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AIP: Jaundice > Infectious intra-hepatic cholestasis > Flashcards

Infectious intra-hepatic cholestasis Flashcards

1
Q

In which patient group is jaundice secondary to bacterial infection more commonly seen?

A

neonates - can occur with sepsis

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2
Q

In adults what are the key types of infectious causes of intra-hepatic cholestasis, leading to jaundice? 6 main types

A
  1. Hepatitis A-E
  2. CMV
  3. EBV
  4. Adenovirus
  5. Leptospirosis
  6. Malaria
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3
Q

What are 8 general clinical features of infectious hepatitis?

A
  1. malaise and fatigue
  2. nausea and vomiting
  3. right upper quadrant pain
  4. diarrhoea (may have pale stools and dark urine)
  5. jaundice
  6. hepatomegaly
  7. splenomegaly and lymphadenopathy
  8. liver failure: characterised by hepatic encephalopathy, jaundice, ascites and abnormal clotting
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4
Q

Which infectious hepatitis causes are notifiable disease in the UK?

A

all infectious hepatitis cases

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5
Q

What are the 3 most common causes of viral hepatitis in the UK?

A

hepatitis A, B and C

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6
Q

Of the types of viral hepatitis A-E, which cause a viral/chronic picture?

A
  • Hepatitis A: acute
  • Hepatitis B: acute and/or chronic
  • Hepatitis C: acute ultimately leading to chronic
  • Hepatitis D: acute and/or chronic
  • Hepatitis E: acute
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7
Q

What are the 2 types of hepatitis which are usually acute only?

A

A and E (for E: can be chronic in pregnancy or weak immune system)

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8
Q

What is the usual course of hepatitis A?

A

causes acute liver injury which is usually self-limiting

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9
Q

What type of virus is hepatitis A?

A

single-stranded RNA virus; enterovirus (picornavirus)

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10
Q

What is the incubation period of hepatitis A?

A

2-6 weeks

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11
Q

What is the route of transmission of hepatitis A?

A

faeco-oral

from contaminated water or shelffish

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12
Q

What are hepatitis A epidemics associated with?

A

overcrowding and poor sanitation; thrives in areas of poor hygiene

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13
Q

When are patients with hepatitis A most infectious?

A

before the onset of jaundice

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14
Q

What are 3 risk factors for hepatitis A virus?

A
  1. Young people most affected
  2. Travellers, especially to developing countries: South America, Africa, Russia, Asia
  3. Childcare workers
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15
Q

What are the clinical features of hepatitis A and how do they change with time?

A
  • flu-like symptoms followed by jaundice, pale stools, dark urine, upper right quadrant abdominal pain
  • nausea/vomiting, diarrhoea, malaise, fatigue, headache
  • hepatomegaly/splenomegaly, lymphadenopathy
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16
Q

What is the only real determinant of hepatitis A disease severity?

A

increasing age: greatest morbidity and mortality in those over 50 years old

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17
Q

Is there increasd risk of hepatocellular cancer with hepatitis A?

A

no

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18
Q

What are 6 indications for hepatitis A vaccination?

A
  1. people travelling to or going to reside in areas of high or intermediate prevalence, if aged >1 year old
  2. people with chronic liver disease
  3. patients with haemophilia
  4. men who have sex with men
  5. injecting drug users
  6. individuals at occupational risk: lab worker, staff of large residential institutions, sewage workers, people who work with primates
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19
Q

How should the hep A vaccine be given?

A

after initial dose, booster should be given 6-12 months later

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20
Q

What are the diagnostic test for hepatitis A? 2 types

A
  1. anti-HAV specific IgM (means current infection), anti-HAV IgG suggests previous infection or vaccination
  2. Stool culture: virus in faeces for 2 weeks before onset of jaundice and a few days after
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21
Q

What will LFTs shown in hepatitis A?

A

↑ raised AST, ALT: usually > 1000, ↑ bilirubin

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22
Q

How long does immunity from the hepatitis A vaccine last?

A

lifelong

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23
Q

What is the management of hepatitis A?

A

conservative/supportive, usually self-limiting with complete resolution

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24
Q

What type of virus is hepatitis B?

A

double-stranded DNA hepadnavirus

has outer envelope and lipid core with associated antigens

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25
Q

What type of illness is caused by hepatitis B virus?

