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III > Hepatitis > Flashcards

Hepatitis Flashcards

1
Q

What is a fibroscan?

A

Elastography (ultrasound) to measure the stiffness of the liver. Painless alternative to biopsy.

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2
Q

What are the functions of the liver? (6)

A

Exocrine: synthesis and secretion of bile salts.
Endocrine: Hormone secretion e.g. IGF-1, TPO.
Clotting functions: produces plasma clotting functions.
Metabolism: Vitamin D and drugs.
Cholesterol metabolism: cholesterol synthesis.
Excretory and degradative functions.

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3
Q

What is viral hepatitis?

A

Blood borne infection. 30-150 million people globally. 350,000-500,000 people die each year from hep-C related complications.

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4
Q

What are the sources of HCV infection?

A

Injecting drug use: 60%
Sexual: 15%
Transfusions: 10%
Other: 15%

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5
Q

How many different genotypes of HCV have been identified?

A
  1. Genotypes 1-3: worldwide.
    Genotypes 1a and 1b: 60% cases.
    Genotype 1: poor response to interferon alone.
    Genotypes 2 and 3: more favourable response to interferon.
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6
Q

Which genotypes of HCV are responsible for most cases?

A

1a and 1b

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7
Q

Which genotypes of HCV are worldwide?

A

1-3.

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8
Q

Which genotypes have a poor response to treatment with interferon alone?

A

1

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9
Q

Which genotypes have a favourable response to treatment with interferon alone?

A

2 and 3

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10
Q

What is the current gold standard in therapy for HCV infection?

A

PEGylated interferon-a in combination with ribavirin.

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11
Q

How does an acute HCV infection differ from a chronic infection?

A

Acute HCV infection is usually asymptomatic, and is only very rarely associated with life-threatening disease.

55-85% of people will go on to develop chronic HCV, risk of cirrhosis is 15-30% in 20 years.

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12
Q

What are the few symptoms that cute HCV can exhibit?

A 
Fever
Fatigue
Decreased appetite 
Nausea
Vomiting 
Abdominal pain 
Dark urine
Grey-coloured faeces
Joint pain
Jaundice
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13
Q

What is HCV? (structure)

A

Positive-stranded RNA virus in the Flaviviridae family.

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14
Q

How does HCV gain entry into hepatocytes?

A

Viral envelope glycoproteins E1 and E2 are essential.

CD81, scavenger receptor BI and the tight junction proteins caudin-1 and occludin are also essential.

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15
Q

What is the lifecycle of HCV? [5]

A
  1. Attachment via CD81, Scavenger receptor B1, Claudin 1.
  2. Engulfment
  3. Replication: NS5B RNA dependent RNA polymerase.
  4. Polypeptide formation: serine proteases.
  5. Viral assembly and budding.
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16
Q

At which stage do Telaprevir and Boceprevir function in the HCV lifecycle?

A

They inhibit polypeptide formation by serine proteases.
Telaprevir inhibits NS3. NS4A serine protease.
Boceprevir binds NS3 active site and inhibits.

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17
Q

What class of anti-HCV treatment are Telaprevir and Boceprevir?

A

Protease inhibitors.
They inhibit polypeptide formation by serine proteases.
Telaprevir inhibits NS3. NS4A serine protease.
Boceprevir binds NS3 active site and inhibits.

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18
Q

How do nucleoside reverse transcriptase inhibitors (NRTIs) work?

A

Cause chain termination in the reverse transcriptase reaction due to absence of the 3’-OH group required for further chain elongation.

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19
Q

Racivir, Apricitabine, Reverset, Elvucitabine, Alovudine and Amdoxovir are all examples of what?

A

Nucleoside reverse transcriptase inhibitors that cause chain termination in the reverse transcriptase reaction due to absence of the 3’-OH group required for further chain elongation.

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20
Q

How do nucleoside RNA replicase inhibitors (NRRI) work?

A

Non-obligate chain terminators.

Interact with the catalytic site by being analogues for the normal substrate.

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21
Q

How do non-nucleoside RNA replicase inhibitors (NNRRI) work?

A

NNRRI interact with a number of different allosteric sites. Example being ABT-333.

22
Q

What kind of drug is ABT-333?

A

It is a non-nucleoside RNA replicase inhibitor which functions by binding to a number of different allosteric sites on the replicase enzyme.

23
Q

What is Hepatitis A?

A

Viral liver disease. Mild - severe illness.

Improved sanitation and the hepatitis A vaccine are the most effective ways to combat the disease.

