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Infection (Semester 4) > 9.1 Hepatitis > Flashcards

9.1 Hepatitis Flashcards

1
Q

What is the anatomical location of the liver? Give 4 functions

A

Located in the RUQ Functions:

1) bile production
2) filtering of toxins
3) excretion of bilirubin cholesterol, hormones, and drugs
4) breakdown of carbohydrates, fats, and proteins

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2
Q

Define Hepatitis and describe the stages of change that occur as it progresses?

A

Hepatitis is a general term referring to inflammation of the liver

Chronic hepatitis: inflammation with little/some damage

Cirrhosis: fibrosis and nodular regeneration

Hepatocellular carcinoma (with cirrhosis)

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3
Q

Give 4 infectious and 4 non-infectious causes of hepatitis

A

Infectious: Viral, bacterial, fungal, parasitic

Non-infectious: Alcohol, drugs, autoimmune, metabolic diseases

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4
Q

Give 4 signs and symptoms of hepatitis

A

1) Fever
2) Malaise
3) Upper abdominal discomfort
4) Jaundice (may not always develop)

Less common: ascites and oedema - very uncommon, but can still occur

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5
Q

In clinical examination, what findings are indicative of Hepatitis

Give 2 finding that may only be present in severe cases

A
  • spider naevi
  • jaundice
  • RUQ tenderness.
  • mild hepatomegaly
  • splenomegaly

Severe cases: Persistent nausea and vomiting and/or Hepatic encephalopathy (rare, indicates liver failure)

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6
Q

Define an antigen

A

Antigens are proteins that are found on the surface of the pathogen

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7
Q

Define antibodies

A

Antibodies are large, Y-shaped proteins produced by plasma cells. They are used by the immune system to neutralize pathogens such as bacteria and viruses (immunoglobulins)

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8
Q

Which hepatitis most commonly lead to chronic disease?

A

B and C

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9
Q

Which hepatitis are comply contracted from ingestion of contaminated food and water?

A

A and E

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10
Q

Which hepatitis are most commonly contracted from bodily fluids, mother-child and blood?

A

A-D

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11
Q

Describe the basic structure of Hep A

What virus family does it belong too?

What is its incubation period?

A

It is a small, naked RNA virus, that is resistant to many disinfectants (so can survive on surfaces for days)

Put in its own family: heptoviridae (related to enteroviruses)

Incubation Period : 2 to 6 weeks

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12
Q

How many serotypes, genotypes and subgroups doe Hep A have?

A

ONE stable serotype only (hence difficult to grow in cell culture)

4 genotypes (most are group 1)

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13
Q

Does the Hep A virus lead to acute or chronic hepatitis?

A

ACUTE ***Hepatitis A does NOT lead to chronic hepatitis.

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14
Q

Describe the 3 main viral transmission modes of Hep A in order of how common it is

A

1) contaminated food and water (e.g. raw shellfish)
2) close personal contact (e.g. household, sex)
3) blood exposure (rare) (e.g. injecting drug use, transfusion)

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15
Q

Describe the pathogenesis of Hep A infection

A

1) HAV invades into human body by fecal-oral route
2) It multiplies in the intestinal epithelium of the GIT
3) It travels in the blood to the liver
4) replicates within the liver hepatocytes (major site of replication)
5) enters intestine by shedding into bile
6) shed in faeces
7) After HAV replicating and discharging cellular immune response and hence liver cell damage begins

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16
Q

What is the main way hepatitis infections are monitored? What does this specifically involve?

A

Hep infections are monitors by serology which involves monitoring the antibodies and antigen levels within a persons blood to identify Hep status of the individual

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17
Q

Describe what changes would be seen in a graph of serology in Hepatitis A (in a healthy individual)

Explain why

A

1) Incubation period: Initial inoculation of virus followed by Prodrome
- increase in viral replication seen as an increase in viral load (pink)
- patient will being feeling slightly unwell (prodrome)

2) Symptoms: initiation of immune response (around 2weeks) in a healthy individual + Jaundice
- main signs and symptoms devlop
- antibodies begin forming against Hep A in order of MAGE, beginning with Anti-A IgM.
- after around 4-5 weeks Anti-A IgG response kicks in (stronger/longer)
- during immune response there is decrease in liver enzyme function which is what results in jaundice

3) Convalescence: recovery from virus OR immunity developed

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18
Q

What are the complications of a Hep A infection?

A

Mortality rate is very low (0.3%): the following complications are very rare but may occasionally occur

Acute fulminant liver failure (0.1 to 0.4%)

Extra-hepatic complications such as arthritis, myocarditis and renal failure.

