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Jess Infection > Hepatitis > Flashcards

Hepatitis Flashcards

1
Q

Name the eight functions of the liver

A
  1. Bile production
  2. Filters toxins
  3. Excretes bilirubin, cholesterol, hormones and drugs
  4. Breaks down carbs, fats and proteins
  5. Activates enzymes
  6. Stores glycogen minerals and vitamins (the fat soluble ones; A, D, E and K)
  7. Synthesizes blood proteins
  8. Synthesizes clotting factors
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2
Q

Name the four infectious and four non-infectious causes for hepatitis

A

Infectious: viral, bacterial, fungal, parasitic

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

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3
Q

Define hepatitis

A

Inflammation of the liver

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4
Q

Name six signs and symptoms of hepatitis

A
  1. Fever
  2. Malaise
  3. Upper abdominal discomfort
  4. Jaundice
  5. Ascites and edema is uncommon but can occur in most serious cases
  6. Persistent nausea and vomiting suggest severe hepatitis
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5
Q

What is the term that refers to hepatitis without jaundice and when can this happen?

A

Anicteric hepatitis, may occur in acute viral infections

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6
Q

Describe the typical pattern in how symptoms occur until the patient recovers

A

May have several ‘waves’ where the patient has episodes of worsening symptoms before making a full recovery

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7
Q

Name five things you may see on a clinical examination of a patient with hepatitis

A
  1. Spider naevi
  2. Jaundice
  3. RUQ tenderness
  4. Splenomegaly
  5. Mild hepatomegaly (although in severe liver failure the liver may also shrink)
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8
Q

What symptom may directly indicate liver failure?

A

Hepatic encephalopathy: decline in brain function (as a result of severe liver disease)

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9
Q

What is the danger of persistent nausea and vomiting?

A

Risk of hypoglycaemia and dehydration

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10
Q

What is an antigen?

A

A protein found on the surface of a pathogen

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11
Q

What are antibodies and who produces them? How do they ‘neutralize’ or destroy antigens?

A

Y-shaped proteins produced mainly by plasma cells that are used by the immune system to neutralize bacteria and viruses (immunoglobulin). At the end of the antibody’s arms there are specific patterns that recognize specific antigens. The antibodies destroy the antigen by attaching to it and ensuring macrophages come along to clear the infection

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12
Q

What are the five most prominent Hep Viruses?

A

A-E

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13
Q

Which Hep viruses can lead to chronic disease and what can this progress to?

A

B and C can cause chronic disease which can progress to cancer

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14
Q

How are Hep A and E typically transmitted and how do they usually enter the body?

A

Ingestion of contaminated food or water (i.e lettuce, shellfish) is the main method of transmission but the viruses can also spread through close personal contact and blood exposure. Thus, they are also both enteroviruses as they enter the body the through the digestive system

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15
Q

How are Hep B, C and D typically spread?

A

Horizontal transmission: Sharing bodily fluids, contaminated blood, IV drug use

Vertical transmission

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16
Q

What kind of virus is Hep A and what makes it particularly resistant? How many genotypes of it exist?

A

A naked RNA virus (no capsid around it), and it’s difficult to grow in cell culture. 4 genotypes

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17
Q

Describe the pathogenesis of Hep A (including how long it takes for it to affect the liver), what is the viruses incubation period and how long does the Hep A vaccine provide immunity for?

A
  1. HAV invades the body through the fecal-oral route and multiples in the intestinal epithelium (or in oropharynx) until it reaches the liver by hematogenous spread
  2. After a week, HAV reaches liver cells and replicates within them and re-enter the intestine with bile and appear in feces
  3. After having replicated and discharged the liver cell damage and consequent inflammation begins

Incubation period is 2-6 weeks
The vaccine provides immunity for about 10 years

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18
Q

What do the severity of Hep A symptoms depend on? What is the mortality rate like?

