Infectious intra-hepatic cholestasis Flashcards
(92 cards)
1
Q
In which patient group is jaundice secondary to bacterial infection more commonly seen?
A
neonates - can occur with sepsis
2
Q
In adults what are the key types of infectious causes of intra-hepatic cholestasis, leading to jaundice? 6 main types
A
- Hepatitis A-E
- CMV
- EBV
- Adenovirus
- Leptospirosis
- Malaria
3
Q
What are 8 general clinical features of infectious hepatitis?
A
- malaise and fatigue
- nausea and vomiting
- right upper quadrant pain
- diarrhoea (may have pale stools and dark urine)
- jaundice
- hepatomegaly
- splenomegaly and lymphadenopathy
- liver failure: characterised by hepatic encephalopathy, jaundice, ascites and abnormal clotting
4
Q
Which infectious hepatitis causes are notifiable disease in the UK?
A
all infectious hepatitis cases
5
Q
What are the 3 most common causes of viral hepatitis in the UK?
A
hepatitis A, B and C
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
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)
8
Q
What is the usual course of hepatitis A?
A
causes acute liver injury which is usually self-limiting
9
Q
What type of virus is hepatitis A?
A
single-stranded RNA virus; enterovirus (picornavirus)
10
Q
What is the incubation period of hepatitis A?
A
2-6 weeks
11
Q
What is the route of transmission of hepatitis A?
A
faeco-oral
from contaminated water or shelffish
12
Q
What are hepatitis A epidemics associated with?
A
overcrowding and poor sanitation; thrives in areas of poor hygiene
13
Q
When are patients with hepatitis A most infectious?
A
before the onset of jaundice
14
Q
What are 3 risk factors for hepatitis A virus?
A
- Young people most affected
- Travellers, especially to developing countries: South America, Africa, Russia, Asia
- Childcare workers
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
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
17
Q
Is there increasd risk of hepatocellular cancer with hepatitis A?
A
no
18
Q
What are 6 indications for hepatitis A vaccination?
A
- people travelling to or going to reside in areas of high or intermediate prevalence, if aged >1 year old
- people with chronic liver disease
- patients with haemophilia
- men who have sex with men
- injecting drug users
- individuals at occupational risk: lab worker, staff of large residential institutions, sewage workers, people who work with primates
19
Q
How should the hep A vaccine be given?
A
after initial dose, booster should be given 6-12 months later
20
Q
What are the diagnostic test for hepatitis A? 2 types
A
- anti-HAV specific IgM (means current infection), anti-HAV IgG suggests previous infection or vaccination
- Stool culture: virus in faeces for 2 weeks before onset of jaundice and a few days after
21
Q
What will LFTs shown in hepatitis A?
A
↑ raised AST, ALT: usually > 1000, ↑ bilirubin
22
Q
How long does immunity from the hepatitis A vaccine last?
A
lifelong
23
Q
What is the management of hepatitis A?
A
conservative/supportive, usually self-limiting with complete resolution
24
Q
What type of virus is hepatitis B?
A
double-stranded DNA hepadnavirus
has outer envelope and lipid core with associated antigens
25
What type of illness is caused by hepatitis B virus?
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
26
In what proportion of patients does hepatitis B infection progress from acute to chronic?
progresses to chronic in 10% of aduls and 90% of infants
27
What is the most common cause of hepatitis globally?
hepatitis B
28
In what region of the world are there high prevalence rates of hepatitis B?
sub-Saharan Africa, Asia, Pacific Islands
29
What is the incubation period of hepatitis B?
60-90 days
30
What are 3 routes of transmission of hepatitis B virus?
1. vaginal/anal intercourse
2. transfusion/ infected blood, IVDU
3. vertical transmission - in 90% of pregnancies where mother is HBeAg positive
31
What are the 3 types of antigens of hepatitis B virus?
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
32
How does acute hepatitis B virus lead to chronic hepatitis B virus?
if immune compettent, virus will be cleared, if not will lead to chronic HBV
33
What are 2 classes into which chronic hepatitis B virus patients are grouped into?
HBeAg +ve chronic HBV
HBeAg -ve chronic HBV
34
What are the 3 ways in which HBV and the body react together?
* **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
35
What are 9 groups of patients who should receive immunisation against hepatitis B in the UK?
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
36
What are the antibodies/antigens that indicate acute hepatitis B, chronic hepatitis B and vaccinated against hepatitis B?
* **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)
37
What is the physioloy of the antibody response to the hepatitis B immunisation?
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
What proportion of adults fail to respond or respond poorly to 3 doses of the hepatitis B vaccine?
10-15%
39
What are 5 risk factors for poor response to the hepatitis B vaccine?
1. age over 40 years
2. obesity
3. smoking
4. alcohol excess
5. immunosuppression
40
In which patients is testing for anti-HBs folowign immunisation indicated, and when?
at risk of occupational exposure (healthcare workers), CKD
check 1-4 months after primary immunisation
41
What are 3 classes of response to the hepatitis B immunisation? What should be done for each result?
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
What does the hepatitis B vaccination involve?
3 doses of virus
43
What does the presence of HBsAg usually imply?
first marker to appear and causes the production of anti-HBs (not immediately present)
normally implies acute disease (present for 1-6 months)
44
What does anti-HBs imply?
immunity, either through exposure or immunisation
negative in chronic disease
45
Waht does anti-HBc imply?
