hep E fun facts go:
- Family/Genus
- Sense and genome type
- Enveloped?
- Zoonotic?
- Vaccine?
- Mode of transmission
- Family/Genus = Hepeviridae/Hepevirus
- Sense and genome type = +ssRNA
- Enveloped? = No (naked)
- Zoonotic? = possible, several non-human primates as well as animals used for agriculture are susceptible to infection
- Vaccine? = Sure is --> Recombinant (only licensed in China though)
- Mode of transmission = contaminated food/water, faecal-oral
42
Name 4 symptoms of HEV (4).
- acute nausea
- vomiting
- diarrhoea
- jaundice
43
Clinically, HEV is most similar to which other form?
HAV - except HEV is worse in pregnant women
44
What does ALT stand for?
Alanine aminotransferase
45
Why was HGV renamed to become GB virus C?
- It replicates primarily in lymphocytes, not hepatocytes
- Investigation failed to identify a link between GBV-C and chronic hepatitis
**Having said that, patients will often be infected with HBV, HCV, GBV-C and HIV simultaneously
46