Post hepatitis syndrome

Note: 10% of patient’s will have a relapse before recovery Remember: Hep A is NOT associated with chronic liver disease

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19
Q

Who are Hep A vaccinations reccomended for?

A

The two dose vaccine is recommended for children and adults travelling to high risk areas and for IV drug users

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20
Q

What treatment is available for Hep A and what does it aim to do?

A

Treatment with immune globulin can provide short-term immunity to hepatitis A if given before exposure or within 2 weeks of exposure

BUT vaccination is preferred since it provides long-term immunity lasting at least 20 years.

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21
Q

List 3 people at higher risk of Hep A infection

A

1) travelers
2) homosexual men
3) injecting drug users

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22
Q

Describe the structure of the Hepatitis E Virus and state what family it belongs to

What is its main mode of transmisson?

A

Belongs to a family of “Calicivirus-like viruses”

It is an unenveloped RNA virus, with a +ve stranded RNA genome

It is very labile and sensitive but has recently been able to be cultured

Transmission: passed through contaminated foetal water

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23
Q

Describe what changes would be seen in a graph of serology in Hepatitis E (in a healthy individual)

Explain why

A

RELISTEN TO SLIDE

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24
Q

Describe the structure of the Hep B virus and state what family it belongs to (what is special about this family?)

What is the name given to the whole virus?

What is its incubation period?

A

It is a double-stranded, enveloped DNA virus that belongs to the hepadnavirus family. Hence it has a DNA genome that is replicated via an RNA intermediate (reverse transcriptase)

The whole virus is called the Dane particle - includes the envelop region, the nucleic acid inside and the filaments that stick out on the outer coat

Incubation period is 60-90 days

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25
Q

What is the name given to the other form of the Hep B virus that is produced alongside whole virions?

What is the purpose of this?

A

Other forms are known as Decoy particles these are immunogenic

They are composed of the same surface antigen (HBsAg) on their outer coat and are spherical or filamentous in sturcture. BUT… they do NOT contain the nucleic acid component (no DNA), hence are not infectious

This DNA component is shed during replication, differtentiating the Dane particle from the Decoy particle. This is a mecahnism that aims to “distract” the host immune system and allow the dane particle to continue infecting

Note: there are more decoy particles release than the dane particles

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26
Q

Does Hep B cause acute or chronic hepatitis

A

CHRONIC: can progress to cirrhosis and in sever cases carcinoma

27
Q

What genes encode virulence features of Hep B and what do they do?

A

S gene = HBsAg = encodes for surface antigen protein (4 phenotypes : adw, adr, ayw and ayr)

C gene = HBcAg = encodes the inner core antigen protein (a single serotype)

E gene = HBeAG = e antigen; an indicator of transmissibility (minor component of core, distinct from C) it is a secreted protein and its function is unknown

P gene = encodes for the DNA polymerase (allows replication through reverse transcriptase)

X gene = codes for regulatory protein called the X protein

28
Q

What are the 2 common modes of transmission of Hep B

A

1) Horizontally:
• Sexual contact (sex workers and homosexuals: high risk)
• Blood transfusions
• Parenterally (contaminated needles and syringes, IV drug abusers and health workers: high risk)

2) Vertical transmission
• from mother to child (MTCT) during childbirth

29
Q

When using bodily fluids to monitor Hep B levels, which 3 fluids will be the highest in concentration

A
30
Q

Describe the process of infection by Hep B into the cell

A

virus enters hepatocytes via blood. Here it attaches and sheds envelop region and injects the core particle into hepatocyte cell

1) RNA intermediate: HBV replicates through an RNA intermediate which produces and releases antigenic decoy particles
2) Reverse transcription: one of the mRNAs is replicated with a reverse transcriptase making the DNA that will eventually be the core of the progeny virion (dane particle)
3) Integration: Some DNA integrates into host genome causing carrier state

The decoy and dane particles are released

31
Q

List the progression of an acute Hep B infection, including the possible outcomes

A

Acute hepatitis B infection ➞ Chronic HBV infection ➞ Chronic hepatitis ➞ Cirrhosis

From cirrhosis 2 things may happen

1) Hepatocellular carcinoma
2) Liver failure

Both of these can only be treated with a liver transplant and if not the outcome will be death

32
Q

How is Hepatitis diagnosed?

A

serological tests: measures levels of antigens and antibodies in order to work out whether they have hepatitis and if so what stage

33
Q

What is seroconvertion? Give 2 examples that would be seen on serology for HepB

What is the serocoverted disease state reffered to as?