A

acute and/or chronic liver injury; infection is dynamic and changes over time, therefore needs lifelong monitoring. starts out as acute and can develop into chronic in a proportion of patients

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26
Q

In what proportion of patients does hepatitis B infection progress from acute to chronic?

A

progresses to chronic in 10% of aduls and 90% of infants

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27
Q

What is the most common cause of hepatitis globally?

A

hepatitis B

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28
Q

In what region of the world are there high prevalence rates of hepatitis B?

A

sub-Saharan Africa, Asia, Pacific Islands

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29
Q

What is the incubation period of hepatitis B?

A

60-90 days

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30
Q

What are 3 routes of transmission of hepatitis B virus?

A
  1. vaginal/anal intercourse
  2. transfusion/ infected blood, IVDU
  3. vertical transmission - in 90% of pregnancies where mother is HBeAg positive
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31
Q

What are the 3 types of antigens of hepatitis B virus?

A
  1. HBV surface antigen (HBsAg): outer lipoprotein envelope
  2. HBV core antigen (HBcAg): internal core which surrounds viral DNA genome
  3. HBV e antigen (HBeAg): previously used as marker of circulating virus and infectivity
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32
Q

How does acute hepatitis B virus lead to chronic hepatitis B virus?

A

if immune compettent, virus will be cleared, if not will lead to chronic HBV

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33
Q

What are 2 classes into which chronic hepatitis B virus patients are grouped into?

A

HBeAg +ve chronic HBV

HBeAg -ve chronic HBV

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34
Q

What are the 3 ways in which HBV and the body react together?

A
  • Immune-tolerant: HBV replicates unchecked and the body acts as if it is unaware of the virus with no immune response, so no liver damage occurs. HBeAg + ve with very high viral load (> 10 8 ). Previously called ‘high infectivity’
  • Immune-active: body recognises the virus but mounts an inappropriate immune response so there are fluctuating levels of virus, infectivity and liver inflammation. Can lead to fibrosis, cirrhosis and HCC. HBeAg + ve or − ve. Viral load usually high
  • Immune-control: body recognises the virus and controls it, so there are low levels of virus (< 1000), low infectivity and little liver damage. HBeAg –ve. Used to be called ‘low risk carrier’ or ‘inactive’. Low risk for complications
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35
Q

What are 9 groups of patients who should receive immunisation against hepatitis B in the UK?

A
  1. all children born: 2, 3 and 4 months of age
  2. healthcare workers
  3. IVDUs
  4. Sex workers
  5. Close family contacts of individual with hepB
  6. individuals receiving regular blood transfusions
  7. CKD patients who may soon require renal replacement therapy
  8. prisoners
  9. chronic liver disease patients
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36
Q

What are the antibodies/antigens that indicate acute hepatitis B, chronic hepatitis B and vaccinated against hepatitis B?

A
  • acute hepatitis B: raised IgM to HBcAg, HBsAg detected 3-5 weeks after infection
  • previous acute hepatitis B, not a carrier: anti-HBc positive, HBsAg negative
  • chronic hepatitis B: anti-HBc positive, HBsAg positive
  • vaccinated: anti-HBs positive only

HBsAg = ongoing infection, either acute or chronic if present >6 months

anti-HBc= indicates current or previous hep B infection (acute or chronic), not present if immunised (c=caught)

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37
Q

What is the physioloy of the antibody response to the hepatitis B immunisation?

A

the vaccine contains HBsAg adsobed onto aluminium hydroxide adjuvant and is prepared from yeast cells using recombinant DNA technology

adequate response = develop anti-HBs, level rises to >100

38
Q

What proportion of adults fail to respond or respond poorly to 3 doses of the hepatitis B vaccine?

A

10-15%

39
Q

What are 5 risk factors for poor response to the hepatitis B vaccine?

A
  1. age over 40 years
  2. obesity
  3. smoking
  4. alcohol excess
  5. immunosuppression
40
Q

In which patients is testing for anti-HBs folowign immunisation indicated, and when?

A

at risk of occupational exposure (healthcare workers), CKD

check 1-4 months after primary immunisation

41
Q

What are 3 classes of response to the hepatitis B immunisation? What should be done for each result?

