Hepatitides Flashcards
1
Q
Presentation of Hep C?
A
Acute: Typically anicteric - only <25% are apparent
Chronic: persistent HCV RNA at 6 months - fatigue, weight loss, muscle and joint pain, RUQ discomfort
2
Q
What Is immunoreactive disease?
A
Inflammation kicks in again, ALT rises, become symptomatic again.
This stage risks fibrosis
3
Q
Loss of Hep B e antigen - what does this mean?
A
Partial host immune response
Not enough to clear the virus entirely
4
Q
Transmission of hep E?
A
Water or food borne faecal oral
5
Q
When do you stop Rx in someone with Hep B on Rx?
A
Cirrhosis - lifelong Rx
No cirrhosis - see chart
6
Q
Cure for Hep D - how do you diagnose?
A
- Clearance of HDV (suppression of HDV RNA 24 weeks after completion)
- Clearance of HBV
- Normalization of ALT levels
7
Q
Which antigens are implicated in active viral replication in the liver in Hep B?
A
Hep E antigen
Hep S antigen
8
Q
Classic leptospirosis and pattern of liver involvement?
A
- Jaundice and fever +/- liver involvement
- Bilirubin very high
- Impairment of secretion of conjugated bilirubin as opposed to hepatocellular damage - therefore ALT usually <3 x ULN
9
Q
Which diseases causes a much higher bilirubin than transaminases?
A
Leptospirosis
Malaria (haemolysis -> shock later)
10
Q
Clinical presentation of Hep E?
A
Acute icteric hepatitis:
* Occurs in 5-30% of cases (more frequently HEV-1 and HEV-2).
* Lasts 2-6 weeks.
* Prodromal phase (~7d) followed by icteric phase.
11
Q
Incubation period hep E?
A
2-6 weeks
12
Q
What Rx should you initiate in Hep B cirrhosis?
A
Tenofavir or entecavir
Entecavir - children!
13
Q
Risk of Hep D and Hep B together?
A
Fulminant hepatitis in 3-4% of coinfected patients.
Highest risk to patient if they already have Hep B for a long time (better prognosis if contract both at the same time)
14
Q
Extra hepatic manifestations?
A
- Neurological: Guillain-Barre syndrome, neuralgic amyotrophy, encephalitis, myelitis.
- Renal: IgA nephropathy, membranoproliferative glomerulonephritis with or without cryoglobulinaemia, membranous glomerulonephritis.
15
Q
How is Hep C transmitted?
A
Mainly transmitted trough percutaneous exposure to blood - needles, IVDU, medical devices in developing countries
Also: sexual, MTC
16
Q
How long until DNA/surface antigen detectable in blood for hep B?
A
4–7 weeks before HBV DNA and HBsAg
become detectable
17
Q
How do you treat Hep E?
A
Ribavarin for 3 months in immunocompromised patients if persistent RNA Hep E at 12weeks
18
Q
What will tests show in a resolved Hep B infection?
A
Anti HBs
Anti HBc
Not antigens or DNA
19
Q
Why is it rare for adults to get Hep A?
A
Previous infection
20
Q
Extra hepatic manifestations of hep B?
A
*Renal
* Membranous glomerulonephritis
* Membranoproliferative glomerulonephritis
Rheumatologic
* Polyarteritis nodosa
Aplastic anemia
Vasculitis
21
Q
Diagnosis of leptospirosis?
A
- Within first week - PCR of blood
- Urine PCR - better as it stays positive for longer
- Serology - IgM ELISA or MAT agglutination test after 1st week
22
Q
What constitutes chronic Hep E?
A
detection of HEV RNA in serum > 6 months
23
Q
Pathogens causing haemolysis?
A
- Viruses: CMV, EBV, Hep B and C, parvovirus
- Bacteria: Leptospirosis, shigella, campylobacter
- Fungus: Aspergillus
- Parasites: malaria***
24
Q
Which hepatitis has the highest rate of HCC and cirrhosis?
A
Hep B
25
Cure in Hep B?
Functional cure:
HBsAg loss
Undetectable levels of HBV DNA in peripheral blood
Could be reactivated if immunosuppressed
Virological cure not currently available but goal is:
Eradication of HBV DNA from blood and liver
Continued positive anti-HBc with or without anti-HBs
26
What would you advise for a Hep B positive mother re: Rx?
If HBV DNA >200,000 -> Rx with TDF
If not, TDF starting 30-32 weeks until 3 months post partum.
C-section not indicated.
27
When will you see IgG Anti HAV and how long for?
7 days following symptom onset
Last for years
28
What is the Hep A vaccine?
- Inactivated HAV vaccine (age >1y)
- 2-dose vaccination has 94% efficacy
- HAV vaccine or immunoglobulin within 2 weeks of exposure.
29
39 yr old male with fever, jaundice, and bleeding, been in the jungle. Decreased GCS and bleeding. ∆∆?
Yellow fever
Dengue
Leptospirosis
Malaria
Hepatitis A/E
30
What is risk of HCC in patient with Hep C?