A

seroconversion is the time period during which a specific antibody develops and becomes detectable in the blood.

eg.

1) If HBsAg seroconversion has occured: there will be antibodies against HBsAg. It signifies clearance of HBsAg and resolution of the chronic infection
2) If HBeAg seroconversion has occured: there will be antibodies against the HBeAg-positive form of the virus.

The seroconverted disease state is referred to as the ‘inactive HBV carrier state’ Once seroconversion has taken place, most people remain in the inactive HBV carrier state

34
Q

Serology Hep B: what would HBV-DNA in the blood indicate?

A

Normally indicates active replication of virus

Can be indicative of either: Disease, Infection or Replication. Which one is dependant on what other markers are present

35
Q

Serology Hep B: what would the presence of HBsAg in the blood indicate?

A

This is hepatitis B surface antigen

Indicates infection with Hep B (acute or chronic)

36
Q

Serology Hep B: what would the presence of Anti-HBs in the blood indicate?

A

These are antigens against the Hep B surface antigens

Indicates immunity against Hep B

shows that at some stage the body has been presented with Hep B surface antigen and has gained immunity and recovered

37
Q

Serology Hep B: what would the presence of HBeAg in the blood indicate?

A

This is Hep B “e” protein antigen

Indicates active replication of virus is occuring

Note: some forms of Hep B dont present with an e antigen, only people infected with the “HBeAg-positive” form of the virus will show antigens/antibodies to this

38
Q

Serology Hep B: what would the presence of Anti-Hbe in the blood indicate?

A

The virus is no longer replicating

39
Q

What is the order in which Ig antibody levels rise in Hep B infections and what do they indicate?

A

MADGE

IgM: shorter lived and more indicative of an acute infection

IgE: longer lived and stronger, more indicative of a chronic infection

40
Q

If a person has developed antibodies to a particular Hep B antigen, can there still be antigens present in serology? If yes which one?

A

The patient can still be positive for HBsAg (surface antigen) which is made by integrated HBV (decoy)

41
Q

Explain what would be seen in serology in terms of antigens and antibodies during an acute Hep B infection

A

1) Hep B infection
- seen as “HBV DNA” increasing alongside increase in the “HBeAg”, because the virus is actively replicating

2) Symptoms occur as immune response begins
- seen as an increase in “IgM anti-HBc”, because IgM is the first antibody triggered and it is targeted against the core (whole virus)

3) Immune response continues
- seen as an increase in IgE anti-HB
- here we will also see increasing levels of various other antibodies because response is no longer just to the core (anti-HBc) but is now also targeted to other components such as the “e” antigen (anti-HBe)

42
Q

In what case would the normal serological profile NOT occur, what would this indicate:

+/- HBV DNA in serum

  • HBsAg (surface antigen)

+ serum anti HBc

A

When a particular form of Hep B known as an “occult HBV” infection occurs.

Here HBV DNA is only present in the liver and hence may or may not be detecable in the serum

As HBsAg (surface antigen) is negative, serum “anti HBc” is the most useful & inexpensive marker for identification of occult HBV infection

43
Q

Serology Hep B: what would the presence of IgM anti-HBc in the blood indicate?

A

This is the core protein antigen of Hep V (whole virus)

Indicates the person has the disease

44
Q

Serology Hep B: what would the presence of Anti-HBc in the blood indicate?

A

These are antibodies against the core protein of Hep B

Indicates person has preveously been exposed

45
Q

How do we treat Hep B?

hat is the best preventative strategy against Hepatitis B?

A

Supportive care is the major treatment but Anti-HBV immune globulin is effective soon after exposure or neonatally to children of HBsAg-positive mothers.

There are 3 FDA approved drugs to treat Hep B

1) Interferon-alpha 2b
2) Hepsera
3) Lamivudine

Prevention = Vaccines!!! (currently have 2)

46
Q

Compare what antibodies would be seen in:

a person who has been naturally been infected with Hep B

a person who has been vaccinated against Hep B

A

Natural infection ➞ + ve Anti HBc antibodies

Vaccination ➞ – ve Anti HBc antibodies BUT + anti HBs antibodies

47
Q

When can you only get Hepatitis D?

Why is this the case?

A

can ONLY contract Hep B if you are already suffering from Hep B (B and D go togther)

This is because it can NOT replicate on its own, it does not carry genes for a capsid so uses the HBV capsomeres

48
Q

Describe the structure of Hep D

What is the most common way it is transmitted?

A

It is a very simple virus: It is a negative RNA and contains a capsid similar to Hep B

Transmission:

Most common with Percutaneous exposures - IV drug use
Can also be trabsmitted through Permucosal exposures -sex contact

49
Q

What are the 2 infections that can arise from a Hep D + Hep B infection?