A
  1. >100: adequate response
    • no further testing required, should still receive booster at 5 years
  2. 10-100: suboptimal response
    • one additional vaccine dose should be given
    • if immunocompetent no further testing required
  3. <10: non-responder
    • test for current or past infection
    • give further vaccine course (i.e. 3 doses again) with testing following
    • if still fails to response then HBIG would be required for protection if exposed to the virus
42
Q

What does the hepatitis B vaccination involve?

A

3 doses of virus

43
Q

What does the presence of HBsAg usually imply?

A

first marker to appear and causes the production of anti-HBs (not immediately present)

normally implies acute disease (present for 1-6 months)

44
Q

What does anti-HBs imply?

A

immunity, either through exposure or immunisation

negative in chronic disease

45
Q

Waht does anti-HBc imply?

A

previous or current infection, negative in immunisation

IgM anti-HBc appears during acute or recent hep B and present for 6 months. IgG anti-HBc persists

46
Q

What is HbeAg a marker of?

A

results from breakdown of core antigen from infected liver cells - marker of infectivity

47
Q

What are 3 aspects of treatment of hepatitis B virus?

A
  1. pegylated interferon-alpha - precipitates seroconversion
  2. tenofovir, entecavir, telbivudine - inhibit HBV replication
    • second line alternatives
  3. transplantation - end-stage cirrhosis or HCC
48
Q

What is the mechanism of action of pegylated interferon-alpha for treating hepatitis B?

A

reduces viral replication, precipitates serovoncersion.

49
Q

What must be given with transplantation for hepatitis B with end-stage cirrhosis or HCC?

A

HBV Immunoglobulin (HBiG) to prevent recurrence in graft

50
Q

What are 4 investigations to consider in hepatitis B?

A
  1. LFTs: AST, ALT high in acute infection (may be normal/slightly raised in chronic infection)
  2. Viral load (HBV DNA)
  3. Serology: antigens/antibodies
  4. Liver biopsy: assess degree of inflammation and fibrosis to decide on phase of disease and guide treatment
51
Q

What will LFTs show in hepatitis B infection?

A

high in acute infection, may be normal/slightly raised in chronic infection

52
Q

What are the clinical features of hepatitis B infection?

A
  • jaundice, fever, malaise, dark urine, pale stool
    • fulminant liver failure with decompensation: ascites, encephalopathy
  • arthritis/arthralgia, rash
  • chronic: asymptomatic, or symptomatic and complicatoins of cirrhosis and portal hypertension, can present with HCC
  • often subclinical in children
53
Q

What should be done to babies born to mothers who are chronically infected with hepatitis B/ have acute hep B in pregnancy?

A

complete course of vaccination + hepatitis B immunoglobulin

54
Q

Can hepatitis B be transmitted via breastfeeding?

A

no (but HIV can)

55
Q

What type of virus is hepatitis C?

A

RNA flavivirus. 6 major genotypes, 1 and 3 most common in UK

56
Q

What is the incubation period of hepatitis C?

A

6-9 weeks

57
Q

What type of course of illness can hepatitis C cause?

A
58
Q

Which hepatitis C genotype is associated with longer treatment and worse prognosis?

A

genotype 1

59
Q

How is hepatitis C transmitted?

A

exchange of blood and bodily fluids

  • IVDU
  • blood transfusion
  • haemodialysis
  • sexual transmission
  • needlestick injuries
  • perinatal infection from infected mother
60
Q

Is there a vaccination available for hepatitis C?

A

no

61
Q

What are the clinical features of hepatitis C?

A

most infections asymptomatic; patients with chronic infection have persistently high LFTs and cirrhosis develops in 20-30%

62
Q

What proportion of patients with hepatitis C clear the virus?

A

15-25% clear the virus

63
Q

What are 6 complications of hepatitis B infection?

A
  1. chronic hepatitis - ground glass hepatocytes on light microscopy
  2. fulminant liver failure
  3. hepatocellular carcinoma
  4. glomerulonephritis
  5. polyarteritis nodosa
  6. cryoglobulinaemia
64
Q

In what regions in hepatitis C more common?

A

Egypt, S Europe, Africa

65
Q

What are 8 investigations which can be performed in hepatitis C?

