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Medical Microbiology > Hepatitis > Flashcards

Hepatitis Flashcards

1
Q

What is Hepatitis B?

A

Small DNA virus
Infects hepatocytes

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2
Q

What can hepatitis B cause?

A

Acute infection
Chronic infection
Predisposes to hepatocellular carcinoma
Extrahepatic disease

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3
Q

Describe hepatitis B in the UK

A

96% of new chronic hepatitis B in UK found in migrants
Intermediate prevalence in large urban centres in low endemic countries

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4
Q

How is hepatitis B spread?

A

Parentally via blood and bodily fluids
Not spread by saliva, insect bites or casual contact
Sexual contact, drug use, blood transfusion, haemodialysis

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5
Q

How are chronic hepatitis B infections transmitted?

A

Mostly vertical (mother to baby) or early horizontal (among individuals of the same generation) globally

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6
Q

How much blood is sufficient for transmission of hepatitis B?

A

0.00004ml - highly infectious

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7
Q

Is hepatitis B more or less infectious than HIV?

A

50-100x more infectious than HIV

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8
Q

What are risk factors of hepatitis B?

A

Age at acquisition determines outcome - 95% or neonates develop chronic infection, 95% of immunocompetent adults spontaneously clear HBV (sAG loss)
Chronicity higher in immunosuppressed (more chronic)

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9
Q

When does vertical transmission occur?

A

Usually at delivery
Depends on viral load and Hepatitis B e-antigen (HBeAg) status of mother - transmission occurs in 90% of HBeAg+ where HBV > 10^7 IU/ml)

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10
Q

Describe hepatitis B structure

A

Small surface proteins
Icosahedral core
Polymerase
DNA
Large surface proteins
Medium surface proteins

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11
Q

Describe the genome of HBV

A

Partially double stranded
Inner strand shorter than outer strand
Enters hepatocytes
In nucleus, inner strand completed by cellular polymerases
Forms covalently closed circular DNA (cccDNA)

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12
Q

How is cccDNA formed?

A

Mutistep process converting relaxed circular DNA of HBV to cccDNA

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13
Q

What happens once cccDNA formed?

A

Incorporated to host genome as an episome
Template for HBV replication
Remains in infected cells for the life of the cell
Implications for reactivation of HBV even after long-term quiescence

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14
Q

What does a HBsAg serology test for?

A

Ongoing HBV infection

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15
Q

What is an anti-HB serology?

A

Tests immunity - natural or vaccine

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16
Q

What is an anti-HBc (IgG) serology for?

A

Current or resolved HBV infection

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17
Q

What is an anti-HBc (IgM) serology for?

A

Acute HBV infection or flare of chronic HBV

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18
Q

What is a HBeAg serology for?

A

Active viral replication (tolaragen - helps evade host immunity)

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19
Q

What is an anti-HBe serology for?

A

May indicate immune control but active replication may occur

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20
Q

What is a HBV DNA serology for?

A

Direct measure of viral particles

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21
Q

Describe the immunopathology of hepatitis B

A

Injury to HSC, fibrocytes, Kpuffer cells and portal fibroblasts cause oxidative stress, TLR4 signalling/innate immunity and NFkB/JNK signalling
Inflammation due to chemokine and cytokine prod
Injury to hepatocytes and cholangiocytes leads to epithelial mesenchymal transition (EMT) and hepatocellular EMT
Fibrogenesis and cancer

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22
Q

What are the stages of infection of HBV?

A

Immune tolerant - high HBV DNA, low ALT (alanine transaminase)
Immune clearance (HBeAg+ chronic hepatitis) - decreased HBV DNA, high ALT
Inactive carrier phase - low HBV and ALT
Reactivation (HBeAg- chronic hepatitis) - low HBV and ALT

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23
Q

Describe post-exposure prophylaxis for HBV

A

For unvaccinated individuals - Hepatitis B immunoglobulin (HBIG) within 48hrs and HBV vaccination
For vaccinated individuals - Anti-HBs titres assessed, if < 10 IU/ml treat as unvaccinated, if > 10 IU/ml no action required

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24
Q

How is prophylaxis done for infants of HBsAg+ mothers?