A

The severity of symptoms depends on:

  1. Age; in children, the infection is usually mild without symptoms but generally increases in severity with age
  2. liver function

Mortality is very low (0.3%, doesn’t tend to cause that much of an issue to many patients)

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19
Q

How are hepatitis infections monitored?

A

Serology; the immunoglobulins in our blood

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20
Q

What is the order we produce antibodies in?

A

M, A, D, G and E

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21
Q

Describe the general serology pattern for Hep A and E infections

A

Beginning with virus in the stool and following a period where liver function is affected and liver enzymes rise (i.e ALT).

About 2 weeks after exposure the immune response is mounted:
Anti-A IgM peaks first - once the immune system is fully activated there is a shift towards production of long-term IgG

Anti-A IgG continually peaks as time continues (but the slope will slow)

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22
Q

Describe the body’s recovery process as it begins to fight the Hep A and E virus, how many patient’s infected with Hep A will have a relapse before recovery?

A

Viral replication should stop and the body should no longer be shedding virus particles through feces (no longer be infectious). However, it may take longer for a person’s liver enzymes to return to normal and for normal liver function to return

10% of patients will have a relapse before recovery

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23
Q

Name 3 potential complications of a Hep A infection
*including three extra-hepatic complications

What is offered to treat Hep A?

A
  1. Acute fulminant (acute/sudden) liver failure is rare
  2. Extra-hepatic complications are rare but can include arthritis, myocarditis and renal failure
  3. Post hepatitis syndrome - long term effects

2 vaccines available (long-term immunity), immunoglobulin treatments can offer short-term immunity when given before exposure or within 2 weeks of exposure

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24
Q

Which persons are at an increased risk of a Hep A infection? Which population group has the highest attack rates?

A
  1. travellers
  2. homosexual men
  3. IV drug users
    Highest attack rates are in 5-14 year olds
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25
Q

Describe the Hep E virus, does it commonly lead to chronic complications?

A

Calcivirus-like unenveloped RNA virus, very labile and sensitive. Rarely results in chronic hepatitis

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26
Q

Geographically where is Hep E most common?

A

Eastern South Asia

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27
Q

How is Hep E treated?

A

Mainly to make person comfortable with paracetamol

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28
Q

Describe the Hep B virus, what is the whole virus called? Name the various structures the virus encodes for and which is an indicator of transmissibility? (hint; there are four mentioned)

A

It’s a double stranded DNA hepadnavirus and the whole virus is called the Dane particle

Virus encodes for very simple structures;

  1. S gene that encodes for a surface antibody HBsAg (has 4 phenotypes)
  2. C gene that encodes for the core antigen HBcAg
  3. P gene that encodes for the DNA polymerase which allows it to replicate (through reverse transcriptase)
  4. X gene that encodes for a regulatory gene called the X protein
  5. E antigen encodes for HBeAG. It is a minor component of the core (but antigenically distinct from HBcAg). However it signifies viral replication and is thus an indicator of transmissibility

*Any one of these proteins can cause an immune response in the body

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29
Q

Which Hep virus cannot yet be propagated in cell culture? What is its incubation period?

A

Hep B, incubation period is ~60-90 days

30
Q

What % of patients will recover from Hep B and what % will develop liver failure? How many will display jaundice?

A

90% will recover, 1% will develop liver failure, ~70% will display jaundice.

31
Q

What % of newborns (infected through vertical transmission) will develop chronic Hep B and further complications

A

90% will develop chronic hep b, 25% of those will develop further complications (i.e cirrhosis, carcinoma, etc)

32
Q

Where are Hep B concentrations highest and lowest in the body?