A
  1. LFTs: raised ALT and AST
  2. INR
  3. Alpha-fetoprotein: often mildly raised
  4. HCV antibody, HCV RNA
  5. HCV genotype
  6. US/CT liver
  7. Transient elastography: non-invasive testing liver stiffness
  8. Liver biopsy: shows extent of fibrosis/cirrhosis
66
Q

What are 5 aspects of the management of hepatitis C virus?

A
  1. Initially symptomatic treatment in early stages
  2. Interferon-alpha (usually pegylated)
  3. Protease inhibitors combination (daclatasvir + sofosbuvir or sofosbuvir + simprevir) with or without ribavirin
  4. Manage underlying cirrhosis
  5. Liver transplant
67
Q

What proportion of patients will develop clinical features of hepatitis C after exposure to the virus?

A

30% e.g. transient rise in aminotrasferases/ jaundice, fatigue, arthralgia

68
Q

What is the investigation of choice to diagnose hepatitis C infection?

A

HCV RNA

69
Q

What is the definition of chronic hepatitis C virus?

A

HCV RNA in blood for 6 months

70
Q

What are 7 potential complications of chronic hepatitis C?

A
  1. Rheumatological problems: arthralgia, arthritis
  2. Eye problems: Sjogren’s syndrome
  3. Cirrhosis
  4. Hepatocellular cancer
  5. Cryoglobinaemia: type II (mixed monoclonal and polyclonal)
  6. Porphyria cutanea tarda (PCT)
  7. Membranoproliferative glomerulonephritis
71
Q

What is the aim of treatment of hepatitis C virus?

A

sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy

72
Q

What are 3 side effects of ribavirin (treatment of hep C)?

A
  1. Haemolytic anaemia
  2. Cough
  3. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic
73
Q

What are 5 side effects of interferon alpha?

A
  1. Flu-like symptosm
  2. Depression
  3. Fatigue
  4. Leukopenia
  5. Thrombocytopenia
74
Q

What type of virus is hepatitis D?

A

RNA (delta) virus; a virus cannot replicate alone, being dependent on HBV

75
Q

What is the likelihood of chronic infection with hepatitis D virus?

A

high risk of chronic infection

76
Q

How is hepatitis D transmitted?

A

parenterally, in similar fashion to hepatitis B (exchange of bodily fluids) and patients may be infected with hepatitis B and D at the same time

  • parenteral
  • sexual less efficient than HBV
  • vertical transmission rare
77
Q

What are 2 ways that a patient may be infected with both hepatitis B and D?

A
  1. co-infection: hepatitis B and D infection at same time
  2. superinfection: hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection
78
Q

In which regions is hepatitis D common?

A

S Italy, N Africa, Middle East

79
Q

How is a diagnosis of hepatitis D made?

A

anti-D IgM in acute infection, anti-D IgG in chronic infection

HDV RNA to demonstrate active infection

80
Q

What are 3 high risks associated with hepatitis D+B superinfection?

A
  1. Fulminant hepatitis
  2. Chronic hepatitis status
  3. Cirrhosis
81
Q

What are 3 aspects of the treatment of hepatitis D?

A
  1. Pegylated interferon alpha
  2. Supportive
  3. Treat underlying hepatitis B
82
Q

How does infection with hepatitis D rather than hepatitis B alone affect prognosis?

A

faster progression to fibrosis and cirrhosis than with hepatitis B alone

83
Q

What type of virus is hepatitis E?

A

single stranded RNA hepevirus, resembles hepatitis A virus

84
Q

How is hepatitis E spread?

A

faecal-oral route

85
Q

What is the incubation period of hepatitis E?

A

3-8 weeks

86
Q

In which areas in hepatitis E common?

A

Central and South-East Asia, Norh and West Africa, Mexico

87
Q

What is a difference in the clinical effects of hepatitis A vs hepatitis E?

A

hepatitis E carries significant mortality during pregnancy

88
Q

Does hepatitis E cause chronic disease?

A

no (rarely)

89
Q

Does hepatitis E cause increased risk of hepatocellular cancer?

A

no

90
Q

Is there a vaccine for hepatitis E?

A

currently in development but not yet in widespread use

91
Q

How is a diagnosis of hepatitis E made?

A

anti-HEV IgM in acute, anti-HEV IgG if previous exposure

92
Q

What is the treatment of hepatitis A?

A

same for A - supportive, usually self-limiting

AIP: Jaundice (10 decks)

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