What are the risks for progression?

How would you treat?

A

1) Coinfection: Hep B + Hep D ➞ severe acute disease with LOW risk of chronic infection
treatment: Pre/post exposure prophylaxis to prevent HBV infection
2) Superinfection: CHRONIC Hep B + Hep D ➞ usually develops into chronic HDV infection that is HIGH risk for developement of cirrhosis and severe chronic liver disease. (may present as an acute hepatitis)
treatment: education to reduce risk behaviors among persons with chronic HBV infection

50
Q

Describe the serology in terms of antigen and antibody detection in a Hep D co-infection

A

1) Infection
- first we would see the HBs Ag (surface antigen) indicating infection
- alongside this we would see the HDV RNA (Hep D infection) and HBV DNA (Hep B infection)

2) Initial acute immune reponse
- here we would see development of Anti HDV (this is the antibody to the whole virus because it is so simple, there are no variations of antibodies that need to be formed)

3) The Anti HDV will increase and the viral load of HDV will go down
- here we will see an increase in IgG Anti HDV and Anti HBs

51
Q

What would you test for in serology if a patient is suspected of Hep D infection and why?

A

Test anti-HDV as there is only one identified antigen of Hep D which is HDV.

52
Q

Describe the structure of Hep C

A
  • a very small single stranded RNA virus
  • contains a nucleocapsid and an envelope
  • envelope contains many glycoproteins (main ones are E1 and E2). These are the antigens to the immune system
  • there is only one serotype BUT 6 main genotypes and 80 subtypes
  • can cause acute but tends to cause chronic hepatitis
53
Q

What is the process of Hep C infection

A

1) Virus travels in blood to the liver
2) It un-coats and enters genetic material into cell
3) as it is an RNA virus it replicates in cytoplasm using an RNA intermediate
5) following replication there is then particle assembly
5) virions are released into system

54
Q

What are the main routes of tranmission of Hep C?

Is there a vaccine?

A

HCV is spread primarily by blood-to- blood contact associated
with intravenous drug use, poorly sterilized medical equipment and transfusions.

NO vaccine available

55
Q

Give 4 signs and symptoms of an acute Hep C infection

Note: these are the same as an infection with acute hepatitis

A
  • fatigue
  • decreased appetite
  • nausea
  • muscle or joint pains
  • weight loss
  • RARELY: acute liver failure and jaundice
56
Q

Give 4 signs and symptoms of a chronic Hep C infection

A
  • Fatigue and mild cognitive problems
  • Fatty liver
  • Cirrhosis
  • Hepatocellular carcinoma
  • Ascites
  • Easy bruising or bleeding
  • varices (enlarged veins)
  • Hepatic encephalopathy
57
Q

List 4 Investigations that are serology based for a Hep C infection

A

1) HCV antibody enzyme immunoassay or ELISA and (PCR)
2) HCV antibody: mainly for diagnosis of HCV. BUT is Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears
3) HCV-RNA: various techniques available e.g. PCR. Most used to monior reponse for antiviral therapy (can diagnose HCV in acute phase)
4) HCV-antigen : an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.

58
Q

On a HCV assays what be indicated by a:

+ve Anti HCV and +ve HCV RNA

A

Acute or chronic HCV, depends upon clinical context

59
Q

On a HCV assays what be indicated by a:

+ve Anti HCV and - ve HCV RNA

A

Resolution of HCV

60
Q

On a HCV assays what be indicated by a:

  • +ve Anti HCV and +ve HCV RNA
A

Early acute HCV

May be chronic HCV in immunosuppressed patients

61
Q

On a HCV assays what be indicated by a:

  • ve Anti HCV and - ve HCV RNA
A

Absence of HCV

62
Q

What would a Hep C infection look like on serology in terms of antigens and antibodies?

If progressed to a Chronic infection what would it then look like?

A

1) Initially liver function test will should increased ALT due to decreased function
2) A rise in HCV RNA would be seen and symptoms would show
2) Immune response triggers antibody formation “anti HCV”
3) overtime this should progress to a complete immune response against HCV

Progression to chronic would be seen as zig zag pattern of the HCV RNA showing constant imbalance between host own immune system and virus
There are moments of raised RNA present when virus is replicating followed by decreases in RNA which are not detectable, again followed by a rise (detectable) and so on…

63
Q

What are the 2 main treatments for Hep C?

A

a combination of pegylated interferon alpha and the antiviral drug ribavirin

Infection (Semester 4) (19 decks)

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