A

Highest in the blood or wound exudate, and lowest in the feces/urine, sweat, tears, breast milk

33
Q

Identify five high risk groups for a Hep B infection

A
  1. Haemophiliacs and other patients requiring blood treatment
  2. People with multiple sex partners
  3. IV drug users
  4. Babies of mothers with chronic HBV
  5. People from endemic regions
34
Q

Briefly describe the pathology of a Hep B infection

*including what is unique about the infectivity of Hep B

A

Virus enters hepatocytes via blood

  1. HBV replicates through an RNA intermediate that releases antigenic ‘decoy particles’; they have no genetic info and are therefore not infectious. However, they do have HBsAg (the outer core), which makes them highly immunogenic.
  2. One of the mRNAs is replicated with reverse transcriptase and makes the zDNA that will eventually form the progeny virions
  3. Some DNA integrates into the host genome causing a carrier state
35
Q

What is the purpose of Hep B decoy particles and what is their relationship with the initial HBV vaccine?

A

They’re made by the virus in an effort to put off the immune system (they are immunogenic) by producing more of these ‘decoy particles’ than they do actual virions.

They were manipulated in order to generate the first HBV vaccine.

36
Q

What are the possible outcomes of an HBV infection and what do they depend on?

A

Depends on the individual and gender; once chronic HBV has been reached 40% of men and 15% of women will die from liver failure

An HBV infection begins as acute (usually asymptomatic). Once an HBV infection becomes chronic it can progress to chronic hepatitis. ~12-25% of people will develop cirrhosis after 5 years which can eventually lead to hepatocellular carcinomas or liver failure (slightly more common). Both can end in a liver transplant or death.

37
Q

When is an HBV infection considered chronic?

A

If the virus is still present 6 months after the initial diagnosis

38
Q

How is Hep B diagnosed?

A

Hep B serology; HBV-DNA in the blood indicates active replication of the virus

Many serological tests are used to detect acute and chronic HPV by detecting

  1. HbsAg; characteristic as the first sign of infection, a general marker of infection
  2. HBeAG; an indicator of viral replication and therefore infectiveness (although some variant forms don’t express HBeAG)
  3. Liver enzymes will also be detected in the bloodstream during the symptomatic phase
39
Q

What does the development of antibodies against HBsAG (HbsAB) signify?

What does it mean for HBsAg to be present in symptomatic patients?

A

Presence of HbsAB indicates an immune response that should clear HBsAg and resolve the chronic infection

HBsAg in symptomatic patients suggests acute HBV infection

40
Q

When does HBeAG seroconversion occur and what does it signify?

A

When people infected with the HBeAg-positive form of the virus develop antibodies against the ‘e’ antigen (Anti-HBe). This means the virus is no longer replicating (but the patient can still be positive for HbsAg). The resulting seroconverted disease state is referred to as the ‘inactive HBV carrier state’.

41
Q

Briefly describe the typical serology pattern observed with an HBV infection
*include when symptoms are typically experienced and when the immune response typically starts

A

Symptoms occur usually when you can detect HBV-DNA rising and HbeAg (indicating viral replication)

Immune response starts about 5-6 weeks
IgM anti-HBc begins but tails off
A stronger immune response also starts from an IgG total anti-HBe which will inevitably prevent the virus from replicating

42
Q

What does the occult HBV infection refer to?

A

The presence of the HBV DNA in the liver but the absence of detectable Hb surface antigens (and anti HBc antibodies). It is a positive indicator for chronic HPV as despite having an antibody to the particle the DNA persists but may not be replicating at the same rate

43
Q 
Describe the significance of each HBV marker 
A) anti Hbs antibodies
B) anti HBc antibodies
C) HBsAG and/or HBV DNA 
D) HBeAG and/or HBV DNA 
E) IgM antiHBc and/or HBV DNA
A 
A) immunity
B) exposure (may also follow a vaccination)  
C) Infection 
D) replication 
E) Disease
44
Q

How is Hep B treated normally?