24
Q

What is Hepatitis B?

A

Viral, acute and chronic.

Transmitted through contact with the blood or other bodily fluids of an infected person.

25
Q

What is Hepatitis E?

A

Transmitted from person-person via the faecal-oral route. Water borne disease. Frequent in children, mostly asymptomatic.

26
Q

What is alcoholic hepatitis?

A

An increased NADH:NAD ratio.
NADH inhibits gluconeogenesis, prevents the oxidation of lactate to pyruvate. Causes a build up of LACTATE. Lactic acidosis and hypoglycemia occurs.

27
Q

Why can hypoglycemia occur in alcoholic hepatitis?

A

Lactate builds ups due to prevention of oxidation of lactate to pyruvate by inhibition of gluconeogenesis by NADH.
This buildup of lactate can cause lactic acidosis.

28
Q

Why is alcoholic hepatitis known as fatty liver?

A

Normally fatty acid oxidation is required to produce NADH. As NADH levels are increased in alcoholic hepatitis (provided by alcohol) then the use of fatty acids decreases and they can accumulate in the liver.

29
Q

How many forms of chronic hepatitis are there?

A

Two. Chronic persistent: minimal degree of inflammation and follows benign course. Active carrier.

Chronic active: continual destruction of hepatocytes.

30
Q

What are the structural changes caused to the liver by hepatitis?

A

Hepatocytes can accumulate large droplets of fat as inclusions between swollen cells. A collagen fibre network develops around liver cells near the hepatic venules leading to cell death and increasing fibrosis.

31
Q

What type of virus is Hep C and why is the genotype important?

A

Enveloped RNA virus with 10 genes. Transmitted through infected blood. Genotype is important as different genotypes respond differently to different treatments,

32
Q

What is the future direction of Hep C treatment?

A

IFN-free combination of direct-acting antiviral drugs.

33
Q

Which genotypes have a nearly 100% response rate?

A

1,2 and 4.

Genotype 3: 60-90%

34
Q

How do we treat genotype 3 (no fibrosis)?

A

PEGylated Interferon alpha 2a (180mcg per week)

Plus ribavirin.

35
Q

How do we treat genotype 3 (treatment naive but with liver fibrosis)? (D+S)

A

Daclatasvir 60mg daily
Sofosbuvir 400mg daily.
12 week treatment.

36
Q

What is Harvoni?

A

Sofosbuvir 400mg and ledipasvir 90mg. Used for Genotype 1a.

37
Q

How do we treat genotype 1a Hep C?

A

Harvoni.

Sofosbuvir 400mg and ledipasvir 90mg.

38
Q

How is genotype 2 treated?

A

Sofosbuvir + Ribavirin. 12-week course.

39
Q

What is ribavirin?

A

Nucleoside guanosine analogue. Interferes with viral replication. Nucleoside inhibitor. Dose is weight dependant.

40
Q

What is sofosbuvir?

A

HCV NS5B RNA polymerase inhibitor with potent antiviral activity against all genotypes. High barrier to resistance.

41
Q

What monitoring of patients receiving anti-viral therapy for Hep C is needed?

A

FBC - neutrophil, TFTs, LFTs, anaphylaxis.

Hepatotoxicity.

42
Q

What is one anti-HEP C drug that inhibits NS5B RNA polymerase?

A

Sofosbuvir.

43
Q

What is one anti-HEP C drug which is a nucleoside guanosine analogue?

A

Ribavirin.

44
Q

How does daclatasvir function?

A

Inhibits the NS5A protein.

45
Q

What is one anti-HEP C drug that inhibits NS5A?

A

Daclatasvir.

46
Q

Which type of Hep infections normally won’t lead to long-term infection and usually doesn’t cause complications?

A

Hep A. The liver heals in about 2 months and Hep A can be prevented with a vaccine.

47
Q

What type of Hep infection can cause long-term infection but most people recover from in 6 months?

A

Hep B. Can cause liver damage. Once infected, patients can spread the virus even if they do not feel sick. Vaccine is effective.

48
Q

Which type of Hep infection cannot be prevented by vaccine?

A

HepC. Many people with this are asymptomatic and 80% will get long-term infection which can lead to cirrhosis.

49
Q

What type of Hep infection is usually self-limiting (resolving in 4-6 weeks) and spread through contaminated water?

A

Hep E.

50
Q

Ganciclovir

A

NOT commonly used for the management of genital herpes

III (24 decks)

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