1-4% a year
31
Difference between acquiring Hep B infection as adult or neonate?
Immunotolerant disease - neonates
Immunoactive disease - adults
Difference is ALT rise (immunoactive)
Very high HBV DNA as very high e antigen (virus is replicating)
32
What is the difference between Hep E in developed vs developing countries?
33
∆ for entamoeba histolytica in context of liver abscess?
Drain abscess, antigen testing of fluid
***ELISA against galactose-lectin antigen***
Fluid culture - usually negative for trophozoites as they are in the wall of the abscess
34
Why do HIV drugs also work for Hep B?
DNA virus but becomes RNA and back to DNA again - reverse transcriptase responsible for the RNA part, HIV drugs can work here!
35
What is the Rx for Hep C?
Interferon free DAA (direct-acting antiviral) regimens
36
∆∆ hepatocellular injury causing jaundice?
- YF - renal failure usually involves **proteinuria! Transaminases much higher than the bili
- Dengue - no proteinuria
- Acute fulminant hepatitis
- Rift Valley fever - depends on epidemiology
- Shock e.g. sepsis, cholera
- Leptospirosis - do not get hepatocellular injury
37
Complications of Hep A?
hepatic failure, relapsing hepatitis, prolonged cholestasis, autoimmune hepatitis
Extra hepatic? Rash, arthritis, vasculitis
38
What is the family and genus of hepatitis E?
*Family: Herpeviridae
*Genus: Orthohepevirus
4 genotypes HEV 1-4
39
How long are patients contagious with Hep A?
Incubation period and 1 week after onset of jaundice
40
What test can you do in resource poor settings to differentiate between fibrosis and cirrhosis? What about resource rich?
AST to platelet ratio index (>2 = cirrhosis)
Fibroscan
41
How many patients with chronic Hep B will develop cirrhosis?
25%
42
How do you monitor for Hep B related HCC?
Ultrasound every 6 months
43
What happens when immune response kicks in for hep B?
Lose the Hep e Antigen
low viral load
No to mild inflammation of liver, asymptomatic
44
Transmission of Hep D?
IVDU and other parenteral exposure
Sexual
Interfamilial
Perinatal
45
Causes of conjugated/direct bilirubin rise?
Post hepatic
Some causes of hepatocellular damage
46
Transmission of Hep A?
Faecal oral (contaminated food/water)
47
Pattern of liver dysfunction in hep A?
ALT > AST
Liver enzymes >1000
Bilirubin not that high (<100)
Mildly raised ALP
Transaminases rise before bili
- Alcohol and YF cause AST>ALT
- Lepto - very high bili
- Peak of bilirubin 7-10 days after onset of jaundice, ALT peaks at 1 month
48
Antigens for hepatitis B?
Core antigen
Surface antigen
Envelope (E) antigen
49
∆∆ of jaundice causing Intrahepatic cholestasis
Lepto ***
Brucella - *** - transaminase rise
Typhoid - *** - transaminase rise
TB miliar disseminated
Pyogenic abscess
Ameobic abscess
Hep A with cholestasis
Non infectious/drugs
50
When do you stop Rx in someone with Hep B on Rx?
Cirrhosis - lifelong Rx
No cirrhosis - see chart
51
How do you diagnose chronic Hep B?
Defined as detection of HBsAg
on 2 occasions measured 6 months apart
52
Single biggest risk factor for hep A?
Lack of access to clean water/sanitation
53
What type of virus is Hep C?
*Family: Flaviridae
*Genus: Hepacivirus
54
What do you see on liver biopsy in yellow fever?
Condensed chromatin in nucleus known as councilman bodies, with little inflammatory cells surrounding
55
What do you need for infection with Hep D?
Hep B infection
56
What type of virus is Hep A?
*Family: Picornaviridae
*Genus: Hepatovirus
57
Partial cure in Hep B?
Continued detection of Hep B surface antigen (last one to go) but Hep B DNA <2000iu/ml
58
Goal of Rx of Hep B?
Lose the Hep B s antigen
Undetectable Hep B DNA
59
What are the WHO guidelines for Rx of Hep C?
60
What does surface antigen in blood mean?
Hep B infection (screening test)
Does not tell you acute vs chronic
61
How do you test for Hep E?
detection of anti-HEV IgM
HEV RNA detectable
62
Prevention of Hep E and Hep A?
Boiling and chlorination of water
Heating food
Screening blood banks
63
Diagnosis of Hep D?
HDV RNA (HDAg - very short-lived)
Anti-HDV IgM* Positive in acute infection
Anti-HDV IgG
HBsAg must also be present
64
Hepatic complications of Hep E?
0.5-4% fulminant hepatic failure
Chronic infection: HEV-3 & HEV-4 - immunocompromised
Pregnant patients - higher risk of fulminant liver failure with high mortality risk
65
Drug options for Hep C?
66
Is there vaccine for Hep E?
Vaccine: recombinant vaccine. 3-dose series has >99% efficacy.