A
  1. Vaccination is the best strategy: A course of 3 vaccine injections given with the 2nd injection at least 1 month after the first and the 3rd injection given 6 months after the first, contains the S gene that encodes for HBsAg
  2. 3 FDA approved drugs: Hepsera, Lamivudine, interferon-alpha- 2b
  3. Anti HBV immunoglobulin effective soon after exposure and neonatal to children with HBsAg positive mothers
45
Q

Describe the HBV vaccine regime for newborns with carrier mothers and the two options for carrier mothers

A

Newborns with carrier mothers: Hep B vaccine (HBV 1) and hepatitis B IgG (HBIG) within 12 hours of birth followed by a second dose of Hep B vaccine (HBV 2) 1-2 after months and a third dose 6 months after HBV 1

Carrier mothers: multiple injections of small doses of HBIG or oral iamivudine in the last trimester for mothers that have a high degree of infectiousness

46
Q

Name five factors that are generally associated with poor responses to the HBV vaccine

A

> 40 years old, obesity, smoking, alcoholics or those with advanced liver disease

47
Q

What is significant about a person with -ve HBsAg following an infection?

A

They are protected!

48
Q

Why won’t individuals who have received the HBV vaccination have Anti HBc antibodies? Consequently, what does it mean if the individual has Anti HBc antibodies?

A

The core element (HBcAg) of the virus isn’t used in the vaccine, so if the individual has it it means they have been naturally infected and developed natural immunity

49
Q

What is unique about the Hep D virus?

A

It doesn’t carry genes for a capsid and instead uses the HBV capsomeres, therefore it requires Hep B to be present in order to replicate and you can only contract hep D if you already had hep B!

50
Q

What tends to happen when you have a Hep B and Hep D infection? What % of people with Heb B will acquire this?

A

~5% of chronic hep B suffered will Get Hep D

Coinfection: In 90% of cases that have it together: the initial severity of the Hep B infection will be reduced because the viral mechanisms are also producing the Hep D particles. Most make a full recovery with only a severe episode of acute hepatitis initially.

Superinfection: Those who had chronic HBV and developed Hep D: The most severe form of chronic viral Hep forms, has a rapid progression towards liver related deaths and carcinomas

51
Q

Describe the typical serology pattern for an HBV-HDV coinfection

A

After the intial 3-7 weeks of infection, HDV RNA and HbsAg may rise and symptoms such as fatigue will begin. ALT may also elevate.

The body starts the immune response by initially attacking HDV, it develops an IgM to the HDV and eventually total anti-HDV, and hopefully an anti HBs to clear the system and have HBsAg immunity.

52
Q

How are the two types of HBV-HDV infections each ‘prevented’?

A

Co-infections: pre or post exposure prophylaxis to prevent the HBV infection

Superinfection: education to reduce risky behaviours amongst persons with a chronic HBV infection

53
Q

Describe the Hep C virus, what kind of hepatitis (acute or chronic) can it cause? What kind of effect does it have on the body? (Include % of 5 year survival and those who develop cirrhosis)

A

Single stranded RNA virus. Can cause both acute or chronic hepatitis and the disease can range from being mild-very severe, ~20% will develop cirrhosis within 20 years and 5% will not survive the first 5 years.

54
Q

How is Hep C treated/prevented?

A

There is NO vaccine as there are many genotypes and subtypes and it’s difficult to have a vaccine that will cover all of them (6 genotypes, ~80 subtypes)

The only way to prevent disease is to reduce risk of exposure

55
Q

Where does Hep C replicate in the cell?

A

In the cytoplasm via an RNA intermediate (as it is an RNA virus)

56
Q

Although there are many possible methods of transmission, what is the major way Hep C is spread? Therefore, what group of individuals are particularly at risk?

A

Blood transfusions and blood products so individuals with hemophilia have a very high risk

57
Q

What is the incubation period for Hep C? List 4 chronic and 4 acute symptoms, how many with an acute HCV infection will show signs and symptoms?