A

HBIG at birth
HBV vaccination schedule
Not 100% effective

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25
Q

Describe prophylaxis in pregnancy

A

Antivirals in third trimester
Infant vaccine only if mother has unkown HBsAg and father HBsAg+ve
Test infants at 9-12 months

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26
Q

Describe prophylaxis in pregnancy

A

Antivirals in third trimester
Infant vaccine only if mother has unkown HBsAg and father HBsAg+ve
Test infants at 9-12 months

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27
Q

Describe HBV therapy

A

Direct-acting antivirals - nucleoside/nucleotide analogues
Immune stimulation - interferon
Important indications for treatment
Reactivation
Extrahepatic manifestations

28
Q

What do nucleotide/nucleoside analogues do?

A

Inhibit reverse transcriptase activity of HBV polymerase
NAs incorporated to virions, leading to chain termination and non-functional viral DNA
Well tolerated oral treatment

29
Q

What does interferon do?

A

Activates antiviral genes in infected cells and adaptive immune systems
PEG-IFN once weekly
No resistance
Poor tolerability - flu-like symptoms, BM suppression, depression, can trigger latent autoimmunity, avoid in cirrhotics with synthetic failure

30
Q

What happens in reactivation of HBV?

A

Sudden reappearance/increase HBV replication in patient with prior evidence of resolved or inactive infection

31
Q

Describe a typical clinical scenario in which the risk of reactivation if very high

A

HBsAg +ve and receiving anti-CD20 (e.g. rituximab) and/or stem cell transplantation

32
Q

Describe a typical clinical scenario in which the risk of reactivation is high

A

HBsAg +ve and will receive high dose steroids (>20mg/d for >4 weeks) or anti-cytokine agents (e.g. Campath)

33
Q

Describe a typical clinical scenario in which the risk of reactivation is moderate

A

HBsAg +ve and chemotherapy without steroids or anti-TNFa treatment or anti-rejection therapy for solid organ transplants

34
Q

Describe a typical clinical scenario in which the risk of reactivation is low

A

HBsAg +ve methotrexate/azathioprine
HBsAg -ve high dose steroids or anti-cytokine agents

35
Q

Describe a typical clinical scenario in which the risk of reactivation is very low

A

HBsAg -ve chemotherapy without steroids or anti-TNFa treatment or anti-rejection therapy for solid organ transplants or methotrexate/azathioprine

36
Q

Describe reactivation

A

Occurs in HBsAg +ve usually
Can occur for HBsAg -ve HBsAb +ve
Always check HBsAg/HBcAb/HBV DNA for any immunomodulation
Especially rituximab and steroids

37
Q

How is reactivation managed?

A

Stop cytotxics/immunosuppressants
Tenofovir/entacavir
+/- liver transplantation

38
Q

Describe the incidence of hepatocellular carcinoma

A

0.3-0.6% incidence in non-cirrhotics
2.2-3.7% incidence in compensated cirrhotics

39
Q

What is hepatocellular carcinoma?

A

Most common type of primary liver cancer
Occurs most often in people with chronic liver diseases e.g. cirrhosis caused by HBV

40
Q

What can cause HBV to be carcinogenic?

A

BCP mutations
Genotype C
Male
Older age
Heavy EtOH
Family Hx HCC
Metabolic syndrome

41
Q

Describe future therapy options for HBV

A

Entry inhibitors (e.g. Bulevirtide)
Core protein binders
RNA interference (e.g. siRNA)
Inhibitors of HBsAg release
HBsAg neutralisation
Inhibitors of cccDNA
TLR agonists (immune modulation)
Immune checkpoint inhibitors
Engineered T cells
Therapeutic vaccines
Multi-targeted immunotherapy

42
Q

Describe delta virus

A

Small enveloped RNA virus
Requires co-infection with HBV (uses HBsAg as its own envelope)
Systematically screen patients with HBVsAg +ve for HDV
Check HDV RNA in anti-HDV Ab
Co-infection or superinfection
Synergistic fibrosis

43
Q

Describe treatment of HDV

A

Traditional = 48 weeks of PEG-IFNa
Poor efficacy and tolerability
Combination IFN and nucleoside/nucleotide not effective
Novel therapies - bulevirtide (HDV entry inhibitor) - approved by EMA, awaiting NICE, lonafarnib in evaluation, other drugs (silencing RNA), combinations

44
Q

Describe the structure and genome of HCV

A

E1 and E2 surface envelope glycoproteins
Core forms nucleocapsid
Non-structural proteins

45
Q

How is HCV diagnosed?