Licensed only in China for people >16y.
67
Who are most at risk of chronic hep B infection?
Children!
90% of infants <1 year
30% of children aged 1-5 y
5-10% of adults
68
Who should get treated for Hep C?
Anti HCV antibodies and HCV RNA at 6 months
Recommended for all people (adults and children) with acute or chronic HCV infection.
69
How many people develop acute hep B infection? Symptoms?
1/3
Fever, fatigue, malaise, jaundice, abdo pain
70
Which helminths cause cholangiocarcinoma?
Chlonorchis sinensis and Opistorchis viverrini
71
29 year old female, onset of jaundice and fever 7 days ago. Febrile, heptaosplenomegaly, low Hb, low WCC, retics 12%, bili raised (indirect), LDH, ALT 2x ULN. ∆∆?
Babesia
Dengue
Malaria*** - strain depends, usually falciparum can be vivax (rare but can happen)
Bartonella bacilliformis causing Oroya fever
Snake and spider bites
72
Incubation period for Hep A?
14-28 days
73
Which test for Hep A and when?
IgM anti-HAV
If patient is symptomatic -> IgM probably effective
74
Causes of unconjugated/indirect bilirubin rise?
pre hepatic/hepatic
75
What is the window period in Hep B and how do you diagnosis Hep B in this period?
HBsAg coming down - too low to detect
Anti HBs not yet high enough
Must test anti Hep core IgM in this period
76
What should you do if a patient is IgM positive?
Test for HEV RNA
If immunocompromised, always test HEV RNA if clinical suspicion even if IgM negative (do not mount response)
77
What do you see under an electron microscope for hep B?
Dane particle (main virus)
Subviral particles shed nearby (contain surface antigen)
78
Rx consideration for Hep D?
PEG-Interferon alpha for 1 year
Consider adding on nucleotide analogies (TDF)
79
Anti HBc only (not surface)?
Previously infected, dormant infection, risk of reactivation
80
Transmission of Hep B
Mother to child transmission
Transfusions
Intrafamilial transmissions
Sex
Percutaneous inoculations
81
∆∆ of obstructive jaundice in the tropics?
Fasciola hepatica (CBD preferentially)
Chlonorchis sinensis and Opistorchis viverrini (intrahepatic ducts)
Ascaris lumbricoides
Echinococcus granulises (atypically)
Cryptosporidium parvum (rarely)
Non infectious causes
82
If no cirrhosis but Hep B positive, how do you determine who needs Rx? (Resource limiting settings)
Age, ALT and HBV DNA
83
What are the phases of Hep A?
Prodromal <7 days: fever, malaise, anorexia, abdo pain, N&V
Icteric >7days: jaundice, dark urine, pale stools, HM
84
Extra hepatic disease manifestations of Hep E?
* Mixed cryoglobulinaemia
* Vasculitis
* Atherosclerotic cardiovascular disease
* Type 1 membranoproliferative glomerulonephritis
* Focal segmental glomerulosclerosis
* Interstitial nephritis
* Type 2 diabetes
* Lymphoproliferative disease
* Non-Hodgkin lymphoma and hepatosplenic T-cell lymphoma
* Porphyria cutanea tarda and lichen planus
* Hashimoto’s thyroiditis and Graves’ disease
* Mooren’sulcers and Sjogren’s syndrome
85
Pattern of disease in yellow fever?
Period of infection 3-6 days - headache, fever, myalgia,leukopenia, bradycardia (pagets), conjunctival injection
1 day symptoms abate
Period of intoxication 3-6 days - jaundice, hypotension, haemorrhage, convulsions, liver failure
86
What is the classic picture of deranged LFTs in yellow fever? Key differential?
Deranged transaminases - very high
AST > ALT
∆∆ - Alc hep
87
What would you expect in immunity to Hep B?
Anti HBs
88
73 yr old male with RUQ pain for 2 and half weeks, fever, chills, jaundice, vomiting. 4 months previously had bloody diarrhoea. WCC raised, normal plts, ALT 50, ALP 395. ∆∆?
Entamoeba Histolytica
Pyogenic abscess
Typhoid/Paratyphoid (but timing not quite right)
89
How do you test for HCV?
*Anti-HCV antibodies (at 12 weeks)
*HCV RNA - confirm and monitor
*HCV core antigen can be used as a surrogate of HCV RNA testing
*HCV genotype and subtype determination
90
What is the Hep A vaccine?
- Inactivated HAV vaccine (age >1y)
- 2-dose vaccination has 94% efficacy
- HAV vaccine or immunoglobulin within 2 weeks of exposure.
91
What are the Rx of all the hepatitides?
A - nil
B - TDF (or entecavir children)
C - Interferon Alpha DAA
D - interferon alpha
E - Ribavarin
92
What does it mean if
1) HBsAb positive only?
2) HBsAb positive and HBcAb positive?
3) HBcAb positive and HBsAg positive?
1) immunity from vaccination
2) Immunity from previous infection
3) Chronic infection