A

Incubation period is 1-26 weeks, only 5% with acute HCV will develop associated signs and symptoms (so usually asymptomatic)

Acute HCV signs/symptoms:

  1. Decreased appetite and/or weight loss
  2. Fatigue
  3. Muscle or joint pain
  4. Jaundice
Chronic HCV signs/symptoms
1. Mild cognitive problems and fatigue
2. Ascites
3. Easy bruising or bleeding
4. Varicies
\+ fatty liver and cirrhosis
58
Q

Name two ways HCV infections investigated and generally diagnosed? Name one con to this diagnosis method

A

ELISA, quantitative HCV RNA polymerase chain reaction (PCR)

Generally diagnosed through identifying the HCV antibody, however this isn’t useful in the acute phase as it takes 4 weeks a after infection before an antibody will appear

59
Q

Other than identifying an antibody, name two other ways an HCV infection be diagnosed (and a pro and con if appropriate)

A
  1. Identifying HCV RNA: can be used to diagnose HCV in the acute phase although its mainly used to monitor the response to anti-viral therapy
  2. Identifying the HCV antigen, can also be used to identify an acute infection but is easier to carry out than the HCV RNA tests
60
Q 
Interpret the following HCV assays:
A) + Anti HCV and HCV RNA 
B) + Anti HCV and - HCV RNA 
C) - Anti HCV and + HCV RNA 
D) - Anti HCV and - HCV RNA
A

A) acute or chronic HCV depending on clinical context
B) Resolution of HCD
C) Early acute HCV or chronic HCV in immunosuppressive states
D) Absence of HCV

61
Q

Define an acute and chronic HCV infection, how many persons with Hep C will and will not progress to a life-threatening disease?

What should those with an HCV infection definitely not do?

A

Acute HCV: short term and occurs within 6 months, 30% spontaneously clear the virus within 6 months

Chronic: 70%, the subsequent risk of cirrhosis is 15-30% but can occur over a long period of time and the individual may be mainly asymptomatic

*Drinking alcohol will accelerate liver damage

62
Q

Describe the typical serology pattern for acute and chronic HCV, why is it important to have a number of blood tests following an infection to ensure its cleared?

A

Both: ALT rises, Anti HCV will appear

Chronic: ALT is up and down, some progressive decline of the anti-HCV as it tries to fight the infection, but hepatocytes eventually become damaged due to constantly trying to repair

Its important to have multiple blood tests as the HCV RNA is not constantly expressed and may go into transient dormant stages.

63
Q

Name three potential treatments for HCV, what do recent studies suggest is the most effective option (before surgery)

A
  1. Liver transplant
  2. Interferon; for chronic active hep (but only 50% respond)
  3. Ribavirin; anti-viral drug
    Recent studies suggest a combination of interferon and ribavirin is more effective than interferon alone
64
Q

Which viral markers are used as a standard for diagnosing an HAV and HBV acute infection?

A

HAV acute infection: IgM HAV

HBV acute infection: IGM HBcAg

65
Q

Is a patient who is Anti HCV or NAAT positive for an HCV infection likely to experience symptoms?

A

No

66
Q

Which treatment for hepatitis does more than just tackle the symptoms and which type of hepatitis is it used for? How can this type of hepatitis be prevented?

A

Hep D cure, alpha interferon for 12 months

HDV can be prevented with an HBV vaccination

67
Q

Name the family that enteroviruses are a genus of

A

picornaviridae

68
Q

Describe the histological appearance of hepatocytes when infected with a Hep B infection

A

‘Ground glass’ hepatocytes

69
Q

What does it mean if an individual infected with HBV doesn’t have Anti Hbs?

How many HbsAb molecules would you expect to see in a vaccinated individual?

A

There is likely a chronic infection if there is no HbsAb, an HBsAb of >10 mIU/ml indicates a prior vaccination

70
Q

How is HBeAg produced?

A

Produced from the breakdown of core antigen from

infected liver cells

71
Q

Other than those with direct contact with an infected individual, who else needs to be informed about someone’s hepatitis status?

A

Local health protection board member

72
Q

What defines a non-responder for a vaccine? What would the consequential treatment advice be?

A

An antibody level below 10mIU/ml is classified as a non-response to a vaccine. In non-responders, a repeat course of vaccine is recommended, followed by
retesting one to four months after the second course. If it still doesn’t work they’re given HBIG

Jess Infection (18 decks)

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