A

History - risk factors
HCV Ab EIA - if negative then immunocompetent and no chronic HCV, if positive then patient has had contact with the virus
Positive HCV Ab means HCV RNA present
Presence of Abs 2 weeks after exposure but can be longer
HCV RNA present early as 1 week
Babies tested after 18months
Check genotype

46
Q

How is HCV treated?

A

Traditionally PEG-IFN and ribavarin but this had poor tolerability and cannot be used in advanced cirrhosis/fibrosis so searching for new drugs

47
Q

What do direct-acting antivirals (DAAs) target?

A

Viral replication

48
Q

What are combinations of DAAs based on?

A

HCV genotype
Presence of cirrhosis
Treatment history
Severity of cirrhosis
Blood counts
Renal impairment

49
Q

How do DAAs work?

A

Inhibit specific non-structural proteins that are vital for HCV replication

50
Q

What DAAs target translation of the virus?

A

NS3/4A protease inhibitors:
- Telaprevir
- Boceprevir
- Simeprevir
- Faldaprevir
- Paritaprevir
- Ritonavir

51
Q

What DAAs target the replication stage of the virus?

A

NS5B polymerase inhibitors:
- Sofosbuvir
- Dasabuvir

52
Q

What other type of DAA is there?

A

NS5A inhibitors (MOA not known):
- Daclatasvir
- Ledipasvir
- Ombitasvir

53
Q

How do resistance mutations occur?

A

Due to high replication rate of virus, leading to novel strains and quasi-species of HCV
Mutations in NS3, NS5A and NS5B genes
Resistance testing may be of less value given the multitude of retreatment options

54
Q

What is extrahepatic disease?

A

Disease located or occurring outside the liver as a result of HCV

55
Q

Give examples of extrahepatic disease

A

Cardiovascular disease
Chronic kidney disease
Insulin resistance and T2D
B cell lymphoma
Cryoglobulinaemic vasculitis - immune complex-mediated inflammation of blood vessels

56
Q

What are the challenges of HCV treatment?

A

Resistance mutations
Cost of DAA regimens and retreatment esp in LMICs
Screening and access to treatment in vulnerable groups

57
Q

What type of virus is hepatitis A?

A

Single stranded RNA

58
Q

How is hepatitis A transmitted?

A

Faeco-oral route

59
Q

Describe effects of hepatitis A

A

Acute self-limiting episode of hepatitis
Asymptomatic/symptomatic
Can survive in dried faeces for 4 weeks
Self-limiting jaundice/cholestasis > 10wks
Acute hepatic failure possible (1%)

60
Q

How long does it take to recover from hepatitis A?

A

Full recovery in almost by 6 months
Relapsing over 2-3 months

61
Q

What kind of virus is hepatitis E?

A

Small RNA virus

62
Q

How is hepatitis E transmitted?

A

Faeco-oral transmission via water or pork products

63
Q

Where is hepatitis E found?

A

North Africa and Middle East

64
Q

What are the effects of hepatitis E?

A

Self-limited acute hepatitis or chronic hepatitis in immunocompromised
Anorexia, nausea, abdominal pain and transaminitis +/- diarrhoea, arthralgia, rash
60% prolonged cholestasis for months
Fulminant hepatic failure (FHF) possible - liver begins to fail very quickly

65
Q

When does FHF occur more frequently?

A

In pregnant women
15-25% mortality and worse fetal outcomes

66
Q

What is used to treat hepatitis E?

A

Ribavarin may be used to treat in certain circumstances

Medical Microbiology (23 decks)

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