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
What is HbeAg a marker of?
results from breakdown of core antigen from infected liver cells - marker of infectivity
47
What are 3 aspects of treatment of hepatitis B virus?
1. **pegylated interferon-alpha** - precipitates seroconversion
2. tenofovir, entecavir, telbivudine - inhibit HBV replication
* second line alternatives
3. transplantation - end-stage cirrhosis or HCC
48
What is the mechanism of action of pegylated interferon-alpha for treating hepatitis B?
reduces viral replication, precipitates serovoncersion.
49
What must be given with transplantation for hepatitis B with end-stage cirrhosis or HCC?
HBV Immunoglobulin (HBiG) to prevent recurrence in graft
50
What are 4 investigations to consider in hepatitis B?
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
What will LFTs show in hepatitis B infection?
high in acute infection, may be normal/slightly raised in chronic infection
52
What are the clinical features of hepatitis B infection?
* 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
What should be done to babies born to mothers who are chronically infected with hepatitis B/ have acute hep B in pregnancy?
complete course of vaccination + hepatitis B immunoglobulin
54
Can hepatitis B be transmitted via breastfeeding?
no (but HIV can)
55
What type of virus is hepatitis C?
RNA flavivirus. 6 major genotypes, 1 and 3 most common in UK
56
What is the incubation period of hepatitis C?
6-9 weeks
57
What type of course of illness can hepatitis C cause?
58
Which hepatitis C genotype is associated with longer treatment and worse prognosis?
genotype 1
59
How is hepatitis C transmitted?
exchange of blood and bodily fluids
* IVDU
* blood transfusion
* haemodialysis
* sexual transmission
* needlestick injuries
* perinatal infection from infected mother
60
Is there a vaccination available for hepatitis C?
no
61
What are the clinical features of hepatitis C?
most infections asymptomatic; patients with chronic infection have persistently high LFTs and cirrhosis develops in 20-30%
62
What proportion of patients with hepatitis C clear the virus?
15-25% clear the virus
63
What are 6 complications of hepatitis B infection?
1. chronic hepatitis - ground glass hepatocytes on light microscopy
2. fulminant liver failure
3. hepatocellular carcinoma
4. glomerulonephritis
5. polyarteritis nodosa
6. cryoglobulinaemia
64
In what regions in hepatitis C more common?
Egypt, S Europe, Africa
65
What are 8 investigations which can be performed in hepatitis C?
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
What are 5 aspects of the management of hepatitis C virus?
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
What proportion of patients will develop clinical features of hepatitis C after exposure to the virus?
30% e.g. transient rise in aminotrasferases/ jaundice, fatigue, arthralgia
68
What is the investigation of choice to diagnose hepatitis C infection?
HCV RNA
69
What is the definition of chronic hepatitis C virus?
HCV RNA in blood for 6 months
70
What are 7 potential complications of chronic hepatitis C?
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
What is the aim of treatment of hepatitis C virus?
sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy
72
What are 3 side effects of ribavirin (treatment of hep C)?
1. Haemolytic anaemia
2. Cough
3. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic
73
What are 5 side effects of interferon alpha?
1. Flu-like symptosm
2. Depression
3. Fatigue
4. Leukopenia
5. Thrombocytopenia
74
What type of virus is hepatitis D?
RNA (delta) virus; a virus cannot replicate alone, being dependent on HBV
75
What is the likelihood of chronic infection with hepatitis D virus?
high risk of chronic infection
76
How is hepatitis D transmitted?
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
What are 2 ways that a patient may be infected with both hepatitis B and D?
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
In which regions is hepatitis D common?
S Italy, N Africa, Middle East
79
How is a diagnosis of hepatitis D made?
anti-D IgM in acute infection, anti-D IgG in chronic infection
HDV RNA to demonstrate active infection
80
What are 3 high risks associated with hepatitis D+B superinfection?
1. Fulminant hepatitis
2. Chronic hepatitis status
3. Cirrhosis
81
What are 3 aspects of the treatment of hepatitis D?
1. Pegylated interferon alpha
2. Supportive
3. Treat underlying hepatitis B
82
How does infection with hepatitis D rather than hepatitis B alone affect prognosis?
faster progression to fibrosis and cirrhosis than with hepatitis B alone
83
What type of virus is hepatitis E?
single stranded RNA hepevirus, resembles hepatitis A virus
84
How is hepatitis E spread?
faecal-oral route
85
What is the incubation period of hepatitis E?
3-8 weeks
86
In which areas in hepatitis E common?
Central and South-East Asia, Norh and West Africa, Mexico
87
What is a difference in the clinical effects of hepatitis A vs hepatitis E?
hepatitis E carries significant mortality during pregnancy
88
Does hepatitis E cause chronic disease?
no (rarely)
89
Does hepatitis E cause increased risk of hepatocellular cancer?
no
90
Is there a vaccine for hepatitis E?
currently in development but not yet in widespread use
91
How is a diagnosis of hepatitis E made?
anti-HEV IgM in acute, anti-HEV IgG if previous exposure
92
What is the treatment of hepatitis A?
same for A - supportive, usually self-limiting
